Citations

Objective: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. Background: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. Methods: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. Results: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P=0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P=0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P=0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. Conclusions: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Importance Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.

Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

PittUDT, a recursive partitioning decision tree algorithm for predicting urine culture (UC) positivity based on macroscopic and microscopic urinalysis (UA) parameters, was developed in support of a broader system-wide diagnostic stewardship initiative to increase appropriateness of UC testing. Reflex algorithm training utilized results from 19,511 paired UA and UC cases (26.8% UC positive); the average patient age was 57.4 years, and 70% of samples were from female patients.

Abstract Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harbouring these gain-of-function ANO1 variants had classic features of moyamoya disease, but also had aneurysm, stenosis and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.

Abstract Introduction Penile duplex Doppler ultrasound (PDDU) is an important test to diagnose and guide treatment recommendations for peyronie’s Disease and erectile dysfunction. When patients do not achieve optimal rigidity during their evaluation we may be underestimating their degree of curvature and erection response which can impact treatment recommendations. Objective To evaluate specific examination conditions that may negatively impact the patient experience in men undergoing PDDU. Methods We developed a survey to evaluate patient experience during PDDU. Specific questions addressed preferences regarding the type of clinician performing the examination (physician versus advanced practice provider), provider gender, and specific modifiable conditions about the examination room. The survey was administered to thirty-five consecutive patients at a single academic practice. Patients were asked to complete portions of the survey before and after the examination to limit bias. Results 113 patients completed the survey. Prior to starting the testing, 48% of patients (n=54) had no provider preference, whereas 43% (n=49) preferred a physician as the performing clinician. 70% of patients (n=79) had no provider gender preference. All patients received at least a single dose of intracavernosal erectogenic medication at the start of their assessment. After completing PDDU, 40% of patients (n=45) reported that room conditions negatively impacted their ability achieve an adequate erectile response in the clinic. As shown in Figure 1, bright fluorescent overhead lighting (29%) and hallway noise (21%) were the most frequent contributing factors. When asked about opportunities to improve future patient experience, 38% (n=43) recommended dimming the room lights, 31% (n=35) would enjoy a warm blanket, and 36% (n=41) would favor gentle music or background sounds. 32% (n=36) felt that using call button, as opposed to routine staff checks to verify erectile response, would be desirable. Despite these preferences, the mean overall patient experience on a scale of 0-10 (0=poor, 10=excellent) was high at 9.3 (SD 1.2). Conclusions Despite high patient-reported satisfaction, we found that patients undergoing PDDU for PD and ED reported a preference towards (i) softer/dimmer lights, (ii) sound machine to drown out hallway noise, (iii) aa warm blanket, (iv) a call system to alert staff of a satisfactory erectile response. Further investigations are necessary to determine whether these simple modifications can improve the patient experience and exam efficiency. Disclosure No

Abstract Introduction Independently performed procedures by well-trained advanced practice providers (APP) facilitate access to specialized care. We sought to compare outcomes between physicians and APPs with intralesional collagenase clostridium histolyticum (CCH). Objective Compare outcomes of CCH injections based on injection provider. Outcomes included curvature improvement and adverse events. Methods Men receiving CCH between 2014-2021 at our institution by four physicians and four APPs were included in an IRB-approved database. CCH was delivered as a series of 8 injections per protocol. Patient demographics, procedural-related adverse events, and curvature changes were recorded. The “APP-ratio” is defined as percentage of total injections administered by an APP per patient. Results After excluding patients who did not complete the entire CCH course or return for final assessment, 150/406 patients were analyzed. Mean baseline penile curvature was 66.2° (SD 23). Mean absolute and percent improvements in curvature were 21.7° (SD 18) and 33% (SD 27). The mean APP ratio was 69%, and 133 patients (89%) had at least 25% of their injections performed by an APP. There was no significant difference (p=0.65, p=0.39) in absolute or relative curvature improvement based on the APP-ratio [Figure 1]. There was also no difference in adverse events (pain, swelling, and hematoma). Conclusions In our high-volume CCH practice, APPs achieve the same outcomes and safety compared to physicians. Greater training efforts expand access to care for patients with PD. Disclosure No

AbstractObjectiveThe goal of the current study is to advance efforts to increase the quality of care for childhood anxiety disorder (CADs) through (1) detailing the content of community‐based treatment sessions, (2) exploring the validity of therapist surveys, (3) examining the influence of setting differences, and (4) testing the effects of a technology‐based training on use of nonexposure strategies.MethodsThirteen therapists were randomly assigned to technology‐based training in the use of exposure therapy or treatment as usual (TAU) for CADs. Therapeutic techniques were coded from 125 community‐based treatment sessions.ResultsConsistent with survey responses community therapists spent the majority of session time reviewing symptoms (34% of session time), implementing nonexposure cognitive behavioral therapy (CBT; 36%), and rarely engaged in exposure (3%). An integrated behavioral health setting was associated with greater endorsement of exposure on survey, p < 0.05, although this difference was not significant in session recordings, p = 0.14. Multilevel models indicated that technology‐based training that has been shown to increase exposure, also decreased use of nonexposure CBT techniques (2% vs. 29%, p < 0.001).ConclusionThe study supports the validity of survey‐based findings that community‐based care for CADs consists of non‐exposure CBT techniques. Efforts should be invested in dissemination of within‐session exposure.

Primary cardiac schwannoma (PCS) is a neurogenic tumor that arises from Schwann cells. Malignant schwannoma (MSh) is an aggressive cancer comprising 2% of all sarcomas. Information on the proper management of these tumors is limited. Four databases were searched for case reports/series of PCS. The primary outcome was overall survival (OS). Secondary outcomes included therapeutic strategies and the corresponding outcomes. Among 439 potentially eligible studies, 53 met the inclusion criteria. The patients included had 43.72 ± 17.76 years and 28.3% were males. Over 50% of patients had MSh, with 9.4% also demonstrating metastases. Schwannoma commonly occurs in the atria (66.0%). Left-sided PCS were more common than right-sided ones. Surgery was performed in almost 90% of the cases; chemotherapy and radiotherapy were used in 16.9% and 15.1% of cases, respectively. Compared to benign cases, MSh occurs at a younger age and is commonly located on the left side. OS of the entire cohort at 1 and 3 years were 60.7%, and 54.0%, respectively. Females and males OS were similar up to 2 years follow-up. Surgery was associated with higher OS (p < 0.01). Surgery is the primary treatment option for both benign and malignant cases and was the only factor associated with a relative improvement in survival.