OpenXGR: a web-server update for genomic summary data interpretation.

How to effectively convert genomic summary data into downstream knowledge discovery represents a major challenge in human genomics research. To address this challenge, we have developed efficient and effective approaches and tools. Extending our previously established software tools, we here introduce OpenXGR (http://www.openxgr.com), a newly designed web server that offers almost real-time enrichment and subnetwork analyses for a user-input list of genes, SNPs or genomic regions. It achieves so through leveraging ontologies, networks, and functional genomic datasets (such as promoter capture Hi-C, e/pQTL and enhancer-gene maps for linking SNPs or genomic regions to candidate genes). Six analysers are provided, each doing specific interpretations tailored to genomic summary data at various levels. Three enrichment analysers are designed to identify ontology terms enriched for input genes, as well as genes linked from input SNPs or genomic regions. Three subnetwork analysers allow users to identify gene subnetworks from input gene-, SNP- or genomic region-level summary data. With a step-by-step user manual, OpenXGR provides a user-friendly and all-in-one platform for interpreting summary data on the human genome, enabling more integrated and effective knowledge discovery.

Endoscopic Evaluation of PET/CT Abnormalities in the Gastrointestinal Tract: Yield and Approach.

BACKGROUND: Unexpected hypermetabolic activity is often encountered in the gastrointestinal tract when PET/CT is performed for various indications, prompting endoscopic evaluation. Our aim was to characterize the types of lesions seen in segments of the gastrointestinal tract with unexpected PET/CT abnormalities as well as clinically significant lesions seen on endoscopy which did not produce a PET/CT abnormality to guide the endoscopist tasked with evaluating these imaging findings. METHODS: We retrospectively reviewed a database of endoscopies performed at City of Hope Comprehensive Cancer Center between January 1, 2016 and September 30, 2021 for an indication of "abnormal PET." We divided the gastrointestinal tract into segments and defined categories of endoscopic/histologic findings for each segment. We counted the number of segments with an abnormal PET/CT finding and corresponding endoscopic/histologic abnormality as well as the number of segments with an endoscopic/histologic abnormality but normal PET/CT. RESULTS: PET/CT identified 209 segments with hypermetabolic activity, 109 of which had corresponding endoscopic/histologic abnormalities. In the jejunum and ileum, all corresponding lesions were malignant. Seventy-three percent of corresponding lesions in the stomach were H. pylori positive. PET/CT failed to detect 34.7% of clinically significant lesions diagnosed endoscopically, including 1 malignancy in the transverse colon and many inflammatory or low-risk premalignant lesions. CONCLUSION: PET/CT abnormalities seen in the small bowel should be evaluated urgently as nearly all correlates were malignant, while abnormalities in the stomach should prompt workup for H. pylori. Most lesions missed by PET/CT were inflammatory or low-risk premalignant yet clinically significant, confirming the need to inspect the entirety of the upper or lower gastrointestinal tract during endoscopy.

Evaluating the Educational Value of Cancer Registries - a Systematic Review and Thematic Analysis.

Cancer registries encompass a broad array of functions that underpin cancer control efforts. Despite education being fundamental to improving patient outcomes, little is known regarding the educational value of cancer registries. This review will evaluate the educational value of cancer registries for key stakeholders as reported within published literature and identify opportunities for enhancing their educational value. Four databases (Ovid Medline, Embase, CINAHL and Web of Science) were searched using a predefined search strategy in keeping with the PRISMA statement. Data was extracted and synthesised in narrative format. Themes and frequency of discussion of educational content were explored using thematic content analysis. From 952 titles, ten eligible studies were identified, highlighting six stakeholder groups. Educational outcomes were identified relating to clinicians (6/10), researchers (5/10), patients (4/10), public health organisations (3/10), medical students (1/10) and the public (1/10). Cancer registries were found to educationally benefit key stakeholders despite educational value not being a key focus of any study. Deliberate efforts to harness the educational value of cancer registries should be considered to enable data-driven quality improvement, with the vast amount of data promising ample educational benefit.

Local recurrence rates of superficial versus deep soft tissue sarcoma.

INTRODUCTION: Soft tissue sarcomas are a group of malignancies that commonly occur in the extremities. As deep lesions may exist within the confines of the muscular fascia, we postulate that local recurrence rates are higher for superficial soft tissue sarcomas managed by the standard of care. MATERIALS AND METHODS: A retrospective review was performed on 90 patients who underwent surgical resection of soft tissue sarcomas of the extremity from 2007 to 2015. Patients with minimum 2-year follow-up and adequate operative, pathologic, and clinical outcomes data were included. RESULTS: Mean age was 54 ± 18 years with 49 (54.4%) patients being male. Lesions in 77.8% of cases were deep, and 22.2% were superficial to fascia. Following the index surgical resection, a total of 33 (36.7%) patients had positive margins. A total of 17 (18.9%) patients had a local recurrence. Overall, 3-year survival was 92.7%, and 5-year survival was 79.0%. Five-year recurrence-free survival of deep sarcomas was 91.1% versus 58.2% of superficial lesions (p = 0.006). Patients with higher tumor depth had lower odds of experiencing a local recurrence (HR 0.26 [95% CI 0.09-0.72]). Local recurence rates was also associated with positive surgical margins on initial resection (33.3% versus 12.3%) (p = 0.027). CONCLUSIONS: In this series, superficial tumor depth was associated with local recurrence of soft tissue sarcomas of the extremity following surgical resection. Positive surgical margins was also associated with local recurrence.

The Fragility of Statistical Findings in Cervical Disc Arthroplasty: a Systematic Review of Randomized Controlled Trials.

PURPOSE: This study employs both the fragility index (FI) and fragility quotient (FQ) to assess the level of robustness in the cervical disc arthroplasty (CDA) literature. We hypothesize that dichotomous outcomes involving CDA would exhibit statistical vulnerability. METHODS: A PubMed search was conducted to evaluate dichotomous data for randomized controlled trials (RCTs) in CDA literature from 2000 to 2023. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 1561 articles screened, 111 met the search criteria, with 35 RCTs evaluating CDA included for analysis. Six hundred and ninety-three outcome events with 130 significant (P < 0.05) outcomes and 563 nonsignificant (P ≥ 0.05) outcomes were identified. The overall FI and FQ for all 693 outcomes were 5 (IQR 3-7) and 0.019 (IQR 0.011-0.043). Fragility analysis of statistically significant outcomes and nonsignificant outcomes both revealed an FI of 5. All of the studies reported loss to follow-up (LTF) data where 65.7% (23) did not report or reported an LTF greater or equal to 5. CONCLUSIONS: The literature regarding CDA RCTs lacks statistical robustness and may misrepresent the conclusions with the sole use of the P value. By implementing the FI and FQ along with the P value, we believe the interpretation and contextualization of the clinical data surrounding CDA will be better understood.

Soil organic carbon, aggregation and fungi community after 44 years of no-till and cropping systems in the Central Great Plains, USA.

Implementing sustainable agricultural land management practices such as no-till (NT) and diversified crops are important for maintaining soil health properties. This study focuses on the soil health of three long-term (44 years) tillage systems, NT, reduced tillage (RT), and conventional tillage (CT), in monoculture winter wheat-fallow (W-F) (Triticum aestivum L.) and wheat-soybean (W-S) (Glycine max (L.) Merrill) rotation. Soil organic carbon (C) was higher in NT than CT in the surface 0-5 cm, but not different in the 5-15 cm, demonstrating SOC stratification on the soil profile. The soil water content was higher in NT followed by RT and CT in the top 0-5 cm. We found an association between increased carbon, aggregation, and AMF biomass. Greater soil aggregation, carbon and AMF were observed in NT at 0-5 cm soil depth. The W-S cropping system had greater soil microbial community composition based on fungi biomass, AMF and fungal to bacteria ratio from phospholipid fatty acid analysis (PLFA). Large macroaggregates were positively correlated with total C and N, microbial biomass, Gram + , and AMF. Soil water content was positively correlated with macroaggregates, total C and N, and AC. No-till increased soil carbon content even after 44 years of cultivation. By implementing conservation tillage systems and diversified crop rotation, soil quality can be improved through greater soil organic C, water content, greater soil structure, and higher AMF biomass than CT practice in the Central Great Plains.

Structure-activity relationship study of central pyridine-derived TYK2 JH2 inhibitors: Optimization of the PK profile through C4' and C6 variations.

Efforts directed at improving potency and preparing structurally different TYK2 JH2 inhibitors from the first generation of compounds such as 1a led to the SAR study of new central pyridyl based analogs 2-4. The current SAR study resulted in the identification of 4h as a potent and selective TYK2 JH2 inhibitor with distinct structural differences from 1a. In this manuscript, the in vitro and in vivo profiles of 4h are described. The hWB IC50 of 4h was shown as 41 nM with 94% bioavailability in the mouse PK study.

Incongruities in recently revised radiofrequency exposure guidelines and standards.

The currently promulgated RF exposure guidelines and standards cover the entire range of RF radiation and apply predominantly to restrict RF-induced short-term heating and in guarding against raising tissue temperatures, including the 5G frequencies. There are substantial abnormalities in these putative health safety protection guidelines and standards. Some of the safety limits are irrelevant, debatable, and absent of scientific justification from the standpoint of safety and public health protection. Also, the cellular mobile 5G technology is hailed as a speedier and more secure wireless communication technology than its predecessor systems. The key supporting architecture uses millimeter-wave (mm-wave) and antenna array technology to achieve better directivity, lower latency, and elevated data transmission rates. For radiation protection, it is not obvious whether the health effects of 5G mm-wave radiations would be analogous or not to radiations from previous generations (which was classified as possibly carcinogenic in humans by IARC). The interaction of mm-waves with the structure and function of pertinent cellular elements and cutaneous neuroreceptors in the skin are of special concern. The current scientific database is inadequate at mm wavelengths to render a trustworthy appraisal or to reach a judgment with confidence.

The iliac kickstand screw: anatomic CT analysis of screw trajectory and osseous corridor for screw placement.

INTRODUCTION: The 'kickstand screw-rod' technique has been recently described for correction of coronal malalignment. This technique utilizes powerful 'construct-to-ilium' distraction between a fixed multi-screw thoracic construct and the ilium, facilitated by a novel 'iliac kickstand screw'. The 'iliac kickstand screw' traverses a previously undescribed osseous corridor in the ilium. OBJECTIVE: Using a radiographic CT study, the objective is to describe a large osseous corridor within the ilium to accommodate the novel iliac kickstand screw. METHODS: 50 consecutive patients with pelvic CTs at an academic medical center were queried. Simulated iliac kickstand screw trajectories for the left and right hemipelvis were analyzed with 3D visualization software. Maximal screw lengths and dimensions, and trajectories in the osseous corridor were measured. RESULTS: 50 patients' (31 female, 19 male) pelvic CTs were measured with a total of 100 simulated screws. The mean age was 52.4 years and BMI 28.1 ± 7.9. The average length is 119.7 ± 6.6 mm (range 98.7 - 135.3). The narrowest width (maximum potential screw diameter) is 17.8 ± 2.9 mm (coronal) and 20.8 ± 5.3 mm (sagittal). The starting point to the top of the iliac crest is 66.4 mm lateral to midline, and 15.9° caudal in the sagittal and 6.1° lateral in the coronal planes. CONCLUSIONS: The novel iliac kickstand screw traverses a consistent and large osseous corridor within the ilium. The average simulated screw length is 119.7 mm and maximum potential diameter of 17.8 mm. Starting points relative to the iliac crest are identified.

Flexible sigmoidoscopy may be sufficient for initial evaluation of suspected immunotherapy-mediated colitis: A cross-sectional study.

BACKGROUND AND AIM: Immune checkpoint inhibitors (ICIs) have shown promise in treating a variety of cancers. Their increased use coincides with increased incidence of immunotherapy-mediated colitis (IMC), a common adverse effect. Optimal strategy for endoscopic evaluation of IMC (full colonoscopy or flexible sigmoidoscopy) is not well-defined. METHODS: Retrospective review of all patients at City of Hope referred to gastroenterology for evaluation of IMC due to gastrointestinal symptoms was performed. Patients with an existing histologic diagnosis of IMC established at an outside hospital or a diagnosis of infectious or chronic colitis were excluded. RESULTS: We identified 51 symptomatic patients on ICIs prompting evaluation for IMC with colonoscopy (47/51) or flexible sigmoidoscopy (4/51). All distal rectosigmoid biopsies during flexible sigmoidoscopy demonstrated histologic evidence of IMC. In full colonoscopy, IMC was either present in all segments of colon simultaneously (35/47) or absent from all segments (12/47). No isolated proximal colonic biopsies demonstrated IMC. Endoscopically normal mucosa demonstrated histologic evidence of IMC up to 68.6% of the time. Endoscopically abnormal right, transverse, and left colon had low sensitivity (35.3%, 34.3%, and 41.7%, respectively) and high specificity (100.0%, 100.0%, and 91.7%, respectively) for histological presence of IMC. CONCLUSIONS: Distal colon biopsies in patients on ICI therapy with diarrhea and suspected IMC were sufficient for diagnosing IMC in our cohort. Further, we found histologic evidence of IMC in biopsies taken from normal-appearing mucosa in a number of patients, suggesting that a normal endoscopic appearance does not preclude the presence of IMC and biopsies should be taken from both normal and abnormal-appearing mucosa.

Dehydroepiandrosterone status and efficacy of dehydroepiandrosterone supplementation for bone health in anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN. METHOD: Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta-analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed. RESULTS: Meta-analysis of 15 cross-sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01-545.25) and reduced DHEAS levels (MD = -24.90 µg/dl; 95% CI, -41.72 to -8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study. DISCUSSION: Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA. PUBLIC SIGNIFICANCE: This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia nervosa.

OBJETIVO: Este estudio fue diseñado para determinar el estado de la dehidroepiandrosterona (DHEA) en mujeres con anorexia nerviosa (AN) y para evaluar la eficacia de la suplementación con DHEA como tratamiento para la salud ósea en mujeres con AN. MÉTODO: Los estudios se obtuvieron de las bases de datos PubMed, Embase, Cochrane library, MEDLINE y Scopus desde su inicio hasta el 14 de febrero de 2022. Se incluyeron estudios observacionales que compararon los niveles séricos de DHEA entre mujeres que padecen AN y controles sanos para el metanálisis, y se revisaron los ensayos controlados aleatorios (ECA) que evaluaron los efectos de la suplementación con DHEA sobre la masa ósea. RESULTADOS: El metanálisis de 15 estudios transversales reveló que los pacientes que padecen AN tenían niveles séricos significativamente elevados de DHEA (diferencia de medias [DM] = 311,63 ng/dL; intervalo de confianza [IC] del 95%, 78,01-545,25) y niveles reducidos de DHEAS (DM = -24,90 µg/dL; IC del 95%, -41,72 a -8,07) en comparación con los controles sanos. La revisión sistemática de siete ECA encontró que la monoterapia con DHEA no mejora la densidad mineral ósea (DMO) en comparación con placebo después de ajustar el aumento de peso. Si bien la combinación de DHEA y anticonceptivos orales conjugados ha llevado a un aumento de la fuerza ósea y una disminución de la pérdida ósea, el efecto beneficioso parece limitarse a adolescentes mayores y adultos con placas de crecimiento cerradas. En un estudio se identificaron posibles efectos perjudiciales sobre la DMO en adolescentes más jóvenes con placas de crecimiento abiertas. DISCUSIÓN: Debido a la falta de beneficio aparente de la DHEA en mujeres que padecen AN y su posible efecto perjudicial sobre la DMO en pacientes jóvenes que padecen AN, la evidencia actual no apoya el uso de la DHEA.

Development and initial validation of the Chinese Version of the Noise Exposure Questionnaire (C-NEQ).

BACKGROUND: With a high prevalence of noise-induced hearing loss (NIHL), the noise survey tools for identifying individuals with high risk of NIHL are still limited. This study was aimed to translate and develop a Chinese version of noise exposure questionnaire (C-NEQ), and validate its reliability and reproducibility. METHODS: This study was conducted from May 2020 to March 2021 in China. The questionnaire was translated from the original NEQ and adapted into Chinese culture using the method according to the International Test Committee. Content validity was evaluated by our expert group. Construct validity and reliability of the C-NEQ was determined through estimating the confirmatory factor analysis and Cronbach's alpha in a cross-sectional analysis among 641 Chinese speaking adults, respectively. The retest reproducibility of the C-NEQ was analyzed by using the intra-group correlation coefficient (ICC) in a follow-up analysis among 151 participants. RESULTS: The C-NEQ comprises ten items covering four domains: occupational, housework, transport and recreational noise exposure. The annual noise exposure (ANE) was calculated as the protocol of original NEQ. A total of 641 adult participants (aged 26.9 ± 10.1 years, 53.4% males) completed the C-NEQ. The average time for completing the C-NEQ was 4.4 ± 3.0 min. Content validity indicated high relevance of the C-NEQ. The confirmatory factor analysis indices illustrated that the items of the C-NEQ were suitable with the data in the study. For the internal reliability, the Cronbach's α coefficients of the total items and four domains (occupational, housework, transport, and recreational noise exposure) were 0.799, 0.959, 0.837, 0.825, and 0.803, respectively. Among them, 151 participants (aged 36.1 ± 11.1 years, 65.6% males) completed the retest of the C-NEQ 1 month after the first test. The ICC value of total ANEs between the first test and the second test was 0.911 (P < 0.001). CONCLUSIONS: In this study, we have validated the C-NEQ with adequate reliability and reproducibility for quantifying an individual's annual daily noise exposure, which provides an effective fast-screen tool for researches and clinics to identify those individuals with high risks of NIHL within the short time duration (no more than five minutes) among Chinese population.

Outcomes of Pediatric Scaphoid Nonunions Treated With Distal Radius Cancellous Autograft.

BACKGROUND: The optimal management of pediatric scaphoid fracture nonunions is controversial. We hypothesize that pediatric patients with scaphoid fracture nonunions will have favorable functional outcomes with the utilization of nonvascularized distal radius cancellous autograft with open reduction and internal fixation (ORIF). METHODS: A review was performed from 2012 to 2017 identifying skeletally immature patients with scaphoid fracture nonunions treated with ORIF and nonvascularized distal radius cancellous autograft, including demographic data, mechanism of injury, length of time from injury to treatment, operative procedure, length of immobilization, time to union, and complications. RESULTS: Ten patients (9 males, 1 female) met inclusion criteria. Mean age was 14.3 SD 1.5 years. The majority of fractures were sustained during sports or secondary to a fall. Mean time between injury and orthopaedic evaluation was 33 weeks (SD 20 wk). Eight fractures occurred at the waist, and 2 occurred at the proximal pole. Four patients had a humpback deformity, and three presented with a dorsal intercalated segmental instability deformity. Nine patients were treated with a single cannulated compression screw with distal radius autograft. One patient also received a single Kirschner wire fixation in addition to a single cannulated screw and graft. Patients underwent a mean postoperative immobilization period of 14 SD 5 weeks. Two patients received a bone stimulator postoperatively. Radiographic union was documented after initial surgery in nine patients, with mean time to union of 17 SD 5 weeks. The 1 patient with persistent radiographic nonunion underwent revision fixation and repeat nonvascularized distal radius autograft, achieving union and resolution of symptoms. All patients ultimately reported full return to activity. CONCLUSIONS: Pediatric scaphoid fracture nonunions that undergo ORIF using nonvascularized distal radius cancellous autograft have favorable rates of consolidation and functional outcomes. Surgeons should consider this source of grafting in operative management of scaphoid nonunions in children and adolescents. LEVEL OF EVIDENCE: Level IV, therapeutic.

How Does Representation of Women on Editorial Boards Compare Among Orthopaedic, General Surgery, and Internal Medicine Journals?

BACKGROUND: Women have historically been underrepresented as editors of peer-reviewed medical journals. Studies have demonstrated that there are differences in editorial board reviewer behavior based on gender, suggesting that greater representation by women on editorial boards may improve the quality and diversity of the review process. Therefore, the current representation of women on the editorial boards of orthopaedic journals, particularly compared with peer-reviewed surgical and medical journals, is of interest. QUESTIONS/PURPOSES: (1) What is the representation of women as members of editorial boards of prominent orthopaedic surgery journals? (2) How does it compare with representation on the editorial boards of journals in general surgery and internal medicine? METHODS: The top 15 journals with a strong clinical emphasis based on Impact Factor (Clarivate Analytics) calculated by the 2018 Journal Citation Reports were identified for orthopaedic surgery, general surgery (and all general surgical subspecialties), and internal medicine (with representative internal medicine subspecialties). Clinical publications with their primary editorial office located in the United States led predominantly by physicians or basic scientists were eligible for inclusion. The members of an editorial board were identified from the journals' websites. The gender of editors with gender-neutral names (and editors whose gender we considered uncertain) was identified by an internet search for gender-specific pronouns and/or pictures from an institutional profile. Fisher exact tests and t-tests were used to analyze categorical and continuous variables, respectively. Significance was set at p < 0.05. RESULTS: Of the editors analyzed, women made up 9% (121 of 1383) of editorial boards in the orthopaedic journals with the highest Impact Factors, compared with 21% (342 of 1665) of general surgery journals (p < 0.001) and 35% (204 of 587) of internal medicine journals (p < 0.001). The overall mean composition of editorial boards of orthopaedic journals was 10% ± 8% women, compared with that of general surgery, which was 19% ± 6% women (p < 0.001), and that of internal medicine, which was 40% ± 19% women (p < 0.001). CONCLUSION: Women make up a smaller proportion of editorial boards at orthopaedic surgery journals than they do at general surgery and internal medicine journals. However, their representation appears to be comparable to the proportion of women in orthopaedics overall (approximately 6%) and the proportion of women in academic orthopaedics (approximately 19%). Ways to improve the proportion of women on editorial boards might include structured mentorship programs at institutions and personal responsibility for championing mentorship and diversity on an individual level. CLINICAL RELEVANCE: Increasing representation of women on editorial boards may improve the diversity of perspectives and quality of future published research, generate visible role models for young women considering orthopaedics as a career, and improve patient care through enriching the diversity of our specialty.

Pediatric Medial Epicondyle Fracture Management: A Systematic Review.

BACKGROUND: There remains controversy surrounding the treatment of pediatric medial epicondyle fractures. This systematic review examines the existing literature with the aim to elucidate optimal management strategies. METHODS: A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was executed. All data collection was completed by August 01, 2018. Functional outcomes, diagnostic imaging, athlete management, union rates, ulnar nerve symptoms, surgical methods, surgical positioning, and posttreatment protocols were categorized and recorded. Frequency-weighted mean values were calculated with associated SDs. RESULTS: Thirty-seven studies with 1022 patients met the inclusion criteria. Functional outcomes for patients were mostly good following operative and nonoperative management. The most common complication was a slight loss of elbow extension (7.6±5.9 degrees) and flexion (13.3±5.8 degrees). Operative treatment was associated with higher union rates than nonoperative management (700/725, 96% vs. 69/250, 28%; P<0.001). Standard diagnostic imaging techniques to measure displacement were unreliable with a newly proposed axial view having high inter-rater and intrarater reliability. The most common surgical method used was open reduction and internal fixation with Kirschner wires. Whereas surgical management of patients with associated ulnar nerve symptoms led to symptom resolution, nonoperative management occasionally led to the development of these symptoms. Elbow range of motion was initiated at ~2.8±1.4 (range, 0 to 8 wk) weeks after surgery and 3.4±1.2 (range, 3 to 5 wk) weeks without surgery (P<0.001). CONCLUSIONS: Although there is still no consensus on treatment of pediatric medial epicondyle fractures, both operative and nonoperative approaches result in good outcomes. LEVEL OF EVIDENCE: Level IV-therapeutic.

Validation of the Pediatric Appendicitis Risk Calculator (pARC) in a Community Emergency Department Setting.

STUDY OBJECTIVE: The pediatric Appendicitis Risk Calculator (pARC) is a validated clinical tool for assessing a child's probability of appendicitis. Our objective was to assess the performance of the pARC in community emergency departments (EDs) and to compare its performance with that of the Pediatric Appendicitis Score (PAS). METHODS: We conducted a prospective validation study from October 1, 2016, to April 30, 2018, in 11 community EDs serving general populations. Patients aged 5 to 20.9 years and with a chief complaint of abdominal pain and less than or equal to 5 days of right-sided or diffuse abdominal pain were eligible for study enrollment. Our primary outcome was the presence or absence of appendicitis within 7 days of the index visit. We reported performance characteristics and secondary outcomes by pARC risk strata and compared the receiver operator characteristic (ROC) curves of the PAS and pARC. RESULTS: We enrolled 2,089 patients with a mean age of 12.4 years, 46% of whom were male patients. Appendicitis was confirmed in 353 patients (16.9%), of whom 55 (15.6%) had perforated appendixes. Fifty-four percent of patients had very low (<5%) or low (5% to 14%) predicted risk, 43% had intermediate risk (15% to 84%), and 4% had high risk (≥85%). In the very-low- and low-risk groups, 1.4% and 3.0% of patients had appendicitis, respectively. The area under the ROC curve was 0.89 (95% confidence interval 0.87 to 0.92) for the pARC compared with 0.80 (95% confidence interval 0.77 to 0.82) for the PAS. CONCLUSION: The pARC accurately assessed appendicitis risk for children aged 5 years and older in community EDs and the pARC outperformed the PAS.

Ethics of organ procurement from the unrepresented patient population.

The shortage of organs for transplantation by its nature prompts ethical dilemmas. For example, although there is an imperative to save human life and reduce suffering by maximising the supply of vital organs, there is an equally important obligation to ensure that the process by which we increase the supply respects the rights of all stakeholders. In a relatively unexamined practice in the USA, organs are procured from unrepresented decedents without their express consent. Unrepresented decedents have no known healthcare wishes or advance care planning document; they also lack a surrogate. The Revised Uniform Anatomical Gift Act (RUAGA) of 2006 sends a mixed message about the procurement of organs from this patient population and there are hospitals that authorise donation. In addition, in adopting the RUAGA, some states included provisions that clearly allow organ procurement from unrepresented decedents. An important unanswered question is whether this practice meets the canons of ethical permissibility. The current Brief Report presents two principled approaches to the topic as a way of highlighting some of the complexities involved. Concluding remarks offer suggestions for future research and discussion.

CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing.

Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24-48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors.

Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism: A Controlled Pragmatic Trial.

Background: Many low-risk patients with acute pulmonary embolism (PE) in the emergency department (ED) are eligible for outpatient care but are hospitalized nonetheless. One impediment to home discharge is the difficulty of identifying which patients can safely forgo hospitalization. Objective: To evaluate the effect of an integrated electronic clinical decision support system (CDSS) to facilitate risk stratification and decision making at the site of care for patients with acute PE. Design: Controlled pragmatic trial. (ClinicalTrials.gov: NCT03601676). Setting: All 21 community EDs of an integrated health care delivery system (Kaiser Permanente Northern California). Patients: Adult ED patients with acute PE. Intervention: Ten intervention sites selected by convenience received a multidimensional technology and education intervention at month 9 of a 16-month study period (January 2014 to April 2015); the remaining 11 sites served as concurrent controls. Measurements: The primary outcome was discharge to home from either the ED or a short-term (<24-hour) outpatient observation unit based in the ED. Adverse outcomes included return visits for PE-related symptoms within 5 days and recurrent venous thromboembolism, major hemorrhage, and all-cause mortality within 30 days. A difference-in-differences approach was used to compare pre-post changes at intervention versus control sites, with adjustment for demographic and clinical characteristics. Results: Among 881 eligible patients diagnosed with PE at intervention sites and 822 at control sites, adjusted home discharge increased at intervention sites (17.4% pre- to 28.0% postintervention) without a concurrent increase at control sites (15.1% pre- and 14.5% postintervention). The difference-in-differences comparison was 11.3 percentage points (95% CI, 3.0 to 19.5 percentage points; P = 0.007). No increases were seen in 5-day return visits related to PE or in 30-day major adverse outcomes associated with CDSS implementation. Limitation: Lack of random allocation. Conclusion: Implementation and structured promotion of a CDSS to aid physicians in site-of-care decision making for ED patients with acute PE safely increased outpatient management. Primary Funding Source: Garfield Memorial National Research Fund and The Permanente Medical Group Delivery Science and Physician Researcher Programs.

Reduction of Opioid Use After Upper-Extremity Surgery through a Predictive Pain Calculator and Comprehensive Pain Plan.

PURPOSE: For outpatient hand and upper-extremity surgeries, opioid prescriptions may exceed the actual need for adequate pain control. The purposes of this study were to (1) determine rates of opioid wasting and consumption after these procedures and (2) create and implement a patient-specific calculator for opioid requirements with a detailed multimodal analgesic plan to guide postoperative prescriptions. METHODS: Patients undergoing hand and upper-extremity surgery at a single ambulatory surgery center were recruited before (n = 305) and after (n = 221) implementation of a postoperative pain control program. On the first postoperative visit, patients were given a questionnaire regarding opioid use and pain control satisfaction. Demographic and procedural data were collected via chart review. With these data from the first cohort, we developed a patient-specific opioid calculator and pain plan that was implemented for the second cohort of patients. Bivariate analysis and multivariable regression analysis were used to determine the effect of the intervention. RESULTS: Pre-intervention data suggested that younger age; baseline opioid use; use of regional block; unemployment; procedures involving bony, tendinous, or ligamentous work (as opposed to soft tissue alone); and longer procedure time were predictive of higher opioid consumption. Pre- and post-intervention cohorts had similar age and sex distributions as well as procedure length. After the intervention, opioids prescribed decreased 63% from a mean of 32.0 ± 15.0 pills/surgery or 194.5 ± 120.2 morphine milligram equivalents (MMEs) to 11.7 ± 8.9 pills/surgery or 86.4 ± 67.2 MMEs. Opioid consumption decreased 58% from a mean of 21.7 ± 25.0 pills/surgery (137.7 ± 176.4 MMEs) to 9.3 ± 16.7 (64.4 ± 113.4 MMEs). Opioid wastage decreased 62% from 13.8 ± 13.5 pills/surgery (62.8 ± 138.0 MMEs) to 5.2 ± 10.3 (24.8 ± 89.9 MMEs). Implementation of the pain plan and calculator did not affect the odds of unsatisfactory patient-rated pain control or unplanned opioid refills. CONCLUSIONS: With implementation of a comprehensive pain plan for ambulatory upper-extremity surgery, it is possible to reduce opioid prescription, consumption, and wastage rates without compromising patient satisfaction with pain control or increasing rates of unplanned pain medication refills. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.