Two-sided Exact Test Research Articles

Abstract PO4-01-11: Ovarian function suppression (OFS) use beyond five years?: Young breast cancer patient preferences

Abstract Background. Breast cancer (BC) is the leading cause of cancer-related death in young women worldwide, and late recurrence of hormone receptor-positive disease plays a substantial role. Adjuvant endocrine therapy with 5 years of ovarian function suppression (OFS) and an aromatase inhibitor or tamoxifen is recommended for many young patients with high risk hormone receptor-positive BC. Data are limited regarding extended endocrine therapy among premenopausal BC survivors, and non-existent to inform treatment decisions regarding extending OFS beyond 5 years. We sought to evaluate young BC survivors’ perceptions and preferences regarding extending OFS beyond 5 years, and consideration of a potential future study to assess the role of extended OFS. Methods. From January-April 2023, email invites were sent to the Young Survival Coalition (YSC) listserv (N=14,291) specifically asking members with a history of invasive BC (≤45 years at diagnosis; stage I-III without metastatic recurrence) receiving OFS injections for adjuvant endocrine treatment to complete a one-time anonymous online survey. The survey was designed to capture information regarding current endocrine therapy use, patient-provider communication regarding extended endocrine therapy including OFS, OFS-related concerns (rating 0-5 [low: 0-1, moderate: 2-3, severe: 4-5]), and interest in a potential future clinical trial utilizing OFS beyond 5 years. Descriptive statistics were utilized to summarize responses, and two-sided Fishers exact tests and chi-square analyses were used for comparisons. Results. A total of 1,030 YSC members completed the survey, and 615 were analyzed due to eligibility and completeness of data. The majority were from the United States (n=579, 94.1%) or Canada (n=8, 1.3%), were non-Hispanic white (n=452, 73.5%), non-Hispanic Black (n=46, 7.5%), or Hispanic (n=43, 7.0%), and had been diagnosed with stage II BC (n=316, 51.4%). The average age at survey was 38.1 years (SD=5.15, range=22-54) and at initial BC diagnosis was 34.6 years (SD=4.96, range=20-49). Most (n=510, 83.0%) were within their first 5 years of OFS treatment while 14.5% (n=89) had already been receiving OFS for more than 5 years. Many respondents (n=344, 55.9%) reported discussing OFS use beyond 5 years with their provider, of whom 39.8% (n=245) reported their provider recommending they continue OFS for more than 5 years. Despite reporting moderate and severe concerns regarding OFS side effects (n=476, 77.4%), inconvenience of injection visits (n=272, 44.2%), and high cost of medication (n=223, 36.3%), most respondents (n=396, 64.4%) would consider continuing OFS beyond 5 years if it would reduce risk of BC recurrence. For nearly half of respondents (n=289, 47.0%) a risk reduction of at least 5% would be required for extended OFS to be worthwhile compared to the remaining 46.3% (n=285) who indicated interest for < 5% risk reduction. When asked hypothetically if they would take part in a clinical trial to determine efficacy of OFS use beyond 5 years, the majority were interested (n=357, 58.0%). Respondents who were interested were less likely to be concerned about the high cost of medication (p=0.003) however they were also less likely to take OFS beyond 5 years if it only led to 1-2% BC risk reduction (p=0.006) compared to those who were not interested. There were no other proportional differences on any other outcome. Conclusion. Many BC survivors and providers are already considering incorporation of OFS beyond 5 years into adjuvant endocrine therapy despite harboring concerns and lack of data. Efforts to determine the efficacy and benefits of extended OFS are necessary given the risk of late recurrence in this population as well as the potential for significant short- and long-term toxicities. The results from this survey study suggest that future clinical trials evaluating potential benefits and risks of long-term OFS use among young BC survivors are needed and likely feasible. Citation Format: Kate Dibble, Tal Sella, Kathryn Ruddy, Craig Snow, Amanda Nixon, Patricia Spears, Karla Ballman, Lisa Carey, Ann Partridge. Ovarian function suppression (OFS) use beyond five years?: Young breast cancer patient preferences [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-11.

Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations

ObjectivesX chromosome has been considered as a risk factor for SLE, which is a prototype of autoimmune diseases with a significant sex difference (female:male ratio is around 9:1). Our study...

Constitutional and Somatic Variants in ARID5B in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

INTRODUCTION Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with the high hyperdiploid (HeH) subtype accounting for approximately 25% of B-cell precursor (BCP) ALL cases. It has been shown that germline variants in the ARID5B gene in chromosome band 10q21.2 are associated with increased risk of BCP ALL, in particular HeH ALL, and that the risk alleles result in lower expression of ARID5B in hematopoietic cells. ARID5B codes for a protein involved in regulating gene expression and chromatin remodeling. We have previously reported somatic deletions in the ARID5B locus in two cases of HeH ALL, but the overall frequency of acquired copy number changes and rearrangements involving ARID5B in BCP ALL remains unknown. Here, we have investigated constitutional and somatic ARID5B variants in pediatric BCP ALL, with a particular focus on HeH cases. METHODS Constitutional variants We studied four known risk single nucleotide polymorphisms (SNPs) in the ARID5B locus (rs7090445, rs7089424, rs7073837 and rs10740055) in HeH ALL cases heterozygous for the risk SNP and with trisomy 10. These were investigated in three different cohorts, including a total of 92 cases informative for rs7090445, 92 cases for rs7089424, 119 cases for rs7073837 and 66 cases for rs10740055. The genotype and relative allele frequencies were ascertained from SNP array or whole genome sequencing (WGS) data. One-sided binomial tests were applied to investigate whether the risk allele was more often in the duplicated chromosome than the non-risk allele. Somatic variants For somatic variants, we ascertained copy number status based on SNP array and/or WGS analysis in the ARID5B region in a total of 466 pediatric HeH ALL cases and structural rearrangements based on WGS in 77 cases. We also studied, using SNP array analysis, somatic copy number variants in a separate cohort consisting of 590 non-HeH BCP ALL cases. To compare the proportions of deletions in the HeH cohort and in the other genetic subtypes, we used Fisher's Exact two-sided test. RESULTS Constitutional variants All four risk SNPs showed a significantly higher proportion of risk allele duplication (one-sided binominal test); rs7090445 ( P=0.009), rs7089424 ( P=0.005), rs7073837 ( P=0.03) and rs10740055 ( P=0.04). This validates that there is a clonal selection for HeH blast cells with gain of the chromosome 10 homologue carrying the risk allele as opposed to gain of the homologue that carries the non-risk allele. Somatic variants Somatic deletions targeting ARID5B were found in 9/466 cases (1.9%) of HeH cases. The deletions covered different parts of ARID5B, with no minimally deleted region, suggesting that the functional outcome was downregulation of ARID5B expression. In the cohort with non-HeH BCP ALL (other genetic subtypes), 4/590 somatic deletions were found (0.68%). There was no statistically significant difference between the frequency of copy number aberrations targeting ARID5B between HeH and the other genetic subtypes of ALL (P=0.09). WGS analysis of the HeH cases revealed one translocation and one missense mutation in 2/77 cases (2.6%). The translocation involved the PAN3 and ARID5B genes and was also present in RNA sequencing data from this case. CONCLUSIONS We show that our previous finding that HeH ALL constitutionally heterozygous for ARID5B risk alleles and with an acquired trisomy 10 more commonly duplicates the chromosome 10 homologue carrying the risk allele holds true in a much larger cohort. Furthermore, somatic deletions involving ARID5B are recurrent in pediatric BCP ALL.

Survival of unconstrained ceramic wrist joint implants

Introduction Survival of implants is an important indicator of improvement in the patient's quality of life. In foreign literature, the issue of implant survival finds special attention.The aim of the work was to evaluate the efficacy and survival of an unconstrained ceramic wrist joint endoprosthesis.Materials and methods We analysed 83 cases of total wrist arthroplasty with an unconstrained ceramic implant at long-term follow-up. At the Novosibirsk RSITO, total wrist arthroplasty was performed in 81 patients with severe changes in the wrist joint from 2011 to 2021. Two patients underwent arthroplasty on two joints. A retrospective uncontrolled cohort study was conducted which divided the hospitalized patients into three groups according to the etiological cause of the disease. Radiological methods were used to control the state of the implant (radiography in two projections and CT-scans of the wrist joint). For binary indicators, the number, rates and 95 % confidence interval of frequencies were calculated according to the Wilson formula in the groups. Comparison was carried out by Fisher's exact two-sided test. The p-error was corrected using the Benjamini – Hochberg method. Kaplan – Meier curves were constructed for survival analysis. The groups were compared using a generalized chi-square test.Results Each case of repeated surgical intervention was evaluated from the standpoint of selected groups. Depending on the time elapsed from surgery to revision, we calculated the time frame for overall and group survival of the components of the wrist joint endoprosthesis. The causes and scope of surgical revision are presented.Discussion There are no data on the survival of unconstrained ceramic wrist joint implants in the foreign literature. Graphic images according to a proposal for the division of the orthopaedic postoperative period are presented. Conclusions 1. Intermediate conclusions in regard to total arthroplasty with an unconstrained ceramic endoprosthesis of the wrist joint inspire optimism in obtaining a stable positive effect of motion range lost due to the degenerative process in the wrist joint. 2. An 11-year follow-up period demonstrates that the survival rate of an unconstrained ceramic wrist endoprosthesis is 88 %.

OATH trial: A phase II clinical trial evaluating the combination of onapristone with anastrozole for women with hormone receptor positive endometrial cancer—Preliminary results.

5601 Background: Endometrial cancer is the most common gynecologic cancer and is primarily treated with chemotherapy. Many endometrial cancers though express hormone receptors and may respond to hormonal therapy, a potentially attractive non-chemotherapy alternative in such a population of women. The aim of OATH is to investigate the potential of dual hormonal blockade through the combination of antiprogesterone and anti-estrogen therapy via the administration of onapristone extended release (ONA) plus anastrozole (ANA), respectively. OATH is an open-label, multicenter, investigator-initiated, non-randomized, phase 2 study to evaluate the safety and efficacy of ONA + ANA in patients (pts) with endometrial cancer (EC). ClinicalTrials.gov Identifier: NCT04719273. Methods: Pts received ONA 50 mg twice daily plus ANA 1 mg once daily and were treated until progressive disease (PD) or unacceptable toxicity. Co-primary endpoints were 4-month progression-free survival (PFS) rate and overall response rate (ORR). A sample size of 25 pts will achieve 80% power to detect an improvement in 4-month PFS estimates from 25% (historical) to 52% and an improvement in response rate from 15% (historical) to 37%, using two-sided exact test at 5% significance level. Secondary endpoints include PFS, disease control rate (DCR), and safety. Results: As of January 20, 2023, 14 pts were enrolled. Median age was 67 years (44-80). ECOG performance status was 0 (36%), and 1 (64%). Number of prior chemotherapy regimens was 0 (1 pt,7%), 1 (9 pts, 64%) and 2 (4 pts, 29%). Seven (50%) pts received radiotherapy and 3 (21%) pts received prior checkpoint inhibitor therapy. Median treatment duration was 4.2 (1.0-19.9) months, and 8 pts remain on treatment. Adverse events were mainly grade 1 and 2. The most common treatment-related adverse events (AEs) and abnormal laboratory values were hot flashes (36%), alanine transferase (ALT) increased (29%), aspartate aminotransferase (AST) increased (29%), nausea (29%), and diarrhea (21%). No treatment-related serious AE, deaths on treatment, or treatment-related drug discontinuations were reported. The 4-month PFS Kaplan-Meier rate was 63.5%. Among 13 pts who had at least one tumor assessment after baseline, the best overall response was: 1 complete response, 1 partial response (response rate: 15.4%), 9 (69%) stable disease, and 2 (15.4%) progressions. Updated results will be presented. Conclusions: Preliminary results of dual hormonal blockade using ONA and ANA in heavily pretreated pts with EC suggest that this combination ONA + ANA has promising activity and is well tolerated. Clinical trial information: NCT04719273 .

Integration of a geospatially targeted community-based testing approach with respondent-driven sampling to identify people who inject drugs living with HIV and HCV in Patti and Gorakhpur, India

BackgroundRespondent-driven sampling (RDS), a network recruitment approach, is effective at reaching people who inject drugs (PWID), but other strategies may be needed to reach PWID at risk or living with HIV and/or Hepatitis C (HCV). We examined the impact of integrating geospatially targeted community-based HIV/HCV testing with an RDS survey. MethodsPWID were recruited between 2019 and 2021 in Patti and Gorakhpur, India, in a two-phased approach for identifying PWID living with HIV/HCV. Phase 1 was an RDS survey, in which participants reported injection venues. Venues with the highest prevalence of HIV/HCV viremia were selected for Phase 2: community-based testing. All participants underwent rapid HIV and HCV testing and viral load quantification. Using Pearson’s chi-squared test, two-sided exact significance tests, and t-tests, we compared prevalence and identification rates for each of the primary outcomes: the number of PWID 1) living with HIV/HCV, 2) undiagnosed, and 3) viremic. ResultsBoth approaches identified large numbers of PWID (n∼500 each; N=2011) who were living with HIV/HCV and had transmission potential (i.e., detectable viremia). The community-based approach identified a higher proportion of individuals living with HCV (76.4% vs. 69.6% in Gorakhpur and 36.3% vs. 29.0% in Patti). Community-based testing was also faster at identifying PWID with detectable HIV viremia. Both approaches identified PWID with varying demographic characteristics. ConclusionsCommunity-based testing was more efficient than RDS overall, but both may be required to reach PWID of varying characteristics. Surveillance should collect data on injection venues to facilitate community-based testing and maximize case identification.

The effectiveness of using “Painmetrica” software for the diagnosis and selection of treatment for chronic pain syndrome in degenerative diseases of the spine

Objective. To evaluate the effectiveness of using the “Painmetrica” software for the diagnosis and selection of treatment for pain in degenerative diseases of the spine. Materials and methods. Software “Painmetrica” was developed for the diagnosis and selection of treatment for pain in degenerative diseases of the spine. Through a bidirectional nonrandomized controlled trial, its effectiveness was evaluated using telephone interviews with 42 patients. For comparison, a telephone interview was conducted with 47 patients for whom the Panimetrica program had not been used in the treatment.Results. The effectiveness of using “Painmetrica” software for the diagnosis and selection of treatment for patients with back pain was demonstrated. In the main group, the decrease in pain syndrome tended to differ due to an increase in the number of patients in whom pain was relieved by more than 50% and completely disappeared (p = 0,09 according to the two-tailed Fisher’s exact test). Patients treated with Painmetrica algorithms experienced sleep recovery due to a decrease in pain: changes persisted in 12 cases (28,6%), while in the comparison group, sleep changes remained in 24 patients (51,1%) (p=0,05 according to two-tailed Fisher’s exact test). Against the background of effective pain relief in patients who used Painmetrica, there was a decrease in the use of non-steroidal anti-inflammatory drugs (NSAIDs) (17 patients (40,5%) of the main group versus 36 patients (76,6%) of the control group, p = 0,001 according to the twotailed Fisher’s exact test ). At the same time, only 8 patients (19.1%) in the main group and 30 patients (63.8%) in the comparison group (p < 0.001 according to Fisher’s two-sided exact test) indicated the need to consult a neurologist.Conclusion. The effectiveness of the use of “Painmetrica” software for the diagnosis and selection of treatment of patients with degenerative diseases of the spine on an outpatient basis in relation to the need for patients to use nonsteroidal anti-inflammatory drugs, the need for additional consultation of a neurologist, as well as effective relief of sleep disorders caused by pain were demonstrated.

209. Epstein-Barr Virus Surveillance in Lung Transplantation: Post-transplant Lymphoproliferative Disorder and Impact on Survival

Abstract Background Epstein-Barr virus (EBV) donor seropositive/recipient seronegative (D+/R-) status is a risk factor for post-transplant lymphoproliferative disorder (PTLD) which is associated with increased mortality post-lung transplant. The optimal surveillance strategy for PTLD post-lung transplant stratified by EBV serostatus for early diagnosis is unknown. We assessed serial EBV viral loads (VL) for early diagnosis of PTLD and compared outcomes in EBV D+/R- and R+ lung transplant recipients at our center. Methods A single-center retrospective study of lung transplants between January 2017 and September 2021 was performed, with a 6-month minimum follow-up. Recipient characteristics, outcomes, and serial EBV VL (biweekly months 1-3, monthly 4-12; using the cobas quantitative PCR assay on serum) were assessed. Results Of the 242 lung transplant recipients, 14 (6%) were EBV D+/R- and 228 (94%) were EBV R+ [Figure 1]. Median age and lung allocation score were similar between the two cohorts [Table 1]. 7 (50%) EBV D+/R- recipients had 2 consecutive, detectable EBV VL in the first-year post-transplant compared to 30 (13%) R+ recipients (p=0.002). 5 (71%) EBV D+/R- recipients with 2 consecutive, detectable EBV VL developed PTLD compared with 2 (7%) R+ recipients (p=0.001). Median weeks post-transplant for two consecutive, detectable EBV VL were 14 (IQR 7, 15) and 10 (IQR 6, 24); and median weeks post-transplant for diagnosis of PTLD were 22 (IQR 17, 31) and 17 (IQR 16, 17) for EBV D+/R- and R+, respectively. Only recipients with at least 2 consecutive, detectable VL in the first-year post-transplant developed PTLD. EBV VL level was not associated with development of PTLD. 6-month outcomes were similar between EBV D+/R- and R+. Though there were no differences in mortality at 1 and 2-years stratified by EBV serostatus, all 5 EBV D+/R- recipients with PTLD were alive 2 years post-transplant, whereas both EBV R+ PTLD recipients died < 2 years post-transplant (p=0.048). Figure 1:Study cohort characteristics and PTLD outcomes based on serial EBV viral loads within the first-year post-lung transplant*7 recipients were excluded per study criteria due to having died less than 1-month post-transplant and therefore not having sufficient EBV VL testing post-transplant for this analysis.Table 1:Baseline characteristics, index hospitalization, and clinical outcomes of lung transplant recipients stratified by EBV serostatus*P-values are based on Fisher’s two-sided exact test (for categorial variables) or the Wilcoxon rank-sum test (for continuous variables).**Time to ≥2 consecutive, detectable EBV VL was calculated based on the date of the second consecutive, detectable result. Conclusion Two consecutive, detectable EBV VL within the first-year post-lung transplant should prompt additional work-up for the early diagnosis of PTLD in all recipients regardless of the EBV VL level or serostatus. Though the attack rate of PTLD was greater in EBV D+/R- recipients, survival outcomes were similar irrespective of serostatus. Disclosures Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support.

Microbial contamination and quantitative microbial risk assessment of high-density polyethylene (HDPE) film sachet drinking water in Ghana.

The present research estimated the impact of storage on the microbial quality of high-density polyethylene drinking water. Samples were taken from two popular companies in Greater Accra using a two-sided exact test in SAS JMP to estimate the sample size. The samples were stored across three temperature profiles at 8 °C, 30 °C (average room temperature), and 40 °C (average outdoor temperature) for 28 days. The samples were examined using standard microbiological methods for heterotrophic plate counts (HPCs), faecal coliforms, and Escherichia coli. The data were described and regressed with Microsoft Excel, Argo 4.3.1, and SAS JMP software. The results demonstrated increasing deterioration of the water samples for all microbial indices at all temperatures with increasing storage duration. The highest HPC, faecal coliforms, and E. coli were 1,312; 622; and 252 cfu/100 mL, respectively, all at 40 °C. The daily risk of infection due to E. coli O157:H7 was 5.22 × 10-5 infections per child per day for children under 5 years, and 1.6 × 10-4 attacks per adult per day, compared to the upper limit of 1.0 × 10-6. These results are higher than recommended exposures, and interventions along the sachet drinking water value chain are needed to protect public health.

The Effect of Radiation Modality on Outcomes of Patients Receiving Adjuvant Chemoradiotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma: A Secondary Analysis of SWOG S0809

<h3>Purpose/Objective(s)</h3> The phase II intergroup S0809 trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in patients with resected EHCC or GBCA demonstrated promising efficacy and tolerability, with a median overall survival of 35 months. Both 3-dimensional radiotherapy (3D) and intensity-modulated radiotherapy (IMRT) were permitted on the trial. Patients received 45 Gy to regional lymph nodes, with a tumor bed boost to a total of 52.5-59.4 Gy in 25-33 fractions, with radiation technique and dose given at the investigator's discretion. Given the range of permitted radiation modalities and doses administered, we performed a post hoc analysis of the effect of radiation modality on outcomes of patients treated on SWOG S0809. <h3>Materials/Methods</h3> Eligibility criteria included diagnosis of EHCC or GBCA after radical surgery, stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to 1. Patients received four cycles of gemcitabine and capecitabine followed by concurrent capecitabine and radiotherapy, 45 Gy to regional nodes, with a tumor bed boost to 52.5-59.4 Gy [3D: 54 or 59.4 Gy (optional for R1) in 1.8 Gy fractions; IMRT 52.5 Gy or 55 Gy (optional for R1) in 2.1-2.2 Gy fractions]. Baseline characteristics were evaluated using the Mann-Whitney U-test for age and chi-squared test for categorical variables. Disease-free survival (DFS), local recurrence-free survival and distant metastasis-free survival were evaluated using the Kaplan-Meier method. Rates of adverse events were evaluated using Fisher's two-sided exact test. <h3>Results</h3> Of the 79 patients enrolled on the trial from 2008 to 2012, 69 patients (87%) received radiotherapy. The minority (20.2%) of patients were treated with 3D, while 79.8% were treated with IMRT. There were no differences in utilization of 3D vs. IMRT based on site of disease, margin status or lymph node status. The 2-year DFS was 60% for 3D and 52% for IMRT (<i>P</i> = 0.73). Only 7.1% of patients treated with 3D experienced local recurrence, while 18.2% of patients treated with IMRT experienced local recurrence (<i>P</i> = 0.41). Distant metastases developed in 21.4% of patients treated with 3D and 47.3% of patients treated with IMRT (<i>P</i> = 0.15). While no patients treated with 3D experienced grade 3+ gastrointestinal (GI) toxicity, 18.2% of patients treated with IMRT experienced grade 3+ GI toxicity (<i>P</i> = 0.19). Grade 3+ hematologic toxicity was seen in 60% of patients treated with IMRT and 71.4% of patients treated with 3D (<i>P</i> = 0.54). One grade 5 GI toxicity was seen in the IMRT cohort. <h3>Conclusion</h3> Both 3D and IMRT are effective modalities for chemoradiotherapy in the adjuvant treatment of EHCC and GBCA, with similar rates of DFS, local control, and toxicity. Given potential for GI toxicity, future trials should include prospective contour and plan review.

Prevalence of cancer in patients with superficial vein thrombosis and its clinical importance

ObjectiveThe objective of the present study was to evaluate the prevalence of cancer in patients with superficial vein thrombosis (SVT) of the legs. Moreover, we evaluated the potential determinants of SVT complications by comparing a subgroup with isolated SVT and a subgroup of SVT complicated by concurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) with respect to the presence of cancer and other clinical and laboratory characteristics. MethodsThe present single-center, retrospective study of prospectively collected data was conducted in a tertiary care setting. We included patients who had been treated in the thrombosis clinic from 2006 to 2018 for symptomatic SVT of the legs, either isolated SVT or SVT complicated by concurrent DVT/PE. We evaluated the prevalence and type of malignancy (diagnosed ≤12 months before SVT and/or ongoing therapy), demographics, and clinical and laboratory characteristics of the patients. For statistical evaluation, we used the Student t test, Kruskal-Wallis test, Fisher exact two-sided test, and logistic regression. ResultsOf 276 patients with SVT (mean age, 58.9 ± 14.7 years; 60.9% women), 191 had had isolated SVT and 85 had had SVT complicated by concurrent DVT/PE. The prevalence of malignancy was 8.7% in the whole group (mainly breast and urinary tract cancer), including 4.2% of those with isolated SVT and 18.8% of those with SVT and concurrent DVT/PE (P < .001). Between the two subgroups, no significant differences were present in the duration of leg symptoms, family or personal history of SVT and/or DVT, SVT location, and smoking. In logistic regression, several factors were significantly associated with the concurrent presence of DVT/PE: age (odds ratio [OR], 1.024; 95% confidence interval [CI], 1.004-1.044), female gender (OR, 0.545; 95% CI, 0.309-0.960), varicose vein SVT (OR, 0.42; 95% CI, 0.194-0.902), thrombophilia (OR, 1.939; 95% CI, 1.089-3.454), and cancer (OR, 4.727; 95% CI, 1.814-12.316). ConclusionsThe prevalence of malignancy in the patients with SVT was 8.7%. Age, thrombophilia, male gender, nonvaricose vein SVT, and cancer were significantly associated with the presence of concurrent DVT/PE. Cancer was the strongest determinant of concurrent DVT/PE.

A reassortant G3P[12] rotavirus A strain associated with severe enteritis in donkeys (Equus asinus)

In contrast to horses, the only evidence suggesting gastrointestinal disease in neonatal donkeys is associated with Group A rotaviruses (RVAs) is the detection of viral antigens by ELISA in just 1 of 82 symptomatic donkey foals. No additional, more comprehensive investigations have been conducted, and RVAs if circulating in donkey populations have not been molecularly characterised. To investigate if RVAs are associated with an outbreak of severe enteritis in neonatal donkeys and if associated determine the genotype(s) along with the phylogenetic relationship to RVA strains circulating in horses. Cross-sectional. RT-PCR-based techniques were used for RVA diagnosis and gene amplification. Statistical significance was determined by Chi-square and Fisher's exact two-sided tests. Genotyping was performed by RotaC and phylogenetic analysis by neighbour joining. In 2019, acute enteritis occurred in 119 of 206 donkey foals (≤4months) at two intensive donkey farms in the Shandong province of China. The highest morbidity (68.1%), mortality (29.5%) and fatality levels (45.5%) occurred in foals in the 30-89day, 30-59day and 0-29day age groups respectively. RVA gene sequences were detected in 107 (89.9%) of the symptomatic individuals while further analysis demonstrated the outbreak was associated with the same G3P[12] RVA strain designated RVA/Donkey-wt/CHN/Don01/2019/G3P[12]. Although the VP4 gene of Don01 exhibited close phylogenetic relationships with equivalent RVA sequences commonly circulating in horses, encoding VP7 was more closely associated with sequences isolated from bats suggesting this new donkey strain arose via an intergenogroup reassortment event. Actual prevalence not determined because <7% of asymptomatic donkey foals were included in this study. The complete genomic sequence of RVA/Donkey-wt/CHN/Don01/2019/G3P[12] remains to be determined. Valuable new information about the molecular epidemiology of rotaviruses in different equid species is provided by isolation and molecular characterisation of a novel RVA strain from neonatal donkeys.

Point-of-care Lung Ultrasound Is Useful to Evaluate Emergency Department Patients for COVID-19.

IntroductionCoronavirus disease 2019 (COVID-19) can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) evaluation of symptomatic patients with normal vital signs is frequently limited to chest auscultation and oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for COVID-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with COVID-19 less than 2% of the time.MethodsWe performed a retrospective, structured, blinded ultrasound review and chart review in patients 14 years or older with symptoms prompting ED evaluation for COVID-19. We excluded those with known congestive heart failure or other chronic lung conditions likely to cause excessive B-lines on LUS. We used a two-sided exact hypothesis test for binomial random variables. We measured LUS diagnostic performance using computed tomography as the gold standard.ResultsWe reviewed 77 charts; 49 met inclusion criteria. Vital signs were normal in 30/49 patients; 10 (33%) of these patients had LUS consistent with viral pneumonitis. We rejected the null hypothesis (p-value <0.001). The treating physicians’ interpretations of their own point-of-care LUS had a sensitivity of 100% (95% confidence interval (CI), 74%, 100%), specificity 88% (95% CI, 47%, 100%), likelihood ratio (LR) positive of 5.8 (95% CI, 1.3, 25), and LR negative of 0.05 (95% CI, 0.03, 0.71) when compared to CT findings.ConclusionLUS had a meaningful detection rate for pneumonitis in symptomatic ED patients with normal vital signs who were being evaluated for COVID-19. We recommend at least LUS be used in addition to polymerase chain reaction testing when evaluating symptomatic ED patients for COVID-19.

Genetic Color Polymorphism of the Whitelined Sphinx Moth larva (Lepidoptera: Sphingidae).

For a trait to be considered polymorphic, it must fulfill both genetic and ecological criteria. Genetically, a polymorphic trait must have multiple heritable variants, potentially from the same female, in high-enough frequency as to not be due to mutation. Ecologically, in a single wild population, these variants must co-occur, and be capable of interbreeding. Polymorphism is frequently considered in the context of either geographical cause or genetic consequence. However, the incorporation of both in a single study can facilitate our understanding of the role that polymorphism may play in speciation. Here, we ask if the two color morphs (green and yellow) exhibited by larvae of the whitelined sphinx moth, Hyles lineata (Fabricius), co-occur in wild populations, in what frequencies, and whether they are genetically determined. Upon confirmation from field surveys that the two color morphs do co-occur in wild populations, we determined heritability. We conducted a series of outcrosses, intercrosses and backcrosses using individuals that had exhibited yellow or green as laboratory-reared larvae. Ratios of yellow:green color distribution from each familial cross were then compared with ratios one would expect from a single gene, yellow-recessive model using a two-sided binomial exact test. The offspring from several crosses indicate that the yellow and green coloration is a genetic polymorphism, primarily controlled by one gene in a single-locus, two-allele Mendelian-inheritance pattern. Results further suggest that while one gene primarily controls color, there may be several modifier genes interacting with it.

Melanoma Skin Self-Examination Education During Mammography: Health Burden of Women Impairs Implementation.

Identification of barriers to seeking health care for a concerning mole found during skin self-examination (SSE) by women educated during screening mammography. In this sequential mixed methods research, interviews with women who found a concerning mole and did not have health-care follow-up were analyzed and a survey was created. One year after SSE education, barriers to having health care for a self-identified concerning mole were assessed. The electronic medical records for all participants, who received education, were reviewed to ascertain who received health care related to a concerning mole or a screening mammogram. Among the 280 women who performed SSE, 85 found a concerning mole. Nine months later 51 women did not receive health care for the mole. Barriers were the burden of other medical concerns, fear of what the doctor will find, feeling like nothing is wrong, and being too busy. A positive screening mammogram (Fisher's two-sided exact test, p < 0.001) and a history of indoor tanning (Fisher's two-sided exact test, p = 0.011) were significantly associated with lack of follow-up for a concerning mole. Targeted melanoma self-identification with SSE relies upon participants initiating performance and seeking medical care for a concerning mole. The burden of a positive screening mammogram reported to women at about the same time as they identified the concerning mole was associated with failing to seek care for their concerning mole. Reminders to check moles for change 4months after identifying a concerning mole may benefit women. Clinicaltrials.gov NCT03512457.

First Results of a Randomized Controlled Trial of Hemoblock in Patients with Large Incisional Hernias

ABSTRACT. When penetrating into the cell, local anesthetics affect some structures and processes, in addition to blocking sodium channels, leading to the development of cell damage. The aim of the article was to study the damaging effect of bupivacaine on the sciatic nerve and biceps femoris in rats.AIM OF STUDY. Analysis of the first results of a randomized clinical trial (RCT) for the use of Hemoblock in patients with large incisional hernias and postoperative ultrasound (US) monitoring.OBJECTIVES. Improving the results of surgical treatment of patients with large incisional hernias.MATERIAL AND METHODS. Design of a simple blind randomized controlled trial with a 90 percent study power, α-error equal to 0.05 and β-error equal to 0.10. For this purpose, the total number of subjects is planned to be 66. Currently, there are 18 patients in the study, 10 in the comparison group (B), and 8 in the main group (A). Surgery is plastic prosthetic mesh implant in the sublay retromuscular position. We applied Hemoblock 15 ml retromuscularly and 15 ml subcutaneousely in group B. Wounds were drained by vacuum suction drains. Postoperatively — monitoring of a wounds by ultrasound examination on day 3, 7, 10, 12, 15, 18, and 21 after the removal of drains. The average age was 58.5±6.3 in group B and 55.6±11.7 years in group A (U=36.5, p&gt;0.05), BMI 33.6±3.44 and 32.2±5.19 kg/m2respectively (U=35, p&gt;0.05), the width of the hernia defect was 11±1.7 cm and 11.1±1.0 (U=33, р&gt;0.05), length 13.6±2.7 cm and 12.5±3.3 cm (U=29.5, p&gt;0.05), the area was 118±22.7 cm2 and 108.1±24.1 cm2 respectively (U=28.5, p&gt;0.05). The average ASA was 2.2 in group B and 2.0 in group A.RESULTS AND DISCUSSION. Median of follow-up for all patients was 30 days. Significant differences obtained in the duration of postoperative wound drainage — 4.2±0.9 days in group B versus 2.5±0.5 days in group A (U=4, p&lt;0.01). In patients of group A, the amount of discharge by drainage and the level of CRP and albumin were lower. On ultrasound examination of the postoperative wound, starting from the 10th day, a significantly smaller volume of fluid accumulations was revealed in patients of this group, and from the 15th day fluid accumulations were not detected. In group B, one patient had seroma IIIc (according to MoralesCondo, 2012), 8 patients had IVa seroma, and one patient had IVb seroma spontaneously opened through the postoperative wound, which required debridement of the cavity on an outpatient for 21 days. In group A, only 3 patients had IVa seroma. The number of punctures was 23 in group B, and 3 in group A (χ2=8.654, p=0.04, Fisher’s exact two-sided test (F) =0.00654, p&lt;0.05). Hospital stay was 8.9±0.6 days in group B and 8.0±0.5 days in group A (U=11.5, p&lt;0.05).CONCLUSION. According to preliminary data using local haemostatic agent Hemoblock allows: 1) to reduce the duration of postoperative wound drainage, 2) to reveal the period of inflammatory exudative processes in the postoperative wound, 3) to reduce the number of puncture interventions after incisional hernia repair, 4) to reduce the severity of pain and the need for analgesics, 5) to reduce the hospital stay time.Authors declare lack of the conflicts of interests.

P1619Polymorphic variants rs6684209 and rs7521023 of the calsequestrin 2 gene as risk factors for adverse course of heart failure

Abstract Calsequestrin 2 protein binds most of Ca2+ ions inside the sarcoplasmic reticulum and is involved in the regulation of Ca2+ release through the ryanodine receptors of the cardiomyocytes. Due to mutations in the CASQ2 gene, there is an enhanced release of ions from the sarcoplasmic reticulum, which leads to disruption of Ca2+ homeostasis. In turn, this is a risk factor for the development and progression of chronic heart failure (CHF) and heart rhythm disturbances. Purpose Investigate the association between polymorphic variants rs6684209, rs7521023 of the CASQ2 gene and heart failure in patients with coronary artery disease (CAD). Methods The sample included 174 patients with CAD complicated by CHF. Of these, 115 (66.1%) are men and 59 (33.9%) are women aged 64 (59; 70) years. The functional class (FC) of CHF was defined according to the classification of the New York Heart Association (NYHA). The distribution of CHF FC I, FC II, FC III was 25 (14.4%), 97 (55.7%), 52 (29.9%). The left ventricular ejection fraction in the patient sample was 62% (52; 66). The polymorphic variants rs6684209 (115707991C&gt;T in the intron) and rs7521023 (115700759G&gt;A in 3-UTR) of the CASQ2 gene were determined by real-time polymerase chain reaction. For the analysis of the qualitative data, Pearson's χ2 test or the Fisher two-sided exact test was used. Results In the total sample of patients, there was no assotiation between the rs6684209 variant of the CASQ2 gene and the clinical picture of CHF. However, among men, but not women, differences in the frequency of FC I, II, III CHF (p=0.029) between CC, CT and TT genotypes were found. In addition, among carriers of the CT genotype, diastolic myocardial dysfunction occurred in 80% of patients, while among CC homozygotes, its frequency was 63.1% and was not observed in TT homozygotes (p=0.034). At the same time, there were more patients with heart rhythm disorders among CC homozygotes than among carriers of the T allele (60.8% vs. 45.2% for CT and 0% for TT, p=0.046). The association of the polymorphic variant rs7521023 with the course of CHF was assessed. A significant (p=0.044) increase in the frequency of left atrial enlargement in GG homozygotes (69.2%) compared with carriers of the AA (45.1%) and AG (41.9%) genotypes was found in the total sample of patients. Gender features were absent in the association of variant rs7521023 with risk factors for the development and progression of CHF. Conclusion The polymorphic variants rs6684209 and rs7521023 of the CASQ2 gene are associated with the severity of CHF and the risk of developing heart rhythm disturbances. With the CT genotype of the rs6684209 variant, diastolic myocardial dysfunction was more common, but the T allele appeared to be protective against the development of heart rhythm disturbances. Carrier genotype GG (rs7521023) is a risk factor for dilatation of the left atrium, which in turn can serve as a substrate for the development of arrhythmias. Acknowledgement/Funding This work was supported in part by the Russian Foundation for Basic Research, No. 17-04-01450 A.

Clinical value of MRI in the diagnosis of placental implantation

Objective To determine imaging features that may help predict the presence of placenta accreta, placenta increta or placenta percreta on prenatal MRI scanning in order to identify the most diagnostic findings. Methods The prenatal MRI scan data of placenta accreta, placenta increta or placenta percreta (placenta implantation group, n=15) and normal placenta(placenta normal group, n=15) diagnosed and treated by surgical pathology from January 2010 to December 2017 in the People's Hospital of Huadu District were retrospectively analyzed.Two expert MRI doctors were blinded to the patients' true diagnosis and were asked to score a total of 10 MRI features of the placenta and adjacent structures.The interrater reliability was assessed using kappa statistics.The features with a moderate kappa statistic or better(kappa>0.40 ) were then compared with the true diagnosis for each observer. Results Eight of the scored features had an interobserver reliability of kappa>0.40: placenta previa(κ=0.89); abnormal uterine bulging(κ=0.57); intraplacental hemorrhage(κ=0.45); the presence of dark intraplacental bands on T2W imaging(κ=0.76); flow-empty blood vessels in placenta(κ=0.67); border on placenta and uterus blurring(κ=0.63); heterogeneity of signal intensity on T2-weighted(T2W) imaging(κ=0.53); and continuity of myometrium was interrupted(κ=0.64). Using Fisher's two-sided exact test, there were statistically significant differences between the proportion of patients with placental invasion and those without placental invasion for three of the features: abnormal uterine bulging(P=0.015, P=0.011); heterogeneity of T2W imaging signal intensity(P=0.006, P=0.013); and presence of dark intraplacental bands on T2W imaging(P=0.032, P=0.010). Conclusion MRI can be a useful adjunct to ultrasound in diagnosing placenta accreta prenatally.Three features that are seen on MRI in patients with placental invasion appear to be useful for diagnosis: uterine bulging; heterogeneous signal intensity within the placenta; and the presence of dark intraplacental bands on T2W imaging. Key words: Magnetic resonance imaging; Placenta diseases; Placenta accreta; Placenta previa; Prenatal diagnosis; Diagnosis

Abstract 4064: Association of molecular signatures, mutations, and sTILs, with pCR in breast cancer patients in NRG Oncology/NSABP B-52

Abstract Background: NRG Oncology/NSABP B-52 neoadjuvant clinical trial was conducted to test if the addition of estrogen deprivation (ED) would improve the pCR rate in HER2+/ER+ breast cancer pts treated with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). A numerical increase in the pCR rate was observed with ED (46.1% v 40.9%), but the difference was not statistically significant. The purpose of this study was to determine the utility of using stromal tumor infiltrating lymphocytes (sTILs), mutations, established, and novel signatures, to assess their value for predicting pCR, particularly in the TCHP + ED arm. Methods: Whole transcriptome RNA-Seq and Ampli-Seq libraries were sequenced on the Ion Torrent platform. Mutations were assessed with a custom Ampli-Seq panel of 117 genes, including HER2-activated pathways and/or trastuzumab (T)-resistance markers. The 8-gene T-benefit signature was prospectively tested for association with pCR, and was previously validated in the adjuvant setting in B-31 and NCCTG N9831. Hot-spot mutations, sTILs, and signatures for immune cells, intrinsic subtypes, risk of recurrence proliferation (RORP), and MammaPrint, were also tested for associations with pCR. RNA-Seq data was also used to identify ED-predictive genes. Differential expression was assessed in normalized RNA-Seq data using DESeq2 and each sample was subtyped with the AIMS classifier. Wilcoxon two-sided test, chi-square, or Fisher's exact tests were used to assess associations with pCR. Results: Subtypes were determined with RNA-Seq data from pretreatment biopsies (N=230). The 8-gene T-benefit signature was associated with pCR. The high-, medium-, and low- T-benefit groups had pCR rates of 55%, 44%, and 6.8%, respectively (p=1.3e-13). Intrinsic subtypes were associated with pCR by comparing HER2E to all other subtypes combined (69% v 28%, p=3.9e-08). Hot spot mutations in PIK3CA alone (p=0.014), or combined with hot spot mutations in ERBB2, ERBB3, AKT1, PTEN, and MAP3K1, were associated with no pCR (p=0.0007) and may be useful as resistance markers. sTILs, MammaPrint, RORP, and some immune cell signatures also showed statistically significant associations with pCR but did not identify a subset of pts with an increased pCR rate in the TCHP + ED arm. In contrast, expression of the SH3BP2 gene was associated with pCR only in the TCHP + ED arm (interaction p=0.03). Conclusion: The previously validated 8-gene T-benefit signature identifies a subset of pts with very low pCR rate (6.8%) with TCHP. PIK3CA and other activating mutations were associated with no pCR. These findings may identify pts with resistant disease who may require a different treatment. Exploratory analyses suggest that SH3BP2 expression may identify pts who may benefit from TCHP + ED, but validation is required for clinically utility. Support: BCRF, U10CA180868, -180822; UG1CA189867, Genentech, PUMA Biother Citation Format: Katherine L. Pogue-Geile, Ying Wang, Huichen Feng, Corey Lipchik, Rim S. Kim, Reena S. Cecchini, Samuel A. Jacobs, Ashok Srinivasan, Joseph P. Costantino, Eleftherios P. Mamounas, Charles E. Geyer, Priya Rastogi, Peter C. Lucas, Soonmyung Paik, C. Kent Osborne, Norman Wolmark, Mothaffar F. Rimawi. Association of molecular signatures, mutations, and sTILs, with pCR in breast cancer patients in NRG Oncology/NSABP B-52 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4064.

Fully Automated Diagnosis of Anterior Cruciate Ligament Tears on Knee MR Images by Using Deep Learning.

To investigate the feasibility of using a deep learning-based approach to detect an anterior cruciate ligament (ACL) tear within the knee joint at MRI by using arthroscopy as the reference standard. A fully automated deep learning-based diagnosis system was developed by using two deep convolutional neural networks (CNNs) to isolate the ACL on MR images followed by a classification CNN to detect structural abnormalities within the isolated ligament. With institutional review board approval, sagittal proton density-weighted and fat-suppressed T2-weighted fast spin-echo MR images of the knee in 175 subjects with a full-thickness ACL tear (98 male subjects and 77 female subjects; average age, 27.5 years) and 175 subjects with an intact ACL (100 male subjects and 75 female subjects; average age, 39.4 years) were retrospectively analyzed by using the deep learning approach. Sensitivity and specificity of the ACL tear detection system and five clinical radiologists for detecting an ACL tear were determined by using arthroscopic results as the reference standard. Receiver operating characteristic (ROC) analysis and two-sided exact binomial tests were used to further assess diagnostic performance. The sensitivity and specificity of the ACL tear detection system at the optimal threshold were 0.96 and 0.96, respectively. In comparison, the sensitivity of the clinical radiologists ranged between 0.96 and 0.98, while the specificity ranged between 0.90 and 0.98. There was no statistically significant difference in diagnostic performance between the ACL tear detection system and clinical radiologists at P < .05. The area under the ROC curve for the ACL tear detection system was 0.98, indicating high overall diagnostic accuracy. There was no significant difference between the diagnostic performance of the ACL tear detection system and clinical radiologists for determining the presence or absence of an ACL tear at MRI.© RSNA, 2019Supplemental material is available for this article.