Two-sided Exact Test Research Articles

Autoantibodies to a novel Rpp38 (Th/To) derived B-cell epitope are specific for systemic sclerosis and associate with a distinct clinical phenotype.

Detection of antinuclear antibodies and specific autoantibodies is important in the diagnosis and classification of SSc. Several proteins of the Th/To complex, including Rpp25, Rpp38 and hPop1 are the target of autoantibodies in SSc patients. However, very little is known about the epitope distribution of this autoantigen. Consequently, we screened Rpp25, Rpp38 and hPop1 for B cell epitopes and evaluated their clinical relevance. Serum pools with (n = 2) and without (n = 1) anti-Th/To autoantibodies were generated and used for epitope discovery. Identified biomarker candidate sequences were then utilized to synthesize synthetic, biotinylated, soluble peptides. The peptides were tested to determine reactivity with sera from SSc cohorts (n = 202) and controls (n = 159) using a chemiluminescence immunoassay. Additionally, samples were also tested for antibodies to full-length recombinant Rpp25 antibodies by chemiluminescence immunoassay. Several immunodominant regions were found on the three proteins. The strongest reactivity was observed with an Rpp38 peptide (aa 229-243). Autoantibodies to the Rpp38 peptide were detected in 8/149 (5.4%) limited cutaneous SSc patients, but not in any of 159 controls (P = 0.003 by two-sided Fisher's exact probability test). Although reactivity to the novel antigenic peptide was correlated with the binding to Rpp25 (rho = 0.44; P < 0.0001), subsets of patient sera either reacted strongly with Rpp25 or with the novel Rpp38-derived peptide. A novel Rpp38 epitope holds promise to increase the sensitivity in the detection of anti-Th/To autoantibodies, thus enhancing the serological diagnosis of SSc.

An outbreak of strangles associated with a novel genotype of Streptococcus equi subspecies equi in donkeys in China during 2018.

Strangles is a highly contagious respiratory disease of equids caused by the bacterium Streptococcus equi subspecies equi. To identify the cause of an outbreak of strangles that occurred on donkey farms within the Shandong Province of China and determine the prevalence of the disease. Cross-sectional. Samples were taken from clinically affected animals to measure the prevalence of strangles within the population of donkeys at six intensive farms in China and identify the SeM type of isolate recovered from affected animals. Diagnosis was confirmed by bacterial isolation, biochemical tests and PCR. Epidemiological data were analysed using Chi-square test and a Fisher's exact two-sided test. The SeM gene of S.equi isolates recovered from affected animals was determined and compared with the SeM database PubMLST-seM. In July and August 2018, an outbreak of strangles occurred on six donkey farms within the Shandong Province of China. The overall prevalence of disease within the different donkey herds was 13.4%. Younger animals were worst affected with 40.3% (83/206) of donkey foals aged under 1year exhibiting clinical signs compared with 12.5% (191/1525) of donkeys aged one to 2years and 3.8% (17/442) of donkeys over 2years of age. Analysis of SeM sequencing data identified that the farms were affected by the same strain of S.equi, SD201807, which contains the novel 136 allele of SeM. Healthy donkeys were not sampled in this study. The number of intensive donkey breeding farms in China has risen recently. The higher numbers of animals that are in closer proximity to one another raise the potential for the transmission of infectious diseases such as strangles. This is the first description of a strangles outbreak among donkey herds in China. The Summary is available in Chinese - see Supporting information.

A phase II study of ADI-PEG 20 and FOLFOX6 in patients (pts) with advanced hepatocellular carcinoma (HCC).

TPS477 Background: Arginine depletion interferes with pyrimidine metabolism as well as DNA damage repair pathways, and preclinical data indicate that pairing pegylated arginine deiminase (ADI-PEG 20) with fluoropyrimidines or platinum enhances cytotoxicity in vitro and in vivo in HCC models. A prior phase 1 study of FOLFOX6 and ADI-PEG 20 established the safety and recommended phase 2 dose of the combination in pts with advanced gastrointestinal tumors (Harding et al. CCP 2018). For 23 treatment-refractory HCC pts who were treated at the recommended phase 2 dose on an expansion cohort of the phase 1, the objective response rate (ORR) was 21% (95% CI 7.5-43.7) and median progression-free survival (PFS) was 7.3 months. These data were favorable when compared to historic data for FOLFOX alone where the ORR was ~8% and PFS was 2.93 months and suggest greater clinical activity of the combination (Qin et al. JCO 2013). Prospective confirmation of these results is required. Methods: This is an international, multicenter, single-arm, open-label phase 2 trial of ADI-PEG 20 and FOLFOX6 for advanced HCC pts with Child-Pugh A liver function who progressed on ≥ 2 prior lines of prior systemic therapy (NCT02102022). The primary objective is to define the ORR by RECIST 1.1 as assessed by blinded independent central review. Secondary objectives include determination of safety, disease control rate (DCR), duration of response (DOR), PFS, overall survival (OS), serum arginine, citrulline and anti-ADI-PEG 20 levels over 24 weeks, and alpha-fetoprotein response. Eligible pts receive intravenous FOLFOX6 biweekly at standard doses and ADI-PEG 20 intramuscularly weekly at 36 mg/m.2 Cross-sectional imaging will be completed every 8 weeks until progression of disease. Based on a two-sided exact test of a one-sample proportion with an alpha of 0.05, under a presumed ORR of 22%, there is 80% power to yield 95% confidence interval of 15-26%, which will require 46 objective responses in 225 subjects. Futility will be assessed three times during the study based on having ORR data available for 56, 110, and 166 patients. This Phase 2 will be stopped for futility if the conditional power drops below 20% at any of these time points. Clinical trial information: NCT02102022.

\u201cTo survey or to register\u201d is that the question for estimating population incidence of injuries?

BackgroundMeasuring the true incidence of injury or medically attended injury is challenging. Population surveys, despite problems with recall and selection bias, remain the only source of information for injury incidence calculation in many countries. Emergency department (ED) registry based data provide an alternative source.The aim of this study is to compare the yearly incidence of hospital treated Home and Leisure Injuries (HLI), and Road Traffic Injuries (RTI) estimated by survey-based and register-based methods and combine information from both sources in to a comprehensive injury burden pyramide.MethodsData from Luxemburg’s European Health Examination Survey (EHES-LUX), European Health Interview Survey (EHIS) and ED surveillance system Injury Data Base (IDB) collected in 2013, were used. EHES-LUX data on 1529 residents 25–64 years old, were collected between February 2013–January 2015. EHIS data on 4004 other residents aged 15+ years old, were collected between February and December 2014. Participants reported last year’s injuries at home, leisure and traffic and treatment received. Two-sided exact binomial tests were used to compare incidences from registry with the incidences of each survey by age group and prevention domain. Data from surveys and register were combined to build an RTI and HLI burden pyramide for the 25–64 years old. This project was part of the European Union project BRIDGE-Health (BRidging Information and Data Generation for Evidence-based Health Policy and Research).ResultsAmong 25–64 years old the incidence of hospital treated injuries per thousand population was 60.1 (95% CI: 59.2–60.9) according to IDB, 62.1 (95% CI: 50.6–75.4) according to EHES-LUX and 53.2 (95% CI: 45.0–62.4) according to EHIS. The incidence of hospital admissions was 3.7 (95% CI: 3.5–4.0) per thousand population from IDB-Luxembourg, 12.4 (95% CI: 7.5–19.3) from EHES-LUX and 18.0 (95% CI: 13.3–23.8) from EHIS. For 15+ years-old incidence of hospital treated HLI was 62.8 (95% CI: 62.1–63.5) per thousand population according to IDB whereas the corresponding EHIS estimate was lower at 46.9 (95% CI: 40.4–54.0). About half of HLI and RTI of the 25–64 years old were treated in hospital.ConclusionThe overall incidence estimate of hospital treated injuries from both methods does not differ for the 25–64 years old. Surveys overestimate the number of hospital admissions, probably due to memory bias. For people aged 15+ years, the survey estimate is lower than the register estimate for hospital treated HLI injuries, probably due to selection and recall biases. ED based registry data is to be preferred as single source for estimating the incidence of hospital treated injuries in all age groups.

Impact of Incomplete Cycles and Dose Attenuation of Rituximab-Bendamustine on Survival Outcomes in Low-Grade Non-Hodgkin Lymphomas

IntroductionRituximab and Bendamustine (BR) has been shown to be effective in the treatment of indolent non-Hodgkin's lymphomas (NHLs) with an acceptable safety profile and comparable to Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP). However, patients may develop significant cytopenias after Bendamustine exposure leading managing physicians to truncate the suggested treatment course or attenuate treatment dosages. We hypothesize that this reduced treatment intensity may negatively affect treatment outcomes.MethodsWe retrospectively analysed patients who were diagnosed with indolent non-Hodgkin lymphomas (NHL) at the Singapore General Hospital from year 2000 and received BR or R-CHOP frontline. Data was locked at 31 October 2017. Histologic diagnosis was made according to published international guidelines. The safety and efficacy of BR and RCHOP as first line treatment of indolent lymphomas was analyzed. We also evaluated if truncation of immunochemotherapy cycles or dosage attenuation impacts on progression-free survival (PFS). We define patients on BR as i) BR full - having received 6 cycles of BR at 90mg/m2/day for 2 days per cycle ii) BR attenuated - received at least 6 cycles of BR at 70mg/m2/day for 2 days per cycle iii) BR truncated - received less than 6 cycles of BR. The chi-squared and Fisher's exact two-sided tests were used for comparisons between categorical variables and the t-test was used for continuous variables. Survival probabilities were calculated using the Kaplan-Meier estimator, with log-rank analysis used to compare between different groups. All analyses were performed using Stata (Statacorp, College Station, TX, USA).ResultsEighty-seven patients were evaluable of whom 47 received BR and 40 received R-CHOP upfront. Amongst patients who received BR and R-CHOP respectively, histological diagnoses were: follicular lymphoma (19.2% vs 72.5%), marginal zone lymphoma (25.5% vs 7.5%), chronic lymphocytic leukaemia / small B-cell lymphocytic lymphoma (29.8% vs 5.0%), lymphoplasmacytic lymphoma (21.3% vs 7.5%), mantle cell lymphoma (2.1% vs 5.0%) and other B-cell lymphoma not classifiable (2.1% vs 2.5%). Baseline characteristics are presented in Table 1 and treatment related toxicities are presented in Table 2. There was no significant difference in treatment emergent grades 3/4 haematological adverse events between BR and R-CHOP. More patients developed infusional reactions (17.0% vs 2.5%, p =0.04) when treated with BR compared to R-CHOP. Conversely, more patients treated with R-CHOP developed peripheral neuropathy (15.0% vs 0%, p=0.008).More patients who were treated with BR as compared to R-CHOP had treatment truncated (i.e. received less than 6 cycles) or dosages attenuated (46.8% vs 5.0%, p<0.005). The median number of cycles completed for patients who had BR treatment course truncated was 4 (interquartile range 2-4). For patients treated with BR, the reasons for treatment truncation were drug-related toxicity (17.0%), patient's decision (10.6%) and physician's decision (2.1%). 2 patients had early termination with R-CHOP treatment, 1 (2.5%) due to disease progression and another patient (2.5%) due to drug-related toxicity.With a median follow-up of 51.0 months, median PFS for patients treated with BR was 69.5 months versus 76.9 months for patients treated with R-CHOP (p=0.26). BR truncated patients had inferior PFS compared to BR full and BR attenuated patients (Median PFS = 36.5mths vs NR, p=0.01). There was no statistically significant difference in PFS between BR full and BR attenuated patients (Median PFS = 69.5 mths vs NR, p=0.25).ConclusionTreatment efficacies and haematological toxicities were comparable in our patients with indolent NHLs treated with BR or R-CHOP. Despite this, more patients treated with BR had treatment truncated prematurely. The majority of such terminations were for drug-related toxicities. We found inferior PFS in patients who received less than 6 cycles of BR. Patients who completed 6 cycles of BR but had attenuated dosages did not have inferior PFS compared to patients who received 6 cycles of BR at full dose. Our findings suggest that treatment truncation with reduced treatment intensity negatively affects survival outcomes. Patients with cytopenias should be supported or have drug dosages attenuated with the aim to complete the entire treatment course for best outcomes. [Display omitted] DisclosuresChen:Takeda: Honoraria, Other: Travel grant; Janssen: Honoraria; Celgene: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding. Goh:Novartis AG: Honoraria, Other: Non-financial support, Research Funding; Takeda: Other: Non-financial support, Research Funding.

Effect of Radiation Field Size and Dose on Local Control or Re-fracture Events after Post-Operative Radiation Following Intramedullary Nailing Procedures for Palliation of Bone Metastases

Pathologic fracture of long bones carries a heavy symptomatic burden in patients with metastatic malignancy. Standard therapy typically includes intramedullary nail placement to stabilize the bone, followed by palliative post-operative radiation therapy (PORT) to reduce the risk of re-fracture or local recurrence. The radiation dose and fields for this treatment approach have wide variation without uniform standards. We sought to estimate the distribution of PORT dose/fractionation, and field size, and estimate any potential association with the risk of re-fracture and/or local recurrence. We retrospectively analyzed patients treated at our institution with pathologic fractures of long bones, treated with intramedullary nailing of the femur, tibia, or humerus, followed by post-operative palliative radiation to that site. We stratified patients by radiation fractionation (single vs multi-fraction regimen) and by radiation field size (coverage of whole hardware [full-field] vs partial coverage of hardware [limited field]), to determine if these factors may be associated with the primary endpoint, which was defined as local re-fracture and/or local recurrence of disease within the long bone. Fisher’s exact test was used for statistical comparison due to the relative paucity of events. Eighty-six evaluable patients, treated between 2010 and 2017, were identified. Median patient age was 60 years. Median Karnofsky performance status was 70. Median follow up was 2.6 months (range, 2 weeks to 74 months). Radiation doses ranged from 8 – 30Gy, apart from one patient who received 45Gy in 3 Gy fractions. Thirty-six patients (42%) received 8 Gy in a single fraction, and fifty (58%) received multi-fraction treatment. Ten patients (12%) underwent limited field radiation, while 47 (55%) underwent full field radiation, and 29 (34%) were unevaluable for field size. Nine patients (10%) reached the primary endpoint of local recurrence and/or local refracture, consistent with historical comparison. On Fisher’s two-sided exact test, field size was not found to correlate with local recurrence/re-fracture (p=0.366). Local recurrence/re-fracture was also not significantly associated with multi-fraction radiation, compared to those who received 8 Gy in a single fraction, although was numerically worse in the multifraction group (p=0.073). Increased total dose beyond 8 Gy was not associated with improvement in local control. Similarly, irradiation of the entire hardware was not associated with improved rates of local control as compared to limited field radiation. Our findings suggest that single-fraction, limited-field palliative PORT may be sufficient to achieve adequate rates of local control, thereby allowing for expedient initiation of systemic therapy and minimal RT toxicity. Further evaluation is needed.

Intrarectal Epinephrine Suspension May Protect Against Radiation Proctitis During Radiation Therapy for Prostate Cancer

The aim was to evaluate the safety and efficacy of intrarectal constrictor epinephrine to relieve symptoms of radiation proctitis. A total of 34 patients with prostate cancer (PC) was randomized to receive daily intrarectal epinephrine (4 mg in 40ml, n=16) or placebo (40ml normal saline, n=18) 5 min right before daily radiotherapy. Blood pressure and heart rate were measured at the time of pre-epinephrine, 5 minutes, and 20 minutes after using epinephrine to evaluate the safety. Side effects were graded using Radiation Therapy Oncology Group (RTOG) standard. A two-sided Fish exact test was used for comparing proportions across groups. A Wilcoxon’s rank-sum test was used to compare medians across groups for continuous variables. No patients reported local or systemic toxicity after intrarectal epinephrine or saline. The differences in blood pressure and heart rate (pretreatment, 5 minutes and 20 minutes after using epinephrine) between these two groups were not statistically significant (p=0.792、0.542). At median follow-up of 24 months, the incidence of ≥ Grade 2 rectal toxicity was significantly lower in epinephrine group compared with the placebo group (p=0.016). After 2 years, no ≥ grade 2 toxicity of rectum was observed between these two groups. Results of this trial have demonstrated that intrarectal administration of epinephrine is safe and effective in relieving radiation-induced proctitis in patients with prostate cancer receiving RT.

Invasive placenta previa: Placental bulge with distorted uterine outline and uterine serosal hypervascularity at 1.5T MRI - useful features for differentiating placenta percreta from placenta accreta.

To characterise MRI features of invasive placenta previa and to identify specific features for differentiating placenta percreta (PP) from placenta accreta (PA). Forty-five women with PP and 93 women with PA who underwent 1.5T placental MRI were included. Two radiologists independently evaluated the MRI features of invasive placenta previa, including our novel type of placental bulge (i.e. placental bulge type-II, characterized by placental bulge with distorted uterine outline). Pearson's chi-squared or Fisher's two-sided exact test was performed to compare the MRI features between PP and PA. Logistic stepwise regression analysis and the area under the receiver operating characteristic curve (AUC) were performed to select the optimal features for differentiating PP from PA. Significant differences were found in nine MRI features between women with PP and those with PA (P <0.05). Placental bulge type-II and uterine serosal hypervascularity were independently associated with PP (odds ratio = 48.618, P < 0.001; odds ratio = 4.165, P = 0.018 respectively), and the combination of the two MRI features to distinguish PP from PA yielded an AUC of 0.92 for its predictive performance. Placental bulge type-II and uterine serosal hypervascularity are useful MRI features for differentiating PP from PA. • Placental bulge type-II demonstrated the strongest independent association with PP. • Uterine serosal hypervascularity is a useful feature for differentiating PP from PA. • MRI features associated with abnormal vessels increase the risk of massive haemorrhage.

Placental recess accompanied by a T2 dark band: a new finding for diagnosing placental invasion.

Our aim was to assess the usefulness of a new magnetic resonance imaging (MRI) finding, the placental recess, for diagnosing placental invasion. This retrospective study included 51 patients (mean age 34.1years, range 26-43years) with suspected placental invasion who underwent cesarean section. Preoperative MRI was performed using a 1.5-T unit and included axial, sagittal, and coronal T2-weighted imaging (T2WI) with half-Fourier fast spin-echo sequences. Overall, 9 patients showed placental invasion, and 42 did not. Placental recess was defined as a placental deformity with contraction of the placental surface and outer rim of the uterus accompanied by a T2 dark band. Two radiologists independently assessed the presence of the placental recess and conventional findings including uterine bulging, abnormal placental vascularity, placental heterogeneous intensity on T2-weighted imaging (T2WI), and the T2 dark band. Fisher's two-sided exact test was used to compare findings between patients with and without placental invasion. Interobserver reliability was assessed using the kappa statistic. MRI features had interobserver reliability of>0.40. Placental recess yielded the highest kappa value (0.898). Significant differences were identified between patients with and without placental invasion regarding abnormal placental vascularity, placental heterogeneous intensity, a T2 dark band, and the placental recess on T2WI (p=0.0282, 0.0003, 0.0003,<0.0001, respectively). The placental recess had sensitivity, specificity, positive and negative predictive values, and accuracy of 56, 100, 100, 91, and 92%, respectively. The placental recess was useful for diagnosing placental invasion, with high interobserver variability and accuracy.

Travellers' diarrhoea-a survey of practice.

Travellers' diarrhoea (TD) is a common problem, affecting millions of tourists each year and creating a large economic burden. Risk factors for TD are known and guidelines exist to assist practitioners in advising travellers on how to prevent and treat TD. However, data are lacking regarding actual prescribing practices or approaches used in TD management. This study aims to establish a baseline which identifies uniformities and diversities in practice. An online survey created using the SurveyMonkey tool was developed to test respondent approaches to TD pre-travel management. An invitation to participate in the survey was distributed early 2016 through selected Australian and New Zealand speciality travel medicine centres and through the electronic mailing list of the International Society of Travel Medicine (ISTM). Descriptive statistics and analyses using Chi Square analysis and two-sided Fishers exact tests for significance were used. Three hundred and sixty-four completed or partially completed surveys were collected from respondents in 23 countries. Approach to TD, antibiotic choice and management of four different clinical scenarios were assessed, with analyses focused on identifying significant differences in approach according to region of practice, professional background and level of experience. The responses to the clinical scenarios suggest most uniformity in recommended treatment strategies in clearly mild or severe disease, and greater variability in moderate disease. There is practice diversity in the discussion of preventative techniques and prescribing of self-treatment medications for TD, especially for moderate TD disease. Evidence-based guidelines that address the competing issues of patient health and morbidity vs the risk of colonization with resistant organisms may lead to more consistent antibiotic prescribing practices.

Post-traumatic acute kidney injury: a cross-sectional study of trauma patients.

BackgroundThe causes of post-traumatic acute kidney injury (AKI) are multifactorial, and shock associated with major trauma has been proposed to result in inadequate renal perfusion and subsequent AKI in trauma patients. This study aimed to investigate the true incidence and clinical presentation of post-traumatic AKI in hospitalized adult patients and its association with shock at a Level I trauma center.MethodsDetailed data of 78 trauma patients with AKI and 14,504 patients without AKI between January 1, 2009 and December 31, 2014 were retrieved from the Trauma Registry System. Patients with direct renal trauma were excluded from this study. Two-sided Fisher’s exact or Pearson’s chi-square tests were used to compare categorical data, unpaired Student’s t-test was used to analyze normally distributed continuous data, and Mann–Whitney’s U test was used to compare non-normally distributed data. Propensity score matching with a 1:1 ratio with logistic regression was used to evaluate the effect of shock on AKI.ResultsPatients with AKI presented with significantly older age, higher incidence rates of pre-existing comorbidities, higher odds of associated injures (subdural hematoma, intracerebral hematoma, intra-abdominal injury, and hepatic injury), and higher injury severity than patients without AKI. In addition, patients with AKI had a longer hospital stay (18.3 days vs. 9.8 days, respectively; P < 0.001) and intensive care unit (ICU) stay (18.8 days vs. 8.6 days, respectively; P < 0. 001), higher proportion of admission into the ICU (57.7% vs. 19.0%, respectively; P < 0.001), and a higher odds ratio (OR) of short-term mortality (OR 39.0; 95% confidence interval, 24.59–61.82; P < 0.001). However, logistic regression analysis of well-matched pairs after propensity score matching did not show a significant influence of shock on the occurrence of AKI.DiscussionWe believe that early and aggressive resuscitation, to avoid prolonged untreated shock, may help to prevent the occurrence of post-traumatic AKI. However, more evidence is required to support this observation.ConclusionCompared to patients without AKI, patients with AKI presented with different injury characteristics and worse outcome. However, an association between shock and post-traumatic AKI could not be identified.Electronic supplementary materialThe online version of this article (doi:10.1186/s13049-016-0330-4) contains supplementary material, which is available to authorized users.

Abstract CT091: A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis

Abstract Background: Patients with TNBC who do not achieve a pathologic complete response (pCR) or near pCR have high rates of relapse, due to chemotherapy resistance, within the first few years after their diagnosis. Molecular biomarkers predictive for chemotherapy sensitivity are lacking. This ongoing trial is evaluating carboplatin and docetaxel in the neoadjuvant setting to determine whether these drugs will increase the pCR rate compared to historical controls. Correlative studies include exome and transcriptome sequencing on samples acquired from patients as a means to decipher the genomic architecture and clonal evolution of those who achieved a pCR compared to those who did not. The simultaneous development of patient derived xenografts (PDX) from host tumors is also planned. Methods: Patients with clinical stage 2 or 3 histologically confirmed TNBC will receive six cycles of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 every 3 weeks, followed by definitive surgery. Forty-one eligible patients will be treated according to this protocol, permitting us to attain a power of 83% to detect our expected pCR rate of 54% compared to the historical 35% rate, based on a two-sided exact binomial test at the 4.8% significance level. Eligibility: tumor size at least 2 cm, adequate organ and bone marrow function, no bilateral or inflammatory breast cancer, no invasive cancer within 5 years, ECOG performance status of ? 2, no prior sentinel lymph node biopsy. Tissue collection for xenografting and correlative studies will occur at baseline, at cycle 1 day 3, and at surgery. The primary objective is to determine the pCR rate, defined as the absence of invasive cancer in breast or nodes at definitive surgery. Secondary and exploratory objectives include xenografting rates, evaluation of mutational signatures of chemotherapy resistance and response, and comparison of chemotherapy responses between patients and their xenografts. The study was activated on 7/7/2014 and is still recruiting. Twenty (48.8% of planned 41) patients have been enrolled and have had baseline tissue banked. Fourteen patients have completed protocol therapy. Three patients have tissue at all 3 time points (9 samples), and are presently being studied by exome and transcriptome sequencing. Citation Format: Foluso O. Ademuyiwa, Shunqiang Li, Jingqin Luo, Tracy Skinner, Jason Hoshower, Cynthia X. Ma, Katherine Weilbaecher, Michael Naughton, Leonel Hernandez-Aya, Elaine R. Mardis, Matthew J. Ellis. A neoadjuvant co-clinical trial in triple-negative breast cancer patients with genomic discovery analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT091.

How Does the Severity of Injury Vary between Motorcycle and Automobile Accident Victims Who Sustain High-Grade Blunt Hepatic and/or Splenic Injuries? Results of a Retrospective Analysis.

Background: High-grade blunt hepatic and/or splenic injuries (BHSI) remain a great challenge for trauma surgeons. The main aim of this study was to investigate the characteristics, mortality rates, and outcomes of high-grade BHSI in motorcyclists and car occupants hospitalized for treatment of traumatic injuries in a Level I trauma center in southern Taiwan. Methods: High-grade BHSI are defined as grade III-VI blunt hepatic injuries and grade III-V blunt splenic injuries. This retrospective study reviewed the data of 101 motorcyclists and 32 car occupants who experienced a high-grade BHSI from 1 January 2011 to 31 December 2013. Two-sided Fisher’s exact or Pearson’s chi-square tests were used to compare categorical data, unpaired Student’s t-test was used to analyze normally distributed continuous data, and Mann–Whitney’s U test was used to compare non-normally distributed data. Results: In this study, the majority (76%, 101/133) of high-grade BHSI were due to motorcycle crashes. Car occupants had a significantly higher injury severity score (ISS; 26.8 ± 10.9 vs. 20.7 ± 10.4, respectively, p = 0.005) and organ injured score (OIS; 3.8 ± 1.0 vs. 3.4 ± 0.6, respectively, p = 0.033), as well as a significantly longer hospital length of stay (LOS; 21.2 days vs. 14.6 days, respectively, p = 0.038) than did motorcyclists. Car occupants with high-grade BHSI also had worse clinical presentations than their motorcyclist counterparts, including a significantly higher incidence of hypotension, hyperpnea, tube thoracostomy, blood transfusion >4 units, LOS in intensive care unit >5 days, and complications. However, there were no differences in the percentage of angiography or laparotomy performed or mortality rate between these two groups of patients. Conclusions: This study demonstrated that car occupants with high-grade BHSI were injured more severely, had a higher incidence of worse clinical presentation, had a longer hospital LOS, and had a higher incidence of complications than motorcyclists. The results also implied that specific attention should be paid to those car occupants with high-grade BHSI, whose critical condition should not be underestimated because of the concept that the patients within in a car are much safer.

Topical vs. intravenous administration of tranexamic acid in knee arthroplasty and prevalence of deep venous thrombosis: a randomized clinical trial.

BackgroundTranexamic acid (TXA) is widely used in orthopedic surgery to reduce perioperative bleeding. Since TXA inhibits fibrinolysis, there is concern that it may increase the risk of thromboembolic events.ObjectivesTo verify the prevalence of deep venous thrombosis (DVT) in patients receiving TXA during total knee arthroplasty and to compare topical with intravenous administration of the drug.MethodsAll patients admitted for total knee arthroplasty due to primary arthrosis between June and November of 2014 were recruited consecutively. Thirty patients were randomized to a “topical group” (1.5 g TXA diluted in 50ml saline sprayed over the area operated, before tourniquet release), 30 to an “intravenous group” (20mg/kg TXA in 100 ml of saline, given at the same time as anesthesia), and 30 to a control group (100 ml of saline, given at the same time as anesthesia). All patients had duplex ultrasound scans of the legs on the 15th postoperative day.ResultsDeep venous thrombosis events occurred in five of the 90 patients operated (one out of 30 in the topical group [3.3%], four out of 30 in the control group [13.3%], and zero in the intravenous group). All were confirmed by duplex ultrasound scans and all were asymptomatic. Prevalence rates of DVT were similar between groups (p = 0.112 for control vs. intravenous; p = 0.353 for control vs. topical; and p =1.000 for intravenous vs. topical, according to two-sided exact tests).ConclusionsBoth topical and intravenous administration of TXA are safe with regard to occurrence of DVT, since the number of DVT cases in patients given TXA was not different to the number in those given placebo.

Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss.

The 8.1 ancestral haplotype (AH) (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2) is a remarkably long and conserved haplotype in the human major histocompatibility complex. It has been associated with both beneficial and detrimental effects, consistent with antagonistic pleiotropy. It has also been proposed that the survival of long, conserved haplotypes may be due to gestational drive, i.e. selective miscarriage of fetuses who have not inherited the haplotype from a heterozygous mother. Recurrent pregnancy loss (RPL) is defined as three or more consecutive pregnancy losses. The objective was to test the gestational drive theory for the 8.1AH in women with RPL and their live born children. We investigated the inheritance of the 8.1AH from 82 heterozygous RPL women to 110 live born children. All participants were genotyped for HLA-A, -B and -DRB1 in DNA from EDTA-treated blood or buccal swaps. Inheritance was compared with a Mendelian inheritance of 50% using a two-sided exact binomial test. We found that 55% of the live born children had inherited the 8.1AH, which was not significantly higher than the expected 50% (P = 0.29). Interestingly, we found a non-significant trend toward a higher inheritance of the 8.1AH in girls, 63%, P = 0.11 as opposed to boys, 50%, P = 1.00. We did not find that the 8.1AH was significantly more often inherited by live born children of 8.1AH heterozygous RPL women. However our data suggest that there may be a sex-specific effect which would be interesting to explore further, both in RPL and in a background population.

MRI features of placenta percreta

Objective To investigate the MRI features of the placenta percreta. Methods A retrospective review of the materials of 46 patients who underwent MRI and confirmed invasive placenta (19 cases of placenta percreta and 27 cases of placenta accreta )clinically or histopathological. All patients underwent half-fourier acquisition single-shot turbo spin-echo and true fast imaging with steady-state precession scans. Two experienced radiologists independently reviewed the MR images blindly. Seven MRI features were evaluated. Direct signs including bulging placenta with cyrtoid outline and the wall of urinary bladder with nodular protrusion; indrect signs including intraplacental thick dark bands of the placenta, intraplacental abnormal vascularity, marked placental heterogeneity, uterine bulging and irregular placenta around the cervix. The features were evaluated using Fisher two-sided exact test for comparing the differences between placenta percreta and placenta accreta. Based on the surgical pathology criteria, sensitivity and specificity of the features diagnosing placenta percreta were calculated. Results In 19 plactenta pertcreta, the features of bulging placenta with cyrtoid outline, marked placental heterogeneity and irregular placenta around the cervix were 16, 16, 12(radiologist 1); 17, 14, 13(radiologist 2) respectively. In 27 placenta accreta, the features were 7, 9, 5(radiologist 1); 6, 8, 5(radiologist 2) respectively. These features were significantly associated with placenta percreta (all P<0.05). In 6 cases of placenta percreta with urinary bladder invaded, 4 cases showed the wall of urinary bladder with nodular protrusion. The mean sensitivity and specificity of the 7 features (bulging placenta with cyrtoid outline, the wall of urinary bladder with nodular protrusion, intraplacental thick dark bands of the placenta, intraplacental abnormal vascularity, marked placental heterogeneity, uterine bulging and irregular placenta around the cervix) differentiating placenta percreta were as follows, sensitivity: 86.9% (33/38), 18.5% (7/38), 89.5% (34/38), 89.5% (34/38), 79.0% (30/38), 94.7% (36/38) and 65.8% (25/38), specificity: 76.0% (41/54), 100.0% (54/54), 37.0% (20/54), 9.3% (5/54), 68.6% (37/54), 11.1% (6/54) and 81.5% (44/54). Conclusions The MRI features of bulging placenta with cyrtoid outline, marked placental heterogeneity and irregular placenta around the cervix are useful for the diagnosis of placenta percreta among invasive placenta. The wall of urinary bladder with nodular protrusion is suggestive of urinary bladder involvement. Key words: Placenta accreta; Magnetic resonance imaging; Comparative study

An Improved Evaluation of Kolmogorov's Distribution

We propose a new algorithm for computing extreme probabilities of Kolmogorov's goodness-of-fit measure, Dn . This algorithm is an improved version of the method originally proposed by Wang, Tsang, and Marsaglia (2003) based on a result from Durbin (1973). The new algorithm keeps the same numerical precision of the Wang et al. (2003) method, but is more efficient: it features linear instead of quadratic space complexity and has better time complexity for a common range of input parameters of practical importance. The proposed method is implemented in the R package kolmim, which also includes an improved routine to perform one-sample two-sided exact Kolmogorov-Smirnov tests.

SAT0023 Clinical and Laboratory Predictors of Distinct Histological Classes of Lupus Nephritis-Can They Substitute the Renal Biopsy?

BackgroundThe type of histological class of lupus nephritis dictates treatment approaches among lupus patients with renal involvement. Risk stratification may facilitate therapeutic decisions, when renal biopsy is contraindicated or poses...

Distribution of superantigens in group A streptococcal isolates from Salvador, Brazil.

BackgroundGroup A streptococcus (GAS) causes invasive disease, superficial disease, and can asymptomatically colonize humans. Superantigens are one virulence factor found in GAS. Previous studies found associations between the genes that encode superantigens and emm type of GAS. It is unknown if these associations are due to underlying biological factors that limit the distribution of superantigens or, alternatively, if these associations are due to the expansion of local GAS linages where these studies took place. To further address this question we screened GAS isolates collected from Salvador, Brazil for 11 known superantigen genes.MethodsSeventy-seven GAS isolates were screened by PCR for superantigen genes. These superantigen genes were speA, speC, speG, speH, speI, speJ, speK, speL, speM, ssa, and smeZ. We used Fisher’s two-sided exact test to identify associations between superantigens and GAS emm type. We then compared our results to previous reports of superantigen prevalence and superantigen association with emm type.ResultsIn our collection we found several emm type and superantigen genotype combinations that have previously been reported in isolates from Europe and Australia. We also found that speA was significantly associated with emm type 1, and that speC was significantly associated with emm type 12.ConclusionsOur study reports superantigen genotypes of GAS from a region of the world that is lacking this information. We found evidence of common GAS superantigen genotypes that are spread worldwide as well as novel superantigen genotypes that, so far, are unique to Brazil.

Mitochondrial DNA variants in obesity.

Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI≥30 kg/m2) and n = 2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and their offspring could not be substantiated by the findings of the present study.