Test For Unpaired Samples Research Articles

An Agreement of Antigen Tests on Oral Pharyngeal Swabs or Less Invasive Testing With Reverse Transcription Polymerase Chain Reaction for Detecting SARS-CoV-2 in Adults: Protocol for a Prospective Nationwide Observational Study.

BackgroundThe SARS-CoV-2 pandemic has resulted in an unprecedented level of worldwide testing for epidemiologic and diagnostic purposes, and due to the extreme need for tests, the gold-standard Reverse Transcription Polymerase Chain Reaction (RT-PCR) testing capacity has been unable to meet the overall worldwide testing demand. Consequently, although the current literature has shown the sensitivity of rapid antigen tests (RATs) to be inferior to RT-PCR, RATs have been implemented on a large scale without solid data on performance.ObjectiveThis study will compare analytical and clinical sensitivities and specificities of 50 lateral flow– or laboratory-based RATs and 3 strand invasion–based amplification (SIBA)-RT-PCR tests from 30 manufacturers to RT-PCR testing of samples obtained from the deep oropharynx. In addition, the study will compare sensitivities and specificities of the included RATs as well as RT-PCR on clinical samples obtained from the deep oropharynx, the anterior nasal cavity, saliva, the deep nasopharynx, and expired air to RT-PCR on deep oropharyngeal samples.MethodsIn the prospective part of the study, 200 individuals found SARS-CoV-2 positive and 200 individuals found SARS-CoV-2 negative by routine RT-PCR testing will be retested with each RAT, applying RT-PCR as the reference method. In the retrospective part of the study, 304 deep oropharyngeal cavity swabs divided into 4 groups based on RT-PCR quantification cycle (Cq) levels will be tested with each RAT.ResultsThe results will be reported in several papers with different aims. The first paper will report retrospective (analytical sensitivity, overall and stratified into different Cq range groups) and prospective (clinical sensitivity) data for RATs, with RT-PCR as the reference method. The second paper will report results for RAT based on anatomical sampling location. The third paper will compare different anatomical sampling locations by RT-PCR testing. The fourth paper will focus on RATs that rely on central laboratory testing. Tests from 4 different manufacturers will be compared for analytical performance data on retrospective deep oropharyngeal swab samples. The fifth paper will report the results of 4 RATs applied both as professional use and as self-tests. The last paper will report the results from 2 breath tests in the study. A comparison of sensitivity and specificity between RATs will be conducted using the McNemar test for paired samples and the chi-squared test for unpaired samples. Comparison of the positive predictive value (PPV) and negative predictive value (NPV) between RATs will be performed by the bootstrap test, and 95% CIs for sensitivity, specificity, PPV, and NPV will be calculated as bootstrap CIs.ConclusionsThe study will compare the sensitivities of a large number of RATs for SARS-CoV-2 to with those of RT-PCR and will address whether lateral flow–based RATs differ significantly from laboratory-based RATs. The anatomical test locations for both RATs and RT-PCR will also be compared.Trial RegistrationClinicalTrials.gov NCT04913116; https://clinicaltrials.gov/ct2/show/NCT04913116International Registered Report Identifier (IRRID)DERR1-10.2196/35706

Facial Emotion Recognition in Children and Adolescents with Specific Learning Disorder.

Background: Some recent studies suggest that children and adolescents with different neurodevelopmental disorders perform worse in emotions recognition through facial expressions (ER) compared with typically developing peers. This impairment is also described in children with Specific Learning Disorders (SLD), compromising their scholastic achievement, social functioning, and quality of life. The purpose of our study is to evaluate ER skills in children and adolescents with SLD compared to a control group without learning disorders, and correlate them with intelligence and executive functions. Materials and Methods: Our work is a cross-sectional observational study. Sixty-three children and adolescents aged between 8 and 16 years, diagnosed with SLD, and 32 sex/age-matched controls without learning disorders were recruited. All participants were administered standardized neuropsychological tests, evaluating facial emotion recognition (NEPSY-II), executive functions (EpiTrack Junior), and intelligence profile (WISC-IV). Results: Emotion recognition mean score was significantly lower in the SLD group than in the controls group on the Mann–Whitney U test for unpaired samples (p < 0.001). The SLD group performed significantly lower than the control group in their abilities to identify neutral expressions, happiness, sadness, anger, and fear compared to controls (p < 0.001). ER scores were positively correlated to the executive functions scores. There was no correlation with the Total Intelligence Quotient scores but there is a significant positive correlation with Working Memory Index and Processing Speed Index measured by WISC.IV. Conclusion: Our study showed that children and adolescents with Specific Learning Disorders have facial emotion recognition impairment when compared with a group of peers without learning disorders. ER abilities were independent of their global intelligence but potentially related to executive functions.

B lymphocytes contribute to indirect pathway T cell sensitization via acquisition of extracellular vesicles.

B cells have been implicated in transplant rejection via antibody-mediated mechanisms and more recently by presenting donor antigens to T cells. We have shown in patients with chronic antibody-mediated rejection that B cells control the indirect T cell alloresponses. To understand more about the role of B cells as antigen-presenting cells for CD4+ T cell with indirect allospecificity, B cells were depleted in C57BL/6 mice, using an anti-CD20 antibody, prior to receiving MHC class I-mismatched (Kd ) skin. The absence of B cells at the time of transplantation prolonged skin graft survival. To study the mechanisms behind this observation, T cells with indirect allospecificity were transferred in mice receiving a Kd skin transplant. T cell proliferation was markedly inhibited in the absence of recipient B cells, suggesting that B cells contribute to indirect pathway sensitization. Furthermore, we have shown that a possible way in which B cells present alloantigens is via acquisition of MHC-peptide complexes. Finally, we demonstrate that the addition of B cell depletion to the transfer of regulatory T cells (Tregs) with indirect alloresponse further prolonged skin graft survival. This study supports an important role for B cells in indirect T cell priming and further emphasizes the advantage of combination therapies in prolonging transplant survival.

PS1018 TUMOR IMMUNE ESCAPE MEDIATED BY TH17CCR4‐CCR6+ CELLS AND IL‐6/IL‐10/IL‐17A IN ACUTE MYELOID LEUKEMIA

Background:Acute myeloid leukemia (AML) is a hematologic neoplasm characterized by the proliferation of bone marrow myeloblasts. Most of patients achieve remission after intensive chemotherapy, although they still relapse. The immune system play an important role in the pathogenesis of AML, where myeloblasts are be able to switch the immunological synapsis disabling the generation of an anti‐tumor response. In this sense, the presence of a greater number of Th17 lymphocytes has been described in AML.Aims:To elucidate whether the myeloblats modulate the Th17 population and more specifically the two Th17 subpopulations: CCR4+ and CCR4‐.Methods:From February 2015 to March 2018, 20 AML diagnosed patients at the CHN and 20 controls were included. Blood samples were collected at diagnosis from AML patients and in controls. We identified by flow cytometry the populations of T helper cells (Th1, Th2, Th17 CCR4‐CCR6+, Th17 CCR4+CCR6+) with the following monoclonal antibodies: CD3 Horizon‐V450, CCR3 FITC, IFNγRβ PE, CCR4 PE‐Cy7, CD4 PerCP, CCR6 APC, CD45 APC‐H7, CCR5 FITC, CXCR3 APC in a FACSCanto II. Serum level of cytokines were also analysed by CBA Human Th1/Th2/Th17 Cytokine Kit (BD) for IL‐2, IL‐4, IL‐6, IL‐10, TNFα, IFNγ, and IL‐17A. We also study the polimorfism of IL‐17A (rs2275913) and IL‐17F (rs763780) by allele discrimination by real‐time PCR. The SPSS software was used to perform Student́s test or Mann‐Whitney test for unpaired samples between patients and controls, and simple linear regression was used to study the association between levels of cytokines and Th subpopulations in AML patients. P &lt; 0,05 was considered to be statistically significant.Results:Patients and controls characteristics were showed in table 1. Th1 and Th2 cells levels did not differ between AML patients and controls. The mean of Th17 CCR4‐CCR6+ cells was significantly higher in AML patients (192 ± 178/μl) than those in controls (67 ± 38/μl), and the difference was statistically significant (p = 0,027). However, Th17 CCR4+CCR6+ cells levels did not differ between groups. We did not find significant differences in the levels of IL‐2, IL‐4, TNFα and IFNγ citokines. Th17 related cytokines were significantly higher in AML patients than in controls and statistically significant. The mean of cytokines (pg/ml) in AML and in controls was 32,79 ± 86,64 vs 0 (p &lt; 0,01), 3,03 ± 2,65 vs 0,24 ± 0,52 (p &lt; 0,001), 14,37 ± 14,12 vs 2,38 ± 4,17 (p = 0,012), for IL‐6, IL‐10 and IL‐17A respectively. No association was find by simple linear regression between the levels of IL‐6, IL‐10 and IL‐17A, and the Th17 subpopulations. There are also no significant differences between the polymorphisms studied of IL‐17 in patients and controls.imageSummary/Conclusion:Th17 subpopulations could play a role in the pathophysiology of AML. The most relevant subpopulation described is the Th17 CCR4+CCR6+. Protumoral and antitumor properties have been described for this subpopulation and associated cytokines (IL‐6, IL‐10 and IL‐17A). However, our results show an increase in the levels of the Th17 CCR4‐CCR6+ subpopulation and in IL‐6, IL‐10 and IL‐17A in untreated AML patients. The lack of association between Th17 subpopulations and cytokines implies that AML generates a protumoral microenvironment, where Th17 subpopulation and associated cytokines are regardless regulated by the tumor. Specifically, the downregulation of CCR4 antigen expression prevents the cells from migrating and having an antitumor effect and the upregulation of IL‐6, IL‐10 and IL‐17A secretion very likely from Th17 CCR4+CCR6+ could contribute to the progression of the disease.

Circular RNA expression profile in peripheral blood mononuclear cells from Crohn disease patients.

Crohn disease (CD) is a multifactorial autoimmune disease which is characterized by chronic and recurrent gastrointestinal tract inflammatory disorder. However, the molecular mechanisms of CD remain unclear. Increasing evidences have demonstrated that circular RNAs (circRNAs) participate in the pathogenesis of a variety of disease and were considered as ideal biomarkers in human disease. This study aimed to investigate circRNA expression profiles and detect new biomarkers in inflammatory bowel disease (IBD). Differentially expression of circRNAs between CD and HCs (health controls) were screened by microarray analysis. Peripheral blood mononuclear cells (PBMCs) from 5 CD patients and 5 HCs were included in the microarray analysis. Then, the differences were validated by quantitative polymerase chain reaction (qPCR) following reverse transcription polymerase chain reaction (RT-PCR) in the patients of CD and sex- and age-matched HCs. The most differential expressed circRNA was further validated in ulcerative colitis (UC) patients. Statistical significance between CD, UC, and HCs was analyzed by Student t test for unpaired samples or one-way analysis of variance (ANOVA). Diagnostic value of each circRNA was assessed by receiver operating characteristic (ROC) curve. We identified 155 up-regulated circRNAs and 229 down-regulated ones by microarray analysis in PBMCs from CD patients compared with HCs. Besides, 4 circRNAs (092520, 102610, 004662, and 103124) were significantly up-regulated validated by RT-PCR and qPCR between CD and HCs. ROC curve analysis suggested important values of circRNAs (092520, 102610, 004662, and 103124) in CD diagnosis, with area under the curve (AUC) as 0.66, 0.78, 0.85, and 0.74, respectively. Then, we further identified that the relative expression levels of circRNA_004662 was upregulated significantly in CD patients compared with UC patients. Herein, the upregulation of the 4 circRNAs (092520, 102610, 004662, or 103124) in PBMCs can be served as potential diagnostic biomarkers of CD, and circRNA_004662 might be a novel candidate for differentiating CD from UC. Moreover, a circRNA–microRNA-mRNA network predicted that circRNA_004662 appeared to be correlated with mammalian target of rapamycin (mTOR) pathway.

PB2296 SURVEILLANCE BREAST SCREENING PROGRAMS FOR PATIENTS WHO UNDERWENT CHEST RADIATION THERAPY (LYMPHOMA SURVIVORS)

Background:Women who underwent chest radiation therapy (CRT) during pediatric/young‐adult age have an increased breast cancer (BC) risk. The cumulative BC incidence in women who underwent CRT is 13‐20%, higher than the incidence observed in the young female general population. BC is diagnosed on average about 15 years after CRT at about 40 years of age, compared with about 61 years in the non‐exposed female general population.Aims:From January 2018 to December 2018, a group of consecutive 46 patients (45 females, 1 male), aged between 23 and 62 (mean 44), who underwent CRT at least in the previous 8 years, underwent breast clinical, ultrasound (US) and mammographic examinations.Methods:Breast density at US was evaluated according to the BIRADS lexicon (homogeneous‐fat; homogeneous‐fibroglandular; heterogeneous) and compared with a control group of healthy patients (n = 46) with similar demographic features. Any statistical significant difference was searched by t‐student test for unpaired samples. The incidence of breast cancer in the examined series was assessed.Results:Among the examined series, 10/46 (22%) patients with homogeneous, 20/46 (43%) with fibroglandular and 16/46 (35%) with heterogeneous density were found. In the control group, 8/46 (17%) patients with homogeneous, 21/46 (46%) with fibroglandular and 17/46 (37%) with heterogeneous density were found. No significant difference occurred among the two groups of patients (p &gt; 0.05). 4/46 (3 females, 1 male) patients were affected by breast cancer (invasive ductal carcinoma, n = 3; ductal carcinoma in situ, n = 1) with a 9% incidence.Summary/Conclusion:A surveillance breast imaging protocol should be strongly recommended to patients with a previous CRT. Breast cancer incidence seems to be higher compared with general population. No significant effect on US breast density seems to exist in CRT patients. Future research should be directed at examining the underlying cancer biology and etiology of treatment induced cancers, as well as inherent and treatment‐induced genetic susceptibility of HL survivors.

How Thinking About the Donor Influences Post-traumatic Growth in Liver Transplant Recipients

ObjectiveThe aim of this work was to find out whether thinking frequently about the donor influences post-traumatic growth of liver transplant recipients. MethodsThe sample of 240 patients selected was made up of 185 men and 55 women with an overall mean age of 60.21 (SD 9.3) years. All of them had received liver transplants from cadaver donors. Transplant recipients were asked whether they thought frequently about the donor (yes or no) and filled out the Post-traumatic Growth Inventory. The t test for unpaired samples was applied to analyze how thinking frequently about the donor or not influenced post-traumatic growth. We also calculated the effect sizes by means of Cohen d or Cohen w depending on the nature of the variables analyzed (quantitative or qualitative). ResultsThe liver transplant recipients who thought frequently about the donor, compared with those who did not, had higher total scores on post-traumatic growth (P = .000; d = 0.57; medium effect size). Furthermore, considering the effect sizes, the differences between the subgroups were more relevant on the following subscales: new possibilities (P = .000; d = 0.53; medium effect size), appreciation of life (P = .000; d = 0.60; medium effect size), and spiritual change (P = .000; d = 0.54; medium effect size). ConclusionsPatients who think frequently about the donor have more post-traumatic growth than those who do not.

Patient-Reported Outcomes Demonstrate The Value Of Non-Operative And Operative Orthopedic Treatments And Predict The Odds Of Improvement With Surgery

Category: Outcomes Measurement Introduction/Purpose: The importance of patient reported outcomes (PROs) has become increasingly recognized as an important tool to measure our clinical value. The National Institute of Health (NIH) created the Patient-Reported Outcomes Measurement Information System (PROMIS), a series of validated item banks, to help clinicians and researches measure key clinical domains. The PROMIS computer adaptive tests (CAT) may be administered with minimal resources or administrative burden. This study describes the results of administering computer adaptive tests (CAT) to every patient in a high volume Orthopedic Surgery practice. We test the hypotheses that both non-operative treatment and operative treatments improve PRO scores. Furthermore, we test the hypothesis that preoperative scores in these domains may be used to predict chances of improvement after surgery. Methods: The PROMIS CAT was administered prospectively for all patients as part of standard clinic intake and recorded in the patient’s electronic medical record (EMR) at each clinic visit. The PROMIS item banks are normalized to mean 50±10 for the US population. De-identified data was retrospectively extracted from the EMR including PROMIS scores, demographic information, as well as surgery specific information. As of this submission, 1688 PROMIS CATs from March 2015 to September 2016 have been analyzed. Data for initial and final clinic visits, as well as for the final preoperative visit for patients who had surgery, are compared using Wilcoxon Matched Pairs Test for paired samples and Mann-Whitney U Test for unpaired samples. Linear regression is used to assess the association of initial values to change in value after treatment. The effect of stratified initial clinic domain value on odds of improving with surgery is assessed using Analysis of Variance. Results: Non-surgical and surgical patients present with similar pain intensity (49.6±7.9 vs. 49.4±7.8). Surgical patients do not improve prior to surgery, but both improve by their final visit (45.7±7.5, 43.7±8.8, p&lt;0.05). Non-surgical and surgical patients present with similar pain interference (60.0±8.4 vs. 60.3±8.9). Surgical patients do not improve prior to surgery, but both improve by their final visit (56.9±8.8, 54.3±9.4, p&lt;0.05). For surgical patients, change in pain intensity and pain interference correlate with initial values (R2 0.32 and 0.27, p&lt;0.05). The percentage whose pain intensity improves after surgery when initial value is over one SD worse than mean is 96%, within one SD worse than mean is 81%, within one SD better than mean is 56%, and over one SD better than mean is 40% (p&lt;0.05). Conclusion: Both non-operative and operative orthopedic treatments improve patient reported pain intensity and pain interference. For patients that have surgery, patients that present with more severe symptoms tend to improve more with surgery. Furthermore, the odds of improving after surgery can be calculated based on preoperative PRO scores. This may allow surgeons to counsel patients about the potential benefits of surgery with personalized precision that is currently unavailable. Measuring PROs using PROMIS CATs demonstrates the value of both non-operative and operative Orthopedic Surgery care for our patients. Preoperative PRO scores may predict the odds of successful surgical intervention.

Chronic Administration of Bauhinia forficata Link Reduced Exploratory Activity Without Affecting Blood Glucose in Healthy Rats

This study provides information about the effect of chronic ingestion of a decoction of Bauhinia forficata on the behavior of rats. The aim of this study was to investigate the exploratory activity, anxiety level, and blood glucose of healthy rats submitted to prolonged treatment with a decoction of B.forficata. Twenty male rats, aged two months and weighing approximately 145g were randomly distributed into two groups. The Bauhinia group freely ingested a decoction of B.forficata for 4 weeks, while the control group received water. Body weight, food and fluid intake, and glycemic index were quantified. The open field (OF) and elevated plus maze (EPM) tests were applied at the end of the experiment. Data were analyzed by Student’s t test for unpaired samples, with a significance level of P<0.05. The results of the EPM test were analyzed by the Wilcoxon Signed Rank Test and blood glucose by the Bonferroni test. There were no significant differences in body weight, food intake or glycemic index between the Bauhinia and control groups. Net liquid intake was higher in the Bauhinia group. EPM results did not differ between groups, but in the OF test, the frequencies of rearing and locomotion were lower and immobility time was increased for rats in the Bauhinia group. In conclusion, B.forficata reduced exploratory activity and did not alter blood glucose in healthy rats.

Hand digit ratio (2d:4d) and gastric cancer risk: a cross-sectional study among southeastern Brazilians

Background: The ratio between the length of the second and fourth digit, known as digit ratio or 2D:4D, has been used as a biomarker for several diseases, clinical conditions and human’s phenotypes, including cancer occurrence. We aimed to investigate whether there is a link between digit ratio and gastric cancer (GCA) risk among southeastern Brazilians. Methods: This was a cross-sectional research, performed with 240 subjects (120 cases and 120 controls). Data source derived from the Oncology Department of Santa Casa Hospital, Montes Claros, Brazil. Digital measurements were performed with a digital Vernier caliper and the digit ratios in both hands were collected; plus, we calculated de difference between the ratios found in the right and the left hand (R-L). Baseline characteristics of both groups, such as smoking status, and alcohol consumption status, were compared between the two groups using Chi-square test. Shapiro-Wilk’s test was used to check sample distribution. Subsequently, a Student’s t -test for unpaired samples was performed to compare the means of 2D:4D ratios and R-L among groups were performed. All analyses included a 5% level of significance. Results: Subjects at the case group had the highest digit ratio, especially on the right hand, when observing the overall average and for the female gender. Regarding the R-L, patients with GCA had higher differences than the control group, most DR-L consequently high levels of estrogen and low testosterone levels. Left digit ratio did not differed significantly between cases and controls; however, R2D:4D and R-L were (P=0.0013). Conclusions: The results suggest that the main reason why a higher estrogen exposure in utero causes higher cancer risk among women still need to be established.

Therapeutic accuracy of the completely customized lingual appliance WIN : A retrospective cohort study.

ObjectiveThe aim of this retrospective cohort study was to assess the accuracy of the completely customized lingual appliance WIN (DW Lingual Systems, Bad Essen, Germany) employing a three-dimensional (3D) comparison between the setup and the final result.Materials and methodsThe setup and final models of 20 consecutively debonded patients (40 jaws; 7 males, 13 females; mean age 15.76 ± 4.45 years) with various malocclusions of a private practice specialized in orthodontics were digitalized using a 3D scanner. The 3D models of the setup and the final model of each jaw were then digitally matched using the best fit algorithm and segmented into single teeth. After placing individual coordinate systems, the homologous teeth of the setup and the final model were matched to be able to calculate the exact deviations of all rotational and translational components. The t test for unpaired samples, Kruskal–Wallis tests, U tests, and ANOVA with Duncan post hoc test were applied statistically.ResultsRegarding the incisors, the angle discrepancies between the setup and the final result appeared to be less than 3° (torque 2.96°; tip 2.04°; rotation 2.00°). The translations showed mean values less than 0.3 mm (mesiodistal 0.16 mm; buccolingual 0.15 mm; vertical 0.29 mm). Slightly higher values could be measured in the lateral segments regarding rotations (torque 5.18°; tip 3.10°; rotation 3.70°) as well as regarding translations (mesiodistal 0.26 mm; buccolingual 0.64 mm; vertical 0.36 mm).ConclusionsUsing the completely customized lingual appliance WIN, it is possible to achieve the final result predicted by the setup with a high accuracy.

Digit ratio (2D:4D) is associated with breast cancer

Purpose: Digit ratio (2D:4D) has been considered as a proxy biomarker for prenatal hormonal exposure and may represent an individual’s predisposition to breast cancer. The purpose of the present study is to investigate whether there is a link between digit ratio and breast cancer in a Brazilian population. Methods: Digital measurements of the lengths of the index and ring fingers of both hands were obtained from women with breast cancer (n = 100) and age-matched controls (n = 100) using a digital Vernier calliper. Mean digit ratios of right hands, left hands, and right minus left hand 2D:4D (DR-L) were compared between both groups. Data were analysed by the Student's t -test for unpaired samples, Mann-Whitney test, and Spearman`s correlation with a significance level of 5%. Results: The patients with breast cancer presented significantly higher right and left 2D:4D (both p < 0.001) and higher DR-L ( p = 0.032) than controls. Among breast cancer cases, there was a significantly negative correlation between left 2D:4D and age diagnosed with breast cancer ( p = 0.018). Conclusion: Digit ratio offers a valid retrospective biomarker of action of prenatal hormones and might be associated with breast cancer risk and age at onset of breast cancer. It suggests that higher exposure or sensitivity to prenatal oestrogen might be associated with a higher risk of breast cancer and with earlier onset of the disease.

Breast Cancer: Influence of Taxanes on Response Assessment with Dynamic Contrast-enhanced MR Imaging.

To prospectively investigate the influence of taxane-containing neoadjuvant chemotherapy (T-NACT) versus non-taxane-containing NACT (NT-NACT) on the contrast material enhancement of breast cancers, benign enhancing lesions (BELs), and background parenchymal enhancement (BPE) at dynamic contrast-enhanced magnetic resonance (MR) imaging. This institutional review board-approved study was performed in 62 patients with invasive breast cancer who underwent multiagent NACT with (n = 49) or without (n = 13) taxanes between 2008 and 2011. Written informed consent was obtained. Patients underwent dynamic contrast-enhanced MR imaging according to a standardized protocol before and 2 weeks after completing NACT. The percentage reduction of enhancement of breast cancers, BELs, and BPEs was calculated for patients undergoing NT-NACT versus those undergoing T-NACT. Final surgical pathologic results served as standard of reference. Changes in mean enhancement of breast cancers, BELs, and BPEs between the regimens were compared by using the Student t test for unpaired samples; for intraindividual comparison, the Student t test for paired samples was used. Similar rates of complete pathologic response were observed after T-NACT and NT-NACT (28 [57.2%] of 49 vs eight [61.5%] of 13). T-NACT was associated with an almost complete suppression of enhancement in not only breast cancers but also BELs and BPE in the same patients, with an average reduction of enhancement of -89.9% ± 9.3, -90.2% ± 11.8, and -91.2% ± 7.5, respectively. After T-NACT, cancers with partial (n = 21) or complete (n = 28) pathologic response exhibited a similar reduction of enhancement (-81.8% ± 17.5 vs -93.9% ± 2.3; P = .22). The reduction of enhancement of cancers after NT-NACT was significantly less pronounced than that after T-NACT (-41.1% ± 22.8 vs 88.1% ± 13.9; P < .0001), and effects on enhancement of BELs and BPE were significantly less pronounced compared with effects on enhancement of cancers in the same women (P < .0001). MR imaging led to an overestimation of response (yielded false-negative results for residual disease) in 66.7% (14 of 21) of patients after T-NACT, versus in 20% (one of five) of patients after NT-NACT. The reduction of enhancement observed in breast cancers after T-NACT is, in part, unrelated to their oncologic response. MR imaging-detectable effects of taxanes represent a combination of specific antimitotic and nonspecific antiangiogenic effects. This impacts the accuracy with which dynamic contrast-enhanced MR imaging helps predict complete pathologic response to T-NACT. (©) RSNA, 2015 Online supplemental material is available for this article.

Intraoperative Blood Loss During Orthognathic Surgery: A Comparison of Remifentanil-Based Anesthesia With Sevoflurane or Isoflurane

The aim of the present study was to compare the blood loss with remifentanil-based anesthesia with sevoflurane or isoflurane during orthognathic surgery. In this randomized controlled clinical trial, the patients who were scheduled for orthognathic surgery were divided into 2 groups: the sevoflurane (Sevo) group and isoflurane (Iso) group. Anesthesia was maintained using end-tidal concentrations of 1.4% sevoflurane or 0.9% isoflurane. Remifentanil was continuously infused at 0.05 to 0.5μg/kg/min to maintain the mean blood pressure (MBP) at 60 to 65mm Hg. The intraoperative blood loss was compared between the 2 groups. The Student t test for unpaired samples was used for statistical analysis. P < .05 was considered statistically significant. The study sample included 19 men and 45 women (n= 64). The mean age was 25years (range 16 to 50). The intraoperative blood loss tended to be greater in the Iso group (n= 32; 4.79 ± 3.22mL/kg) than in the Sevo group (n= 32; 4.00 ± 1.98mL/kg). However, the difference between the 2 groups was not significant. In a comparison of intraoperative blood loss during remifentanil-based anesthesia with sevoflurane or isoflurane during orthognathic surgery, no difference was observed between the 2 groups.

Coagulation support algorithm with rapid TEG and functional fibrinogen TEG in critical bleeding: more results and less time

Early coagulation support is essential in massively bleeding patients. A Coagulation Support Algorithm (CSA), integrating rapid TEG (r-TEG) and functional fibrinogen TEG (ff-TEG) could shorten the time to a tailored treatment (Figure ​(Figure11). Figure 1 Coagulation Support Algorithm. Methods A retrospective comparison of the time to available TEG and Standard Coagulation Tests (SCT: INR, aPTTr, fibrinogen level) results in two groups of bleeding and coagulopathic patients using citrate kaolin-TEG (k-TEG) or the CSA protocol (r-TEG/ff-TEG). Statistical analysis was performed with Student's t test for unpaired samples.

Influence of Acute Cellular Rejection and Depressive Symptomatology on Liver Transplant Recipients' Quality of Life

BackgroundThe objective of this study was to analyze the influence of two variables (acute cellular rejection and depressive symptomatology) on liver transplant recipients' quality of life. MethodsUsing a 2 × 2 factorial design, two groups were selected: 44 patients who had acute cellular rejection and 44 patients without this medical complication. After an average of 6 years since the transplant, patients were assessed with the Hospital Anxiety and Depression Scale and the SF-36 Health Survey. Analysis of variance, t test for unpaired samples, and Cohen's d effect size index were applied. ResultsThe presence of clinical depressive symptomatology negatively affected all dimensions of quality of life (P < .001; large effect sizes); and interactive effects between factors acute cellular rejection and depressive symptomatology were found in the dimensions role-physical (P = .049) and bodily pain (P = .017). Transplant recipients with clinical depressive symptomatology scored lower on both dimensions (role-physical, P = .110, d = 0.52, medium effect size; bodily pain, P = .001, d = 1.25, large effect size) if they had an acute cellular rejection. In contrast, if they did not exceed the clinical threshold for depressive symptomatology, there were no differences in these dimensions (role-physical, P = .239, d = −0.33, small effect size; bodily pain, P = .555, d = 0.16, null effect size) between transplant recipients with and without acute cellular rejection. ConclusionsClinical depressive symptomatology is associated with poorer quality of life in liver transplant recipients; and the long-term differences in the dimensions role-physical and bodily pain between liver transplant recipients with and without acute cellular rejection depend on patients' mental health.

Role of preoperative retrograde enema on inflammatory and healing parameters in colonic anastomosis: experimental study in dogs

ObjectiveThe purpose of this experimental study was to compare the inflammatory and wound healing response of dogs submitted to colonic anastomosis with and without preoperative retrograde enema. MethodsThe study included two groups of 31 female dogs (Canis familiaris). G-I (control): no preoperative bowel preparation; G-II (study): preoperative retrograde enema using a 10% glycerin solution. All the animals were submitted to laparotomy and colotomy at 20cm from the anal verge, followed by closure with a running extramucosal single-layer suture (Prolene® 000). The animals were then anesthetized and euthanized on the 7th (n=10) or 21st (n=20) postoperative day (POD) to remove the anastomosed colon segment for histological and immunohistochemical analysis evaluating the parameters: anastomotic edema, vasoproliferation, abdominal adhesions, type I and III collagen, nitric oxide and myeloperoxidase. The observed differences were analyzed with the Mann–Whitney test for nonparametric data and Student's t test for unpaired samples and parametric data. ResultsOne animal from G-I and one from G-II died on POD 7 and POD 10 due to anastomotic complications and sepsis, respectively. The groups did not differ significantly with regard to inflammatory and healing parameters, although the levels of mature collagen were significantly lower in the animals submitted to preoperative bowel preparation. ConclusionIt has been shown that both procedures are safe to be used, however, the group with bowel preparation showed a lower amount of mature collagen in the immediate postoperative period and may be constituted a preventive factor for surgical complications for this type of surgical procedure, although no evidence in this study could be determined.

Correlation of KRAS mutational state with the expression of the hedgehog pathway in patients with pancreatic ductal adenocarcinoma.

227 Background: Pancreatic ductal adenocarcinoma (PDAC) is commonly associated with mutations in the KRAS gene. However, how KRAS mutations promote pancreatic carcinogenesis has not been fully established. Here we examine the association between KRAS mutational state and the expression of different tumor markers in PDAC samples. Methods: Immunohistochemical analysis was performed on PDAC specimens to identify the levels of expression of 28 surface and nuclear proteins: BRCA1, BRCA2, NOTCH1, SPARC, SHH, DHH, IHH, SMO, PTCH1, PTCH2, ALCAM, OCT3.4, PROM1, CD44, CD24, LGR5, BMP4, KDR, FLT1, PDGFRB, VEGFA, VEGFB, PGF, CDKN2A, SMAD4, MET, HGF, MUC6. All samples were also tested for identification of KRAS isoforms (wild type (WT) vs mutated type (MT)) expression by means of RT-PCR. Levels of mRNA expression were matched with a common standard tissue marker. Expression levels of PDAC markers were compared between MT and WT KRAS groups. Differences between groups were tested using Mann-Whitney U test for unpaired samples. Exploratory univariate logistic regression was also performed to evaluate possible correlations between increasing levels of each marker and KRAS mutational state. Results: 110 samples were collected. Of them, data on KRAS were provided for 86 samples; 40 and 46 samples expressed the WT and MT KRAS isofo rms, respectively. Preliminary analysis showed that the expression of SHH and IHH resulted significantly higher in KRAS MT samples (U=1097 p= 0.013 and U=1072 p= 0.028 respectively), whereas higher levels of SMAD4 (U=634, p= 0.012) and HGF (U= 655, p= 0.03) were expressed in the KRAS WT group. A weak difference between groups was found for the MUC6 pathway (U= 666, p= 0.056). No differences of VEGFA, VEGFB and VEGFRB expression were found between MT and WT groups. At univariate logistic regression we found that increased levels of SHH correlated with the expression of KRAS MT phenotype (OR 57.5, p= 0.011), while IHH showed only a weaker significance level (OR 13.1, p= 0.069). Conclusions: These results indicate that oncogenic KRAS is directly associated with SHH expression in PDAC tissues. They also mark Hedgehog pathway components as relevant therapeutic targets for KRAS-mutant patients.

The NFKB1 Promoter Polymorphism (−94ins/delATTG) Alters Nuclear Translocation of NF-κB1 in Monocytes after Lipopolysaccharide Stimulation and Is Associated with Increased Mortality in Sepsis

Because the nuclear factor-κB (NF-κB) coupled pathway is believed to amplify inflammation prevailing in sepsis, the authors tested the hypotheses that the insertion-deletion polymorphism (-94ins/delATTG) (1) alters nuclear translocation of nuclear factor-κB and activator protein-1 (NF-κB1) in monocytes after lipopolysaccharide stimulation; (2) affects lipopolysaccharide-induced NF-κB1 messenger RNA expression, tumor necrosis factor α concentrations, and tissue factor activity; and (3) may be associated with increased 30-day mortality in patients with sepsis. Nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation from healthy blood donors was performed with immunofluorescence staining (n = 5 each). Lipopolysaccharide-induced NF-κB1 messenger RNA expression was measured with real-time polymerase chain reaction (PCR; n = 60), tumor necrosis factor α concentrations with a multiplexing system kit (n = 60), and tissue factor activity with thromboelastometry (n = 105). In a prospective study, multivariate proportional hazard analysis tested 30-day mortality in patients with sepsis (n = 143). The homozygous deletion genotype compared with the homozygous insertion genotype was associated with a nearly twofold increase in nuclear translocation of NF-κB1 (P = 0.001), a threefold difference in NF-κB1 messenger RNA expression (P = 0.001), and a twofold increase in tissue factor expression (P = 0.021). The deletion allele in adults with severe sepsis was tested as an independent prognostic factor for 30-day mortality (hazard ratio, 2.3; 95% CI, 1.13-4.8; P = 0.022). Mortality was 25% for homozygous insertion genotypes but 41% for combined heterozygous deletion/homozygous deletion genotypes (P = 0.034). The deletion allele of the NFκB1 insertion-deletion (-94ins/delATTG) polymorphism is associated with increased 30-day mortality in patients with severe sepsis and increased reaction of the innate immune system.

Índices geométricos de variabilidade da frequência cardíaca na doença pulmonar obstrutiva crônica

Background It was already evidenced decreased heart rate variability (HRV) in chronic obstructive pulmonary disease (COPD) patients at rest. Objective In order to insert new elements in the literature regarding this issue, we evaluated geometric index of HRV in COPD subjects. Method We analyzed data from 34 volunteers, divided into two groups according to spirometric values: COPD (17 volunteers, FEV1/FVC = 47.3 ± 10.2; FEV1 = 50.8 ± 15.7) and control (17 volunteers, FEV1/FVC = 78.8 ± 10.8; FEV1 = 100.1 ± 14.7). For analysis of HRV indexes the volunteers remained in the supine position for 30 minutes. We analyzed the following indexes: triangular index (RRtri), triangular interpolation of RR intervals (TINN) and Poincaré plot (SD1, SD2 and SD1/SD2). Student t test for unpaired samples and Mann-Whitney test were used for data analysis. Results We observed statistically significant reductions in geometric indexes in the COPD group: RRtri (0.043 ± 0.01 vs. 0.059 ± 0.02; p = 0.018), TINN (105.88 ± 51.82 vs. 151.47 ± 49.9; p = 0.014), SD1 (9.76 ± 4.66 vs. 14.55 ± 6.04; p = 0.014) and SD2 (34.86 ± 17.02 vs. 51.51 ± 18.38; p = 0.010). SD1/SD2 (0.30 ± 0.11 vs. 0.28 ± 0.07; p = 0.605) were not significantly different between groups. Patients with COPD presented a visual analysis of Poincaré plot of lower dispersion of RR intervals both beat to beat and the long term. Conclusion Subjects with COPD present reduction of geometric indexes of HRV, indicating reduced heart rate variability.