Wilcoxon Signed Rank Sum Test Research Articles

The effort and outcomes of the Pediatric Surgery match process: Are we interviewing too many?

PurposeIncreasing numbers of programs participating in the pediatric surgery match has resulted in economic and logistical issues for candidates, General Surgery residencies, and Pediatric Surgery training programs (PSTP). We sought to determine the ideal number of interviews conducted by programs based on resultant rank order lists (ROL) of matched candidates. MethodsPSTPs received 4 online surveys regarding interview practices (2011–2012, 2014), and matched candidate ROL (2008–2010, 2012, 2014). Program directors (PD) also provided estimates regarding minimum candidate interview numbers necessary for an effective match (2011–2012, 2014). Kruskal–Wallis equality-of-populations rank tests compared ROL and interview numbers conducted. Quartile regression predicted ROL based on the interview numbers. Wilcoxon signed rank-sum tests compared the interview numbers to the minimal interview number using a matched pair. p Values<0.05 were significant. ResultsSurvey response rates ranged from 85–100%. Median ROL of matched candidates (2–3.5) did not differ between programs (p=0.09) and the lowest matched ROL for any year was 10–12. Interview numbers did not affect the final candidate ROL (p=0.22). While PDs thought the minimum median interview number should be 20, the number actually conducted was significantly higher (p<0.001). ConclusionThese data suggest that PSTPs interview excessive numbers of candidates. Programs and applicants should evaluate mechanisms to reduce interviews to limit costs and effort associated with the match.

Can Functional Septorhinoplasty Independently Treat Obstructive Sleep Apnea?

The purpose of this study was to determine whether functional rhinoplasty alone results in a significant improvement in obstructive sleep apnea parameters in patients with nasal obstruction. Records of consecutive adult patients with nasal obstruction who underwent surgery to repair their nasal inlet and completed preoperative and postoperative polysomnography were reviewed. Patients underwent polysomnography before and after functional septorhinoplasty. Long-term follow-up using Nasal Obstruction Symptom Evaluation scores was conducted. Statistical analysis was performed using the Wilcoxon signed rank sum test. A Holm-Bonferroni sequential correction was also used because of multiple statistical comparisons being made. Twenty-six patients were included in this study. Mean apnea-hypopnea index scores preoperatively was 24.7, which dropped to a mean postoperative apnea-hypopnea index of 16, a reduction of 35 percent (p = 0.013). Excluding patients with a body mass index greater than 30 resulted in improved apnea-hypopnea index scores, from 22.5 to 9.6, a mean 57 percent reduction (p < 0.01). Functional rhinoplasty may have the potential to significantly improve the severity of obstructive sleep apnea for select patients with nasal obstruction. The nasal airflow improvement may modify pharyngeal aerodynamics. This is a fast and minimally invasive approach to consider in patients with obstructive sleep apnea and nasal obstruction, especially in patients with a body mass index less than 30. Therapeutic, IV.

Impact of lymphoceles on organ at risk doses in patients undergoing adjuvant pelvic radiation for carcinoma cervix

Purpose: Lymphoceles form part of target volume during adjuvant radiation for cervical cancer. The impact of lymphocele on doses to adjacent organs at risk (OAR) has not been studied. The present study was designed to investigate the same. Methods : From January 2011- December 2013 all patients were evaluated for presence of postoperative lymphocele. Planned target volume (PTV) was generated with and without lymphocele volume. Intensity modulated radiation therapy (IMRT) plans were generated and dose to OARs was determined. The impact of lymphocele volume on OAR dose was determined by Spearman rank test and Wilcoxon sign rank sum test was performed to determine the impact of lymphocele on OAR dose. Results : A total of 11/93 patients had postoperative lymphoceles. Of these 63% were located in internal iliac region. The median lymphocele volume at simulation was 42.8 cc (range 6.4-105cc) and remained almost stable at 44 cc (range 3-100 cc) at fifth week of radiation. Negative correlation was observed between mean lymphocele volume and dose to bladder, rectum and bowel bag. Presence of lymphocele led to reduction in V30 and V40 of bladder (84 cc vs 77 cc, p = 0.004; 68 cc vs 63 cc; p = 0.01) and rectum (87 cc vs 80 cc, p = 0.0001; 73.5 cc vs 65 cc, p = 0.01) and V15 of bowel bag (843 cc vs 804 cc; p = 0.01). Conclusion : Presence of lymphoceles displaced OARs leading to reduction in high dose volumes of rectum and bladder.

Abstract P1-15-20: Prospective study of proton radiotherapy for treatment of regional lymphatics in breast cancer

Abstract Purpose: To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and to determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. Methods: From May 2012 to February 2014, 18 women (stage IIA-IIIB) prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right and left-sided cancers. Treatment targets (CTVs for breast/chest wall, supraclavicular, axillary, internal mammary nodes [IMNs]) and organs at risk were delineated on CT scans, and PT and conventional plans were developed. PT alone was used for 10 patients (9 post-mastectomy, 1 after BCT) and combined proton-photon in 8 (all BCT). Acute toxicity was prospectively recorded using CTCAE v4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. Results: Median followup was 10.6 months (range, 1.1-19.1). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Breast/chest wall coverage was adequate (V47.5=96.6% for both plans). PT improved coverage of level II axilla (median D95, 48.9Gy [range, 44.8-51.4Gy] with PT vs 45.4Gy [range, 39.8-51Gy] with conventional; p=0.0005). Adequate coverage of IMNs was consistently achieved with PT (median D95, 48.9Gy with a range of 44.8-51.4Gy) but not with conventional (median D95, 45.4Gy with range of 39.8-51Gy; p=0.0005); PT reduced heart dose in all patients. Median ipsilateral lung V5 measured 35.3% for PT compared to 60.5% for conventional (p&amp;lt;0.0001). Ipsilateral lung V20 improved with PT (median, 21.6% vs 35.5%; p&amp;lt;0.0001). Table 1: Cardiac dose in left-sided patients (comparison of medians of the cohort; range in parentheses) Heart V5Mean Heart DoseVentricle V5Mean Ventricle DoseMaximum LAD doseMean LAD doseProton Plan2.7% (0-12%)0.6Gy (0-3.2Gy)0.5% (0-15.6%)0.1Gy (0-4Gy)30.5 (13.4-42.6Gy)1.7Gy (0.5-28.5Gy)Conventional Plan34% (7-60%)5.9Gy (2-9.1Gy)31.4% (8.7-79.8%)5.4Gy (2.4-11Gy)44.6Gy (35.1-54.7Gy)27Gy (16.8-41.9Gy)p-value0.0040.0040.0040.0040.040.02 Table 2. Cardiac dose in right-sided patients (comparison of medians of the cohort; range in parentheses) Heart V5Mean Heart DoseVentricle V5Mean Ventricle DoseProton Plan0.3% (0-2.9%)0.5Gy (0-0.8Gy)3.3% (0-1%)0.2Gy (0-0.5Gy)Conventional Plan13.2% (0.4-24.7%)2.9Gy (1-5.1Gy)3.3% (0-7.1%)1.2Gy (0.8-1.7Gy)p-value0.0040.0040.0080.004 Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. All patients developed grade 2 dermatitis; other acute grade 2 toxicities included fatigue (n= 6) and esophagitis (n=5). No grade 4+ toxicities developed. Dermatitis resolved by 1 month after PT for all but 1 patient who developed cellulitis (grade 2). Conclusion: PT for RNI after mastectomy or BCT significantly improves cardiac dose especially for left-sided patients and lung V5 and V20 in all patients without excessive acute toxicity. PT simultaneously improves target coverage for the IMN and level II axilla, which may positively impact long-term survival in breast cancer patients. Citation Format: Julie A Bradley, Roi Dagan, Meng Wei Ho, Christopher G Morris, Zuofeng Li, Nancy P Mendenhall. Prospective study of proton radiotherapy for treatment of regional lymphatics in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-20.

Psychological health in the summer team of an Indian expedition to Antarctica

Context: Number of scientific personnel traveling to Antarctica for short summer stay far outnumbers winter personnel. Hence, psychological issues confronting such personnel need to be analyzed in detail. This study aims to study changes in psychological health, cognitive functioning, changes in motivation levels, and tobacco and alcohol consumption during a summer in Antarctica. Aims: To study changes in psychological health, cognitive functioning, changes in motivation levels and tobacco and alcohol consumption during a summer in Antarctica. Setting and Design: This cohort study was conducted on 33 summer team members of 27 th Indian Scientific Expedition to Antarctica. Subjects and Methods: Seven instruments were administered to assess general health, alcohol and tobacco dependence, memory and cognitive functioning of the team members. Statistical Analysis Used: The data were analyzed for statistical significance using nonparametric Wilcoxon Signed Rank Sum Test. Results: Scores on social dysfunction, depression, and somatic symptoms increased. Tobacco consumption also increased concomitantly. However, memory and cognitive function were not impaired. Alcohol consumption did not change. None of the subjects needed medication or evacuation for psychological difficulties. Conclusion: Psychological issues might manifest themselves even during a short stay in Antarctica during the summer season.

Effects of tongue cleaning on plaque and salivary mutans streptococci levels: A randomized controlled trial

Introduction: Tongue cleaning has been shown to be effective in preventing plaque formation and reducing oral mutans streptococci (MS) when used in combination with other oral hygiene procedures. However, correlation between MS counts and plaque levels remains to be demonstrated. Aim: To evaluate the effect of tongue scraping and tongue brushing on salivary MS and plaque levels. Materials and Methods: A triple-blind three arm randomized controlled parallel-group trial was carried out among 54, 12–15-year-old boys in a residential school in Bengaluru city. The study participants were randomly allocated into Group A (toothbrushing and tongue scraping; n = 19), Group B (toothbrushing and tongue brushing; n = 18) and Group C (only toothbrushing; n = 17). The clinical procedure included a collection of saliva and recording of plaque index at baseline, 10th and 21st day. Salivary MS counts were determined using mitis salivarius bacitracin Agar media. ANOVA, Wilcoxon's signed-rank sum test, Mann–Whitney U-test and Spearman's correlation test were performed on log-transformed CFU/mL of MS. Results: The tongue scraping and tongue brushing groups showed statistically significant reductions in salivary MS counts after 10 days (4.76 ± 0.54) (4.79 ± 0.44) and 21 days (4.50 ± 0.44) (4.41 ± 0.57) respectively when performed along with toothbrushing. However, differences between the interventions were not statistically significant. Furthermore, there was no statistically significant reduction in plaque levels after 10 and 21 days. Conclusions: Tongue scraping and tongue brushing were equally effective in reducing salivary MS counts when used in combination with toothbrushing, however, their effect on reducing plaque levels was not significant. Hence, tongue cleaning is recommended as an adjunct to toothbrushing.

Increased Incidence of Thromboembolic Event Rates in Patients Diagnosed with Polycythemia Vera: Results from an Observational Cohort Study

Background: Polycythemia vera (PV) is a rare hematologic neoplasm with significant morbidities. Blood hyperviscosity reflected by elevated hematocrit (HCT) levels is believed to contribute to most disease symptoms and complications including thrombotic events (TE), which are among the most serious clinical manifestations of PV. Concurrent with ongoing Phase III trials in PV, this study assesses treatment patterns, TE event rates, and direct costs associated with PV in real-world practice settings. Preliminary results on incidence of TE events in a privately insured US population are presented here.Methods: Data for this retrospective observational study were taken from the MarketScan database containing medical and drug utilization data for ~40 million unique individuals enrolled in employer-sponsored private health insurance plans in the United States. Patients with at least two claims of a PV diagnosis (International Classification of Diseases, 9th Clinical Modification [ICD-9-CM] code 238.4) at least 30 days apart, between July 1, 2008 and December 31, 2011, were selected for study inclusion. Using propensity score (PS) methods, we identified a non-PV control group matched with PV cases on demographics and comorbidities. PS matching is frequently used in observational studies to achieve balance on observed covariates between cases and controls. Incident TE events were identified using ICD-9 diagnosis codes and were assessed from the index date (first PV diagnosis) until the earliest of plan disenrollment or end of the database. Both fatal and nonfatal events were included, although a distinction could not be ascertained in these data. The TE event rate was defined as the number of unique patients with a new TE occurrence (i.e., incident cases) per 1000 person-years (PYs) of observation time. Unadjusted TE event rates and incident rate ratios (RR) expressing the increased frequency of events in PV cases relative to controls were estimated for overall (i.e., any), cerebral, arterial, and venous TE events. Kaplan-Meyer (KM) analyses were performed to estimate time to event for each of the event categories listed above.Results: The cohort comprised 8,124 PV patients with mean age of 51 years; 71% of patients were male. Table 1 describes the quality of balance between cases and matched controls for selected variables that differed significantly before PS matching. As shown in Figure 1, TE event rates were significantly higher among PV cases compared to matched controls (overall: 14.3 vs. 4.9/1000 PYs [RR 2.90 (95% CI: 2.28-3.68)], cerebral: 3.5 vs. 1.3/1000 PYs [RR 2.66 (95% CI: 1.66-4.24)], arterial: 6.9 vs. 2.4/1000 PYs [RR 3.16 (95% CI: 2.05-4.87)], and venous: 4.7 vs. 1.5/1000 PYs [RR 2.94 (95% CI: 2.08-4.15)]). KM analyses showed that event probabilities over time were significantly higher among PV cases (Figure 2). Due to high censoring in both the groups, median time to TE event could not be calculated. However, among those with an event, median time to event was shorter (but not statistically significant) among PV cases compared to controls for overall (7.0 vs. 9.7 months [P=0.0817]), cerebral (8.5 vs. 13.1 months [P=0.0634]), and arterial (9.2 vs. 14.7 months [P=0.0768]), but slightly higher for venous (5.3 vs. 4.8 months [P=0.5583]).Conclusion: Patients with PV have significantly higher rate of TE events compared with matched controls. This rate may be higher in patients with HCT > 45%. Further analyses in this ongoing study will assess patient level predictors of cardiovascular and TE events and their impact on overall economic burden of PV.Table 1Comparison of Baseline Characteristics between PV Cases and Matched ControlsPV Cases (n=8124)Control (n=8124)P-value ‡PercentAge Group (years)<181.71.70.2418 - 4419.919.045 - 5958.459.960 - 6420.119.4GenderMale71.571.20.65Geographic regionNorth Central20.620.90.48North East16.516.7South40.841.1West19.218.1Unknown3.03.2Year of diagnosis200817.317.60.16200927.729.0201027.527.2201127.526.2Charlson comorbidity index (CCI) score (mean [SD])0.8 (1.4)0.7 (1.4)0.00Note: Other covariates in the PS estimation include payer type, plan type, employment status, and relationship to employee.‡P-values based on McNemar’s test for categorical variables and Wilcoxon Signed Rank Sum test for continuous variables. [Display omitted] [Display omitted] DisclosuresGoyal:Novartis Pharmaceuticals Corp: Employee of RTI Health Solutions, which received research funding for this work. Other. Davis:Novartis Pharmaceuticals Corporation: Research Funding. Mounedji:Novartis Pharma: Employment. Kaye:Novartis Pharmaceuticals Corp: Employee of RTI Health Solutions, which received research funding for this work. Other.

Combined Modality Approach for Early Stage Unfavorable Hodgkin Lymphoma- Can We Avoid Radiation Therapy Based on Interim PET Imaging?

Background: Prior studies have demonstrated the utility of involved field radiation therapy to reduce relapse rates and improve local control in Hodgkin Lymphoma (HL). The standard treatment for early stage unfavorable HL is combined modality approach with chemotherapy and radiation therapy (XRT). Despite reduction in the fields of XRT, long term adverse outcomes are associated with the combined modality approach. Recent clinical trials have focused on adapting therapy based on interim PET scans. There is, however, limited data evaluating patient outcomes with chemotherapy alone in unfavorable, bulky HL patients.Methods: Two hundred and fifteen patients diagnosed with HL at our institution were included in our retrospective analysis after obtaining IRB approval. Statistical analysis was performed by chi-square analysis, Wilcoxon signed rank sum test and Kaplan-Meier plots using SPSS.19 software.Results: Of the 215 patients, 48 had early stage unfavorable HL and were included in this analysis. Unfavorable HL was defined as bulky disease (>10cm or >1/3 thoracic diameter), ESR >50 or >3 extra nodal sites involvement at presentation. The median age at diagnosis was 31 years (range 17-58). Twenty-two patients (46%) were male. All patients had an Eastern Cooperative Oncology Group performance status of either 0 or 1. Nineteen patients (40%) presented with B symptoms. The majority (83%) of patients were treated with 4-6 cycles of ABVD as first line therapy, while the remainder were treated with COPP/ABV, Stanford V, ABV or MOPP/ABV. Approximately half of the patients received XRT (54%), which was determined by physician choice. Forty-six patients (96%) were alive at the time of analysis. Seven patients (15%) underwent autologous stem cell transplantation for either disease relapse or for an incomplete response. Interim PET data was missing in 8 patients, who were excluded from subsequent analysis. Interim PET was positive in 13 of the remaining 40 patients, 9 of whom received consolidative radiation therapy and 4 of whom received high dose therapy followed by autologous stem cell transplantation. Among the 27 patients with negative interim PET, 12 received XRT. The median overall survival (OS) of all patients was 38.8 months. In patients with negative interim PET scan, the PFS was 83% and 80% in patients who received chemotherapy with and without XRT, respectively. The OS was 83% and 100% in patients who received chemotherapy with and without XRT, respectively. The differences in PFS and OS were not statistically significant between the two groups. Two patients died in the group that received combined modality treatment after negative interim PET, one from pre-existing cardiomyopathy and one from progression of disease. No death was related to XRT. In a subgroup analysis, eleven of the 27 patients with negative interim PET had bulky disease, 8 of whom received XRT. The PFS in this subgroup was 75% and 100% in patients who received chemotherapy with and without XRT, respectively. The OS in this subgroup was 88% and 100% in patients who received chemotherapy with and without XRT, respectively.Conclusion: Our data suggests that radiation therapy can be avoided based on interim PET scan in early stage unfavorable HL without compromising OS. The high overall survival of these patients may be accounted for by the fact that many who fail initial treatment can be salvaged with high dose chemotherapy and autologous stem cell transplantation. Given the potential for reduction in radiation related adverse outcomes, we encourage participation in ongoing prospective, PET-adapted, clinical trials investigating the need for consolidative XRT following chemotherapy in patients with unfavorable, bulky disease. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cassia cinnamon does not change the insulin sensitivity or the liver enzymes in subjects with impaired glucose tolerance.

BackgroundPublished studies have reported conflicting results regarding the effects of cinnamon on glucose, lipids and insulin. To gain further insight into the metabolic effects of Cinnamomum cassia we performed randomized, double-blinded placebo-controlled study using euglycaemic-hyperinsulinaemic clamp.MethodsTwenty-one subjects with impaired glucose tolerance (IGT) were included in the study (10 or 11 subjects in each group). The study groups were matched for age, gender and body mass index (BMI). Waist-to-hip ratio, BMI, blood pressure, fasting blood glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein , HbA1c, ASAT, ALAT, bilirubin, ALP, GT and PK were measured before and after the intake of capsules equivalent to 6 g cinnamon twice a day for 12 weeks. The changes in insulin resistance were measured by euglycaemic-hyperinsulinaemic clamp. The Wilcoxon signed rank sum test, the Mann-Whitney U test and Pearson’s chi-squared test were used to analyse the data. Values of p < 0.05 were considered to indicate statistically significant differences.ResultsAt enrolment, the groups were similar in terms of age, gender and BMI. Of the 21 randomized patients with IGT, 17 completed the study (8 controls vs. 9 treated). The ingestion of 6 g cinnamon twice a day for 12 weeks had no significant effect on insulin sensitivity, HbA1c, fasting glucose or BMI. No significant changes were seen in lipids or liver enzymes.ConclusionsThis study showed that ingestion of 6 g C. cassia twice a day for 12 weeks did not change the insulin sensitivity or liver enzymes in subjects with IGT.

Efficacy of a novel two-day EMT refresher training program focused on essential EMS knowledge and skills

Methods Study participants were GVK EMRI EMT instructors who attended the inaugural EMT refresher training course. These participants were from nine states within India and represented mixed educational backgrounds, including doctors and EMTs. After receiving a confidential unique ID, each study participant took a 30 multiple-choice question (MCQ) pre-test and a 60 MCQ post-test before and after the course, respectively. Differences between preand post-test scores were analyzed using the Wilcoxon signed rank sum test paired by participant.

Effect of upper costal and costo-diaphragmatic breathing types on electromyographic activity of respiratory muscles

Aim:To compare electromyographic (EMG) activity in young–adult subjects with different breathing types.Methodology:This study included 50 healthy male subjects with complete natural dentition, and no history of orofacial pain or craniomandibular-cervical-spinal disorders. Subjects were classified into two groups: upper costal breathing type, and costo-diaphragmatic breathing. Bipolar surface electrodes were located on sternocleidomastoid, diaphragm, external intercostal, and latissimus dorsi muscles. Electromyographic activity was recorded during the following tasks: (1) normal quiet breathing; (2) speaking the word ‘Mississippi’; (3) swallowing saliva; and (4) forced deep breathing.Results:Sternocleidomastoid and latissimus dorsi EMG activity was not significantly different between breathing types, whereas diaphragm and external intercostal EMG activity was significantly higher in the upper costal than costo-diaphragmatic breathing type in all tasks (P<0·05; Wilcoxon signed rank-sum test).Conclusion:Diaphragm and external intercostal EMG activity suggests that there could be differences in motor unit recruitment strategies depending on the breathing type.

Abdominal CT: An intra-individual comparison between virtual monochromatic spectral and polychromatic 120-kVp images obtained during the same examination

ObjectivesTo compare quantitative and subjective image quality between virtual monochromatic spectral (VMS) and conventional polychromatic 120-kVp imaging performed during the same abdominal computed tomography (CT) examination. Materials and methodsOur institutional review board approved this prospective study; each participant provided written informed consent. 51 patients underwent sequential fast kVp-switching dual-energy (80/140kVp, volume CT dose index: 12.7mGy) and single-energy (120-kVp, 12.7mGy) abdominal enhanced CT over an 8cm scan length with a random acquisition order and a 4.3-s interval. VMS images with filtered back projection (VMS-FBP) and adaptive statistical iterative reconstruction (so-called hybrid IR) (VMS-ASIR) (at 70keV), as well as 120-kVp images with FBP (120-kVp-FBP) and ASIR (120-kVp-ASIR), were generated from dual-energy and single-energy CT data, respectively. The objective image noises, signal-to-noise ratios and contrast-to-noise ratios of the liver, kidney, pancreas, spleen, portal vein and aorta, and the lesion-to-liver and lesion-to-kidney contrast-to-noise ratios were measured. Two radiologists independently and blindly assessed the subjective image quality. The results were analyzed using the paired t-test, Wilcoxon signed rank sum test and mixed-effects model with Bonferroni correction. ResultsVMS-ASIR images were superior to 120-kVp-FBP, 120-kVp-ASIR and VMS-FBP images for all the quantitative assessments and the subjective overall image quality (all P<0.001), while VMS-FBP images were superior to 120-kVp-FBP and 120-kVp-ASIR images (all P<0.004). ConclusionsVMS images at 70keV have a higher image quality than 120-kVp images, regardless of the application of hybrid IR. Hybrid IR can further improve the image quality of VMS imaging.

Choroidal structure in normal eyes and after photodynamic therapy determined by binarization of optical coherence tomographic images.

To determine changes in choroidal structure by binarization of optical coherence tomographic (OCT) images. Choroidal images were recorded by enhanced depth imaging OCT. The subfoveal choroidal images were analyzed, and the luminal and interstitial areas were converted to binary images by the Niblack method. The interrater, intrarater, and intersession agreements of the binary images were determined for healthy eyes. In eyes with age-related macular degeneration (AMD), the binary images of the choroid before photodynamic therapy (PDT) were compared to those after PDT. The untreated fellow eyes were studied as controls. In healthy eyes, the average ratio of the luminal to choroidal area was 65.4%. The interrater agreement rate was high, with intraclass correlation coefficient (ICC) 0.985 and 0.988 for the choroid and luminal areas, respectively. The intrarater ICC was 0.996 for the choroid and 0.997 for the luminal areas. The intersession ICC was 0.993 for the choroid and 0.984 for the luminal areas. In eyes with AMD, the subfoveal choroidal area, the luminal area, and the interstitial areas were thinner 6 months after PDT (all P < 0.01, Wilcoxon signed-rank sum test). The ratio of the luminal to choroidal area was significantly decreased to 62.8% (P < 0.01, Wilcoxon signed-rank sum test). The ratio for the fellow eyes was not significantly changed. The Niblack binarization method can be used to analyze the luminal area of choroid in an OCT image with good repeatability and reproducibility. The change in the subfoveal choroidal area after PDT is due mainly to a decrease in the luminal areas.

Early Pattern of Degenerative Changes in Individual Components of Intervertebral Discs in Stressed and Nonstressed Segments of Lumbar Spine

A retrospective imaging review. To assess differences in burden and pattern of disc degeneration in segments of lumbar spine with and without signs of increased mechanical stresses. Young patients with magnetic resonance imaging signs of increased mechanical stress in pedicles or pars interarticularis provide an excellent in vivo model to study early effects of mechanical stresses on lumbar intervertebral discs without the confounding effects of genetics or environmental factors. Detailed in vivo evaluation for early degenerative changes in all individual disc components of stressed intervertebral discs has not been done. Using magnetic resonance imaging, 2 radiologists assessed intervertebral discs around 93 stressed lumbar spinal segments in 87 patients (55 males, 32 females; mean age, 15.3 ± 3.3 yr; range, 5-25 yr) as well as lumbar discs in nonstressed segments for signs of degeneration in annulus fibrosus, nucleus pulposus, and endplates. Differences between stressed, control, and loading-matched control discs were assessed using Wilcoxon signed rank sum test. Burden of annular tears, radial tears, herniations, and nuclear degeneration was significantly higher in stressed discs (0.70 ± 0.34, 0.48 ± 0.39, 0.07 ± 0.19, and 0.17± 0.31, respectively) than control (0.29 ± 0.25, 0.09 ± 0.17, 0.01 ± 0.04, and 0.02 ± 0.08, respectively) or loading-matched control discs (0.44 ± 0.47, 0.16 ± 0.36, 0.01 ± 0.04, and 0.01 ± 0.11, respectively) (P < 0.01 for all). Stressed segments did not show any significant increase in endplate degeneration. Intervertebral discs in stressed spinal segments show an increased burden of disc degeneration involving annulus fibrosus and nucleus pulposus, but not the endplates. N/A.

Abstract 234: Changes in Plasma Nitration of High-Density and Low-Density Lipoproteins in Patients With Chronic Kidney Disease Receiving Kidney Transplants

Background: Functional abnormalities of high-density lipoprotein (HDL) and elevated concentration of low-density lipoprotein (LDL) could contribute to cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. Both qualitative and quantitative changes in HDL have been described in patients with CKD. Specifically, HDL abundance is reduced and HDL acquires a pro-inflammatory properties. In this study, we hypothesized that a functioning kidney transplant reduces serum nitrated apoA-I concentration. Methods: Concentrations of nitrated apoA-I, nitrated apoB, total apoA-I and total apoB were measured using indirect sandwich ELISA on sera collected from each transplant subject pre-transplant and at 1, 3, and 12 months post-transplant. Patients were excluded if they had a history of diabetes, prednisone dose &gt; 15 mg/day, nephrotic range proteinuria, serum creatinine (Cr) &gt; 1.5mg/dL or active inflammatory disease, or were treated with lipid-lowering medication or HIV protease inhibitors. Paired values of percent nitrated Apo A-I or nitrated apoB before and after kidney transplantation were compared using Wilcoxon signed rank sum test. Results: We screened 75 transplant patients, and 14 were found to meet the selection criteria. Amongst these patients, twelve and eight patients had Cr &lt; 1.5 mg/dL at 3 and 12 months post-transplant, respectively. There was a significant reduction in % nitrated apoA-I at 12 months post-transplant compared to pre-transplant values in patients with Cr&lt;1.5 mg/dL (p=0.04) but neither at 3 months post-transplant nor in patients with Cr &gt;1.5. Reduction of nitrated apoA-I was associated with slight increase in HDL levels 12 months post-transplantation. In contrast to apoA-I, there was no significant change in % nitrated apoB at 3 months and 12 months post-transplant. No significant corelation was observed between nitrated lipoproteins and CRP levels. Conclusion: Patients with well functioning grafts had significant reduction in percent nitrated apoA-I without any effect on apoB nitration 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in CKD.

An extensive analysis of disease-gene associations using network integration and fast kernel-based gene prioritization methods.

ObjectiveIn the context of “network medicine”, gene prioritization methods represent one of the main tools to discover candidate disease genes by exploiting the large amount of data covering different types of functional relationships between genes. Several works proposed to integrate multiple sources of data to improve disease gene prioritization, but to our knowledge no systematic studies focused on the quantitative evaluation of the impact of network integration on gene prioritization. In this paper, we aim at providing an extensive analysis of gene-disease associations not limited to genetic disorders, and a systematic comparison of different network integration methods for gene prioritization.Materials and methodsWe collected nine different functional networks representing different functional relationships between genes, and we combined them through both unweighted and weighted network integration methods. We then prioritized genes with respect to each of the considered 708 medical subject headings (MeSH) diseases by applying classical guilt-by-association, random walk and random walk with restart algorithms, and the recently proposed kernelized score functions.ResultsThe results obtained with classical random walk algorithms and the best single network achieved an average area under the curve (AUC) across the 708 MeSH diseases of about 0.82, while kernelized score functions and network integration boosted the average AUC to about 0.89. Weighted integration, by exploiting the different “informativeness” embedded in different functional networks, outperforms unweighted integration at 0.01 significance level, according to the Wilcoxon signed rank sum test. For each MeSH disease we provide the top-ranked unannotated candidate genes, available for further bio-medical investigation.ConclusionsNetwork integration is necessary to boost the performances of gene prioritization methods. Moreover the methods based on kernelized score functions can further enhance disease gene ranking results, by adopting both local and global learning strategies, able to exploit the overall topology of the network.

Comprehensive Analysis of Vascular Endothelial Growth Factor-C Related Factors in Stomach Cancer

Vascular endothelial growth factor-C (VEGF-C), which contributes to lymphatic metastasis (LM) in malignant disease, is one of the most important factors involved in physical and pathological lymphangiogenesis. Some VEGF-C related factors such as sine oculis homeobox homolog (SIX) 1, contactin (CNTN) 1 and dual specificity phosphatase (DUSP) 6 have been extensively studied in malignancies, but their expression levels and associations have still to be elucidated in stomach cancer. We detected their expression levels in 30 paired stomach cancer tissues using quantitative real-time reverse transcription-PCR (qRT-PCR). The expression and clinical significance of each factor was analyzed using Wilcoxon signed rank sum test. The correlation among all the factors was performed by Spearman rank correlation analysis. The results suggest that VEGF-C and CNTN1 are significantly correlated with tumor size, SIX1 with the age and CNTN1 also with the cTNM stage. There are significant correlations of expression levels among VEGF-C, SIX1, CNTN1 and DUSP6. There exists an important regulatory crosstalk involving SIX1, VEGF-C, CNTN1 and DUSP6 in stomach cancer.

Tracheal intubation with a flexible fibreoptic scope or the McGrath videolaryngoscope in simulated difficult airway scenarios

Flexible fibreoptic endoscopic (FFE) intubation is considered the 'gold-standard' when difficult airway management is anticipated. Several videolaryngoscopes have been developed to facilitate intubation by laryngoscopy. The aim of the study was to compare the performance of the McGrath series 5 videolaryngoscope (McGrath videolaryngoscope) and the FFE for tracheal intubation in manikins with a simulated difficult airway, hypothesizing that the McGrath videolaryngoscope intubation would prove faster than FFE intubation. A randomised controlled study. The Danish Institute for medical simulation between December 2009 and June 2010. Twenty-eight anaesthesia residents participating in the Danish mandatory 3-day airway management course. All participants received instructions and training in the use of the McGrath videolaryngoscope and FFE. The participants then performed tracheal intubation on a SimMan manikin once with the McGrath videolaryngoscope and once with the FFE in three difficult airway scenarios: (1) pharyngeal obstruction; (2) pharyngeal obstruction and cervical rigidity; (3) tongue oedema. We measured successful intubations, defined as intubation within 120 s, and time to tracheal intubation. The trachea was intubated within 120 s with the McGrath videolaryngoscope in 25 out of 27 (93%), 25 out of 28 (89%) and 18 out of 28 (64%) occasions compared with 11 out of 28 (40%), 11 out of 28 (40%) and 16 out of 28 (57%) with the FFE in scenarios (1), (2) and (3), respectively. Time to tracheal intubation was shorter with the McGrath videolaryngoscope in scenarios (1) and (2) than with the FFE (Wilcoxon signed rank sum test, P < 0.0001). The McGrath videolaryngoscope is a valuable device with higher success rate and a quicker performance in simulated difficult airways. In patients, videolaryngoscopy may have a role in difficult airway algorithms, but the optimal device has yet to be found.

Comparison of four cardiovascular risk prediction functions among Chinese patients with diabetes mellitus in the primary care setting.

To assess the feasibility, convergent validity and sensitivity of four cardiovascular risk prediction functions in Chinese diabetic patients in the primary care setting. A cross-sectional study of 1,140 diabetic patients was carried out to compare four cardiovascular risk functions, which were respectively developed from the Framingham heart study, the USA-People's Republic of China Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology cohort (PRC), the United Kingdom Prospective Diabetes Study (UKPDS) and the Joint Asia Diabetes Evaluation program (JADE). Feasibility was assessed by the percentage of patients with complete data for risk prediction. Convergent validity was measured by Spearman's rank correlation, paired Wilcoxon signed-rank sum test and Bland-Altman plots. Effect size differences between clinical risk groups were used to assess the sensitivity. Risk prediction was feasible by the Framingham, UKPDS and PRC risk functions in more than 98% patients, whereas just 74% of patients had complete data for the JADE function. The annual total coronary heart disease (CHD) risk predicted by the JADE and the UKPDS functions showed excellent agreement with no significant difference, and a correlation of 0.8048. The Framingham and the PRC functions predicted significantly lower CHD risk than those by the UKPDS and the JADE functions. The UKPDS and the Framingham functions were more sensitive in differentiating clinical risk groups. The UKPDS risk engine showed good feasibility, convergent validity and sensitivity in predicting CHD risk in Chinese diabetic patients. The JADE function showed excellent agreement with the UKPDS risk engine, but it was less feasible in the primary care setting.

Application of three kinds of non-invasive positive pressure ventilation as a primary mode of ventilation in premature infants with respiratory distress syndrome: a randomized controlled trial

Non-invasive positive pressure ventilation has increasingly been chosen as the primary ventilation mode in respiratory distress syndrome (RDS) in preterm infants. In order to further understand the application of various non-invasive positive pressure ventilation modes, we compared the advantages and disadvantages of three modes as a primary mode of ventilation in premature infants with RDS. From December 2011 to March 2013, 107 preterm infants with RDS who received intubation-pulmonary surfactant (PS) -extubation in our NICU were randomly divided (by means of random number table) into three groups based on the primary mode of ventilation: nasal continuous positive airway pressure [NCPAP, n = 39, male/female ratio was 27/12, mean gestational age (GA) was (32.0 ± 2.1)weeks, mean birth weight (BW) was (1752 ± 457)g], bi-level positive airway pressure [BiPAP, n = 35, male/female ratio was 25/10, GA was (31.4 ± 2.0) weeks, BW was (1530 ± 318) g], and synchronized bi-level positive airway pressure [SBiPAP, n = 33, male/female rate was 25/8, GA was (31.5 ± 2.2) weeks, BW was (1622 ± 447) g]. Ventilation settings including FiO(2) were adjusted according to transcutaneous SPO(2) monitoring or blood gas analysis. Various settings and adverse events were recorded as well. The main parameter was the FiO(2) at 24 h post-positive-pressure ventilation. Statistical analyses were performed using χ(2) test, rank sum test, one-way analysis of variance for least-significant difference value, paired-sample t-test, two related sample Wilcoxon signed rank sum test and Logistic regression. The PaCO(2) (mmHg, 1 mmHg = 0.133 kPa), oxygen index (OI) at 12-24 h, and FiO(2) at 24 h post-ventilation in BiPAP and SBiPAP groups were lower than that in NCPAP groups with significant difference (44 ± 9 and 45 ± 9 vs. 50 ± 9, 2.76 ± 0.96 and 2.79 ± 0.60 vs. 3.24 ± 0.72, 0.34 ± 0.10 and 0.35 ± 0.07 vs. 0.39 ± 0.07; F = 4.456, 5.146 and 4.123; P = 0.014, 0.007 and 0.019, respectively). There was no significant difference between BiPAP and SBiPAP groups. There was no significant difference among three groups (all P > 0.05) in the following events: respiratory index (RI) at 12-24 h post-ventilation, abdominal distension, period of non-invasive ventilation, ratio of intubation for invasive ventilation if failed noninvasive ventilation, air-leak syndrome, neonatal necrotizing enterocolitis, periventricular-intraventricular haemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity, mortality rate after 36 h of age or rate of abandon for discharge. The independent risk factors for failure of non-invasive positive pressure ventilation were gender, gestational age, antepartum steroid at 24 h before birth to 7 d, and birth weight, with the OR (95% confidence interval) being 14.120 (1.135, 175.662), 2.862 (1.479, 5.535), 61.084 (3.115, 1 198.031), and 8.306 (1.488, 46.383), respectively. As the primary mode of ventilation in premature infants with RDS, both BiPAP and SBiPAP are more beneficial than NCPAP in improving oxygenation and reducing CO(2) retention without increasing the incidence of adverse events.