Two-sample Wilcoxon Rank-sum Test Research Articles

PS01.242: HIATAL HERNIA AFTER MINIMALLY INVASIVE ESOPHAGECTOMY

Abstract Background Hiatal hernias (HH) are a known, yet poorly studied, post-surgical complication of esophagectomy. The aim of this study was to analyze in a retrospective fashion the MIE experience at our institution, in order to individuate factors associated with post-surgical HH development. Methods We reviewed data from MIE performed at University of Colorado from July 2013 to July 2017. Our most common approach of choice is Ivor Lewis MIE with circular stapled end to side anastomosis. We divided our patient population in two groups: those who developed a HH at any time post operatively and those who did not. We compared pre-, intra- and post-operative clinical variables of interest in the two groups using Pearson chi-squared and Fisher's exact test for binomial variables and Two-sample Wilcoxon rank-sum (Mann-Whitney) test for continuous variables. Results 91 patients underwent MIE in the study period: 11 developed HH in a time frame ranging from one week to two years post operatively. 8 patients had a HH involving one or more intra-abdominal organs other than the stomach; 3 patients had a HH interesting mostly the tubulized stomach. 7 patients required a reoperation. There were no statistically significant differences in the prevalence of pre-operative comorbidities between the two groups. Patient who developed a HH were significantly less likely to have had prior abdominal or thoracic surgery (Pr = 0.039). As expected, they were also significantly more likely to require a reoperation (Pr = 0.000). There were no statistically significant differences in intra-operative variables between the two groups, including operative time and anastomotic technique, nor where there differences in incidence of post operative complications other than HH. We did observe a trend towards higher rate of preoperative chemotherapy and radiation in the HH group. Of note, we did attempt to prevent HH by means of tacking abdominal organs to the abdominal wall, however this did not prove to significantly decrease HH incidence. Conclusion HH occurs in a non-negligible percentage of patients undergoing MIE. Lack of prior surgery appears to be significantly associated with HH, perhaps due to lesser adhesion burden acting as a mean of organ fixation. Disclosure All authors have declared no conflicts of interest.

Natural history of echocardiographic abnormalities in mucopolysaccharidosis III

BackgroundMucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. MethodsA single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. ResultsTwenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). ConclusionsIndividuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range.

By Default: The Effect of Prepopulated Prescription Quantities on Opioid Prescribing in the Emergency Department.

IntroductionOpioid prescribing patterns have come under increasing scrutiny with the recent rise in opioid prescriptions, opioid misuse and abuse, and opioid-related adverse events. To date, there have been limited studies on the effect of default tablet quantities as part of emergency department (ED) electronic order entry. Our goal was to evaluate opioid prescribing patterns before and after the removal of a default quantity of 20 tablets from ED electronic order entry.MethodsWe performed a retrospective observational study at a single academic, urban ED with 58,000 annual visits. We identified all adult patients (18 years or older) seen in the ED and discharged home with prescriptions for tablet forms of hydrocodone and oxycodone (including mixed formulations with acetaminophen). We compared the quantity of tablets prescribed per opioid prescription 12 months before and 10 months after the electronic order-entry prescription default quantity of 20 tablets was removed and replaced with no default quantity. No specific messaging was given to providers, to avoid influencing prescribing patterns. We used two-sample Wilcoxon rank-sum test, two-sample test of proportions, and Pearson’s chi-squared tests where appropriate for statistical analysis.ResultsA total of 4,104 adult patients received discharge prescriptions for opioids in the pre-intervention period (151.6 prescriptions per 1,000 discharged adult patients), and 2,464 post-intervention (106.69 prescriptions per 1,000 discharged adult patients). The median quantity of opioid tablets prescribed decreased from 20 (interquartile ration [IQR] 10–20) to 15 (IQR 10–20) (p<0.0001) after removal of the default quantity. While the most frequent quantity of tablets received in both groups was 20 tablets, the proportion of patients who received prescriptions on discharge that contained 20 tablets decreased from 0.5 (95% confidence interval [CI] [0.48–0.52]) to 0.23 (95% CI [0.21–0.24]) (p<0.001) after default quantity removal.ConclusionAlthough the median number of tablets differed significantly before and after the intervention, the clinical significance of this is unclear. An observed wider distribution of the quantity of tablets prescribed after removal of the default quantity of 20 may reflect more appropriate prescribing patterns (i.e., less severe indications receiving fewer tabs and more severe indications receiving more). A default value of 20 tablets for opioid prescriptions may be an example of the electronic medical record’s ability to reduce practice variability in medication orders actually counteracting optimal patient care.

Menarche, menopause, and pregnancy data in untreated females and females treated with agalsidase alfa in the Fabry Outcome Survey

Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials.A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables.Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3).Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range.

Abstract 71: Circulating Inter-alpha Inhibitor Protein Levels Decline After Stroke in Humans: Exogenous Supplementation is Protective in Multiple Animal Models of Ischemic Stroke

Introduction: Inter-alpha Inhibitor Proteins (IAIP) are a family of endogenous plasma and extracellular matrix molecules. IAIPs have been shown to down-regulate inflammation, inhibit destructive serine proteases, and bind extracellular histones to neutralize cytotoxicity. Interestingly, many of these factors also regulate neuroprotection after stroke. In our initial studies, we found that IAIP treatment was neuroprotective in the middle cerebral artery occlusion model. Here, we analyzed if stroke alters IAIP using plasma samples from both mice and human stroke patients, and we investigated whether IAIP could provide neuroprotection using multiple stroke models. Methods: C57BL/6 mice were subjected to stroke with an autologous thromboembolic clot followed by reperfusion using t-PA. A separate cohort underwent the permanent occlusion model. Mice were randomized to receive IAIP or vehicle at 6h and 18h after stroke onset. Infarct was assessed 48h after reperfusion with t-PA, or 72h after permanent occlusion. Plasma samples from stroke patients and vascular risk factor matched controls were used for changes in IAIP levels using ELISA. Statistics were performed by two-sample t-test or Wilcoxon rank-sum test. P &lt;0.05 considered significant. Results: IAIP treatment significantly reduced total injury size (t-PA alone 22±2% vs. t-PA+IAIP 13±3%; n=4-5/grp). Protection was also seen after permanent occlusion (vehicle 59.4±3.9% vs IAIP 39.5±5.9%; n=6-8/gp, p&lt;.05), showing efficacy of IAIP in two different models. IAIP treatment improved survival rates (82% with IAIP vs 63% with vehicle) and neurological scores compared to vehicle group (p&lt;0.05). Mean IAIP levels were significantly lower (stroke patients 134.4 ug/ml; n=51 vs controls 157.5 ug/ml; n=40), in parallel, increased IAIP-Histone complexes were seen in these patients. Similar changes were identified in mouse samples. Conclusions: Our results show that delayed IAIP treatment can significantly reduce cell death in both permanent ischemia and/or in combination with t-PA. IAIP could potentially represent an important, novel treatment for stroke. Our studies in combination with t-PA further strengths this clinical translatability and to design personalized dosing based on IAIP levels.

Mitochondrial DNA copy number instability in ERBB2-amplified breast cancer tumors.

Increase in the copy number of ERBB2, a Tyrosine Kinase Receptor (TKR) leads to the overexpression of oncogene product and consequently uncontrolled cell proliferation which has been reported in different aggressive cancers with mitochondrial malfunctions. Although, amplification of ERBB2 has been reported in different studies; however, the association between changes in mitochondrial DNA content and the ERBB2 gene copy number is poorly understood. The relative mitochondrial DNA content of breast cancer tumor tissues of 70 patients who were referred to Imam Khomeini Hospital Complex was determined using quantitative Real-time PCR. Multiplex ligation-dependent probe amplification (MLPA) was conducted to evaluate the ERBB2 gene copy number variation and finally, two-sample Wilcoxon rank-sum (Mann-Whitney) test was used to investigate the possible association between mitochondrial DNA (mtDNA) content and the ERBB2 gene amplification. Seventeen out of 70 breast cancer tumor tissues were found with ERBB2 gene amplification. Comparison of the mitochondrial DNA content of the aforementioned samples with the rest of the cases showed a significant decrease in the mitochondrial DNA content of the ERBB2-amplified samples (P=0.01). Our data provided evidence that ERBB2 have the potential to have a regulatory role over mitochondrial activity by controlling the mtDNA content.

The role of Mycobacterium tuberculosis antigen specific cytokines in determination of acid fast bacilli culture status in pulmonary tuberculosis patients co-infected with human immunodeficiency virus.

IntroductionThe interaction between Mycobacterium tuberculosis and HIV leads to rapid progression of tuberculosis (TB) and human immunodeficiency virus (HIV)-induced immunosuppression. Diagnosis of TB in these patients is more difficult due to its atypical presentations giving contradicting results. The overall aim of this study was to evaluate the ability of pro-inflammatory cytokine (Th1) and anti-inflammatory cytokine (Th2) to discriminate between culture-positive and -negative smear status in HIV-TB co-infected patients.MethodsIn a prospective cohort, a total of 86 study participants were recruited: 46 culture-negative and 40 culture-positive. Blood and sputum samples were collected from all participants. The blood was then analyzed using FACSCalibur flow cytometer to immunophenotype the cells and ELISA performed for cytokine profiles. Sputum samples were analyzed to determine smear status using direct microscopy and Lowenstein Jensen medium. Statistical analyses were performed using R software. Independent samples t-test was used to compare means between the two groups, while the medians were compared using two-sample Wilcoxon rank sum test. Pearson's Chi-square test was used to compare the proportion of male and female participants across the culture and AFB smear status. In order to determine the predictive power of Th1 and Th2 in discriminating Pulmonary Tuberculosis status (PTB) (culture status was used as a confirmatory test), binary logistic regression models were fitted for Th1 covariates [IFN-γ, TNF-α, IL-2 and IL-12(p70)] and Receiver Operating Characteristic (ROC) curves plotted.ResultsThe overall mean age of the participants was 39 years (SD=12), 42% being male. Although, lymphocytes counts were higher in culture-positive relative to culture-negative, the CD8, CD19, and CD16/CD56 were comparable in the two groups. The CD4 counts differed between the two groups (P=0.012). The Th1 showed a better discrimination between culture-positive and -negative PTB individuals; IFN-γ (P=0.001), TNF-α (P=0.001), IL-2 (P=0.001) and IL-12(p70) (P=0.016). The Th2 cytokines (IL-4, IL-6 and IL-10) were comparable between the culture-positive and -negative groups. However, when the combination of Th1 cytokines [IFN-γ, TNF-α, IL-2 and IL-12(p70)] was fitted in binary logistic regression models, the predictive power was high with area under curve (AUC) being 89.7% in discriminating PTB.ConclusionThis study provides evidence for the ability of a combination of Th1 cytokines in discriminating against culture-positive and culture-negative PTB.

High transverse skin incisions may reduce wound complications in obese women having cesarean sections: a pilot study

Objective: Women having cesarean section have a high risk of wound complications. Our objective was to determine whether high transverse skin incisions are associated with a reduced risk of cesarean wound complications in women with BMI greater than 40.Methods: A retrospective cohort study was undertaken of parturients ages 18–45 with BMI greater than 40 having high transverse skin incisions from January 2010 to April 2015 at a tertiary maternity hospital. Temporally matched controls had low transverse skin incisions along with a BMI greater than 40. The primary outcome, wound complication, was defined as any seroma, hematoma, dehiscence, or infection requiring opening and evacuating/debriding the wound. Secondary outcomes included rates of endometritis, number of hospital days, NICU admission, Apgar scores, birth weight, and gestational age at delivery. Analysis of outcomes was performed using two-sample t-test or Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables.Results: Thirty-two women had high transverse incisions and were temporally matched with 96 controls (low transverse incisions). The mean BMI was 49 for both groups. There was a trend toward reduced wound complications in those having high transverse skin incisions, but this did not reach statistical significance (15.63% versus 27.08%, p = .2379). Those having high transverse skin incisions had lower five minute median Apgar scores (8.0 versus 9.0, p = .0021), but no difference in umbilical artery pH values. The high transverse group also had increased NICU admissions (28.13% versus 5.21%, p = .0011), and early gestational age at delivery (36.8 versus 38.0, p = .0272).Conclusion: High transverse skin incisions may reduce the risk of wound complications in parturients with obesity. A study with more power should be considered.

A comparison of Numeric Pain Rating Scale (NPRS) and the Visual Analog Scale (VAS) in patients with chronic cancer-associated pain.

217 Background: Though numerical rating scales (NRS) are frequently used, a subset of patients do not understand the abstract nature on NRS and use quality descriptors of severity. We used a visual analog scale (VAS) using descriptors of “good day”, “average day” and “bad day” along a 10-cm line and compared it to a NRS in patients with cancer diagnosis and pain 1 month or longer. Methods: Eligible patients were verbally consented and completed the two scales. We asked patients thoughts about which they felt was the more appropriate scale to gauge their pain. The scales were compared by the distance from the extreme left of the line to the mark the patient placed on the VAS. Additional data included demographic and diagnosis information. The VAS and NRS were compared using two-sample t-tests or Wilcoxon rank-sum tests and Pearson’s chi-square or Fisher’s exact tests, as appropriate. The relationship between the numeric pain scale and the visual analog scale is described using Pearson’s correlation coefficient. Results: Full data was provided from 94 patient surveys who completed surveys. The mean age was 61 years old, 56.4% were female, and 78.0% had metastatic cancer. Numerous cancer types were reported with gastrointestinal and lung cancers being the most common (30.1% and 23.7%, respectively). The mean NRS rating reported by patients was 5.9 and for the VAS 4.9. Sixty patients (63.8%) preferred the NRS, 32 (34.0%) preferred the VAS, and 2 (2.1%) reported no preference. Patients who preferred the NRS reported a higher NRS rating than patients who preferred the VAS (mean NRS of 6.3 compared to 5.2, p = 0.0409). VAS ratings were higher among patients who preferred the NRS but the difference was not statistically significant (mean rating of 5.2 vs. 4.4, p = 0.1894). There were no differences in patient characteristics between the two groups. There was a moderate association between patients’ NRS and VAS ratings. The Pearson correlation coefficient was 0.653 (p &lt; 0.0001). Conclusions: Majority of patients of all ages and both genders prefer NRS. Future studies involving larger number of patients and adding a question about the reason of scale preference may provide better understanding for scale preference.

Voxel-by-voxel 4D flow MRI-based assessment of regional reverse flow in the aorta.

Complex and reverse flow in the aorta has been implicated in aneurysm development and stroke via retrograde embolization. To evaluate global and regional differences between standard 2D plane-based and volumetric voxel-based quantification of regional forward/reverse flow, and reverse flow fraction (RFF) in the aorta. Retrospective. In all, 35 subjects: 10 healthy controls (age: 57 ± 7 years, nine male), nine patients without aortic valve regurgitation (AR) (age: 63 ± 10 years, seven male), six patients with mild AR (age: 66 ± 6 years, five male), and 10 with moderate or severe AR (age: 60 ± 16 years, eight male). 4D flow MRI (3T and 1.5T) was employed to acquire 3D blood flow velocities with entire thoracic aorta in all subjects. Data analysis included standard 2D plane-based quantification of forward/reverse flow, and RFF-plane. In addition, a new semiautomatic workflow based on 3D segmentation and extraction of an aorta centerline was developed for voxel-by-voxel visualization (forward/reverse flow and RFF-voxel maps) and quantification of regional voxel-by-voxel forward/reverse flow in the entire thoracic aorta. Kruskal-Wallis tests were performed to test for differences between groups. A two-sample t-test or Wilcoxon rank sum test was used to compare voxel-based and plane-based results. Semiautomatic plane-based analysis showed excellent agreement with standard manual plane-based analysis for net flow and RFF-plane (RFF-plane: y = 0.99x-0.0, net flow: y = 1.00x-0.21, R > 0.99, P < 0.0001). Voxel-by-voxel maps demonstrated marked regional flow reversal in the ascending aorta in all patients and RFF-voxel was significantly increased (P < 0.001) compared to RFF-plane for all four groups, with the most pronounced differences for mild AR (18.0 ± 15.2% vs. 4.7 ± 5.4%). Voxel-based flow and RFF-voxel along the aorta showed areas with marked regional flow reversal (eg, vortex flow) compared to plane-based analysis. Voxel-based analysis demonstrated regional flow reversal that was not detected by plane-based analysis. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1276-1286.

Anterior Ankle Incision Complications

Category: Ankle Introduction/Purpose: The anterior incision is commonly used for total ankle replacement (TAR), and anterior approach ankle arthrodesis. Historically, the anterior incision has demonstrated a high incidence of complications, specifically with early generation TAR. Modern TAR designs have provided instrumentation and techniques that better respect the vulnerability of the anterior soft tissues, potentially reducing the incidence of anterior incision related complications. To our knowledge, anterior wound healing rates have not been evaluated in the context of modern anterior approach ankle arthrodesis and arthroplasty. The purpose of this study was to evaluate and compare the incisional healing and complications of the anterior approach for ankle arthrodesis and arthroplasty. Methods: This was an IRB-approved retrospective review of wound healing and complications among 304 patients who underwent primary TAR or ankle arthrodesis via the anterior approach between August 1, 2011 and August 31, 2015. Of the 304 patients, 191 (62.8%) underwent TAR and 113 (37.2%) underwent arthrodesis. The surgical approach, intraoperative soft tissue handling, and postoperative protocol for the first 30 days was the same between groups. Demographics, clinical characteristics of the wound healing, and neurovascular status were analyzed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher’s exact tests for categorical variables. To diminish the effect of selection bias, a subgroup analysis was performed comparing 91 TAR patients matched to an equal number of ankle arthrodesis patients based upon gender, age, diabetes, and smoking status. Results: The mean follow-up was 11.8 (range, 1.4 to 62.2) months. Overall, 19.7% of patients experienced delayed wound healing greater than 30 days, 15.8% required office-based wound care, 12.2% had a wound infection, 15.1% were prescribed antibiotics, 9.5% underwent wound debridement in the office, 4.6% had nerve injury, and 0.7% had a vascular injury. Implant revision or removal occurred in 10.5%, with a bias towards hardware removal in ankle arthrodesis. In the entire group of 304 patients, there was no difference between TAR and arthrodesis in risk of incisional wound challenges or complications nor neurovascular injury. In the subgroup matched for gender, age, diabetes status and smoking history there was no difference in outcomes. Conclusion: In this large cohort of 304 patients undergoing anterior approach to the ankle, postoperative complication rates were constant at all levels of analysis, with no difference seen between anterior ankle arthrodesis or ankle approach total ankle arthroplasty. This suggests that the primary determinates of complications were neither the demographic nor implant factors considered herein. The anterior ankle incision has a documented wound complication risk, regardless of the surgical procedure, and any modifiable risk factors remain elusive.

Nilotinib Plus Ruxolitinib Produces Anti-Fibrotic Effect

Myelofibrosis (MP) is characterized by stem cell-derived clonal myeloproliferation and a reactive cytokine-driven inflammatory bone marrow fibrosis (BMF). BMF plays an important role in MF symptom such us extramedullary hematopoiesis that implies hepatosplenomegaly and bone marrow failure with anemia and thrombocytopenia.Ruxolitinib is the only drug approved for MF therapy. It was associated with significant reduction in symptomatic splenomegaly and improved constitutional symptoms (Harrison et al. N Engl J Med. 2012 Mar 1;366(9):787-98; Verstovsek et al. Haematologica2015 Apr;100(4):479-88). Recently, Masarova and co-workers reported a case a MF patient who achieved a complete remission, including the complete disappearance of BMF (Masarova et al. Blood. 2016 Jun 20).In a previous work (Arenas et al. Blood Volume 122, Issue 21 (ASH Annual Meeting Abstrat)), we tried to identify the most promising synergistic drugs combinations for a Ruxolitinib. Nilotinib was selected between a set of synergistic drug. It is a BCR-ABL inhibitor but also is a potent PDGF-R inhibitor. Interestingly, different studies reported an anti-fibrotic activity in liver (Liu et al. J Hepatol. 2011 Sep;55(3):612-25.) and skin (Akhmetshina et al. FASEB J. 2008;22(7):2214-22). For these reasons we decided study the effect of the combination of Ruxolitinib and Nilotinib in BMF.To determine the ideal concentration of TGF-β to induce collagen mRNA expression in HS27a, we treated the culture of HSP27a with increasing concentration of TGF-β (0.625-10 ng/mL) during 24h. The best TGF-β concentration was 2ng/mL, with a fold change of 2.74 (SD=0.89) (p<0.05) relative to control without TGF (figure 1).Figure 1: Fold change in COL1 mRNA expression in HSP27a cell line relative to control without TGF-β. Two-sample Wilcoxon rank-sum (Mann-Whitney) test was performed. * p<0.05. R: Ruxolitinib. N: Nilotinib.To assess the anti-fibrotic activity of Ruxolitinib and Nilotinib individually, we preincubated the HSP27a cultures with 0.1 - 0.5 µM of Ruxolitinib or 0.5 - 1 µM of Nilotinib during 1 h. After that, we added TGF-β during 24h. Both 0.5 - 1 µM of Nilotinib reduced the mRNA expression of COL1 with a fold change of 0.75 (SD = 17.6) (p<0.05) and 0.78 (SD = 11.5) (p<0.05) respectively, relative to control with TGF-β but without drug (figure 2).Figure 2: Fold change in COL1 mRNA expression in HSP27a cell line relative to control with TGF-β but without drugs. Two-sample Wilcoxon rank-sum (Mann-Whitney) test was performed. * p<0.05. R: Ruxolitinib. N: Nilotinib.Finally, to verify if the combination of both drug had the capacity of reducing COL1 expression, we pretreated the HS27a cultures with 0.1 µM of Ruxolitinib and 1 µM of Nilotinib simultaneously. The expression of COL1 were 74 % (SD = 27.32%) (p<0.05) relatively to control with TGF-β but without drug (figure 2).In conclusion, Nilotinib have synergistic and anti-fibrotic activity individually, but also in combination with Ruxolitinib. For these reasons, the combined therapy Ruxolitinib-Nilotinib could be a promising therapy to MF and these results support a clinical trial of this combination in MF patients. [Display omitted] [Display omitted] DisclosuresMartínez-López:Novartis: Honoraria, Speakers Bureau.

Postpartum laparoscopic sterilisation: A role in South African healthcare?

Objective. To assess the advantages and feasibility of performing postpartum sterilisations laparoscopically in a public healthcare facility in South Africa (SA). Methods. Retrospective review of postpartum sterilisations between June 2012 and December 2013 at Worcester Hospital, Western Cape, SA. A total of 78 postpartum sterilisations were included in the study (open n =26, laparoscopic n =52). Data analysis was performed using means and medians with range and standard deviations, two-sample Wilcoxon rank sum test, two-sample t -test and χ 2 test. Results. It was considered preferable to perform laparoscopic sterilisations than the open procedure on patients with a higher body mass index (BMI). Duration of surgery was shorter in the laparoscopic group, especially in patients with BMI >30, and more patients were discharged on the same day as surgery in the laparoscopic group. There were fewer overall complications in the laparoscopic group (odds ratio 0.35, 95% confidence interval 0.08 - 1.43). Conclusion. It is feasible to perform postpartum sterilisations laparoscopically in a public healthcare facility in SA. Advantages of the procedure are clinically significant and in keeping with international literature. Future research should be undertaken regarding acceptability of the procedure in the study population, laparoscopic training and the improvement of provision of requested postpartum sterilisations in public hospitals.

Decreased Anti-Tumor Cytotoxic Immunity among Microsatellite-Stable Colon Cancers from African Americans.

Colorectal cancer is a leading cause of cancer related deaths in the U.S., with African-Americans having higher incidence and mortality rates than Caucasian-Americans. Recent studies have demonstrated that anti-tumor cytotoxic T lymphocytes provide protection to patients with colon cancer while patients deficient in these responses have significantly worse prognosis. To determine if differences in cytotoxic immunity might play a role in racial disparities in colorectal cancer 258 microsatellite-stable colon tumors were examined for infiltrating immune biomarkers via immunohistochemistry. Descriptive summary statistics were calculated using two-sample Wilcoxon rank sum tests, while linear regression models with log-transformed data were used to assess differences in race and Pearson and Spearman correlations were used to correlate different biomarkers. The association between different biomarkers was also assessed using linear regression after adjusting for covariates. No significant differences were observed in CD8+ (p = 0.83), CD57+ (p = 0.55), and IL-17-expressing (p = 0.63) cell numbers within the tumor samples tested. When infiltration of granzyme B+ cells was analyzed, however, a significant difference was observed, with African Americans having lower infiltration of cells expressing this cytotoxic marker than Caucasians (p<0.01). Analysis of infiltrating granzyme B+ cells at the invasive borders of the tumor revealed an even greater difference by race (p<0.001). Taken together, the data presented suggest differences in anti-tumor immune cytotoxicity may be a contributing factor in the racial disparities observed in colorectal cancer.

Serological evidence of acute rubella infection among under-fives in Mwanza: a threat to increasing rates of congenital rubella syndrome in Tanzania.

BackgroundControl of rubella infection is essential for preventing congenital rubella syndrome (CRS) and one of the important steps is to define a target population for vaccination. Therefore this study was done to determine serological evidence of acute rubella infection among under-fives in order to anticipate the magnitude of rubella virus transmission in Tanzania.MethodsA cross-sectional study involving children aged between 1 and 59 months was conducted between September and October 2014 before national rubella vaccination campaigns commenced. Rubella IgM antibodies were detected using commercial indirect enzyme-linked immunosorbent assay (ELISA). Data were analyzed using STATA version 11.ResultsA total of230 under-fives were enrolled, their median age was 14 (Interquartile range (IQR) 7–26) months. The overall seroprevalence of rubella IgM antibodies was 10.9 % (25/230) with two confirmed cases of CRS. Two-sample Wilcoxon rank-sum test showed that the median age of rubella IgM seropositive children was significantly higher than that of IgM seronegative children (39 IQR: 18-51months vs. 14 IQR: 7–24 months, P < 0.001). On multivariate logistic regression analysis increase in age (OR: 1.07, 95 % CI; 1.03–1.1, P < 0.001) and residing in rural areas (OR: 8.07, 95 % CI; 1.43–45.6, P = 0.018) were independently found to predict acute rubella infection among under-fives.ConclusionOur findings indicate that rubella virus is prevalent in our setting posing a risk of transmitting to childbearing aged women hence increasing the risk of CRS. Increasing prevalence of acute infection with age in under-fives indicates the protective role of maternal antibodies among infants. The sustained vaccination programme of under-fives as effective measure to control CRS should be emphasized in developing countries.

Idiopathic polyhydramnios: persistence across gestation and impact on pregnancy outcomes

PurposeTo investigate the likelihood of resolution of idiopathic polyhydramnios in pregnant women and compare outcomes between resolved and persistent cases. MethodsOne hundred and sixty-three women with idiopathic polyhydramnios who delivered at two medical centers during a 3 year period (January 2012–January 2015) were included in the study. Exclusion criteria included congenital fetal anomalies, maternal diabetes, isoimmunization, fetal infection, placental tumors or anomalies, and multiple gestation. Polyhydramnios was defined as SDP≥8cm or AFI≥24cm. Resolved cases were defined as those with AFI and/or SDP falling and remaining below 24cm and 8cm respectively. Pregnancy outcomes were compared between resolved and persistent cases. Two-sample t-test or Wilcoxon rank-sum test was used for continuous variables while chi-square test or Fisher's exact test was used for categorical measures. ResultsResolution was noted in 61 of 163 (37%) patients. There were no differences in maternal age, gravidity or parity between resolved and persistent cases. Mean gestational age at diagnosis of polyhydramnios and overall mean AFI were significantly lower in the cases that resolved (29.7±4.5 weeks vs 33.4±4.1 weeks, p<0.0001; 23.3±3.5cm vs 25.8 23.3±4.0cm, p=0.0002). Similar to AFI measurements, mean SDP was also lower in cases with resolution (p=0.002). There was no difference in induction rates, mode of delivery, amnioinfusion rates, meconium staining of amniotic fluid and fetal heart rate abnormalities influencing intrapartum management between the two groups. Induction of labor for fetal indication and rupture of membranes were significantly more common in the persistent group. Cesarean delivery for abnormal lie and fetal distress did not differ between the groups. There was an increased risk of macrosomia (>4000g) and preterm delivery (<37 weeks) in the persistent group (p<0.05). ConclusionsResolution rate was approximately 37% and more likely in cases diagnosed earlier in pregnancy and with lower mean amniotic fluid volume. Preterm delivery and macrosomia were more common in cases that persisted across gestation.

Sniff to see. Comparing sniffing position versus simple head extension position for glottic exposure - A prospective, randomized cross over study

Background: Traditional teaching dictates that direct laryngoscopy is best performed with the patient's head in the sniffing position. However, of late, many authors have challenged this concept. In a recent meta-analysis, based on studies involving 2759 participants researchers have found that sniffing position affords no added advantage over simple head extension. Our study highlights an important scientific fact overlooked in all previously done studies on the subject. Aim: We aimed to compare sniffing position and simple head extension position for ease of laryngoscopic intubation using an interval scale. Materials and Methods: A prospective single-blind crossover study of 200 patients, where glottic exposure in both positions was compared in the same patient using Cormack-Lehane (CL) grading and percentage of glottic opening (POGO) score. Intubation difficulty was compared using the intubation difficulty score. Results: In every study, CL grading, an ordinal scale, has been used for comparison of glottic exposure. In our set of patients, CL grading showed 'no change' in glottic exposure quality in 85% of the laryngoscopies. When we used POGO system of classification which is an interval scale, for the same laryngoscopies in the same patients, sniffing position improved exposure in 106 patients, whereas simple head extension position improved exposure in 76 patients. Only 18 patients showed no glottic exposure. Statistical Analysis: Two-sample Wilcoxon rank-sum (Mann-Whitney) test and Chi-square tests showed sniffing position to be significantly better position for glottic exposure and for ease of intubation. Conclusion: Sniffing position provides better glottis exposure and it is easier to intubate a patient in the sniffing position as compared to simple head extension position. Sniffing position should therefore be used as initial position when attempting intubation.

Inpatient Costs for Patients with Inflammatory Bowel Disease and Acute Pancreatitis

Introduction: Inflammatory bowel disease (IBD) is associated with an increased risk of acute pancreatitis. Hospitalizations for acute pancreatitis in patients with IBD are anticipated to be more economically complex. Our group examined differences in length of stay (LOS) and costs for patients with IBD hospitalized for acute pancreatitis and the general population. Methods: A retrospective study of the 2005-2011 National Inpatient Sample (NIS) was conducted. The NIS is the largest publicly available inpatient healthcare database in the US. The primary diagnoses of acute pancreatitis and co-diagnoses of IBD, ulcerative colitis (UC) and Crohn's disease (CD) were identified by ICD-9 codes. Continuous variables were reported as mean ± standard deviations and compared between IBD and controls by two-sample T-tests or Wilcoxon rank-sum tests, with normality assumptions based on the Shapiro-Wilk test. Categorical variables were analyzed by Chi-square tests or Fisher's exact tests. Propensity score matching method is widely used in observational studies to reduce selection bias. To fairly compare the outcomes of interest, we conducted 1:3 propensity score matching using a matching algorithm based on following: Age, gender, race, numbers of co-morbidities, procedure number, insurance, income quartiles, hospital bed size, hospital location, region and teaching status. Statistical analyses were performed on SAS 9.3 (Cary, NC), Windows platform. Results: There were a total of 4,291 hospitalizations of IBD patients with acute pancreatitis over the 7 year period and 379,627 hospitalizations of non-IBD patients with acute pancreatitis. The mean LOS of patients with acute pancreatitis and a co-diagnosis of IBD was 5.7 days versus 4.9 days for controls (p < 0.0001). Hospital costs were higher in patients with IBD compared to controls ($29,724.89 vs. $27,916.76 respectively, p < 0.0001). Survival rates were high in both groups, but slightly lower in patients with IBD (99.4% vs. 99.3% respectively). Higher LOS and costs were seen in patients with acute pancreatitis and a co-diagnosis of CD or UC (table 1). Rate of alcohol abuse was lower and drug abuse was higher in patients with a co-diagnosis of IBD (table 2). Conclusion: Our study suggests that cost and length of stay in patients with acute pancreatitis is influenced by a co-diagnosis of IBD. A co-diagnosis of CD or UC incurs a greater economic burden in patients with acute pancreatitis.Figure 1Figure 2

An In Vivo Evaluation of the Fit of Zirconium-Oxide Based, Ceramic Single Crowns with Vertical and Horizontal Finish Line Preparations.

Different types of tooth preparations influence the marginal precision of zirconium-oxide based ceramic single crowns. In this in vivo study, the marginal fits of zirconium-oxide based ceramic single crowns with vertical and horizontal finish lines were compared. Forty-six teeth were chosen in eight patients indicated for extraction for implant placement. CAD/CAM technology was used for the production of 46 zirconium-oxide-based ceramic single crowns: 23 teeth were prepared with vertical finishing lines, 23 with horizontal finishing lines. One operator accomplished all clinical procedures. The zirconia crowns were cemented with glass ionomer cement. The teeth were extracted 1 month later. Marginal gaps along vertical planes were measured for each crown, using a total of four landmarks for each tooth by means of a microscope at 50× magnification. On conclusion of microscopic assessment, ESEM evaluation was completed on all specimens. The comparison of the gap between the two types of preparation was performed with a nonparametric test (two-sample Wilcoxon rank-sum test) with a level of significance fixed at p < 0.05. All data were analyzed with STATA12. In the group with horizontal finish line preparations, the median value of the gap was 35.45 μm (Iqr, 0.33); for the vertical finish line group, the median value of the gap was 35.44 μm (Iqr, 0.40). The difference between the two groups was not statistically significant (two-sample Wilcoxon rank-sum test, p = 0.0872). Within the limitations of this study, the gaps of the zirconium-oxide-based ceramic CAD/CAM crowns with vertical and horizontal finish line preparations were not different.

A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder.

BackgroundCurrent standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS) is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD) have not yet been investigated.MethodsA parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA) over the left dorsolateral prefrontal cortex or sham stimulation.ResultsA nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney) test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham) in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures—correct responses, impulsivity and omission errors—were small. No adverse events resulting from stimulation were reported.ConclusionAccording to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population.Trial RegistrationClinicalTrials.gov NCT01968512