bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes Influences Peritoneal Morphology in Uremic Patients at the Initiation of Peritoneal Dialysis
Authors: Mizumasa Tohru , Hirakata Hideki , Kuroki Yusuke , Katafuchi Ritsuko , Yotsueda Hideki , Mitsuiki Koji , Nakashima Yutaka , Tsuruya Kazuhiko 
Published: September 2012

Background The peritoneum begins to undergo morphologic changes before the start of peritoneal dialysis (PD), particularly in diabetic patients. The present study was conducted to investigate the effects of diabetes on the peritoneum. Methods This study involved 17 patients who began receiving PD and had diabetes as an underlying disease (DM group), and 30 patients without diabetes who served as a control group (nonDM group). At the start of PD, the parietal peritoneum was sampled to assess submesothelial connective tissue thickness, number of capillaries and postcapillary venules, and indications of vasculopathy (grades 0 – 3). Results Submesothelial connective tissue thickness was significantly greater in the DM group than in the nonDM group ( p < 0.01). The number of capillaries was significantly greater in the DM group ( p < 0.01). Based on multivariate linear regression analysis, diabetes was identified as a significant independent variable of both submesothelial connective tissue thickness and number of capillaries ( p < 0.01). Conclusions In diabetic patients, morphologic changes of the peritoneum are marked at the start of PD.
Minilaparotomy Salvage of Malfunctioning Catheters in Peritoneal Dialysis
Authors: Li Jian-ri , Cheng Chi-hung , Chiu Kun-yuan , Cheng Chen-li , Yang Chi-rei , Ho Hao-chung , Ko Jiunn-liang , Ou Yen-chuan 
Published: September 2012

♦Background Catheter malfunction is a common and significant complication during peritoneal dialysis (PD). We developed a minilaparotomy procedure to rescue malfunctioning catheters and to prevent recurrence of malfunction. ♦Methods From 2006 to 2011, 11 patients receiving PD had a malfunctioning catheter. In all patients, a 2-cm incision, 5 cm caudally to the previous peritoneal entry site was used to correct the malfunctioning catheter, with concomitant fixation of the catheter to the peritoneum. ♦Results Catheter tip migration occurred in 7 patients, omental wrapping in 3, and blood clot obstruction in 1. The mean onset time to catheter malfunction was 197.5 days (range: 4 – 1270 days), and the mean operating time was 41 minutes (range: 35 – 56 minutes). There was no recurrence of catheter malfunction and no surgery-related peritonitis. ♦Conclusions Our minilaparotomy procedure is safe and feasible for the salvage of malfunctioning PD catheters.
Frequency and Microbiology of Peritonitis and Exit-Site Infection among Obese Peritoneal Dialysis Patients
Authors: Nessim Sharon J. , Komenda Paul , Rigatto Claudio , Verrelli Mauro , Sood Manish M. 
Published: September 2012

Background Data on obesity as a risk factor for peritonitis and catheter infections among peritoneal dialysis (PD) patients are limited. Furthermore, little is known about the microbiology of PD-related infections among patients with a high body mass index (BMI). Methods Using a cohort that included all adult patients residing in the province of Manitoba who received PD during the period 1997 – 2007, we studied the relationship between BMI and PD-related infections. After categorizing patients into quartiles of BMI, a multivariate Cox regression model was used to determine the independent relationship between BMI and peritonitis or exit-site infection (ESI). We also studied whether increasing BMI was associated with a propensity to infections with particular organisms. Results Among 990 PD patients, 938 (95%) had accurate BMI data available. Those 938 patients experienced 1338 peritonitis episodes and 1194 exit-site infections. In unadjusted analyses, patients in the highest BMI quartile (median: 33.5; interquartile range: 31.9 – 36.4) had an increased risk of peritonitis overall, and also an increased risk of peritonitis with gram-positive organisms and coagulase-negative Staphylococcus (CNS). After multivariate adjustment for age, sex, diabetes, cause of renal disease, Aboriginal race, PD modality, and S. aureus nasal carriage, the relationship between overall peritonitis risk and BMI disappeared, but the increased risk of CNS peritonitis among patients in the highest BMI quartile persisted (hazard ratio: 1.80; 95% confidence interval: 1.06 to 3.06; p = 0.03). There was no increased risk of ESI among patients in the highest BMI quartile on univariate analysis or after multivariate adjustment. Conclusions Among Canadian PD patients, obesity was not associated with an increased risk of peritonitis overall, but may be associated with a higher risk of CNS peritonitis.
Effects of Climatic Region on Peritonitis Risk, Microbiology, Treatment, and Outcomes: A Multicenter Registry Study
Authors: Cho Yeoungjee , Badve Sunil V. , Hawley Carmel M. , McDonald Stephen P. , Brown Fiona G. , Boudville Neil , Wiggins Kathryn J. , Bannister Kym M. , Clayton Philip , Johnson David W. 
Published: September 2012

♦Background The impact of climatic variations on peritoneal dialysis (PD)–related peritonitis has not been studied in detail. The aim of the current study was to determine whether various climatic zones influenced the probability of occurrence or the clinical outcomes of peritonitis. ♦Methods Using ANZDATA registry data, the study in cluded all Australian patients receiving PD between 1 October 2003 and 31 December 2008. Climatic regions were defined according to the Köppen classification. ♦Results The overall peritonitis rate was 0.59 episodes per patient–year. Most of the patients lived in Temperate regions (65%), with others residing in Subtropical (26%), Tropical (6%), and Other climatic regions (Desert, 0.6%; Grassland, 2.3%). Compared with patients in Temperate regions, those in Tropical regions demonstrated significantly higher overall peritonitis rates and a shorter time to a first peritonitis episode [adjusted hazard ratio: 1.15; 95% confidence interval (CI): 1.01 to 1.31]. Culture-negative peritonitis was significantly less likely in Tropical regions [adjusted odds ratio (OR): 0.42; 95% CI: 0.25 to 0.73]; its occurrence in Subtropical and Other regions was comparable to that in Temperate regions. Fungal peritonitis was independently associated with Tropical regions (OR: 2.18; 95% CI: 1.22 to 3.90) and Other regions (OR: 3.46; 95% CI: 1.73 to 6.91), where rates of antifungal prophylaxis were also lower. Outcomes after first peritonitis episodes were comparable in all groups. ♦Conclusions Tropical regions were associated with a higher overall peritonitis rate (including fungal peritonitis) and a shorter time to a first peritonitis episode. Augmented peritonitis prophylactic measures such as antifungal therapy and exit-site care should be considered in PD patients residing in Tropical climates.
Outcome of Lamivudine-Resistant Chronic Hepatitis B after up to 5 Years of Combination Therapy with Adefovir
Authors: Seto Wai-Kay , Liu Kevin , Fung James , Wong Danny Ka-Ho , Yuen John Chi-Hang , Hung Ivan Fan-Ngai , Lai Ching-Lung , Yuen Man-Fung 
Published: September 2012

Background There is a paucity of data on the long-term efficacy of combination lamivudine and adefovir therapy in patients with lamivudine-resistant chronic hepatitis B. Methods We determined the cumulative virological, serological and biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir for up to 5 years. Resistance profiles using a line probe assay were determined among patients with detectable viraemia. The significance of different baseline and on-treatment virological parameters was analysed. Results The median age and duration of follow-up were 45.1 years and 37.1 months, respectively. The cumulative rates of HBV DNA undetectability (<20 IU/ml), alanine aminotransferase normalization and hepatitis B e antigen seroconversion up to 5 years were 74.0%, 95.1% and 44.4%, respectively. One patient achieved hepatitis B surface antigen seroclearance. The 5-year cumulative resistance rate to adefovir was 10.2%. Among different baseline and on-treatment virological parameters, week 24 HBV DNA<200 IU/ml was associated with an increased chance of long-term virological suppression ( P<0.001, OR 13.89, 95% CI 3.90, 49.46). Primary non-response and high baseline viral titres were not useful in predicting long-term virological outcomes. The 5-year cumulative rate of serum creatinine elevation >0.5 mg/dl was 4.1%. Conclusions Combination lamivudine and adefovir therapy for up to 5 years achieved modest rates of virological suppression, but resistance developed in only 10.2% of patients. Week 24 HBV DNA<200 IU/ml was predictive of favourable long-term virological outcomes and could be used to assist treatment decisions on continuing lamivudine and adefovir or switching to more potent therapy.
Cytolytic Nanoparticles Attenuate HIV-1 Infectivity
Authors: Hood Joshua L , Jallouk Andrew P , Campbell Nancy , Ratner Lee , Wickline Samuel A 
Published: September 2012

Background We investigated whether cytolytic melittin peptides could inhibit HIV-1 infectivity when carried in a nanoparticle construct that might be used as a topical vaginal virucide. Free melittin and melittin-loaded nanoparticles were prepared and compared for cytotoxicity and their ability to inhibit infectivity by CXCR4 and CCR5 tropic HIV-1 strains. Methods TZM-bl reporter cells expressing luciferase under the control of the HIV-1 promoter were incubated with HIV-1 NLHX (CXCR4) or HIV-1 NLYU2 (CCR5) viral strains and different doses of soluble CD4 (positive control) or free melittin to determine infectivity and viability. Melittin-loaded nanoparticles were formulated and different doses tested against VK2 vaginal epithelial cells to determine cell viability. Based on VK2 viability, melittin nanoparticles were tested for prevention of CXCR4 and CCR5 tropic HIV-1 infectivity and viability of TZM-bl reporter cells. Low-speed centrifugation was used to compare the ability of blank non-melittin nanoparticles and melittin nanoparticles to capture CCR5 tropic HIV-1. Results As expected, the soluble CD4 positive control inhibited CXCR4 (50% inhibitory concentration [IC50] 3.7 μg/ml) and CCR5 (IC50 0.03 μg/ml) tropic HIV-1 infectivity. Free melittin doses <2 μM were not cytotoxic and were highly effective in reducing HIV-1 infectivity for both CXCR4 and CCR5 strains in TZM-bl reporter cells, while VK2 vaginal cell viability was adversely affected at all free melittin doses tested. However, VK2 cell viability was not affected at any dose of melittin-loaded nanoparticles. Melittin nanoparticles safely and significantly decreased CXCR4 (IC50 2.4 μM and IC90 6.9 μM) and CCR5 (IC50 3.6 μM and IC90 11.4 μM) strain infectivity of TZM-bl reporter cells. Furthermore, melittin nanoparticles captured more HIV-1 than blank nanoparticles. Conclusions These data illustrate the first proof-of- concept for therapeutic and safe nanoparticle-mediated inhibition of HIV-1 infectivity. Future investigations appear warranted to explore the antiviral prophylactic potential of melittin nanoparticles to capture, disrupt and prevent initial infection with HIV-1 or potentially other enveloped viruses.
Pharmacokinetics of Darunavir/Ritonavir in Asian HIV-1-Infected Children Aged ≥7 Years
Authors: Chokephaibulkit Kulkanya , Prasitsuebsai Wasana , Wittawatmongkol Orasri , Gorowara Meena , Phongsamart Wanatpreeya , Sophonphan Jiratchiya , Kerr Stephen J , Vanprapar Nirun , Puthanakit Thanyawee , Pasomsap Chayapa , Suwanlerk Tulathip , Sekar Vanitha , Burger David , Ananworanich Jintanat ,   the HIV-NAT 113 Pharmacokinetic Study Group
Published: September 2012

Background The Asian population, in general, has higher antiretroviral concentrations than those who are not Asian, but there are limited pharmacokinetic data for darunavir/ritonavir in Asian children. Methods Thai children aged ≥7 years and with body weight (BW)≥20 kg who were on darunavir/ritonavir for ≥2 weeks underwent 12-h pharmacokinetics with blood sampling before and at 1, 2, 4, 6, 8, 10 and 12 h post-dosing. Darunavir/ritonavir doses were 375/100 mg twice daily (BW 20 to <30 kg, n=12), 450/100 mg twice daily (BW 30 to <40 kg, n=2) or 600/100 mg twice daily (BW ≥40 kg, n=5). Ritonavir 100 mg soft gel capsules were used instead of solution. Results Of the 19 children, 8 were female, median age was 13 years (range 7-16) and median BW was 29.4 kg. The median duration of darunavir/ritonavir treatment was 11 months. The geometric mean values for darunavir were 60.3 hxmg/l for the area under the concentration–time curve at 0–12 h (AUC0–12), 8.3 mg/l for the maximum concentration (Cmax) and 3.1 for the concentration prior to the next dose (C12) with no differences between dosing groups. All had C12 above the protein binding adjusted 50% effective concentration (EC50) of protease inhibitor-resistant virus (0.55 mg/l). The darunavir pharmacokinetic parameters were similar to those in non-Asian individuals from the DELPHI study, in which 13 of 20 with BW<40 kg used 50 or 60 mg ritonavir boosting. Conclusions Thai children aged ≥7 years who were on standard darunavir dosing with 100 mg ritonavir boosting had adequate and comparable darunavir AUC0–12, Cmax and C12 to non-Asian children who mainly used lower doses of ritonavir boosting. A ritonavir boosting dose of 100 mg can be used for children weighing ≥20 kg, particularly when lower dose formulations are unavailable or if intolerant to the solution.
Monocyte Chemoattractant-1 as a Urinary Biomarker for the Diagnosis of Activity of Lupus Nephritis in Brazilian Patients
Authors: ROSA RENATA FERREIRA , TAKEI KIOKO , ARAÚJO NAFICE C. , LODUCA SÔNIA M.A. , SZAJUBOK JOSÉ C.M. , CHAHADE WILIAM H. 
Published: September 2012

Objective.Monocyte chemotactic protein (MCP-1), involved in the pathogenesis of lupus nephritis (LN), has recently been indicated as a new biomarker of kidney activity in systemic lupus erythematosus (SLE). Our aim was to assess urinary MCP-1 (uMCP-1) as a biomarker of renal activity in patients with SLE and to compare it to other disease activity markers, using the ELISA.Methods.Seventy-five female Brazilian patients with SLE and a control group participated in our study. Patients with SLE were distributed among 3 groups according to kidney involvement and classified according to disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, C3, C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The serum and uMCP-1 concentrations were measured by sandwich ELISA.Results.In the A-LN group (active lupus nephritis: SLE with kidney involvement), the concentration of uMCP-1 was significantly higher than in other groups. A cutoff point was established using the results of the control group to apply this test in the detection of LN. A-LN had a higher frequency of positive results for uMCP-1 in comparison to the other groups (p < 0.001). To detect disease activity in patients with LN, a new cutoff was determined based on the results of patients with SLE with kidney involvement. Setting specificity at 90%, the sensitivity of the test was 50%.Conclusion.The high specificity makes uMCP-1 a useful test as a predictor of kidney activity in SLE, especially when associated to other measures used in clinical practice.
Risk of Failure of a Clinical Drug Trial in Patients with Moderate to Severe Rheumatoid Arthritis
Authors: JAYASUNDARA KAVISHA S. , KEYSTONE EDWARD C. , PARKER JAYSON L. 
Published: September 2012

Objective.We conducted a systematic review to determine the risk of drug failure in clinical testing with patients with moderate to severe rheumatoid arthritis (RA).Methods.Therapies for RA were investigated by reviewing phase I to phase III studies conducted from December 1998 to March 2011. Clinical trial success rates were calculated and compared to industry standards. Trial failures were classified as either commercial or clinical failures. The exclusion criteria for drugs in this study: drugs that were started in phase I studies prior to January 1998 for this indication; or studies that enrolled patients who were methotrexate-naive and/or had failed biologic therapy.Results.A search in clinicaltrials.gov and approved drugs for the indication yielded a total of 69 drugs that met the study criteria. The cumulative success rate was determined to be 16%, which is equivalent to the industry standard of 16%. For each phase, the frequency of clinical failures exceeded commercial failures. Clinical studies equally comprised investigations of small molecules and biological agents, but biologics seemed to exhibit a higher success rate overall.Conclusion.Clinical trial risk in RA with the 84% failure rate reported here is at par with industry performance and phase II success rate seems to be highly predictive of phase III success.
Low Copy Number of the Fc-γ Receptor 3B GeneFCGR3BIs a Risk Factor for Primary Sjögren’s Syndrome
Authors: NOSSENT JOHANNES C. , RISCHMUELLER MAUREEN , LESTER SUE 
Published: September 2012

Objective.Immune complexes play an important role in the pathogenesis of primary Sjögren’s syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of theFCGR3Bgene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whetherFCGR3BCNV is a risk factor for pSS.Methods.This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162).FCGR3BCNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association withFCGR3Bcopy number (CN).Results.LowFCGR3BCN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, lowFCGR3BCN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031).Conclusion.We confirmed that, similarly to other systemic autoimmune diseases,FCGR3BCN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
Increasing Treatment in Early Rheumatoid Arthritis Is Not Determined by the Disease Activity Score But by Physician Global Assessment: Results from the CATCH Study
Authors: PYNE LONNIE , BYKERK VIVIAN P. , BOIRE GILLES , HARAOUI BOULOS , HITCHON CAROL , THORNE J. CARTER , KEYSTONE EDWARD C. , POPE JANET E. 
Published: September 2012

Objective.To determine the factors most strongly associated with an increase in therapy of early rheumatoid arthritis (ERA).Methods.Data from the Canadian Early Arthritis Cohort (CATCH) were included if the patient had ≥ 2 visits and baseline and 6 months data. A regression analysis was done to determine factors associated with treatment intensification.Results.Of 1145 patients with ERA, 790 met inclusion criteria; mean age was 53.4 years (SD 14.7), mean disease duration 6.1 months (SD 2.8), 75% were female, baseline Disease Activity Score-28 (DAS28) was 4.7 (SD 1.8) and 2.9 (SD 1.8) at 6 months for included patients. Univariate factors for intensifying treatment were physician global assessment (MDGA; OR 7.8 and OR 7.4 at 3 and 6 months, respectively, p < 0.0005), swollen joint count (SJC; OR 4.7 and OR 7.3 at 3 and 6 months, p < 0.0005), and DAS28 (OR 3.0 and OR 4.6 at 3 and 6 months, p < 0.0005). In the regression model only MDGA was strongly associated with treatment intensification (OR 1.5 and OR 1.2 at 3 and 6 months, p < 0.0005); DAS28 was not consistently predictive (OR 1.0, p = 0.987, and OR 1.2, p = 0.023, at 3 and 6 months). DAS28 was the reason for treatment intensification 2.3% of the time, compared to 51.7% for SJC, 49.9% for tender joint count, and 23.8% for MDGA. For the same SJC, larger joint involvement was more likely to influence treatment than small joints at 3 months (OR 1.4, p = 0.027).Conclusion.MDGA was strongly associated with an increase in treatment at 3 and 6 months in ERA, whereas DAS28 was not. Physicians rarely stated that DAS28 was the reason for increasing treatment.
Anti-DFS70/LEDGF Antibodies Are More Prevalent in Healthy Individuals Compared to Patients with Systemic Autoimmune Rheumatic Diseases
Authors: MAHLER MICHAEL , PARKER TODD , PEEBLES CAROL L. , ANDRADE LUIS E. , SWART ANDREAS , CARBONE YVETTE , FERGUSON DAVID J. , VILLALTA DANILO , BIZZARO NICOLA , HANLY JOHN G. , FRITZLER MARVIN J. 
Published: September 2012

Objective.Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD.Methods.Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium–derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti-DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies.Results.The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti-DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves’ disease, and 6.0% in Hashimoto’s thyroiditis. Of note, the prevalence of anti-DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity.Conclusion.“Monospecific” anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70.
Rehabilitation Strategies for Prolonged Recovery in Pediatric and Adolescent Concussion
Authors: Vidal Paul G. , Goodman Arlene M. , Colin Amy , Leddy John J. , Grady Matthew F. 
Published: September 2012

CME Educational Objectives

1.
Identify the time frame that distinguishes concussion with typical recovery trajectory vs. atypical prolonged recovery trajectory.

2.
Use directed physical examination to identify deficits that may be addressed by targeted rehabilitation strategies.

3.
Implement exercise strategies in the rehabilitation of concussion with atypical prolonged recovery outside of the typical return-to-play protocol.

Most pediatric and adolescent concussion patients will heal within 1 month. However, 10% to 20% of adolescent concussions will take longer than 1 month to heal. In this subgroup, prolonged symptoms might include vestibular system deficits, residual neck muscle whiplash injury, exercise intolerance/dysautonomia, and memory issues. At this stage in recovery, these problems respond better to “active rehabilitation” via specific targeted strategies rather than to strict rest. During follow-up office visits, a careful history and physical exam can elicit specific deficits and help customize a rehabilitation program to maximize recovery.