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1.
Johannes Brettschneider Hayrettin Tumani Ulrike Kiechle Rainer Muche Gayle Richards Vera Lehmensiek Albert C. Ludolph Markus Otto 《PloS one》2009,4(11)
Background
Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called “MRZ reaction” (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI.Methodology/Principal Findings
MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10).MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p = 0.04 and p = 0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54–94%), which could be further increased by combination with MRI (91%, 95%-CI: 59–99%).Conclusions/Significance
Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy. 相似文献2.
Makbule Senel Hayrettin Tumani Florian Lauda Stefan Presslauer Rehaneh Mojib-Yezdani Markus Otto Johannes Brettschneider 《PloS one》2014,9(4)
Background
Oligoclonal bands (OCB) are the most widely used CSF test to support the diagnosis of MS and to predict conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS). Since OCB tests are based on non-quantitative and difficult to standardise techniques, measurement of immunoglobulin kappa free light chains (KFLC) may represent an easier to use quantitative test.Methods
KFLC were measured in CSF and serum of 211 patients using ELISA. These include patients without any inflammatory central nervous system reaction (NIND, n = 77), MS (n = 20), viral CNS infections (V-CNS-I, n = 10), neuroborreliosis (NB, n = 17) and other bacterial CNS infections (B-CNS-I, n = 10). Furthermore a cohort of 77 patients with CIS, including 39 patients that remained CIS over follow-up of two years (CIS-CIS) and 38 patients that developed MS over the same follow-up time (CIS-MS).Results
CSF-serum ratio of KFLC (Q KFLC) was elevated in all patients with MS, 86.8% of patients with CIS-MS and 61.5% of patients with CIS-CIS. It was significantly elevated in CIS with presence of OCB (p<0.001). Q KFLC significantly correlated with other CSF variables such as CSF leukocyte count (p<0.001, R = 0.46), CSF CXCL13 levels (p<0.001, R = 0.64) and also intrathecal IgG synthesis (p<0.001, R = 0.74) as determined by nephelometry and quotient diagram. OCB were detected in 66.7% of CIS-CIS and in 92.1% of CIS-MS.Conclusions
Although the measurement of CSF KFLC is a rapid and quantitative easy to standardize tool, it is almost equal but not superior to OCB with regard to diagnostic sensitivity and specificity in patients with early MS. 相似文献3.
Georgina Arrambide Carmen Espejo Jennifer Yarden Ella Fire Larissa Spector Nir Dotan Avinoam Dukler Alex Rovira Xavier Montalban Mar Tintore 《PloS one》2013,8(3)
Background
Anti-glycan antibodies can be found in autoimmune diseases. IgM against glycan P63 was identified in clinically isolated syndromes (CIS) and included in gMS-Classifier2, an algorithm designed with the aim of identifying patients at risk of a second demyelinating attack.Objective
To determine the value of gMS-Classifier2 as an early and independent predictor of conversion to clinically definite multiple sclerosis (CDMS).Methods
Data were prospectively acquired from a CIS cohort. gMS-Classifier2 was determined in patients first seen between 1995 and 2007 with ≥ two 200 µL serum aliquots (N = 249). The primary endpoint was time to conversion to CDMS at two years, the factor tested was gMS-Classifier2 status (positive/negative) or units; other exploratory time points were 5 years and total time of follow-up.Results
Seventy-five patients (30.1%) were gMS-Classifier2 positive. Conversion to CDMS occurred in 31/75 (41.3%) of positive and 45/174 (25.9%) of negative patients (p = 0.017) at two years. Median time to CDMS was 37.8 months (95% CI 10.4–65.3) for positive and 83.9 months (95% CI 57.5–110.5) for negative patients. gMS-Classifier2 status predicted conversion to CDMS within two years of follow-up (HR = 1.8, 95% CI 1.1–2.8; p = 0.014). gMS-Classifier2 units were also independent predictors when tested with either Barkhof criteria and OCB (HR = 1.2, CI 1.0–1.5, p = 0.020) or with T2 lesions and OCB (HR = 1.3, CI 1.1–1.5, p = 0.008). Similar results were obtained at 5 years of follow-up. Discrimination measures showed a significant change in the area under the curve (ΔAUC) when adding gMS-Classifier2 to a model with either Barkhof criteria (ΔAUC 0.0415, p = 0.012) or number of T2 lesions (ΔAUC 0.0467, p = 0.009), but not when OCB were added to these models.Conclusions
gMS-Classifier2 is an independent predictor of early conversion to CDMS and could be of clinical relevance, particularly in cases in which OCB are not available. 相似文献4.
Background
B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR). Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic resonance imaging (MRI) findings in patients with first MS diagnosis.Methods/Results
MRZR was determined in 68 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting MS (RRMS). Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI) and cMRI combined with spinal MRI (sMRI). Measles virus AI correlated significantly with T2 lesion load on cMRI (p = 0.0312, Mann-Whitney U test) and the sum of lesions on cMRI and sMRI (p = 0.0413). Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p = 0.2893).Conclusion
The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters.Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS. 相似文献5.
《PloS one》2013,8(6)
Objective
to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods
We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results
HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1–2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09–1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB− (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10−7) outside the HLA region (65 Mb).Discussion
genetic factors predispose to the development of OCB. 相似文献6.
Nele Claes Tessa Dhaeze Judith Fraussen Bieke Broux Bart Van Wijmeersch Piet Stinissen Raymond Hupperts Niels Hellings Veerle Somers 《PloS one》2014,9(10)
Background and objective
The long term effects of fingolimod, an oral treatment for relapsing-remitting (RR) multiple sclerosis (MS), on blood circulating B and T cell subtypes in MS patients are not completely understood. This study describes for the first time the longitudinal effects of fingolimod treatment on B and T cell subtypes. Furthermore, expression of surface molecules involved in antigen presentation and costimulation during fingolimod treatment are assessed in MS patients in a 12 month follow-up study.Methods
Using flow cytometry, B and T cell subtypes, and their expression of antigen presentation, costimulation and migration markers were measured during a 12 month follow-up in the peripheral blood of MS patients. Data of fingolimod-treated MS patients (n = 49) were compared to those from treatment-naive (n = 47) and interferon-treated (n = 27) MS patients.Results
In the B cell population, we observed a decrease in the proportion of non class-switched and class-switched memory B cells (p<0.001), both implicated in MS pathogenesis, while the proportion of naive B cells was increased during fingolimod treatment in the peripheral blood (PB) of MS patients (p<0.05). The remaining T cell population, in contrast, showed elevated proportions of memory conventional and regulatory T cells (p<0.01) and declined proportions of naive conventional and regulatory cells (p<0.05). These naive T cell subtypes are main drivers of MS pathogenesis. B cell expression of CD80 and CD86 and programmed death (PD) -1 expression on circulating follicular helper T cells was increased during fingolimod follow-up (p<0.05) pointing to a potentially compensatory mechanism of the remaining circulating lymphocyte subtypes that could provide additional help during normal immune responses.Conclusions
MS patients treated with fingolimod showed a change in PB lymphocyte subtype proportions and expression of functional molecules on T and B cells, suggesting an association with the therapeutic efficacy of fingolimod. 相似文献7.
Stephanie M. Topp Julien M. Chipukuma Mark Giganti Linah K. Mwango Like M. Chiko Bushimbwa Tambatamba-Chapula Chibesa S. Wamulume Stewart Reid 《PloS one》2010,5(7)
Introduction
HIV care and treatment services are primarily delivered in vertical antiretroviral (ART) clinics in sub-Saharan Africa but there have been concerns over the impact on existing primary health care services. This paper presents results from a feasibility study of a fully integrated model of HIV and non-HIV outpatient services in two urban Lusaka clinics.Methods
Integration involved three key modifications: i) amalgamation of space and patient flow; ii) standardization of medical records and iii) introduction of routine provider initiated testing and counseling (PITC). Assessment of feasibility included monitoring rates of HIV case-finding and referral to care, measuring median waiting and consultation times and assessing adherence to clinical care protocols for HIV and non-HIV outpatients. Qualitative data on patient/provider perceptions was also collected.Findings
Provider and patient interviews at both sites indicated broad acceptability of the model and highlighted a perceived reduction in stigma associated with integrated HIV services. Over six months in Clinic 1, PITC was provided to 2760 patients; 1485 (53%) accepted testing, 192 (13%) were HIV positive and 80 (42%) enrolled. Median OPD patient-provider contact time increased 55% (6.9 vs. 10.7 minutes; p<0.001) and decreased 1% for ART patients (27.9 vs. 27.7 minutes; p = 0.94). Median waiting times increased by 36 (p<0.001) and 23 minutes (p<0.001) for ART and OPD patients respectively. In Clinic 2, PITC was offered to 1510 patients, with 882 (58%) accepting testing, 208 (24%) HIV positive and 121 (58%) enrolled. Median OPD patient-provider contact time increased 110% (6.1 vs. 12.8 minutes; p<0.001) and decreased for ART patients by 23% (23 vs. 17.7 minutes; p<0.001). Median waiting times increased by 47 (p<0.001) and 34 minutes (p<0.001) for ART and OPD patients, respectively.Conclusions
Integrating vertical ART and OPD services is feasible in the low-resource and high HIV-prevalence setting of Lusaka, Zambia. Integration enabled shared use of space and staffing that resulted in increased HIV case finding, a reduction in stigma associated with vertical ART services but resulted in an overall increase in patient waiting times. Further research is urgently required to assess long-term clinical outcomes and cost effectiveness in order to evaluate scalability and generalizability. 相似文献8.
Elisabeth M. van der Elst Haile Selassie Okuku Phellister Nakamya Allan Muhaari Alun Davies R. Scott McClelland Matthew A. Price Adrian D. Smith Susan M. Graham Eduard J. Sanders 《PloS one》2009,4(5)
Background
Audio computer-assisted self-interview (ACASI) may elicit more frequent reporting of socially sensitive behaviours than face-to-face (FtF)-interview. However, no study compared responses to both methods in female and male sex workers (FSW; MSW) in Africa.Methodology/Principal Findings
We sequentially enrolled adults recruited for an HIV-1 intervention trial into a comparative study of ACASI and FtF-interview, in a clinic near Mombasa, Kenya. Feasibility and acceptability of ACASI, and a comparative analysis of enrolment responses between ACASI and FtF on an identical risk assessment questionnaire were evaluated. In total, 139 women and 259 men, 81% of eligible cohort participants, completed both interviews. ACASI captured a higher median number of regular (2 vs. 1, p<0.001, both genders) and casual partners in the last week (3 vs. 2, p = 0.04 in women; 2 vs. 1, p<0.001 in men). Group sex (21.6 vs. 13.5%, p<0.001, in men), intravenous drug use (IDU; 10.8 vs. 2.3%, p<0.001 in men; 4.4 vs. 0%, p = 0.03 in women), and rape (8.9 vs. 3.9%, p = 0.002, in men) were reported more frequently in ACASI. A surprisingly high number of women reported in ACASI that they had paid for sex (49.3 vs. 5.8%, p<0.001). Behaviours for recruitment (i.e. anal sex, sex work, sex between males) were reported less frequently in ACASI. The majority of women (79.2%) and men (69.7%) felt that answers given in ACASI were more honest. Volunteers who were not able to take ACASI (84 men, and 37 women) mostly lacked reading skills.Conclusions/Significance
About 1 in 5 cohort participants was not able to complete ACASI, mostly for lack of reading skills. Participants who completed ACASI were more likely to report IDU, rape, group sex, and payment for sex by women than when asked in FtF interview. ACASI appears to be a useful tool for high risk behaviour assessments in the African context. 相似文献9.
Christine Johnston Jackson Orem Fred Okuku Mary Kalinaki Misty Saracino Edward Katongole-Mbidde Merle Sande Allan Ronald Keith McAdam Meei-Li Huang Linda Drolette Stacy Selke Anna Wald Lawrence Corey Corey Casper 《PloS one》2009,4(1)
Introduction
Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.Methods
Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).Results
78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7–6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7–9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0–2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8–5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).Conclusions
HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda. 相似文献10.
Hanne Marie B?e Lunde Tommy F. Aae William Indrev?g Jan Aarseth Bj?rn Bjorvatn Kjell-Morten Myhr Lars B? 《PloS one》2012,7(11)
Background
Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). Sleep may be influenced by MS-related symptoms and adverse effects from immunotherapy and symptomatic medications. We aimed to study the prevalence of poor sleep and the influence of socio-demographic and clinical factors on sleep quality in MS- patients.Methods
A total of 90 MS patients and 108 sex-and age- matched controls were included in a questionnaire survey. Sleep complaints were evaluated by Pittsburgh Sleep Quality Index (PSQI) and a global PSQI score was used to separate good sleepers (≤5) from poor sleepers (>5). Excessive daytime sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain, depression, fatigue and MS-specific health related quality of life were registered. Results were compared between patients and controls and between good and poor sleepers among MS patients.Results
MS patients reported a higher mean global PSQI score than controls (8.6 vs. 6.3, p = 0.001), and 67.1% of the MS patients compared to 43.9% of the controls (p = 0.002) were poor sleepers. Pain (p = 0.02), fatigue (p = 0.001), depression (p = 0.01) and female gender (p = 0.04) were associated with sleep disturbance. Multivariate analyses showed that female gender (p = 0.02), use of immunotherapy (p = 005) and a high psychological burden of MS (p = 0.001) were associated with poor sleep among MS patients.Conclusions
Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS. 相似文献11.
Objectives
The Liver X receptors (LXRs), Liver X receptor A (LXRA) and Liver X receptor B (LXRB), regulate lipid metabolism and antimicrobial response. LXRs have a crucial role in the control of Mycobacterium tuberculosis (M.tb). Lacking LXRs mice is more susceptibility to infection M.tb, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRs and risk of tuberculosis.Methods
We sequenced the LXRs genes to detect SNPs and to examine genotypic frequencies in 600 patients and 620 healthy controls to investigate for associations with tuberculosis (TB) in the Chinese Han population. DNA re-sequencing revealed eight common variants in the LXRs genes.Results
The G allele of rs1449627 and the T allele of rs1405655 demonstrated an increased risk of developing TB (p<0.001, p = 0.002), and the T allele of rs3758673, the T allele of rs2279238, and the C allele of rs1449626 in LXRA and the C allele of rs17373080, the G allele of rs2248949, and the C allele of rs1052677 in LXRB were protective against TB patients compared to healthy controls (p = 0.0002, p = 0.006, p<0.001, p = 0.004, p = 0.008, p = 0.003, respectively). All SNP genotypes were significantly associated with TB. An estimation of the frequencies of haplotypes revealed two potential risk haplotypes,GGCG in LXRB (p = 0.004,) and TTCG in LXRA (p<0.001, p = 0.004). Moreover, three protective haplotypes, TTAT and CCAT in LXRA and CATC in LXRB, were significantly “protective” (p = 0.008, p<0.001, p = 0.031) for TB. Furthermore, we determined that the LXRs SNPs were nominally associated with the clinical pattern of disease.Conclusions
Our study data supported that LXRs play a fundamental role in the genetic susceptibility to TB and to different clinical patterns of disease. Thus, further investigation is required in larger populations and in additional areas. 相似文献12.
Ligia Petrica Adrian Vlad Gheorghe Gluhovschi Florica Gadalean Victor Dumitrascu Cristina Gluhovschi Silvia Velciov Flaviu Bob Daliborca Vlad Roxana Popescu Oana Milas Sorin Ursoniu 《PloS one》2014,9(11)
Background
There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor.Materials and Methods
Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric) and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried.Results
Urinary alpha1-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R2 = 0.269; p<0.001; R2 = 0.125; p<0.001), nephrinuria (R2 = 0.529; p<0.001; R2 = 0.203; p<0.001), urinary vascular endothelial growth factor (R2 = 0.709; p<0.001; R2 = 0.360; p<0.001), urinary advanced glycation end-products (R2 = 0.578; p<0.001; R2 = 0.405; p<0.001), serum cystatin C (R2 = 0.130; p<0.001; R2 = 0.128; p<0.001), and glomerular filtration rate (R2 = 0.167; p<0.001; R2 = 0.166; p<0.001); nephrinuria and urinary vascular endothelial growth factor correlated with urinary albumin:creatinine ratio (R2 = 0.498; p<0.001; R2 = 0.227; p<0.001), urinary advanced glycation end-products (R2 = 0.251; p<0.001; R2 = 0.308; p<0.001), serum cystatin C (R2 = 0.157; p<0.001; R2 = 0.226; p<0.001), and glomerular filtration rate (R2 = 0.087; p = 0.007; R2 = 0.218; p<0.001).Conclusions
In Type 2 diabetes mellitus there is an association of proximal tubule dysfunction with podocyte damage biomarkers, even in the normoalbuminuria stage. This observation suggests a potential role of the proximal tubule in urinary nephrin and urinary vascular endothelial growth factor processing in early diabetic nephropathy, a fact which could be related to advanced glycation end-products intervention. Podocyte damage and proximal tubule dysfunction biomarkers could be validated as a practical approach to the diagnosis of early diabetic nephropathy by further studies on larger cohorts. 相似文献13.
Kathleen F. Brookfield Michael C. Cheung Relin Yang Margaret M. Byrne Leonidas G. Koniaris 《PloS one》2009,4(1)
Objective
Patient chances for cure and palliation for a variety of malignancies may be greatly affected by the care provided by a treating hospital. We sought to determine the effect of volume and teaching status on patient outcomes for five gynecologic malignancies: endometrial, cervical, ovarian and vulvar carcinoma and uterine sarcoma.Methods
The Florida Cancer Data System dataset was queried for all patients undergoing treatment for gynecologic cancers from 1990–2000.Results
Overall, 48,981 patients with gynecologic malignancies were identified. Endometrial tumors were the most common, representing 43.2% of the entire cohort, followed by ovarian cancer (30.9%), cervical cancer (20.8%), vulvar cancer (4.6%), and uterine sarcoma (0.5%). By univariate analysis, although patients treated at high volume centers (HVC) were significantly younger, they benefited from an improved short-term (30-day and/or 90-day) survival for cervical, ovarian and endometrial cancers. Multivariate analysis (MVA), however, failed to demonstrate significant survival benefit for gynecologic cancer patients treated at teaching facilities (TF) or HVC. Significant prognostic factors at presentation by MVA were age over 65 (HR = 2.6, p<0.01), African-American race (HR = 1.36, p<0.01), and advanced stage (regional HR = 2.08, p<0.01; advanced HR = 3.82, p<0.01, respectively). Surgery and use of chemotherapy were each significantly associated with improved survival.Conclusion
No difference in patient survival was observed for any gynecologic malignancy based upon treating hospital teaching or volume status. Although instances of improved outcomes may occur, overall further regionalization would not appear to significantly improve patient survival. 相似文献14.
Lo?c Bière Erwan Donal Gwenola Terrien Ga?lle Kervio Serge Willoteaux Alain Furber Fabrice Prunier 《PloS one》2014,9(1)
Objectives
We assessed the value of speckle tracking imaging performed early after a first ST-segment elevation myocardial infarction (STEMI) in order to predict infarct size and functional recovery at 3-month follow-up.Methods
44 patients with STEMI who underwent revascularization within 12 h of symptom onset were prospectively enrolled. Echocardiography was performed 3.9±1.2 days after myocardial reperfusion, assessing circumferential (CGS), radial (RGS), and longitudinal global (GLS) strains. Late gadolinium-enhanced cardiac magnetic imaging (CMR), for assessing cardiac function, infarct size, and microvascular obstruction (MVO), was conducted 5.6±2.5 days and 99.4±4.6 days after myocardial reperfusion.Results
GLS was evaluable in 97% of the patients, while CGS and RGS could be assessed in 85%. Infarct size significantly correlated with GLS (R = 0.601, p<0.001), RGS (R = −0.405, p = 0.010), CGS (R = 0.526, p = 0.001), ejection fraction (R = −0.699, p<0.001), wall motion score index (WMSI) (R = 0.539, p = 0.001), and left atrial volume (R = 0.510, p<0.001). Baseline ejection fraction and GLS were independent predictors of 3-month infarct size. MVO mass significantly correlated with GLS (R = 0.376, p = 0.010), WMSI (R = 0.387, p = 0.011), and ejection fraction (R = −0.389, p = 0.011). In multivariate analysis, GLS was the only independent predictor of MVO mass (p = 0.015). Longitudinal strain >−6.0% within the infarcted area exhibited 96% specificity and 61% sensitivity for predicting the persistence of akinesia (≥3 segments) at 3-month follow-up.Conclusions
Speckle-tracking strain imaging performed early after a STEMI is easy-to-use as a marker for persistent akinetic territories at 3 months. In addition, GLS correlated significantly with MVO and final infarct size, both parameters being relevant post-MI prognostic factors, usually obtained via CMR. 相似文献15.
Soren Snitker Keming Xie Kathleen A. Ryan Daozhan Yu Alan R. Shuldiner Braxton D. Mitchell Da-Wei Gong 《PloS one》2013,8(6)
Background
Matrix metalloproteinase-9 (MMP-9) is an emerging biomarker for several disease conditions, where white blood cell (WBC) count is also elevated. In this study, we examined the relationship between MMP-9 and WBC levels in apparently healthy smoking and non-smoking human subjects.Methods
We conducted a cross-sectional study to assess the relationship of serum MMP-9 with WBC in 383 men and 356 women. Next, we divided the male population (women do not smoke in this population) into three groups: never (n = 243), current (n = 76) and former (n = 64) smokers and compared the group differences in MMP-9 and WBC levels and their correlations within each group.Results
Circulating MMP-9 and WBC count are significantly correlated in men (R2 = 0.13, p<0.001) and women (R2 = 0.19, p<0.001). After stratification by smoking status, MMP-9 level was significantly higher in current smokers (mean ± SE; 663.3±43.4 ng/ml), compared to never (529.7±20.6) and former smokers (568±39.3). WBC count was changed in a similar pattern. Meanwhile, the relationship became stronger in current smokers with increased correlation coefficient of r = 0.45 or R2 = 0.21 (p<0.001) and steeper slope of ß = 1.16±0.30 (p<0.001) in current smokers, compared to r = 0.26 or R2 = 0.07 (p<0.001) and ß = 0.34±0.10 (p<0.001) in never smokers.Conclusions
WBC count accounts for 13% and 19% of MMP-9 variance in men and women, respectively. In non-smoking men, WBC count accounts for 7% of MMP-9 variance, but in smoking subjects, it accounts for up to 21% of MMP-9 variance. Thus, we have discovered a previously unrecognized correlation between the circulating MMP-9 and WBC levels in humans. 相似文献16.
Luc Lorgis Daniel Moreau Laurent Mock Bernadette Daumas Daniel Potard Claude Touzery Yves Cottin Marianne Zeller 《PloS one》2012,7(10)
Aim
We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV) and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP) in patients with acute myocardial infarction (MI).Methods and Results
The mean of standard deviation of RR intervals (SDNN), the percentage of RR intervals with >50 ms variation (pNN50), square root of mean squared differences of successive RR intervals (rMSSD), and frequency domain parameters (total power (TP), high frequency and low frequency power ratio (LF/HF)) were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche) was measured from blood samples taken on admission. The median (IQR) Nt-proBNP level was 681(159–2432) pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = −0.19, p<0.001), LF/HF (r = −0.37, p<0.001), and LF (r = −0.29, p<0.001) but not HF (r = −0.043, p = 0.172). Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE) = −0.065(0.015), p<0.001)), even after adjustment for confounders.Conclusions
In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI. 相似文献17.
Hyeon Hui Kang Ji Young Kang Jick Hwan Ha Jongmin Lee Sung Kyoung Kim Hwa Sik Moon Sang Haak Lee 《PloS one》2014,9(12)
Background
Obesity is a major risk factor for the development of obstructive sleep apnea (OSA). Although clinical and epidemiological studies have shown that OSA and obesity are strongly associated, few Asian studies have examined the associations between anthropometric obesity indices and OSA, especially in the Korean population. The purpose of this study was to evaluate the influence of anthropometric obesity indices on OSA in a Korean population.Methods
Anthropometric indices, including neck circumference, waist circumference, and body mass index, were assessed in 383 consecutive subjects with suspected OSA.Results
Of the 383 subjects assessed, 316 (82.5%) were diagnosed with OSA. Neck circumference (r = 0.518), waist circumference (r = 0.570), and body mass index (r = 0.512) were correlated with the apnea-hypopnea index (p<0.001, for all). After adjusting for age, sex, alcohol consumption, and smoking, a logistic regression model showed that neck circumference [odds ratio (OR), 1.414; p<0.001)], waist circumference (OR, 1.114; p<0.001), and body mass index (OR, 1.364; p<0.001) were associated with OSA. The linear regression model showed that neck circumference (β = 3.748, p<0.001), waist circumference (β = 1.272, p<0.001), and body mass index (β = 3.082, p<0.001) were associated with apnea-hypopnea index. The cut-off values for predicting OSA were determined as 34.5 cm for neck circumference, 76.5 cm for waist circumference, and 23.05 kg/m2 for body mass index for females, and 38.75 cm for neck circumference, 88.5 cm for waist circumference, and 24.95 kg/m2 for body mass index for males.Conclusion
Increased anthropometric indices were significantly associated with the presence and severity of OSA in a Korean population. In addition, this study demonstrated the cut-off values for body mass index, waist circumference, and neck circumference for increased OSA risk. 相似文献18.
Tuula K. Outinen Laura Tervo Satu M?kel? Reetta Huttunen Niina M?enp?? Heini Huhtala Antti Vaheri Jukka Mustonen Janne Aittoniemi 《PloS one》2013,8(8)
Objectives
Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to β3-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR) levels were evaluated as a predictor of severe Puumala hantavirus (PUUV) infection and as a possible factor involved in the pathogenesis of the disease.Design
A single-centre prospective cohort study.Subjects and Methods
Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA).Results
The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0–18.2 ng/ml vs. median 4.7 ng/ml, range 2.4–12.2 ng/ml, P<0.001). The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r = 0.475, p<0.001), maximum plasma creatinine concentration (r = 0.378, p<0.001), change in weight during the hospitalization (r = 0.406, p<0.001) and the length of hospitalization (r = 0.325, p = 0.001), and an inverse correlation with minimum platelet count (r = −0.325, p = 0.001) and minimum hematocrit (r = −0.369, p<0.001).Conclusion
Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates β3-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease. 相似文献19.
Background
Oral HPV infections detected six-months apart were compared to those detected bi-weekly, in an HIV-positive cohort, during the intervening months to elucidate systematic biases introduced into natural history studies by sampling interval.Methods
Fourteen consecutive oral rinse samples were collected every two weeks for six months from an HIV-positive cohort (n = 112) and evaluated for the presence of 37 HPV types. The cumulative probability of type-specific HPV detection at visits 1 through 14 was determined as a function of infection categorized at visits 1 and 14 as persistent, newly detected, cleared or absent. Transition models were used to evaluate the effect of HPV viral load (measured by RT-PCR for HPV 16, 18, 31, 33, 35) on infection persistence.Results
The average point prevalence of oral HPV infection was similar at two-week and six-month sampling intervals (45% vs. 47%, p = 0.52), but cumulative prevalence was higher with the former (82% vs. 53%, p<0.001) as was the cumulative prevalence of type-specific infections (9.3% vs 3.8%, p<0.0001). Type-specific infections persistent under a six-month sampling interval had a high probability (0.93, 95%CI 0.83–0.98) of detection at 50% or more of the intervening visits and infections that were absent had a high probability (0.94, 95% CI 0.93–0.95) of no interval detection. The odds of detection at any visit significantly increased for each unit increase in HPV viral load at the previous visit.Conclusions
Six-month sampling is appropriate to model factors associated with type-specific oral HPV infection persistence but may misclassify HPV-exposed individuals as unexposed. 相似文献20.
Roberto Muga Arantza Sanvisens Daniel Fuster Jordi Tor Elisenda Martínez Santiago Pérez-Hoyos Alvaro Mu?oz 《PloS one》2012,7(10)