Univariate Cox Proportional-hazards Regression Analysis Research Articles

Identification of the Novel Methylated Genes' Signature to Predict Prognosis in INRG High-Risk Neuroblastomas.

Background Neuroblastomas are the most frequent extracranial pediatric solid tumors. The prognosis of children with high-risk neuroblastomas has remained poor in the past decade. A powerful signature is required to identify factors associated with prognosis and improved treatment selection. Here, we identified a strong methylation signature that favored the earlier diagnosis of neuroblastoma in patients. Methods Gene methylation (GM) data of neuroblastoma patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were analyzed using a multivariate Cox regression analysis (MCRA) and univariate Cox proportional hazards regression analysis (UCPHRA). Results The methylated genes' signature consisting of eight genes (NBEA, DDX28, TMED8, LOC151174, EFNB2, GHRHR, MIMT1, and SLC29A3) was selected. The signature divided patients into low- and high-risk categories, with statistically significant survival rates (median survival time: 25.08 vs. >128.80 months, log-rank test, P < 0.001) in the training group, and the validation of the signature's risk stratification ability was carried out in the test group (log-rank test, P < 0.01, median survival time: 30.48 vs. >120.36 months). The methylated genes' signature was found to be an independent predictive factor for neuroblastoma by MCRA. Functional enrichment analysis suggested that these methylated genes were related to butanoate metabolism, beta-alanine metabolism, and glutamate metabolism, all playing different significant roles in the process of energy metabolism in neuroblastomas. Conclusions The set of eight methylated genes could be used as a new predictive and prognostic signature for patients with INRG high-risk neuroblastomas, thus assisting in treatment, drug development, and predicting survival.

Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study

BackgroundLarge outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions.MethodsWe undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation.ResultsOf 389 cases, median presentation time was 6 days (IQR 4–10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13–17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0–4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5–12 and 13–17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5–9 days and 20–60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41–95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time.ConclusionsWhilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.

Bleeding risk of cerebral cavernous malformations in patients on β-blocker medication: a cohort study.

Cerebral cavernous malformations (CCMs) are frequently diagnosed vascular malformations of the brain. Although most CCMs are asymptomatic, some can be responsible for intracerebral hemorrhage or seizures. In selected cases, microsurgical resection is the preferred treatment option. Treatment with the unselective β-blocker propranolol has been presumed to stabilize and eventually lead to CCM size regression in a limited number of published case series; however, the underlying mechanism and evidence for this effect remain unclear. The aim of this study was to investigate the risk for CCM-related hemorrhage in patients on long-term β-blocker medication. A single-center database containing data on patients harboring CCMs was retrospectively interrogated for a time period of 35 years. The database included information about hemorrhage and antihypertensive medication. Descriptive and survival analyses were performed, focusing on the risk of hemorrhage at presentation and during follow-up (first or subsequent hemorrhage) in patients on long-term β-blocker medication versus those who were not. Follow-up was censored at the first occurrence of new hemorrhage, surgery, or the last clinical review. For purposes of this analysis, the β-blocker group was divided into the following main subgroups: any β-blocker, β1-selective β-blocker, and any unselective β-blocker. Of 542 CCMs among 408 patients, 81 (14.9%) were under treatment with any β-blocker; 65 (12%) received β1-selective β-blocker, and 16 (3%) received any unselective β-blocker. One hundred thirty-six (25.1%) CCMs presented with hemorrhage at diagnosis. None of the β-blocker groups was associated with a lower risk of hemorrhage at the time of diagnosis in a univariate descriptive analysis (any β-blocker: p = 0.64, β1-selective: p = 0.93, any unselective β-blocker: p = 0.25). Four hundred ninety-six CCMs were followed up after diagnosis and included in the survival analysis, for a total of 1800 lesion-years. Follow-up hemorrhage occurred in 36 (7.3%) CCMs. Neither univariate descriptive nor univariate Cox proportional-hazards regression analysis showed a decreased risk for follow-up hemorrhage under treatment with β-blocker medication (any β-blocker: p = 0.70, HR 1.19, 95% CI 0.49-2.90; β1-selective: p = 0.78, HR 1.15, 95% CI 0.44-3.00; any unselective β-blocker: p = 0.76, HR 1.37, 95% CI 0.19-10.08). Multivariate Cox proportional-hazards regression analysis including brainstem location, hemorrhage at diagnosis, age, and any β-blocker treatment showed no reduced risk for follow-up hemorrhage under any β-blocker treatment (p = 0.53, HR 1.36, 95% CI 0.52-3.56). In this retrospective cohort study, β-blocker medication does not seem to be associated with a decreased risk of CCM-related hemorrhage at presentation or during follow-up.

Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in resected non-small cell lung cancer patients

We tested the hypothesis that circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in resected non-small cell lung cancer (NSCLC) patients. CTCs were separated from blood using magnetic beads coated with antibodies against epithelial-cell adhesion molecule (EpCAM) via magnetic-activated cell sorting (MACS). CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with resected NSCLC. The association between CTCs and prognosis in these patients was evaluated after a 5-year follow-up. In NSCLC patients, outcomes were assessed according to CTC levels at surgery. NSCLC patients identified as high-risk groups exhibited >5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that the CTC count in PPB or IPVB was an independent risk factor for tumor-free surivival (TFS) and overall survival (OS). The high-risk group of patients had a shorter median TFS (22 months vs. >60.0 months, p < 0.0012) and shorter OS (27 months vs. >60 months, p < 0.0015). The number of CTCs counted in PPB and IPVB was an independent risk factor for TFS and OS in resected NSCLC patients.

External validation of four nephrometry scores for trans-peritoneal robotic partial nephrectomy.

IntroductionExternal validation of four nephrometry scores (NS): Centrality index (C-index), arterial based complexity (ABC), preoperative aspects and dimensions used for an anatomical (PADUA) and radius expohytic/endophytic nearness anterior/posterior location (RENAL) scoring systems in patients who have undergone trans-peritoneal robotic assisted partial nephrectomy (RAPN).Material and methodsA prospective database for RAPN has been maintained. Individual NSs were performed on 3-dimensional reconstructions of MDCT/MRI studies retrospectively by a board certified uroradiologist. Univariate Cox Proportional-Hazard Regression Analysis was performed for each NSs to valuate its predictability for the following parameters: Warm Ischemia Time (WIT), Estimated Blood Loss (EBL), Operative Time (OT), Complication Rates and Positive Margin Rates.Results78 RAPNs were performed for suspected renal malignancies. The mean OT, EBL and WIT time was 186.5 minutes (SD – 33.8), 125.5 mls (SD – 188.91) and 16.7 minutes (SD – 5.6) respectively. The overall complication rate was 20.5% (16/78) of which only 2.6% (2/78) were Clavien Grade 3 or higher complications. The mean change in creatinine change at Day – 1 was 12.54 μmol/L (SD – 18.05). On the Cox regression analysis only the Centrality index predicted prolonged WIT with statistical significance: C-Index (0.02), ABC (0.2), PADUA (0.2), RENAL (0.9). ABC predicted operative time with statistical significance: C-index (0.45), ABC (0.0004), PADUA (0.25), RENAL (0.3). None of the NSs could predict overall complication: C-index (0.5), ABC (0.2), PADUA (0.13), RENAL (0.5). None of the NSs predicted EBL: C-index (0.3)0, ABC (0.8), PADUA (0.2), RENAL (0.7). None of the NSs predicted Positive Margin Rates: C-index (0.4), ABC (0.4), PADUA (0.9), RENAL (0.8).ConclusionsC-index was able to predict prolonged WIT. ABC was a strong predictor of OT. PADUA and RENAL were poor predictors for all measured parameters.

Long-term Prognosis of Anti-Neutrophil Cytoplasmic Antibody-Negative Renal Vasculitis: Cohort Study in Korea.

Few studies have reported on the long-term prognosis of anti-neutrophil cytoplasmic antibody (ANCA)-negative renal vasculitis. Between April 2003 and December 2013, 48 patients were diagnosed with renal vasculitis. Their ANCA status was tested using indirect immunofluorescence and enzyme-linked immunosorbent assays. During a median (interquartile range) follow-up duration of 933.5 (257.5–2,079.0) days, 41.7% of patients progressed to end stage renal disease (ESRD) and 43.8% died from any cause. Of 48 patients, 6 and 42 were ANCA-negative and positive, respectively. The rate of ESRD within 3 months was higher in ANCA-negative patients than in ANCA-positive patients (P = 0.038). In Kaplan-Meier survival analysis, ANCA-negative patients showed shorter renal survival than did ANCA-positive patients (log-rank P = 0.033). In univariate Cox-proportional hazard regression analysis, ANCA-negative patients showed increased risk of ESRD, with a hazard ratio 3.190 (95% confidence interval, 1.028–9.895, P = 0.045). However, the effect of ANCA status on renal survival was not statistically significant in multivariate analysis. Finally, ANCA status did not significantly affect patient survival. In conclusion, long-term patient and renal survival of ANCA-negative renal vasculitis patients did not differ from those of ANCA-positive renal vasculitis patients. Therefore, different treatment strategy depending on ANCA status might be unnecessary.

How to select elderly colorectal cancer patients for surgery: a pilot study in an Italian academic medical center.

ObjectiveCancer is one of the most common diagnoses in elderly patients. Of all types of abdominal cancer, colorectal cancer (CRC) is undoubtedly the most frequent. Median age at diagnosis is approximately 70 years old worldwide. Due to the multiple comorbidities affecting elderly people, frailty evaluation is very important in order to avoid over- or under-treatment. This pilot study was designed to investigate the variables capable of predicting the long-term risk of mortality and living situation after surgery for CRC.MethodsPatients with 70 years old and older undergoing elective surgery for CRC were prospectively enrolled in the study. The patients were preoperatively screened using 11 internationally-validated-frailty-assessment tests. The endpoints of the study were long-term mortality and living situation. The data were analyzed using univariate Cox proportional-hazard regression analysis to verify the predictive value of score indices in order to identify possible risk factors.ResultsForty-six patients were studied. The median follow-up time after surgery was 4.6 years (range, 2.9-5.7 years) and no patients were lost to follow-up. The overall mortality rate was 39%. Four of the patients who survived (4/28, 14%) lost their functional autonomy. The preoperative impaired Timed Up and Go (TUG), Eastern Cooperative Group Performance Status (ECOG PS), Instrumental Activities of Daily Living (IADLs), Vulnerable Elders Survey (VES-13) scoring systems were significantly associated with increased long term mortality risk.ConclusionSimplified frailty-assessing tools should be routinely used in elderly cancer patients before treatment in order to stratify patient risk. The TUG, ECOG-PS, IADLs and VES-13 scoring systems are potentially able to predict long-term mortality and disability. Additional studies will be needed to confirm the preliminary data in order to improve management strategies for oncogeriatric surgical patients.

S74 Circulating Tumour Cells In Peripheral And Pulmonary Venous Blood Predict Poor Long-term Survival In Surgically Resected Non-small Cell Lung Cancer Patients

Background We tested the hypothesis that the circulating tumour cells (CTCs) in preoperative peripheralblood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long term survival in surgically resected NSCLC patients. Method CTCs were separated from the blood using magnetic beads coated by antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence labelled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, wherethe mean and 95% CI of CTCs counts were all 5 CTCs/15 mL in PPB and >50 CTCs/15 mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumour-free and overall survivals. The high risk group of patients had a shorter median tumour-free survival (22 months vs. >60.0 months, P 60 months, P Conclusions CTCs countin PPBand IPVB was an independent risk factor for tumour-free and overall survivalin surgically resected NSCLC patients.

Abstract LB-293: Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in surgical resected non-small cell lung cancer patients

Abstract Background: We tested the hypothesis that the circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long term survival in surgically resected NSCLC patients. Methods: CTCs were separated from the blood using magnetic beads coated by antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results: In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, where the mean and 95%CI of CTCs counts were all 5 CTCs/15mL in PPB and &amp;gt;50 CTCs/15mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumor-free and overall survivals. The high risk group of patients had a shorter median tumor-free survival (22 months vs. &amp;gt;60.0 months, P60 months, P&amp;lt;0.0015). Conclusions: CTCs count in PPB and IPVB was an independent risk factor for tumor-free and overall survival in surgically resected NSCLC patients. Citation Format: Zhidong Liu, Yunsong Li, Chongyu Su, Yi Han, Shaofa Xu. Circulating tumor cells in peripheral and pulmonary venous blood predict poor long-term survival in surgical resected non-small cell lung cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-293. doi:10.1158/1538-7445.AM2014-LB-293

Circulating Tumor Cells in Peripheral and Pulmonary Venous Blood Predict Poor Long-Term Survival in Surgically Resected Non-Small Cell Lung Cancer Patients

ABSTRACT Aim: We tested the hypothesis that the circulating tumor cells (CTCs) in preoperative peripheral blood (PPB) and intraoperative pulmonary venous blood (IPVB) could predict poor long-term survival in surgically resected NSCLC patients. Methods: CTCs were separated from the blood using magnetic beads coated with antibody against epithelial-cell adhesion molecule (EpCAM) through magnetic activated cell sorting (MACS). The CTCs were quantified with fluorescence-labeled antibodies against pan-cytokeratin through flow cytometry. CTCs were prospectively quantified in PPB and IPVB in 23 consecutive stage I-IIIA patients with surgically resected NSCLC. Association between CTCs and prognosis of these patients was evaluated after 5-year follow-up. Results: In the NSCLC patients, outcomes were assessed according to levels of CTCs at surgery, and compared with CTCs detected in benign pulmonary diseases, and healthy volunteers, where the mean and 95% CI of CTCs counts were all 5 CTCs/15mL in PPB and >50 CTCs/15mL in IPVB. Univariate Cox proportional-hazards regression analysis showed that CTCs count in PPB or IPVB was an independent risk factor for tumor-free and overall survivals. The high risk group of patients had a shorter median tumor-free survival (22 months vs. >60.0 months, P 60 months, P Conclusions: CTCs count in PPB and IPVB was an independent risk factor for tumor-free and overall survival in surgically resected NSCLC patients. Disclosure: All authors have declared no conflicts of interest.

Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease

Background: Soluble ST2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. There is no published data on sST2 in patients with stable coronary artery disease (CAD). Therefore, the aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable CAD. Methods: sST2 plasma concentrations were measured in 1345 patients with stable CAD referred to coronary angiography at a single tertiary care center. The primary enpoint was all-cause mortality. Results: During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs. 18.5 U/mL; p<0.001). In univariate Cox proportional-hazard regression analysis sST2 (per 1SD increase in log transformed values) displayed a risk ratio (RR) of 1.5 (95% CI 1.4-1.6; p<0.001) for all-cause mortality. After adjustment for clinical variables (including age, diabetes, and left ventricular ejection fraction) and several other biomarkers (including hs-cTnT and NT-proBNP), sST2 remained an independent predictor of mortality (RR 1.1, 95% CI 1.0-1.3; p=0.004). When stratifying the entire cohort according to cut-offs between the third and the fourth quartiles for sST2, hs-cTnT and NT-proBNP, Kaplan-Meier curve analysis revealed that patients with all three biomarkers below these cut-offs displayed survival probability of 80%. In contrast, patients with elevation of all three biomarkers displayed a survival probability of only 14% (Figure 1). ![Figure][1] All-cause mortality in stable CAD Conclusions: In this cohort of patients with stable CAD, increased sST2 was an independent predictor of long-term all-cause mortality and provided complementary prognostic information to hs-cTnT and NT-proBNP. [1]: pending:yes

Retrospective analysis of the prognosis factors in patients with idiopathic pulmonary fibrosis

To investigate the prognostic implications of clinical and physiological variables, and the cellular classification of bronchoalveolar lavage fluid (BALF) in patients with idiopathic pulmonary fibrosis (IPF). The effect of treatment with glucocorticoids with or without cytotoxic drugs was also evaluated. The significances of clinical, arterial blood gas analysis, pulmonary function test, lung high-resolution computed tomography, echocardiography and BALF in the prognosis of patients with IPF were assessed in 65 patients with IPF at diagnosis. Univariate Cox proportional-hazards regression analysis was used to evaluate the various parameters associated with hazard ratio. The survival rates of all groups were compared using the Kaplan-Meier method. In 38 months of average follow-up time, the survival rate of the patients was 43.1%, and the median survival time was 39 months after diagnosis. Univariate Cox proportional-hazards regression analysis showed that body mass index, clubbing fingers, ESR, PaO(2)/FiO(2), SaO(2), TLC%, D(L)CO%, pulmonary arterial pressure and the percent of neutrophil in BALF were factors that affected the prognosis of the patients with IPF (HR 0.842 - 1.945, Wald 3.782 - 12.963, P < 0.05). In the meanwhile, the patients were divided into 2 groups by the median of significant variables in univariate Cox proportional-hazards regression analysis (the cut off point value), and the survival rate group comparison showed statistically significant difference in body mass index, clubbing fingers, ESR, TLC% as well as D(L)CO% (Log-rank 3.907 - 10.452, P < 0.05), while glucocorticoids with or without cytotoxic drugs for patients with IPF did not change the prognosis (Log-rank 2.405, P > 0.05). Body mass index, clubbing fingers, ESR, PaO(2)/FiO(2), TLC%, and D(L)CO% maybe the factors affecting the prognosis of patients with IPF, while glucocorticoids with or without cytotoxic drugs did not change the course of IPF.

A retrospective cohort study of prognostic factors for death in patients with idiopathic pulmonary fibrosis

To investigate the prognostic implications of clinical, radiographic, and physiological variables in idiopathic pulmonary fibrosis (IPF). The clinical, pulmonary physiological, bronchoalveolar lavage fluid (BALF) cell differentials and lung high-resolution computed tomography (HRCT) at diagnosis in 126 patients with IPF were retrospectively analyzed. Univariate and multivariate Cox proportional-hazards regression analysis was used to evaluate various parameters associated with hazard ratio (HR). The survival rates of all groups were compared using the Kaplan-Meier method. In 29.6 months of average follow-up time, the survival rate of the IPF patients was 46.8% (59/126), and the median survival time was 30 months after diagnosis. Glucocorticoids and/or cytotoxic drugs for patients with IPF did not change the prognosis. The survival rates between groups by gender and smoking status showed no statistically significant difference (Ward: 0.11, 1.65, P>0.05). The patients were divided into 2 groups by the median (the cutoff point value) of significant variables in univariate Cox proportional-hazards regression analysis, and the survival rates showed statistically significant difference by dyspnea scale, FVC%, TLC%, DLCO%, neutrophil percentage and eosinophil percentage in BALF, and the reticular and honeycomb lung score (Logrank: 13.52-57.52, P<0.05). The results of multivariate Cox proportional-hazards regression analysis showed that TLC%, DLCO%, HRCT reticular score and honeycomb lung score were factors that affected the prognosis of patients with IPF (Wald=5.76-21.48, P<0.05). TLC%, DLCO%, cell differentials of BALF and the degree of pulmonary fibrosis were the main factors affecting the prognosis of patients with IPF. TLC% and DLCO% showed a negative correlation with the prognosis of patients with IPF. Glucocorticoids and/or cytotoxic drug therapy had no effect on the prognosis of patients with IPF.

Pregnancy-associated plasma protein-A as a marker for long-term mortality in patients with peripheral atherosclerosis: inconclusive findings from the Linz Peripheral Arterial Disease (LIPAD) study

Pregnancy-associated plasma protein-A (PAPP-A) has been associated with peripheral artery disease (PAD). The aim of this study was to evaluate the utility of PAPP-A as a marker for long-term mortality in patients with atherosclerotic PAD. PAPP-A serum concentrations were measured using an enzymatically amplified two-step sandwich-type immunoassay in 487 consecutive patients admitted to a tertiary care hospital with symptomatic PAD. The main outcome measure was all-cause mortality at 5 years. During follow-up, 114 patients died and 373 survived. The median PAPP-A concentration was higher among decedents compared with survivors (0.96 vs. 0.78 mU/L, p=0.024). The area under the receiver operating characteristic curve for the prediction of 5-year mortality by PAPP-A was 0.57 [95% confidence interval (CI), 0.53-0.61; p=0.026]. Survival probability was not significantly associated with PAPP-A concentrations using Kaplan-Meier curve analysis. However, univariate Cox proportional-hazards regression analysis revealed that PAPP-A was associated with 5-year mortality [risk ratio 1.25; 95% CI, 1.05-1.50; p=0.013 per one standard deviation (SD) increase in log transformed values]. In the multivariate model using a bootstrapping method, the predictive value of PAPP-A remained significant (risk ratio 1.31; 95% CI, 1.01-1.73; p=0.024 per 1 SD increase in log transformed values), even after adjustment for clinical confounders and other biomarkers, such as high-sensitivity C-reactive protein and amino terminal pro-B-type natriuretic peptide. In this study, PAPP-A was an independent predictor of 5-year all-cause mortality in patients with symptomatic PAD. However, based on the weak association between PAPP-A and outcome in our cohort, we consider PAPP-A measurements to not be useful in clinical practice for prognostic purposes in patients with PAD.

Value of adiponectin as predictor of 5-year all-cause mortality in patients with symptomatic peripheral arterial disease: Results from the Linz Peripheral Arterial Disease (LIPAD) study

Background We have previously demonstrated that adiponectin is associated with amino terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with peripheral artery disease (PAD). Furthermore, we have shown that NT-proBNP is a strong predictor of mortality in these patients. The aim of this study was therefore to evaluate the value of adiponectin as long-term prognostic marker in patients with atherosclerotic PAD in the same cohort. Methods We measured adiponectin serum concentrations in 487 consecutive patients with symptomatic PAD admitted to a tertiary care hospital. The endpoint was defined as all-cause mortality, and the study participants were followed for 5 years. Results Of the 487 patients enrolled, 114 died and 373 survived during follow-up. The median adiponectin concentration was higher among decedents than survivors (11.3 vs. 9.1 mg/L; p < 0.001). Univariate Cox proportional-hazard regression analysis revealed that adiponectin concentrations were associated with 5-year mortality in PAD patients (risk ratio 1.05, 95% CI 1.03–1.07; p < 0.001 per 1 mg/L increase). Even after adjustment for age, sex, body mass index, estimated glomerular filtration rate, clinical stage of PAD, cardiovascular comorbidity, and other potential confounders, the predictive value of adiponectin serum concentrations remained statistically significant (risk ratio 1.03, 95% CI 1.00–1.05; p = 0.030 per 1 mg/L increase). However, adiponectin lost its independent association with mortality in symptomatic PAD after additional adjustment for NT-proBNP. Conclusions In this study, adiponectin serum concentrations predicted 5-year all-cause mortality in patients with symptomatic PAD independently of other established and emerging outcome predictors. Only after adjustment for NT-proBNP, adiponectin lost its independent predictive value.

Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity.

A total of 121 infants who required indomethacin for persistent ductus arteriosus in Liverpool and Cambridge over a four year period were randomised to receive either 0.1 mg/kg daily for six days or 0.2 mg/kg every 12 hours for three doses. The groups were of similar birth weight and gestational and postnatal age, though those treated with a low dose were by chance receiving a higher percentage of oxygen at the start of treatment and there were more deaths from bronchopulmonary dysplasia in this group. Of 59 infants treated with the prolonged course 53 (90%) responded initially to indomethacin compared with 48 of 62 (77%) treated conventionally--a difference of 13% (95% confidence interval for the difference 0 to 26%). Of the 53 responders 11 (21%) relapsed after low dose indomethacin, whereas after the shorter course 19 of 48 (40%) relapsed. This difference was significant (95% confidence intervals 3 to 37%). Side effects, mainly gastrointestinal haemorrhage, were similar in both groups. Significantly fewer infants experienced a rise in serum creatinine or urea concentration after treatment with low dose indomethacin. A prolonged low dose course of indomethacin offers advantages over conventional treatment.