Crude HR Research Articles

The association between Single Nucleotide Polymorphisms of Klotho Gene and Mortality in Elderly Men: The MrOS Sweden Study

The Klotho (KL) gene is involved in phosphate homeostasis. Polymorphisms in this gene have been reported to be associated with the risk of cardiovascular disease. Here we used computational tools to predict the damage-associated single nucleotide polymorphisms (SNPs) in the human KL gene. We further investigated the association of SNPs in the KL gene and mortality in the Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort. This study included 2921 men (aged 69–81 years) with mean 4.49 ± 1.03 years follow-up. 18 SNPs in the KL gene were genotyped using Sequenom. These SNPs were identified by in silico tools for the coding and noncoding genome to predict the damaging SNPs. After quality analyses, SNPs were analyzed for mortality risk using two steps approach on logistic regression model screening and then Cox regression model confirmation. Two non-synonymous SNPs rs9536314 and rs9527025 were found to be potentially damaging SNPs that affect KL protein stability and expression. However, these two SNPs were not statistically significantly associated with all-cause mortality (crude Hazard ratio [HR] 1.72, 95% confidence interval [CI] 0.96–3.07 in rs9536314; crude HR 1.82, 95% CI 0.998–3.33 in rs9527025) or cardiovascular mortality (crude HR 1.52, 95% CI 0.56–4.14 in rs9536314; crude HR 1.54, 95% CI 0.55–4.33 in rs9527025) in additive model using Cox regression analysis. In conclusion, these two potentially damaging SNPs (rs9536314 and rs9527025) in the KL gene were not associated with all-cause mortality or cardiovascular mortality in MrOs cohort. Larger scales studies and meta-analysis are needed to confirm the correlation between polymorphisms of the KL gene and mortality.

P1168ABDOMINAL AORTIC CALCIFICATION SCORE MODIFIES THE PROGNOSTIC VALUE OF SERUM MAGNESIUM LEVELS ON ALL CAUSE MORTALITY IN PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Low serum Mg (s-Mg) concentration has been associated with an increased risk of death in both the general and dialysis populations. In peritoneal dialysis (PD) patients, an inverse correlation between s-Mg and abdominal aortic calcification (AAC), estimated by plain lateral lumbar x-rays, as Leena Kauppila (LK) score (range 0-24), is well documented. LK score of 0-4 has been associated with the best event free survival (CORD study CJASN 2011). Here, we explored the possibility whether AAC could modify the relationship between s-Mg and all-cause mortality in PD patients. Method We studied 95 stable PD patients, 51 men 44 women, with a mean age of 63 ±14 years. The degree of AAC was evaluated with on plain lateral abdominal radiographs, as LK score. After completion of baseline assessment, including s-Mg measurements, patients were followed up for all-cause mortality. Results The mean of s-Mg and AAC in the whole group were 2.25±0.47 mg/dl and 6.65 ± 5.94 respectively. There was an strong inverse correlation (rho = -0.225; p=0.029) between s-Mg and AAC. During a median follow-up period of 23 months, 16 (17%) deaths occurred. There was a 78% reduction of all-cause mortality for every 1 mg/dl of increase in s-Mg {crude HR: 0.22 (95% CI, 0.06 - 0.78)}. An interacting effect between s-Mg and AAC was significant (p=0.005) after controlling for main effects. Then, the association between s-Mg and all-cause mortality by subgroups of AAC: higher tertile vs all lower, was examined (cut-offs of the tertiles for AAC were 3 and 9). In patients grouped in the lower tertiles, s-Mg was a significant predictor of all-cause mortality, even after adjustment for univariate significant predictors of all-cause mortality: age, cardiovascular disease, PD vintage and malnutrition-inflammation score (MIS) {adjusted HR: 0.14 (95% CI, 0.02-0.0.98)}. On the contrary, patients with AAC in the higher tertile of the baseline distribution, s-Mg levels were not predictive of outcome in either crude or the adjusted models. Conclusion The predictive value of s-Mg in all-cause mortality in PD patients appears to be critically dependent on AAC score. Thus, sustaining higher sMg levels, as by using higher Mg dialysate concentration, may have beneficial effects on clinical outcomes only in patients without AAC or at least in those with early lesion development.

Blood Conservation Strategy at Time of Left Ventricular Assist Device Placement Improves Survival

Bleeding is the most common complication of left ventricular assist device (LVAD) placement. However, excessive transfusion has been linked to heart failure, stroke, and alloimmunization. We compared 90-day outcomes in patients receiving a blood conservation (BCS) versus liberal transfusion strategy during surgery and the subsequent 24 hours. 173 LVAD implants at a single center between June 2011 and September 2018 were reviewed. Due to incomplete data, 3 patients were excluded. The BCS (≤1 packed red blood cell (pRBC)) was employed in 56/170 patients. In the liberal group, 41 received 2-5 units, 24 received 6-10 units, 24 received 11-15 units, and 25 received ≥15 units of PRBC. Anti-platelet use was equal across groups whereas anticoagulants were more readily used in the conservative group (55 vs 38%, p=0.04) at implantation. The liberal group had greater use of circulatory support devices (47 vs 29%, p=0.02) whereas the BCS group had larger ventricular size. Pre-operative laboratory values were similar among groups except for hemoglobin g/dL (12.6 conservative vs 11.6 liberal, p=0.02). Both the length of hospital and ICU stay were lower in the BCS group (17 vs 24 days, p<0.001 and 9 vs 12 days, p=0.02). Bleeding events (p-0.02) and reoperation were more frequent in the liberal group (13 vs 32 %, p=0.007). No difference between stroke, infection and right ventricular assist device use rates were seen. 90-day mortality was significantly higher in the liberal group (p=0.03). However, multivariate analysis did not show a significant benefit of the BCS despite trend towards survival with a crude HR 2.23 (0.86-5.82, p=0.10) and adjusted HR 2.21 (0.82-5.75, p=0.10). BCS at time of LVAD implant is associated with improved early survival. Identified transfusion triggers and standardized transfusion protocols for LVAD patients have the potential to reduce blood product utlization.

Impact of anticoagulants in elderly patients who suffer a hip fracture. Should we have a different approach?

Introduction:Hip fracture in the elderly is a frequent problem. Chronic treatment with anticoagulants is common in these patients and may delay surgery.Objectives:To compare time to surgery, hospital stay, in-hospital and 90 days complications between anticoagulated and non-anticoagulated groups.Methods:Retrospective cohort of >64 years-old patients with acute hip fracture. Period June-2014 to December 2019. We estimated crude and adjusted Odds Ratio (95%CI) for in-hospital complications with logistic regression model. We report the crude and adjusted Hazard Ratio for readmission and 90-days mortality with Cox proportional hazards model.Results:Of the 1058 patients, 123 (11%) were anticoagulated. Time to surgery was 26.4 hours (IIQ 13.9-48) in anticoagulated and 24 hours (IIQ 2.3-48) in non-anticoagulated, p 0.001. Hospital stay was 7 days (IIQ 5-9) in anticoagulated and 6 days (IIQ 5-10.5) in non-anticoagulated, p 0,000. In-hospital complications were 17 (14%) in anticoagulated and 81 (9%) in non-anticoagulated, p 0.064. The adjusted OR was 1.53 (95%CI 0.8-2.7) p 0.138. For 90-days readmission, the crude HR was 1.51 (95%CI 0.99-2.29) p 0.053 and the adjusted HR was 1.31 (95%CI 0.85-2.00) p0,09. For 90-days mortality, the crude HR was 0.80 (95%CI 0.45-1.43) p 0.464 and the adjusted HR was 0.70 (95% CI 0.39-1.25) p 0.239.Discussion:While we found differences between groups in time to surgery and hospital statistics these differences may not be clinically relevant. (www.actabiomedica.it)

Sociodemographic, Clinical, and Pathological Factors Influencing Outcomes in Locally Advanced Triple Negative Breast Cancer: A Brazilian Cohort.

Objective:To evaluate the association of sociodemographic, clinical, and pathological factors with response and survival in triple negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NACT).Methods:Clinical-pathological and sociodemographic data were obtained from medical records of 235 eligible women with TNBC diagnosed between 2010 and 2014 undergoing NACT and surgery at the Brazilian National Cancer Institute. They have been assessed for pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). Both univariate and multivariate Cox regression analyses were performed.Results:The median follow-up was 64.3 months. Most patients had advanced clinical stage (III: 85.1%; cT3/T4: 86.4%; cN1-3: 74.4%) and high-grade tumors (72.1%). Clinical staging (III vs II, adjusted hazard ratio [HR] = 2.95, P = .012) significantly influenced the pCR rate. Alcohol intake negatively influenced EFS (adjusted HR = 1.67, P = .006) and OS (adjusted HR = 1.89, P = .005). Women with pCR showed better EFS (crude HR = 0.15, P < .001) and OS (crude HR = 0.12, P < .001) compared with non-pCR. The ypT (<0.001) and ypN (<0.001) gradually influenced survival outcomes.Conclusion:Clinical stage III were associated with lower response rate and worse survival. Alcohol intake, pCR, and burden of post-NACT residual disease have shown considerable influence on survival outcomes.

P1580 Global regurgitant volume - approaching the critical mass in valvular-driven heart failure

Abstract Aims Recent progress in the diagnosis of functional valve regurgitation forms a coherent perception of severity thresholds by quantitative assessment. However, thresholds focused on either valve in isolation -not accounting for the global hemodynamic burden arising from concomitant functional regurgitation of the mitral and tricuspid valves. We sought to determine whether the global regurgitant volume is associated with adverse cardiac remodeling and mortality. Methods and results This long-term observational study included 414 patients on guideline-directed medical therapy. Baseline global regurgitant load defined as the sum of mitral and tricuspid regurgitant volume was assessed by the proximal flow convergence method. All-cause mortality during five years follow-up served as the primary endpoint. The median global regurgitant load was 30ml (IQR 15-49) with 67% accounting for mitral and 33% accounting for tricuspid regurgitant volume. The global regurgitant load had significant impact on outcome with a crude HR of 1.46 (1.28-1.66; P &amp;lt; 0.001) for a 1-SD increase in global regurgitant volume, results that remained virtually unchanged after bootstrap or clinical confounder-based adjustment (P &amp;lt; 0.001 for adjusted models). Spline curve analysis showed a linearly increasing risk with a threshold of 50ml and sustained increasing risk thereafter. Conclusions The present study demonstrates the detrimental effect of the global regurgitant load in patients with HFrEF. The threshold where heart failure is driven by the valve lesions is a global regurgitant volume of 50ml with continuously increasing risk beyond that threshold. Future studies need to address whether an attempt to reduce the global regurgitant volume can improve outcome. Abstract P1580 Figure 1 - Global RegVol

Home treatment of patients with cancer-associated venous thromboembolism – An evaluation of daily practice

BackgroundHome treatment of cancer-associated venous thromboembolism (VTE) is challenging due to the high risk of adverse events. While home treatment is quite agreeable to cancer patients, studies evaluating the safety of VTE home treatment in this setting are largely unavailable. MethodsThis was an observational study in patients with cancer-associated VTE. The main outcomes were the proportion of patients treated at home (hospital discharge <24 h after diagnosis) and the 3-month incidence of VTE-related adverse events (major bleeding, recurrent VTE and/or suspected VTE-related mortality) in patients managed in hospital versus at home. ResultsA total of 183 outpatients were diagnosed with cancer-associated VTE: 69 had deep vein thrombosis (DVT) and 114 had pulmonary embolism (PE ± DVT). Of those, 120 (66%) were treated at home; this was 83% for patients with DVT and 55% for patients with PE (±DVT). The 3-month incidence of any VTE-related adverse event was 13% in those treated at home versus 19% in the hospitalized patients (HR 0.48; 95%CI 0.22–1.1), independent of initial presentation as PE or DVT. All-cause 3-month mortality occurred in 33 patients treated as inpatient (54%) compared to 29 patients treated at home (24%; crude HR 3.1 95%CI 1.9–5.0). ConclusionsTwo-third of patients with cancer-associated VTE - including PE - were selected to start anticoagulant treatment at home. Cancer-associated VTE is associated with high rates of VTE-related adverse events independent of initial in hospital or home treatment. However, home treatment may be a good option for selected patients with cancer-associated DVT or PE.

P3624Prevalence and severity of coronary artery disease linked to prognosis in psoriasis patients referred for coronary computed tomography angiography: A multicentre cohort study

Abstract Background Psoriasis (Pso) is a disease characterized by systemic inflammation and is associated with an increased risk of cardiovascular disease. However, the degree of coronary artery calcification in Pso and its relation to prognosis is largely unknown. Purpose The aim of this study was 1) to estimate the prevalence and severity of coronary artery disease (CAD) in this patient group and 2) to asses the risk of major adverse cardiovascular events (MACE) including revascularization and all-cause mortality after initial diagnosis and treatment in a large-scale cohort of patients who underwent coronary computed tomography angiography (CCTA) due to angina symptoms. Methods This study consists of two parts using data from the Western Denmark Heart Registry; a cross-sectional study included 40,125 patients and a follow-up study included 42,861 patients. Pso patients were identified by the National Patient Registry and verified by nationwide prescription and treatment code registers. Primary outcome in the cross-sectional study was a coronary artery calcium score (CACS) &gt;0, with a secondary outcome defined as a CACS ≥400. In the follow-up study, the primary outcome was a combined outcome including myocardial infarction, revascularization, ischemic or unspecified stroke and all-cause mortality. Events within the first 90 days after CCTA were attributed to initial treatment and consequently excluded. All outcomes were adjusted for common cardiovascular risk factors and comorbidities. Results In the cross-sectional study 1,407 (3.5%) Pso patients were identified. OR was 1.31 (95% CI; 1.15–1.49) for CACS &gt;0 and 1.33 (95% CI; 1.10–1.62) for CACS ≥400 in Pso patients compared to non-Pso patients. In the follow-up study 1,591 (3.7%) Pso patients were identified. The mean duration of follow-up after CCTA was 4.0 years (min/max 0.0/10.2). Crude HR for the combined outcome was 1.52 (95% CI; 1.24–1.87), while adjusted HR was 1.16 (95% CI; 0.95–1.43). Conclusion In this clinically relevant cohort of patients referred to CCTA for CAD rule out, coronary artery calcification was more frequent and more severe in Pso patients even compared to the control patients with several risk factors and angina symptoms, but without inflammatory diseases. An increased risk of the combined outcome of MACE including revascularization and all-cause mortality after initial treatment in Pso patients was found in the crude analysis. The increased risk seemed predominantly carried by an increase in traditional risk factors.

Haploidentical transplant in adult patients with acute lymphoblastic leukemia in Argentina: a comparison with matched related and unrelated donors.

We aimed at analyzing the outcome of allogeneic stem cell transplant (ASCT) in adult patients with acute lymphoblastic leukemia (ALL), comparing Haploidentical (Haplo) with HLA-matched (sibling and unrelated) donors. Between 2008 and 2017, we collected data from 236 patients (median age 31 years; range 16-64; 90% HCT-CI 0-1) who underwent unmanipulated ASCT in first complete remission and subsequent remissions in 15 Argentinian centers. Donors were HLA-matched (n = 175; 74%) and Haplo (n = 61; 26%). Two-year overall survival (OS) was 55% (95% CI 47-63) for the HLA-matched group and 49% (95% CI 34-62) for the Haplo group (p = 0.351). For OS, crude HR, adjusted HR for covariates (HR 1.24; 95% CI 0.77-1.99; p = 0.363) and HR including a propensity score in the model (HR 1.22; 95% CI 0.71-2.08; p = 0.414) showed no impact of donor category on the OS. No difference was found in terms of nonrelapse mortality, relapse, leukemia-free survival, and grade 3-4 acute graft-versus-host disease (GVHD); 2-year incidence of chronic GVHD was higher in HLA-matched vs Haplo group (p = 0.028). Patients with ALL who underwent ASCT were young subjects with low HCT-CI. In this setting, a Haplo donor represents an alternative widely available in the absence of an HLA-matched donor. Relapse remains a challenge for all donor categories.

The comparison of percent body fat estimated by different anthropometrics to predict the incidence of hypertension.

Percent body fat (%BF) is associated with the development of hypertension. However, the power of %BF estimated by different anthropometrics to predict incident hypertension was unknown. This study was from the China Health andNutrition Survey (CHNS). %BF was calculated using the equations with BMI, WC, and skinfold thickness and divided into low and high %BF according to ROC. Cox regression was employed to evaluate the power of different %BFs to predict the development of hypertension. When not adjusting for covariates, %BFs defined by BMI, WC, and ST were the significant predictors of the development of hypertension (all P < 0.0001; crude HR: 2.238, 3.243, and 1.574; and HR 95% CI: 2.098-2.387, 2.905-3.619, and 1.464-1.692). When three %BFs entered into model simultaneously, the significance in %BF estimated by ST disappeared (P = 0.0765; adjusted HR: 1.124; and HR 95% CI: 0.988-1.280). For males, %BFs by BMI, WC, and ST significantly affected the incidence of hypertension as they were separately analyzed (all P < 0.0001; crude HR: 2.445, 2.335, and 1.828; and HR 95% CI: 2.220-2.693, 2.011-2.712, and 1.636-2.042, respectively). For females, %BFs estimated by BMI, WC, and ST were the determinants of the development of hypertension whether covariates were adjusted or not (all P < 0.0001). In conclusion, there was a poor and ineffective association of %BF estimated by triceps skinfold thickness with the development of hypertension, especially when three %BFs were analyzed together. High %BFs estimated by BMI and WC were the true and effective predictors of the incidence of hypertension.

Very elderly patients with venous thromboembolism on oral anticoagulation with VKAs or DOACs: Results from the prospective multicenter START2-Register Study

IntroductionFew data are available on the safety of anticoagulation in very elderly patients treated with Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for venous thromboembolism (VTE). MethodsWe carried out a prospective cohort study on VTE patients aged ≥85 years enrolled in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) on treatment with VKAs or DOACs, with the aim to evaluate mortality, bleeding and thrombotic rates (venous and arterial). ResultsWe enrolled 272 patients, 58.7% on VKA and 41.3% on DOACs. Baseline characteristics were similar between treatment groups, with a higher prevalence of renal failure in VKAs patients and of a history of bleeding and previous stroke/TIA in DOACs patients. During follow-up of 429 patient-years, 15 major and non-major clinically relevant bleedings were recorded (rate 3.5 × 100 pt-yrs), 5 were major bleeds (rate 1.2 × 100 pt-yrs), 1 in a patient on aspirin (rate 4.3 × 100 pt-yrs). Bleeding rate was higher in patients on DOACs (crude HR 4.7; 95%CI 1.5–15.01). Eight thrombotic events were recorded (rate 1.9 × 100 pt-yrs), 3 recurrent VTE and 5 stroke/TIA. Overall, the incidence of thrombotic events was higher in DOACs patients (crude HR 4.5; 95% CI 1.5; 13.3). The rate of recurrent VTE was similar in the two group. Mortality rate was significantly lower in DOACs patients (crude HR 0.30; 95% CI 0.1;0.9). ConclusionA higher bleeding risk was found in very elderly VTE patients on DOACs despite the wide use of low-dosages. Similarly a higher thrombotic risk was found while the incidence of recurrent VTE was low and similar between the groups. Mortality rate were significantly lower in DOACs patients.

Lifestyle Risk Factors and All-Cause and Cardiovascular Disease Mortality: Data from the Korean Longitudinal Study of Aging.

This study examined the association between lifestyle risk factors and all-cause and cardiovascular disease (CVD) mortality in 9945 Korea adults (56% women) aged 45 years and older. Smoking, heavy alcohol intake, underweight or obesity, physical inactivity, and unintentional weight loss (UWL) were included as risk factors. During 9.6 ± 2.0 years of follow-up, there were a total of 1530 cases of death from all causes, of which 365 cases were from CVD. Compared to a zero risk factor (hazard ratio, HR = 1), the crude HR of all-cause mortality was 1.864 (95% CI, 1.509–2.303) for one risk factor, 2.487 (95% confidence interval, CI, 2.013–3.072) for two risk factors, and 3.524 (95% CI, 2.803–4.432) for three or more risk factors. Compared to a zero risk factor (HR = 1), the crude HR of CVD mortality was 2.566 (95% CI, 1.550–4.250) for one risk factor, 3.655 (95% CI, 2.211–6.043) for two risk factor, and 5.416 (95% CI, 3.185–9.208) for three or more risk factors. The HRs for all-cause and CVD mortality remained significant even after adjustments for measured covariates. The current findings showed that five lifestyle risk factors, including smoking, at-risk alcohol consumption, underweight/obesity, physical inactivity, and UWL, were significantly associated with an increased risk of all-cause and CVD mortality in Korean adults.

Primary Tumor Sidedness Predicts Bevacizumab Benefit in Metastatic Colorectal Cancer Patients.

The emerging debate between primary tumor location and clinical outcome of bevacizumab treated metastatic colorectal cancer (mCRC) continues. The aim of the present study is to investigate the association between the primary tumor location and clinical outcome of 115 mCRC patients receiving bevacizumab based treatment. A meta-analysis including 21 studies was carried out to confirm the conclusion. In our prospective study, we found that right-sided mCRC commonly occurred in older cases (p = 0.03) with multiple-site metastasis (p = 0.03). Progression-free survival (PFS) of the left-sided patients undergoing bevacizumab plus a FOLFIRI regimen was superior to the right-sided cases (p = 0.03, crude HR = 0.31, 95%CI = 0.11–0.87; adjusted HR = 0.21, 95%CI = 0.06–0.66). The meta-analysis confirmed that efficacy of bevacizumab-based treatment in left-sided mCRC patients was better than the right-sided cases in the overall population (Ph = 0.24, combined OR = 1.36, 95%CI = 1.07–1.72), RAS/BRAF wild-type (Ph = 0.19, combined OR = 1.66, 95%CI = 1.17–2.34), clinical trial (Ph = 0.23, combined OR = 1.42, 95%CI = 1.07–1.88), Caucasian population (Ph = 0.18, combined OR = 1.37, 95%CI = 1.02–1.85) and first-line (Ph = 0.19, combined OR = 1.48, 95%CI = 1.13–1.96) subgroups. Improved survival of bevacizumab plus chemotherapy treated left-sided mCRC patients was observed in the overall population [Ph < 0.01, combined MSR = 1.09, 95%CI = 1.00–1.18 for PFS; Ph < 0.01, combined MSR = 1.24, 95%CI = 1.13–1.36 for overall survival (OS)], especially in the RAS/BRAF wild-type (Ph = 0.09, combined MSR = 1.10, 95%CI = 1.03–1.19 for PFS; Ph = 0.02, combined MSR = 1.34, 95%CI = 1.21–1.49 for OS). These findings indicate that primary tumor sidedness can predict clinical outcome of bevacizumab-treated RAS/BRAF wild-type mCRC patients and the left-sided patients may benefit more from bevacizumab plus FOLFIRI.

Prevention of recurrent idiopathic gastroduodenal ulcer bleeding: a double-blind, randomised trial

ObjectivePatients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have a considerable risk of recurrent ulcer complications. We hypothesised that a proton pump inhibitor (lansoprazole) is superior to a...

Central venous catheter use increases ischemic stroke risk: a nationwide population-based study.

Central venous catheter (CVC) placement is a common procedure used for the treatment of critically ill patients. However, ischemic stroke is a complication after CVC placement. This study investigated the association between CVC placement and ischemic stroke risk in an Asian population. Population-based retrospective study. We enrolled 37623 patients who ever-received CVC placement over 2000-10 and propensity score-matched individuals without CVC placement as the comparison cohort from the Taiwan National Health Insurance Research Database. We determined the cumulative incidence rates and adjusted hazard ratios (aHRs) for ischemic stroke. We finally identified and enrolled 34164 propensity score-matched pairs of individuals. Compared with the comparison group, CVC placement increased the average annual ischemic stroke incidence [19.5 vs. 11.6 per 10000 person-years; crude HR=1.28, 95%, confidence interval (CI)=1.21-1.35; adjusted subhazard ratio (aSHR)=1.4, 95% CI = 1.33-1.47; P<0.001). In addition, compared with those aged >35 years, stroke risk was significantly higher in <35-year-old patients with CVC placement (aSHR=14.3, 95% CI=6.11-33.4; P<0.001). After <1-year follow-up, the ischemic stroke incidence rate in the CVC placement group was ∼3.25-fold higher than that in the comparison group (aHR=3.25, 95% CI=2.9-3.63; P<0.0001). CVC placement increases ischemic stroke risk, particularly in those aged ≤35 years; this trend warrants further investigation.

The Apparent Genetic Anticipation in PMS2-Associated Lynch Syndrome Families Is Explained by Birth-cohort Effect.

PMS2-associated Lynch syndrome is characterized by a relatively low colorectal cancer penetrance compared with other Lynch syndromes. However, age at colorectal cancer diagnosis varies widely, and a strong genetic anticipation effect has been suggested for PMS2 families. In this study, we examined proposed genetic anticipation in a sample of 152 European PMS2 families. The 152 families (637 family members) that were eligible for analysis were mainly clinically ascertained via clinical genetics centers. We used weighted Cox-type random effects model, adjusted by birth cohort and sex, to estimate the generational effect on the age of onset of colorectal cancer. Probands and young birth cohorts were excluded from the analyses. Weights represented mutation probabilities based on kinship coefficients, thus avoiding testing bias. Family data across three generations, including 123 colorectal cancers, were analyzed. When compared with the first generation, the crude HR for anticipation was 2.242 [95% confidence interval (CI), 1.162-4.328] for the second generation and 2.644 (95% CI, 1.082-6.464) for the third generation. However, after correction for birth cohort and sex, the effect vanished [HR = 1.302 (95% CI, 0.648-2.619) and HR = 1.074 (95% CI, 0.406-2.842) for second and third generations, respectively]. Our study did not confirm previous reports of genetic anticipation in PMS2-associated Lynch syndrome. Birth-cohort effect seems the most likely explanation for observed younger colorectal cancer diagnosis in subsequent generations, particularly because there is currently no commonly accepted biological mechanism that could explain genetic anticipation in Lynch syndrome. This new model for studying genetic anticipation provides a standard for rigorous analysis of families with dominantly inherited cancer predisposition.

Evaluation of the diagnostic and prognostic performance of the modified G8 screening instrument in oncological patients with age of 60 YEARS or age: Prospective cohort of 889 Brazilian elderly cancer patients.

e23040 Background: Elderly oncology patients are not often included in studies of new therapeutic guidelines. The modified-G8 is easy to use, has satisfactory accuracy and does not require additional tools. Its value for predicting early death has not been evaluated. Objective: To evaluate accuracy of the modified G8 instrument for prediction of early death (up to 6 months) in elderly Brazilian patients (≥ 60 years). Methods: We used data from a prospective cohort with participants aged 60 years or older and a recent diagnosis of a solid neoplasm, followed in a geriatric oncology outpatient clinic between 2015 and 2017. Sociodemographic, clinical and laboratory data were obtained, along with CGA. From the primary data, we developed a modified-G8 score using 6 as the cut-off point, normal being &lt; 6 and abnormal being ≥ 6. The primary outcome was early death (occurring within up to 6 months) considered the gold standard for the accuracy study of modified-G8 as a predictor of early death. Through bivariate and Cox multivariate analysis, the risk for early death (Hazard Ratio - HR crude and adjusted) was determined. Overall survival was estimated using the Kaplan-Meier method, and the log-Rank test was used for comparisons according to the categorization of the scores. Results: Of the 889 participants included, 537 (60%) had modified G8 scores ≥ 6 (abnormal). The overall mean score was 9.9 ± 8.4; mean age was 72,5 years (range, 60–97 years), 38% were 60 and 70 years of age. Fifty-two percent of the participants were male. The most common tumor sites were prostate (31%) and breast (16%), followed by digestive and gynecological (both with 11%). On analysis of accuracy, we found sensitivity 91.7% (95% CI 86–95.7), specificity 45.7% (95% CI 42.1–49.4), positive predictive value 24.8% (95% CI 21.2–28.6) and negative predictive value 96.6% (95% CI 94.1–98.2), area under the ROC curve 81.7% (95% CI 77.9–85.4). The crude HR for early death among those who had abnormal scores was 8.3 (95% CI 4.6–14.9) and the age-adjusted HR, tumor site and metastatic disease at diagnosis was 4.5 (95% CI 2.5–8.3) times greater and survival was lower (log-rank p 0.001). Conclusions: The modified G8 predicted early death in an elderly population (≥ 60 years) with cancer in a northeastern Brazilian institution. Satisfactory prognostic accuracy was obtained. This instrument could reduce the number of patients who would follow-up with CGA, saving time and resources, and accelerating individualized treatment.

Delayed Colonoscopy Following a Positive Fecal Test Result and Cancer Mortality.

BackgroundA fecal test followed by diagnostic colonoscopy for a positive result is a widely endorsed screening strategy for colorectal cancer (CRC). However, the relationship between the time delay from the positive test to the follow-up colonoscopy and CRC mortality has not been established.MethodsFrom a population-based screening program, we identified CRC patients newly diagnosed from 2005 through 2015 by a positive fecal occult test followed by a colonoscopy. The primary outcome measure was CRC-specific mortality according to four categories for the time elapsed between the positive result and the subsequent colonoscopy.ResultsThe 1749 patients underwent colonoscopies within 0–3 months (n = 981, 56.1%), 4–6 months (n = 307, 17.5%), 7–12 months (n = 157, 9.0%), and later than 12 months (n = 304, 17.4%). CRC-specific deaths according to exposure groups were: 13.8% (135 of 981) for 0–3 months, 10.7% (33 of 307) for 4–6 months (crude hazards ratio [HR] = 0.74, 95% confidence interval [CI] = 0.51 to 1.14), 11.5% (18 of 157) for 7–12 months (crude HR = 0.83, 95% CI = 0.51 to 1.42), and 22.7% (69 of 304) for longer than 12 months (crude HR = 1.40, 95% CI = 1.04 to 1.90). The only variable that was associated with mortality risk was the number of positive slides (P = .003). High positivity was twice the value in the 0–3 as the longer-than-12 months group: 51.9% vs 25.0% and similar for the 4–6 and 7–12 months groups (38.1% and 36.5%), respectively. The adjusted HRs for CRC mortality were 0.81 (95% CI = 0.55 to 1.19); 0.83 (95% CI = 0.50 to 1.41), and 1.53 (95% CI = 1.13 to 2.12, P = .006) for the 4–12, 7–12, and longer-than-12-months groups, respectively, compared with the shortest delay group.ConclusionsAmong screen-diagnosed CRC patients, performance of colonoscopy more than 12 months after the initial positive fecal occult blood test was associated with more advanced disease and higher mortality due to CRC.

IgM antibodies against phosphorylcholine measured early after acute ST-elevation myocardial infarction in relation to atherosclerotic disease burden and long-term clinical outcome.

PurposeStudies have reported an association between low levels of natural immunoglobulin M antibodies against phosphorylcholine(IgM anti-PC) and worse prognosis in patients with coronary artery disease (CAD). The aims of the present study were, in patients with ST-elevation myocardial infarction (STEMI); 1) to compare serum levels of IgM anti-PC measured acutely and after 3 months; 2) to study an association between levels of IgM anti-PC and the severity ofCAD, and; 3) to investigate whether IgM anti-PC levels are associated with long-term clinical outcome.MethodsA total of 213 patients without known diabetes (median age 59 years) with a PCI treated STEMI were enrolled. IgM anti-PC was measured in-hospital and after 3 months. Median follow-up time was 6.5 years (all-cause mortality, non-fatal myocardial re-infarction, recurrent ischemia causing hospital admission, heart failure and stroke). The severity of CAD was evaluated by coronary angiograms and patients were classified as having single- or multi-vessel disease and by SYNTAX score (SXscore).ResultsIgM anti-PC levels were stable over time when measured acutely and after 3 months. Patients with multi-vessel disease and high SXscore had significantly lower levels of IgM anti-PC in the acute phase of STEMI. Low levels of IgM anti-PC (the 25 percentile) measured acutely were associated with a 2-fold increase in the odds of having multi-vessel disease (adjusted OR 2.28 (95% CI 1.17, 4.44), p = 0.016), but not with high SXscore (Crude OR 2.20 (95% CI 0.96, 5.07), p = 0.06). Fifty-three patients experienced a new clinical event during long-term follow-up. Low levels of IgM anti PC were not associated with worse prognosis, (crude HR 1.54 (0.87–2.76), p = 0.14).ConclusionSTEMI patients with multi-vessel disease or high SXscore had significantly lower levels of IgM anti-PC in the acute phase and low levels were associated with multi-vessel disease, but not with worse clinical outcome during long-term follow-up.

Bidirectional association between migraine and fibromyalgia: retrospective cohort analyses of two populations

ObjectiveFibromyalgia (FM) and migraine are common pain disorders that tend to coexist. This study determined whether these two conditions exhibited any mutual influences.SettingCohort study.ParticipantsA retrospective, longitudinal cohort study was conducted...