Platelet hyperaggregability in patients with atrial fibrillation

Objective

Atrial fibrillation (AF) is a condition where platelet hyperaggregability is commonly present. We examined potential physiological bases for platelet hyperaggregability in a cohort of patients with acute and chronic AF. In particular, we sought to identify the impact of inflammation [myeloperoxidase (MPO) and C-reactive protein (CRP)] and impaired nitric oxide (NO) signaling.

Methods

Clinical and biochemical determinants of adenosine diphosphate (ADP)-induced platelet aggregation were sought in patients (n?=?106) hospitalized with AF via univariate and multivariate analysis.

Results

Hyper-responsiveness of platelets to ADP was directly (r?=?0.254, p?<?0.01) correlated with plasma concentrations of thrombospondin-1 (TSP-1), a matricellular protein that impairs NO responses and contributes to development of oxidative stress. In turn, plasma TSP-1 concentrations were directly correlated with MPO concentrations (r?=?0.221, p?<?0.05), while MPO concentrations correlated with those of asymmetric dimethylarginine (ADMA, r?=?0.220, p?<?0.05), and its structural isomer symmetric dimethylarginine (SDMA, r?=?0.192, p?=?0.05). Multivariate analysis identified TSP-1 (β?=?0.276, p?<?0.05) concentrations, as well as female sex (β?=?0.199, p?<?0.05), as direct correlates of platelet aggregability, and SDMA concentrations (β?=???0.292, p?<?0.05) as an inverse correlate.

Conclusion

We conclude that platelet hyperaggregability, where present in the context of AF, may be engendered by impaired availability of NO, as well as via MPO-related inflammatory activation.

     

Intermittent and constant pain and physical function or performance in men and women with knee osteoarthritis: data from the osteoarthritis initiative

Severe constant and intermittent knee pain are associated with “unacceptable” symptoms in older adults with osteoarthritis (OA) [22]. We hypothesized that constant and intermittent pain would be independently related to physical function, with intermittent knee pain being a better predictor of future declines in physical function in early symptomatic knee OA. This study included men (n?=?189) and women (n?=?133) with radiographic, unilateral knee OA, observed using data from the Osteoarthritis Initiative (OAI). Pain types were measured using the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale. Physical function was measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC-PF) and Knee Injury and Osteoarthritis Outcome Score (KOOS-FSR) and physical performance tests. High baseline intermittent (B?=?0.277; p?=?0.001) and constant (B?=?0.252; p?=?0.001) knee pain were related to poor WOMAC-PF. Increased constant (B?=?0.484; p?=?0.001) and intermittent (B?=?0.104; p?=?0.040) pain were related to 2-year decreased WOMAC-PF. High baseline intermittent knee pain predicted poor KOOS-FSR at year 2 (B?=??0.357; p?=?0.016). Increased constant pain was related to decreased chair stand test performance over 2 years in women (B?=?0.077; p?=?0.001). High baseline intermittent pain was related to poor performance on repeated chair stands (B?=?0.035; p?=?0.021), while baseline constant pain was related to poor 400-m walk performance in women (B?=?0.636; p?=?0.047). Intermittent and constant knee pain were independent factors in self-perceived physical function and were important predictors of future limitations in physical function. Identifying intermittent and constant pain in early symptomatic OA may allow patients to adopt strategies to prevent worsening pain and future declines in physical function.     

Volatile Organic Compounds in Exhaled Breath of Idiopathic Pulmonary Fibrosis for Discrimination from Healthy Subjects

Purpose Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p?<?0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p?<?0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r?=?0.393, p?=?0.013), %VC (r?=?0.569, p?<?0.001), FVC (r?=??0.440, p?=?0.004), %FVC (r?=?0.539, p?<?0.001), DLco (r?=?0.394, p?=?0.018), and %DLco (r?=?0.413, p?=?0.008) and a positive correlation with KL-6 (r?=?0.432, p?=?0.005) were found for p-cymene. Conclusion We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.     

<Emphasis Type="Italic">Vegf-A</Emphasis> mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation

Aims/hypothesis

The initial avascular period following islet transplantation seriously compromises graft function and survival. Enhancing graft revascularisation to improve engraftment has been attempted through virus-based delivery of angiogenic triggers, but risks associated with viral vectors have hampered clinical translation. In vitro transcribed mRNA transfection circumvents these risks and may be used for improving islet engraftment.

Methods

Mouse and human pancreatic islet cells were transfected with mRNA encoding the angiogenic growth factor vascular endothelial growth factor A (VEGF-A) before transplantation under the kidney capsule in mice.

Results

At day 7 post transplantation, revascularisation of grafts transfected with Vegf-A (also known as Vegfa) mRNA was significantly higher compared with non-transfected or Gfp mRNA-transfected controls in mouse islet grafts (2.11- and 1.87-fold, respectively) (vessel area/graft area, mean?±?SEM: 0.118?±?0.01 [n?=?3] in Vegf-A mRNA transfected group (VEGF) vs 0.056?±?0.01 [n?=?3] in no RNA [p?<?0.05] vs 0.063?±?0.02 [n?=?4] in Gfp mRNA transfected group (GFP) [p?<?0.05]); EndoC-bH3 grafts (2.85- and 2.48-fold. respectively) (0.085?±?0.02 [n?=?4] in VEGF vs 0.030?±?0.004 [n?=?4] in no RNA [p?<?0.05] vs 0.034?±?0.01 [n?=?5] in GFP [p?<?0.05]); and human islet grafts (3.17- and 3.80-fold, respectively) (0.048?±?0.013 [n?=?3] in VEGF vs 0.015?±?0.0051 [n?=?4] in no RNA [p?<?0.01] vs 0.013?±?0.0046 [n?=?4] in GFP [p?<?0.01]). At day 30 post transplantation, human islet grafts maintained a vascularisation benefit (1.70- and 1.82-fold, respectively) (0.049?±?0.0042 [n?=?8] in VEGF vs 0.029?±?0.0052 [n?=?5] in no RNA [p?<?0.05] vs 0.027?±?0.0056 [n?=?4] in GFP [p?<?0.05]) and a higher beta cell volume (1.64- and 2.26-fold, respectively) (0.0292?±?0.0032 μl [n?=?7] in VEGF vs 0.0178?±?0.0021 μl [n?=?5] in no RNA [p?<?0.01] vs 0.0129?±?0.0012 μl [n?=?4] in GFP [p?<?0.001]).

Conclusions/interpretation

Vegf-A mRNA transfection before transplantation provides a promising and safe strategy to improve engraftment of islets and other cell-based implants.

     

Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4–14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p?=?0.007), lower physical activity (p?=?0.028), longer disease duration (p?=?0.019), worse predicted DLCO/VA and FVC (p?=?0.009, respectively), worse disease severity according to Medsger severity score (p?<?0.001), lower hemoglobin (p?=?0.023), and fat-free mass (p?<?0.001) and were more often sarcopenic (p?<?0.001). In multivariate analysis, only FVC (p?=?0.006) and disease severity (p?=?0.003), in particular for the lungs (p?=?0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\140 patients (20.7%; 95% CI, 14.0–27.4%); 11\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p?=?0.049), worse DLCO/VA (p?=?0.002), and lung (p?=?0.006) and skin (p?=?0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.     

Neutrophil-to-Lymphocyte Ratio Predicts Outcome in Limited Disease Small-cell Lung Cancer

Introduction

Patients with limited disease small-cell lung cancer (SCLC) receive radiochemotherapy followed by prophylactic cranial irradiation. The prognosis of these patients remains poor with a median survival of 16–24 months. Systemic inflammation was suggested as an important prognostic factor for outcomes. This study investigated the impact of systemic inflammation measured with neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at first diagnosis in patients with limited disease SCLC for outcomes.

Methods

Data of 65 patients receiving radiochemotherapy for limited disease SCLC were analyzed. NLR and PLR were obtained from blood sample at first diagnosis of SCLC and 12 characteristics including gender, age, ECOG, T-category, N-category, pack years, smoking during radiotherapy, respiratory insufficiency, hemoglobin levels during radiotherapy, radiation dose (<56 vs. ≥56 Gy), concurrent radiochemotherapy, and prophylactic cranial irradiation (PCI) were evaluated for local control, metastasis-free survival, and overall survival.

Results

Survival rates at 1, 2, and 3 years were 71, 45, and 28%, respectively. Median survival time was 20 months. Independent factors for improved survival were NLR?<?4 (p?=?0.03), ECOG 0–1 (p?=?0.002), and PCI (p?=?0.015). Lower T-category was an independent positive factor of local control (p?=?0.035). Improved metastasis-free survival was associated with NLR?<?4 (p?=?0.011), ECOG 0–1 (p?=?0.002), N-category 0–1 (p?=?0.048), non-smoking during radiotherapy (p?=?0.009), and PCI (p?=?0.006).

Conclusion

NLR was found to be an independent prognostic factor for overall survival. The evaluation of NLR can help identify patients with poor prognosis and appears a useful prognostic marker in clinical practice. A prospective analysis is warranted to confirm these findings.

     

Time from colorectal cancer diagnosis to laparoscopic curative surgery—is there a safe window for prehabilitation?

Background

There is a growing interest in the adoption of formal prehabilitation programmes prior to elective surgery but regulatory targets mandate prompt treatment following cancer diagnosis. We aimed to investigate if time from diagnosis to surgery is linked to short- and long-term outcomes.

Methods

An exploratory analysis was performed utilising a dedicated, prospectively populated database. Inclusion criteria were biopsy-proven colorectal adenocarcinoma undergoing elective laparoscopic surgery with curative intent. Demographics, date of diagnosis and surgery was captured with patients dichotomised using 4-, 8- and 12-week time points. All patients were followed in a standardised pathway for 5 years. Overall survival was assessed with the Kaplan-Meier log-rank method.

Results

Six hundred sixty-eight consecutive patients met inclusion criteria. Mean time from diagnosis to surgery was 53 days (95% CI 48.3–57.8). Identified risk factors for longer time to surgery were males (OR 1.92 [1.2–3.1], p?=?0.008), age?≤?65 (OR 1.9 [1.2–3], p?=?0.01), higher ASA scores (p?=?0.01) stoma formation (OR 6.9 [4.1–11], p?<?0.001) and neoadjuvant treatment (OR 5.06 [3.1–8.3], p?<?0.001). There was no association between time to surgery and BMI (p?=?0.36), conversion (16.3%, p?=?0.5), length of stay (p?=?0.33) and readmission or reoperation (p?=?0.3). No differences in five-year survival were seen in those operated within 4, 8 and 12 weeks (p?=?0.397, p?=?0.962 and p?=?0.611, respectively). Multivariate analysis showed time from diagnosis to surgery was not associated with five-year overall survival (HR 0.99, p?=?0.52).

Conclusion

Time from colorectal cancer diagnosis to curative laparoscopic surgery did not impact on overall survival. This finding may allow preoperative pathway alteration without compromising safety.

     

Does laparoscopic intracorporeal ileocolic anastomosis decreases surgical site infection rate? A propensity score-matched cohort study

Aim

Foreshortened mesentery or thick abdominal wall constitutes a rationale for laparoscopic intracorporeal ileocolic anastomoses (ICA). The aim of this study was to compare intracorporeal to extracorporeal ICA in terms of surgical site infections in patients with Crohn’s ileitis and overweight patients with right colon tumors.

Method

This was a prospective propensity score-matched cohort study enrolling consecutive patients with Crohn’s terminal ileitis and overweight patients with right colon tumors undergoing elective laparoscopic right colon resection with intracorporeal or extracorporeal ICA. Propensity score matching with a 1:1 ratio was employed to compare diagnosis-matched patients for age, BMI, ASA, and previous abdominal surgery.

Results

Overall, 453 patients were enrolled: 233 intracorporeal vs. 220 extracorporeal. Propensity score matching left 195 intracorporeal and 195 extracorporeal patients comparable for age (p?=?0.294), gender (p?=?0.683), ASA (p?=?0.545), BMI (p?=?0.079), previous abdominal surgery (p?=?0.348), and diagnosis (p?=?0.301). Conversion rates (5.1 vs. 3.6%; p?=?0.457) and intraoperative complications (1 vs. 2.1%; p?=?0.45) were similar. Overall morbidity (5.1 vs. 12.8%; p?=?0.008) and re-intervention rates (3.1 vs. 8.7%; p?=?0.029) were significantly higher in extracorporeal patients. Anastomotic leak rates (0.5 vs. 1.5%; p?=?0.623) did not differ. Incisional SSI rate was significantly higher in extracorporeal patients (p?=?0.01).

Conclusion

Laparoscopic intracorporeal ICA reduced incisional SSI rates as compared to its extracorporeal counterpart.

     

Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p?<?0.001), followed by recovery over 6 months. The conditioning regimen for SCT showed no correlation with HRQOL at T2 (p?=?0.283) or T3 (p?=?0.799), with no significant difference in HRQOL between allogeneic and autologous SCT recipients at T2 (p?=?0.829) or T3 (p?=?0.824). Depression (p?=?0.042), pain (p?=?0.023), and appetite loss (p?=?0.004) negatively influenced HRQOL at T1, whereas only pain (p?=?0.048) remained an important factor at T2. Six months after SCT, the two most frequent symptoms, fatigue and financial problems, became major factors (p?=?0.004 and p?=?0.005, respectively). Depression began to play an important role in HRQOL again at T3 (p?=?0.040). These findings demonstrate that SCT recipients need both psychological and medical support to achieve a better HRQOL after SCT.     

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n?=?15) had definite PAH; group 2 (n?=?19) had interstitial lung disease (ILD); group 3 (n?=?30) were SSc-controls; and group 4 (n?=?34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0?±?85.4 vs 380.4?±?168.3 ng/mL, p?=?0.136), SSc-controls (263.0?±?85.4 vs 253.1?±?98.0 ng/mL, p?=?1.00), or healthy controls (263.0?±?85.4 vs 201.8?±?57.2 ng/mL, p?=?0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2?±?434.9 vs 1424.8?±?527.6 ng/mL, p?=?1.00) and SSc-controls (1476.2?±?434.9 vs 1409.5?±?341.1 ng/mL, p?=?1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4?±?134.0 vs 201.8?±?57.2 ng/mL, p?<?0.0001) and VCAM-1 compared to healthy controls (1432.7?±?427.4 vs 1125.6?±?273.4 ng/mL, p?<?0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.     

Association between arterial stiffness,disease activity and functional impairment in ankylosing spondylitis patients: a cross-sectional study

Cardiovascular risk is an important factor for increased morbidity and mortality in patients with ankylosing spondylitis. The aim of this study is to assess arterial stiffness in relation to the disease activity and functional limitation in patients with ankylosing spondylitis. Twenty-four patients (mean age 45.8?±?11.7 years) suffering of ankylosing spondylitis (disease duration 11.1?±?5.1 years) and 24 gender and age-matched healthy controls were included in the study. Clinical, biological, and functional status of ankylosing spondylitis patients was recorded. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) and pulse wave analysis (PWA) was performed using applanation tonometry. We found significant differences between ankylosing spondylitis patients and healthy controls in regard to PWV (p?=?0.047), aortic augmentation pressure—AP (p?=?0.028), augmentation index—AIx (p?=?0.038) and aortic augmentation index adjusted for heart rate—AIx75 (p?=?0.011). PWV and AIx75 were significantly associated with the disease functioning score—BASFI (p?=?0.012, r?=?0.504; p?=?0.041, r?=?0.421). Aortic AP and augmentation indexes (AIx and AIx75) were all associated to ASDAS score (p?=?0.028, r?=?0.448; p?=?0.005, r?=?0.549; p?=?0.025, r?=?0.455). Our study showed that ankylosing spondylitis patients have a higher arterial stiffness than the age-matched controls, leading to an increased cardiovascular risk. We found that arterial stiffness is positively associated with disease activity and functional impairment. Chronic spondiloarthropaties should be screened for arterial stiffness, even in the absence of traditional cardiovascular risk factors, in order to benefit from primary prevention measures.     

Disease severity impacts the relationship of apelin with arterial function in patients with rheumatoid arthritis

Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic pressure (CSP), central pulse pressure (CPP), peripheral pulse pressure (PPP), pulse pressure amplification (PPamp), and forward wave pressure (Pf)) among 170 RA patients without cardiovascular disease. In multivariable regression models, apelin concentrations were not independently associated with arterial function measures (p?≥?0.15) in all patients. Inflammation markers were not consistently associated with apelin levels but joint deformity counts, Disease Activity Score in 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) impacted apelin-pressure pulsatility relations (interaction p?≤?0.05). In stratified analysis, apelin was associated with CSP (partial r?=???0.33, p?=?0.01), CPP (partial r?=???0.26, p?=?0.04), PPamp (partial r?=?0.27, p?=?0.03), and Pf (partial r?=???0.33, p?=?0.01) in patients without but not with joint deformities; apelin was related to CSP (partial r?=???0.24, p?=?0.05) in those with a DAS28 joint <?2.8 (median value) (partial r?=???0.24, p?=?0.05) but not ≥?2.8, and to CSP (partial r?=???0.36, p?=?0.003) in those with an erythrocyte sedimentation rate <?13 mm/h (median value) but not ≥?13 mm/h. Apelin is associated with reduced pressure pulsatility in RA patients without but not with a high inflammatory burden. A loss of apelin protective effects on arterial function may contribute to the link between RA severity and cardiovascular risk.     

Differential methylation of genes in individuals exposed to maternal diabetes in utero

Aims/hypothesis

Individuals exposed to maternal diabetes in utero are more likely to develop metabolic and cardiovascular diseases later in life. This may be partially attributable to epigenetic regulation of gene expression. We performed an epigenome-wide association study to examine whether differential DNA methylation, a major source of epigenetic regulation, can be observed in offspring of mothers with type 2 diabetes during the pregnancy (OMD) compared with offspring of mothers with no diabetes during the pregnancy (OMND).

Methods

DNA methylation was measured in peripheral blood using the Illumina HumanMethylation450K BeadChip. A total of 423,311 CpG sites were analysed in 388 Pima Indian individuals, mean age at examination was 13.0 years, 187 of whom were OMD and 201 were OMND. Differences in methylation between OMD and OMND were assessed.

Results

Forty-eight differentially methylated CpG sites (with an empirical false discovery rate ≤0.05), mapping to 29 genes and ten intergenic regions, were identified. The gene with the strongest evidence was LHX3, in which six CpG sites were hypermethylated in OMD compared with OMND (p?≤?1.1?×?10^?5). Similarly, a CpG near PRDM16 was hypermethylated in OMD (1.1% higher, p?=?5.6?×?10^?7), where hypermethylation also predicted future diabetes risk (HR 2.12 per SD methylation increase, p?=?9.7?×?10^?5). Hypermethylation near AK3 and hypomethylation at PCDHGA4 and STC1 were associated with exposure to diabetes in utero (AK3: 2.5% higher, p?=?7.8?×?10^?6; PCDHGA4: 2.8% lower, p?=?3.0?×?10^?5; STC1: 2.9% lower, p?=?1.6?×?10^?5) and decreased insulin secretory function among offspring with normal glucose tolerance (AK3: 0.088 SD lower per SD of methylation increase, p?=?0.02; PCDHGA4: 0.08 lower SD per SD of methylation decrease, p?=?0.03; STC1: 0.072 SD lower per SD of methylation decrease, p?=?0.05). Seventeen CpG sites were also associated with BMI (p?≤?0.05). Pathway analysis of the genes with at least one differentially methylated CpG (p?<?0.005) showed enrichment for three relevant biological pathways.

Conclusions/interpretation

Intrauterine exposure to diabetes can affect methylation at multiple genomic sites. Methylation status at some of these sites can impair insulin secretion, increase body weight and increase risk of type 2 diabetes.

     

Pulmonary Arterial Hemodynamic Assessment by a Novel Index in Systemic Sclerosis Patients: Pulmonary Pulse Transit Time

Objectives

Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune connective tissue disease that is associated with vascular lesions, and fibrosis of the skin and visceral organs. Cardiac complications may occur as a secondary effect of SSc as a result of pulmonary arterial hypertension and interstitial lung disease. The objective of this study was to assess whether the pulmonary pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary arterial alterations in patients with SSc, prior to development of pulmonary hypertension.

Methods

Twenty-five SSc patients as a study group and 25 age- and sex-matched healthy volunteers for the control group were recruited to the study. Right ventricle function parameters, such as tricuspid annular plane systolic excursion (TAPSE), estimated pulmonary artery systolic pressure (ePASP), right ventricular dimensions, right ventricle fractional area changes, and myocardial perfusion index (MPI) were measured and calculated. Pulmonary pulse transit time was defined as the time interval between the R-wave peak in the ECG and the corresponding peak late systolic pulmonary vein flow velocity.

Results

Right ventricle myocardial performance index (RVMPI) and eSPAP were significantly higher in the SSc group than the controls (p?=?0.032, p?=?0.012, respectively). Pulmonary pulse transit time and TAPSE was shorter in the patients with SSc (p?=?0.006, p?=?0.015, respectively). In correlation analysis, pPTT was inversely correlated with RVMPI (r?=???0.435, p?=?0.003), eSPAP (r?=???0.434, p?=?0.003), and disease duration (r?=???0.595, p?=?0.003). Conversely, it positively correlated with TAPSE (r?=?0.345, p?=?0.022).

Conclusion

pPTT was found to be shorter in SSc patients. pPTT might serve as a surrogate marker of pulmonary hemodynamics in patients with SSc, even prior to the development of pulmonary hypertension.

     

Non-driver mutations in patients with <Emphasis Type="Italic">JAK2</Emphasis>V617F-mutated polycythemia vera or essential thrombocythemia with long-term molecular follow-up

JAK2V617F monitoring and NGS of non-driver genes was performed in 100 patients with polycythemia vera (PV) or essential thrombocythemia (ET) with long molecular follow-up. Patients who did not progress to myelofibrosis (MF) or acute myeloid leukemia (AML) after more than 10 years (n?=?50) showed a low frequency of mutations at first sample (18%) and an incidence rate of 1.7 new mutations?×?100 person-years. Mutations were detected at first sample in 83% of PV/ET patients who later progressed to AML (n?=?12) with these patients having a rate of 25.6 mutations?×?100 person-years. Presence of mutations at diagnosis was the unique risk factor for acquiring a new genetic event (HR 2.7, 95% CI 1.1–6.8, p?=?0.03) after correction for age, PV diagnosis, and total duration of hydroxyurea (HU) exposure. Patients with additional mutation at first sample showed a higher probability of developing cytopenia under HU therapy and a higher risk of AML (HR 12.2, 95% CI 2.6–57.1, p?=?0.001) with mutations in ASXL1 (p?<?0.0001), TP53 (p?=?0.01), SRSF2 (p?<?0.0001), IDH1/2 (p?<?0.0001), and RUNX1 (p?<?0.0001) being associated with a higher probability of AML. Myelofibrotic transformation was more frequent in patients with additional mutations, especially in SF3B1 (p?=?0.02) and IDH1/2 (p?<?0.0001) although a persistently high or a progressive increase of the JAK2V617F allele burden while receiving cytoreduction was the strongest predictor of MF transformation (HR 10.8, 95% CI 2.4–49.1, p?=?0.002). In conclusion, NGS may be useful to identify a minority of PV and ET patients with high genetic instability and increased risk of AML transformation.     

Neutrophil-lymphocyte ratio is associated with arterial stiffness in patients with peritoneal dialysis

Background

Patients with peritoneal dialysis are in the persistent inflammation state and have elevated arterial stiffness. Neutrophil-lymphocyte ratio(NLR) is a new inflammatory marker in renal and cardiac disorders. Brachial-ankle pulse wave velocity (baPWV) is a non-invasive measurement, which is widely used as a surrogate marker of arterial stiffness. However, there is little evidence to show an association between NLR and baPWV in patients with peritoneal dialysis. The aim of this cross-section study was to investigate the relationship between NLR and arterial stiffness measured by baPWV in patients with peritoneal dialysis.

Methods

In this cross-section study, 101 patients with peritoneal dialysis were enrolled from January 2014 to June 2015. According to average baPWV level (1847.54 cm/s), the patients were categorized into two groups, low group and high group. baPWV, which reflects arterial stiffness, was calculated using the single-point method. Clinical data were collected in details. NLR was calculated using complete blood count. Associations between NLR and baPWV were assessed using Pearson’s correlation and linear regression analysis.

Results

The NLR was significantly lower in the low baPWV group than in the high baPWV group (p?=?0.03). There were positive correlations between baPWV and neutrophil count (r?=?0.24, p?=?0.01) and NRL(r?=?0.43, P?<?0.01), and there was a negative correlation between baPWV and lymphocyte count (r?=?-0.23, p?=?0.01). In addition, albumin, phosphorous and intact parathyroid hormone showed negative correlations with baPWV (r?= ?0.32, p?<?0.01; r?= ?0.28, p?<?0.01; r?= ?0.25, p?=?0.01, respectively). Age and hsCRP showed positive correlations with baPWV (r?=?0.47, p?<?0.01; r?=?0.25, p?=?0.01). In multivariate analysis, NLR independently correlated with baPWV in patients with peritoneal dialysis (β?=?0.33, p?<?0.01), even after adjustment for various confounders.

Conclusion

Our study suggests that NLR was an independently associated with arterial stiffness in patients with peritoneal dialysis. However, further prospective studies are needed to confirm cause-and-effect relationship between NLR and baPWV, and to investigate whether anti-inflammatory treatment could improve arterial stiffness in patients with peritoneal dialysis.

     

Atherogenic index of plasma: a useful marker for subclinical atherosclerosis in ankylosing spondylitis

Ankylosing spondylitis (AS) is associated with an increased risk of atherosclerotic cardiovascular disease (ACD). The atherogenic index of plasma (AIP), which is the logarithmic transformation of the plasma triglyceride (TG) level to the high-density lipoprotein level (HDL) ratio, has been suggested to be a novel marker in the identification of atherosclerosis risk. Therefore, this study aims to determine if the AIP can act as an accurate marker for the detection of subclinical atherosclerosis. Fifty-two male patients with AS and 52 age-, gender-, and body mass index (BMI)-matched healthy control subjects were included in the study. For each patient, AIP and total cholesterol (TC)/HDL values were calculated and carotid artery intima-media thickness (cIMT) was measured. The mean (SD) cIMT and median (range) AIP values for AS patients were higher than that of the healthy control subjects (0.60?±?0.18 vs. 0.51?±?0.10, p?=?0.003 and 0.23 [??0.32 to 0.85] vs. 0.09 [??0.53 to 0.49], p?=?0.007, respectively). A positive correlation was found between the patients’ cIMT and AIP values (r?=?0.307, p?=?0.002) and TC/HDL values (r?=?0.241, p?=?0.014). Regression analysis revealed an independent association between the subclinical atherosclerosis and AIP (beta [β]?=?0.309, p?=?0.002). There were no independent correlations between subclinical atherosclerosis and TC (β?=?0.245, p?=?0.065), TG (β?=?0.185, p?=?0.515), HDL (β?=?0.198, p?=?0.231), TC/HDL (β?=?0.032, p?=?0.862), and low-density lipoprotein (LDL) (β?=?0.151, p?=?0.246). A strong and independent correlation exists between AIP and cIMT values. Therefore, the AIP could serve as a better marker than the TC/HDL ratio for the detection of subclinical atherosclerosis in AS patients.     

Fear of falling and foot pain,impairment and disability in rheumatoid arthritis: a case-control study

Fear of falling, foot pain, impairment and disability are commonly reported in rheumatoid arthritis (RA). However, the relationship between fear of falling and foot pain, impairment and disability has not been investigated in established RA. The aim of the study was to evaluate the relationship between fear of falling and foot pain, walking velocity and foot impairment and disability in women with established RA. A secondary aim was to evaluate differences between fear of falling, foot pain, walking velocity and foot impairment and disability in women with established RA and age- and sex-matched control participants. Twenty-one women with established RA and twenty-one age- and sex-matched controls were assessed for fear of falling, foot pain, foot impairment and disability and walking velocity. Pearson’s r-correlations were used to examine relationships between fear of falling and the foot measures. Independent samples t tests evaluated the differences in fear of falling and foot measures between the two groups. In people with RA, significant correlations were found between fear of falling and foot impairment (r?=?0.53, p?=?0.015), foot disability (r?=?0.77, p <0.001) and walking velocity (r?=?0.56, p?<?0.001). No correlation was found between fear of falling and foot pain (r?=?0.36; p?=?0.11). Significant differences between cases and control participants were found between fear of falling (p?=?0.001), foot impairment (p?=?0.004) and foot disability (p?<?0.001). Foot impairment and disability relates to fear of falling in women with established RA. A better understanding of fear of falling in people with established RA may contribute to more efficient falls assessments in order to identify at risk individuals.     

Arterial stiffness is associated with left ventricular dysfunction in patients with rheumatoid arthritis

Arterial stiffness (AS) has a detrimental effect on cardiovascular system particularly on left ventricle (LV). The aim of the study was to evaluate the impact of AS on LV functions in patients with rheumatoid arthritis (RA). Forty patients with RA and 25 age-sex matched control subjects (mean age 48.5?±?6.3 vs. 45.1?±?6.9 years, respectively, p?=?0.06) were enrolled in study. AS was assessed by carotid-femoral pulse wave velocity (CF-PWV) and heart rate corrected augmentation index (AIx@75) measured by applanation tonometry (SphygmoCor). LV function was evaluated using tissue Doppler-derived myocardial performance index (MPI) from lateral mitral annulus. CF-PWV (28.3?±?10.3 vs. 21.8?±?9.3 m/s, p?=?0.03), AIx@75 (10.2?±?2.3 vs. 9.2?±?1, %, p?=?0.01) and MPI (0.46?±?0.12 vs. 0.36?±?0.1, p?<?0.001) were significantly higher in patients with RA than in controls. LV MPI was found to be significantly positive correlated with CF-PWV, AIx@75, and ESR (r?=?0.360, p?=?0.005; r?=?0.334, p?=?0.009; r?=?0.293, p?=?0.023, respectively). Arterial stiffness parameters including CF-PWV and AIx@75 are associated with subclinical left ventricular dysfunction in patients with RA.