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.     

Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student’s t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p?<?0.0001). SP levels correlated with DAS28-CRP (r =?0.5050, p?<?0.0001), number of tender joints (NTJ, r =?0.4668, p?<?0.0001), number of swollen joints (NSJ, r?=?0.4439, p?<?0.0001), visual analogue scale (VAS, r?=?0.5131, p?<?0.0001). However, SP did not correlate with CRP levels (r?=?0.0468, p?=?0.6613), nor with the USPD (r?=?0.1740, p?=?0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.     

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.     

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.

     

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus

Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n?=?42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p?<?0.001). P-gp expression and function correlated with SLEDAI (r?=?0.49, p?=?0.005; and r?=?0.49, p?=?0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p?<?0.001 and p?<?0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.     

Serum ischemia modified albumin is a possible new marker of oxidative stress in phenylketonuria

The role of oxidative stress in the pathogenesis of phenylketonuria (PKU)-associated disorders has been implicated. Ischemia modified albumin (IMA) is a modified form of serum albumin, which is produced under the conditions of oxidative stress. The aim of this study was to measure the serum level of IMA in the PKU patients and to investigate its ability in predicting the status of oxidative stress in these patients. Fifty treated-PKU patients and fifty age- and sex-matched healthy subjects were included in the study. The blood samples were obtained and the serum level of phenylalanine (Phe) was measured using reverse phase HPLC method. The levels of IMA, malondialdehyde (MDA), gamma-glutamyl transferase (GGT) activity, and uric acid (UA) were determined using colorimetric methods. The levels of serum Phe, IMA, and MDA were significantly higher (p?<?0.001) and the level of UA (p?<?0.05) was lower in the PKU patients compared to control group. Serum IMA level was positively correlated with MDA (r?=?0.585, p?<?0.001) and UA (r?=?0.6, p?<?0.001). An inverse relationship was observed between the serum level of IMA and Phe (r?=?? 0.410, p?<?0. 01). Results of the present study suggest that serum IMA level could be used as a novel marker for the evaluation of oxidative stress in the PKU patients.     

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.

     

Seminal plasma zinc and magnesium levels and their relation to spermatozoa parameters in semen of diabetic men

There is a growing body of evidence that diabetic conditions are associated with sexual problems. Metabolism of trace elements is altered in diabetic mellitus, and they may have a specific role in the pathogenesis and progression of the disease. The aims of this study are to investigate the levels of zinc and magnesium in semen of patients with diabetes mellitus and to find out if there is any association between trace elements and semen parameters in these diabetic subjects. Semen samples from 25 diabetic men and 25 nondiabetic were analyzed for physical and biochemical parameters. Zinc (Zn) and magnesium (Mg) levels were estimated by atomic absorption spectrophotometry. Zn and Mg concentrations in seminal plasma of nondiabetic men were more elevated than in diabetic groups. Zn showed positive and significant correlations with sperm motility (p?<?0.05, r?=?0.52) and morphology (p?<?0.05, r?=?0.44). Mg was significantly correlated with sperm motility (p?<?0.05, r?=?0.51) and morphology (p?<?0.05, r?=?0.48). Seminal plasma Zn and Mg showed a negative correlation with HbA1c, which was statistically significant (r?=??0.380 and r?=??0.367, p?<?0.05). Zn and Mg deficiencies become visible as an additional risk factor in the development of diabetes, and they are involved in the pathogenesis of diabetes mellitus and its complications. Adequate administration of these elements may be an effective therapeutic intervention in the prevention of the progression of the diabetes and its complications, along with a glycemic control and control of other risk factors.     

Role of anti-GAD,anti-IA2 antibodies and C-peptide in differentiating latent autoimmune diabetes in adults from type 2 diabetes mellitus

Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes affecting adult patients who do not require insulin at diagnosis, positive for circulating islet autoantibodies and characterized by slower beta cell destruction. The study was aimed to identify and characterize LADA patients from clinically diagnosed type 2 diabetes mellitus (DM). We estimated anti-glutamic acid decarboxylase (anti-GAD), anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2) antibodies, fasting connecting peptide (C-peptide) and other clinical and biochemical parameters in 297 clinically diagnosed type 2 DM patients. The diagnosis of LADA was made by the presence of at least one pancreatic autoantibody, and thereafter LADA groups were compared with those of autoantibody-negative type 2 DM groups. The prevalence of LADA was found to be 15.2 % among patients presumed to have type 2 DM. There was significant difference concerning age of patients (p?<?0.001), body mass index (p?<?0.001), serum levels of C-peptide (p?<?0.001), insulin (p?<?0.001), total cholesterol (p?<?0.001), triglycerides (p?=?0.025), high-density lipoprotein cholesterol (HDL-C; p?=?0.004), low-density lipoprotein cholesterol (LDL-C; p?=?0.001) as well as insulin resistance (p?<?0.001) between LADA group and type 2 DM patients. In conclusion, anti-GAD antibody and C-peptide level determination can be considered as confirmatory diagnostic markers for LADA, along with anti-IA2 assay, while other clinical and biochemical parameters can be useful for further characterizing LADA patients.     

Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG)

Objective

We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement.

Methods

Statistical analysis was used to compare MRI measurements [midsagittal vermis relative diameter (MVRD) and volume] of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages.

Results

Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis. Results from a linear regression model showed that patients have a significantly lower MVRD and cerebellar volume compared to controls (p?<?0.001 and p?<?0.001 respectively). There was a significant negative correlation between age and MVRD for patients (p?=?0.014). The rate of cerebellar atrophy measured by the loss of MVRD and cerebellar volume per year was higher at early ages (r?=??0.578, p?=?0.012 and r?=??0.323, p?=?0.48 respectively), particularly in patients under 11 years (p?=?0.004). There was a significant positive correlation between MVRD and cerebellar volume in PMM2-CDG patients (r?=?0.669, p?=?0.001).

Conclusions

Our study quantifies a progression of cerebellar atrophy in PMM2-CDG patients, particularly during the first decade of life, and suggests a simple and reliable measure, the MVRD, to monitor cerebellar atrophy. Quantitative measurement of MVRD and cerebellar volume are essential for correlation with phenotype and outcome, natural follow-up, and monitoring in view of potential therapies in children with PMM2-CDG.

     

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.     

<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.

     

Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis

The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 μmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p?<?0.001), tumor necrosis factor alpha (TNF-α, p?<?0.001), TNF receptor 1 (TNFR1, p?=?0.038), TNF receptor 2 (TNFR2, p?<?0.001), and lower levels of PECAM (p?=?0.001), ICAM (p?<?0.001) and VCAM (p?=?0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p?<?0.001), disability evaluated by Expanded Disability Status Score EDSS (p?<?0.001), TNFR1 (p?=?0.039) and ICAM (p?=?0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p?<?0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.     

Predictors of impaired quality of life in patients with rheumatic diseases

Quality of life (QoL) is a complex outcome and rheumatologic patients typically exhibit several comorbidities with a negative impact. In this study, we analyzed with respect to QoL for the first time a wide range of physical and psychological factors, including individual, clinical and disease-related parameters, mental health disorders, sexual dysfunction, and cardiovascular comorbidities among consecutive rheumatologic patients. QoL was evaluated using the EuroQol 5D (EQ-5D) utility index. The Health Assessment Questionnaire (HAQ) Disability Index, and the HAQ Pain Visual Analogue Scale were used as measures of physical disability and arthritis-related pain, respectively. The Hamilton Anxiety Scale and Zung Self-Rating Depression Scale, the International Index of Erectile Function and the Female Sexual Functioning Index were completed by all patients. In total, 360 patients were included, 301 females and 59 males. In the univariate analysis, pain, physical disability (p?<?0.001 for both), disease duration (p?=?0.014), anxiety and depression (p?<?0.001 for both), as well as sexual dysfunction (p?=?0.001 for females, p?=?0.042 for males), correlated with QoL. Female sex (p?<?0.001), advanced age (p?=?0.029), lower educational level (p?=?0.005), and cardiovascular factors (hypertension, dyslipidemia, diabetes, lack of systemic exercise) also appeared to negatively affect QoL. However, in the multiple regression model, only anxiety, pain, physical disability (p?<?0.001 for all), and disease duration (p?=?0.019) remained significant predictors of QoL. The emotional side and the disease-related physiological mode of rheumatic diseases appear as major independent correlates of QoL among rheumatologic patients, who may thus benefit the most from combined supportive psychological and pain-relieving interventions.     

The influence of tumour site on prognosis in metastatic colorectal carcinomas with primary tumour resection

Purpose

The aim of our study was to compare the characteristics and prognosis between right- and left-sided metastatic colorectal carcinomas.

Methods

Data from 937 patients with stage IV colorectal carcinomas (synchronous distant metastasis) who had a resection of the primary tumour between 1985 and 2014 were analysed. Carcinomas in the caecum to transverse colon were defined as right-sided (n?=?250; 26.7%). They were compared to tumours located from the splenic flexure to the rectum categorised as left-sided (n?=?687; 73.3%).

Results

In right-sided carcinomas, we observed significantly more female patients (50.8 vs 36.2%; p?<?0.001), more unfavourable histological types (24.0 vs 8.6%; p?<?0.001), more M1c carcinomas (metastases to the peritoneum?±?others; 32.0 vs 14.4%; p?<?0.001) and more emergencies (11.6 vs 7.1%; p?=?0.029), while multimodal treatment was utilised in fewer patients (51.6 vs 63.8%; p?=?0.001) and curative resections were less frequently (24.1 vs 35.4%; p?=?0.002). Prognosis was significantly worse in patients with right-sided carcinomas (2-year-survival 27.2 vs 44.6%, p?<?0.01). This difference was more pronounced after R2 resection (15.3 vs 29.7%; p?<?0.001), than after macroscopic curative resection (2-year-survival 63.9 vs 71.9%; p?=?0.106). In multivariate Cox regression analysis, tumour site was found to be an independent prognostic factor for overall survival (HR 1.2; 95% CI 1.0–1.5; p?=?0.012). During the three 10-year periods, the prognosis improved equally in patients with right- and left-sided carcinomas, while the differences in survival remained identical.

Conclusions

In a surgical patient cohort undergoing primary tumour resection, significant differences in prognosis were observed between patients with metastatic right- and left-sided colorectal carcinomas.

     

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.     

Clinical Determinants of Incremental Shuttle Walk Test in Adults with Bronchiectasis

Introduction

Exercise capacity is impaired in patients with bronchiectasis. Incremental shuttle walk test (ISWT) stresses cardiorespiratory system physiologically to symptom-limited maximal exercise capacity. The purpose of this study was to investigate the clinical determinants of ISWT in adults with non-cystic fibrosis (CF) bronchiectasis.

Methods

Forty-one clinically stable bronchiectasis patients aged 18–72 years (27 females, 14 males) participated in the study. Subjects’ demographics and physical characteristics were recorded. Bronchiectasis Severity Index was used to identify disease severity. Pulmonary function test was performed. Dyspnea perception was assessed using the modified Medical Research Council Dyspnea Scale. Maximum inspiratory and expiratory pressures were measured. Peripheral muscle strength using a hand held dynamometer was measured. ISWT was performed to determine exercise capacity. Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Leicester Cough Questionnaire were used to determine fatigue, psychosocial status, and quality of life.

Results

Patients’ mean ISWT distance was 469.5 m. The ISWT distance was significantly related with age (r?=???0.472), height (r?=?0.469), gender (r?=?0.520), FEV₁ (r?=?0.651), and FVC (r?=?0.545, p?<?0.05). Quadriceps muscle strength was higher in males (p?=?0.001) as compared to females. Age and gender were identified as independent predictors of the ISWT, explaining 42% of variance in ISWT distance (r?=?0.649, r²?=?0.421, F_(2,38)?=?13.794, p?<?0.001).

Conclusion

The clinical determinants of ISWT in clinically stable patients with non-CF bronchiectasis are age and gender. Pulmonary function, dyspnea perception, muscle strength, disease severity, fatigue, psychosocial factors, and health-related quality of life seems to have an independent effect on ISWT in this group of patients with bronchiectasis.

     

The significance of urinary beta-2 microglobulin level for differential diagnosis of familial Mediterranean fever and acute appendicitis

The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. The present study aims to investigate the urinary beta-2 microglobulin (U-β₂M) level as a potential parameter to identify these two diseases mimicking each other. A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1–1.5 mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens U-β₂M, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. U-β₂M levels were significantly higher in acute appendicitis group compared to FMF attack, FMF non-attack, and control groups (p?<?0.001, p?<?0.001, and p?<?0.001, respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF attack, and FMF non-attack groups compared to controls (U-NAG p?<?0.001, p?=?0.016, p?=?0.004, microalbuminuria p?<?0.001, p?<?0.001, p?<?0.001, respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF attack group (p?=?0.004). Determination of U-β₂M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment and acute appendicitis. However, this finding should be substantiated with other studies.     

Fractional anisotropy of white matter,disability and blood iron parameters in multiple sclerosis

Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n?=?107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS). FA was recorded in 48 white matter tracts in 11 of the female patients with MS and 12 female controls. Results: In patients with high disability scores the mean FA was significantly lower (0.34?±?0.067) than in the control group (0.45?±?0.036; p?=?0.04), while patients with low disability had mean FA values (0.44?±?0.014) similar to controls (p?=?0.5). Positive associations were found between FA and the iron parameters serum iron, ferritin and percentage transferrin saturation (%Tfsat) in all the white matter tracts. For % Tfsat, the associations were highly significant in 14 tracts (p?<?0.01; r-values 0.74–0.84) and p?<?0.001 (r?=?0.83) in the superior fronto occipital fasciculus (LH). In the whole patient group a trend was found towards an inverse association between the EDSS and the %Tfsat (r?=??0.26, p?=?0.05) after excluding male gender and smoking as confounders, suggesting reduced disability in the presence of higher blood iron parameters. Additionally, significant inverse associations between disease duration and haemoglobin (p?=?0.04) as well as %Tfsat (p?=?0.02) suggested that patients with MS may experience a decrease in blood iron concentrations over time.     

Oncologic outcome of colorectal cancer patients over age 80: a propensity score-matched analysis

Purpose

It remains unclear whether old age is a poor prognostic factor in colorectal cancer (CRC). We compared oncologic outcomes in CRC patients according to age, using 80 as the dividing point.

Methods

CRC patients who underwent radical surgery from 2000 to 2011 were evaluated. We performed matched and adjusted analyses comparing oncologic outcomes between patients with ≥?80 and <?80 years old.

Results

Among 9562 patients, 222 were elderly. The median age was 82.0 years in elderly patients and 59.0 years in young patients. Elderly patients received less neoadjuvant or adjuvant therapy compared to young patients (p?<?0.001). After recurrence, significantly fewer elderly patients received additional treatments (p?<?0.001). Before matching, disease-free survival (DFS) and cancer-specific survival (CSS) were significantly lower for elderly patients compared to those for young patients (p?<?0.001 and p?<?0.001, respectively). After matching, DFS and CCS were not significantly different between the two groups (p?=?0.400 and p?=?0.267, respectively). In a multivariate analysis for prognostic factors, old age was not an independent poor prognostic factor of DFS and CCS (p?=?0.619 and p?=?0.137, respectively).

Conclusions

Elderly patients aged ≥?80 years with CRC had similar oncologic outcome to young patients, and age was not an independent prognostic factor.