Functioning and health-related quality of life in Chinese patients with systemic sclerosis: a case–control study

The objective of the study was to study the functioning and health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) and its associated factors. Consecutive SSc patients and an equal number of age- and gender-matched healthy controls were recruited for the assessment of functioning and HRQoL by the Health assessment questionnaire disability index (HAQ-DI) and Medical Outcomes Study Short Form 36 (SF-36), respectively. The extent of skin involvement of SSc was assessed by the modified Rodnan skin score (mRSS), and disease severity was assessed by the Medsger severity index. Factors associated with functioning and HRQoL in SSc patients were studied by linear regression. Seventy-eight Chinese SSc patients were studied (87 % women; age 50.2?±?12.1 years; disease duration 7.8?±?6.5 years; 81 % limited cutaneous subtype). The median mRSS of the patients was 8 (IQR 0–10). Patients with SSc had significantly higher HAQ-DI (0.69?±?0.69 vs 0.04?±?0.18; p?<?0.001) but lower SF36 scores (p?<?0.05 in all domains) than matched controls. Linear regression revealed that the mRSS was inversely associated with the physical component (beta?=??0.39; p?=?0.001) and mental component scores (beta?=??0.27; p?=?0.031) of the SF36 but positively correlated with the HAQ-DI score (beta?=?0.51; p?<?0.001) adjusted for age, sex, and disease duration. The SF36 and HAQ-DI scores also correlated significantly with the Medsger SSc severity index in the general, peripheral vascular, skin, tendon/joint, and heart domains. SSc patients had impaired physical and social functioning and poorer HRQoL than healthy individuals. The extent of skin involvement, tendon/joint contracture, damage in the heart, and peripheral vascular system were associated with poorer functioning and HRQoL.     

Decreased interleukin-20 level in patients with systemic sclerosis: are they related with angiogenesis?

In this study, we aimed to evaluate the relation between angiogenesis indicators and T helper 17 cytokine group in patients with systemic sclerosis (SSc) which is a disease characterized by impaired angiogenesis and autoimmune response. In our study, patients with SSc are compared with patients with primary Raynaud’s phenomenon (RP) and healthy controls. Forty SSc patients, 18 primary RP cases, and 20 healthy controls were included in our study. The demographic and clinical features of patients with SSc were recorded. The serum levels of vascular endothelial growth factor (VEGF), vascular endothelial (VE)-cadherin, interleukin (IL)-20, IL-22, and IL-23 were assessed. In the SSc group, IL-20 level was significantly lower than in both primary RP group and controls (p values <0.001). VE-cadherin level in SSc was significantly higher than in primary RP (p?=?0.016). The IL-22 and IL-23 and VEGF levels of SSc, primary RP, and control groups were similar (p values >0.05). In SSc patients, IL-23 correlated negatively with VEGF (r?=??0.36, p?=?0.025) and positively with VE-cadherin (r?=?0.55, p?<?0.001). IL-20 levels in SSc patients correlated with disease duration (r?=?0.32, p?=?0.044). SSc patients with limited involvement had significantly higher VE-cadherin levels than SSc patients with diffuse involvement (p?=?0.044). We observed that IL-20 which is an IL-10 group angiogenesis indicator was observed to be suppressed in SSc, suggesting abnormal angiogenesis.     

Peripheral neuropathy: a complication of systemic sclerosis

We performed bedside testing for peripheral neuropathy in our systemic sclerosis (SSc) population to determine whether foot care guidelines should be developed for SSc. Twenty consecutive SSc patients and 20 healthy control (HC) patients were evaluated for peripheral neuropathy in both feet using the 10-g Semmes–Weinstein monofilament examination (SWME) and 128 Hz vibration sensation using the on–off method. Independent, blinded, vibratory sensation, and SWME evaluations were performed on each subject by two investigators who had completed a training session to standardize each exam. An additional consecutive 20 patients with type 2 diabetes mellitus (DM) were examined by a diabetologist to compare with peripheral neuropathy prevalence in SSc patients. We examined the inter-rater variability using Cohen’s kappa. We compared SWME and vibratory sensation in SSc to HC using Fisher’s exact. The t test was used to compare duration of disease and modified Rodnan skin score (mRSS) for those with abnormal SWME or vibratory sensation. Two of 20 SSc patients reported sensory foot symptoms consistent with peripheral neuropathy prior to the examination. Inter-rater agreement for both SWME and vibratory sensation was strong (kappa: 0.72 and 0.83, respectively). Two HC and 12 SSc patients demonstrated abnormal vibratory sense (one-sided Fishers’ exact, p?<?0.002). No HC and four SSc patients had abnormal monofilament exams (one-sided Fisher’s exact, p?=?0.053). Neither mRSS (p?=?0.28) nor duration of non-Raynauds (p?=?0.07) symptoms differed between those with peripheral neuropathy and those without. Duration of Raynaud’s symptoms were clinically significantly associated with presence of peripheral neuropathy (p?=?0.04). The prevalence of sensory loss to monofilament in SSc was identical to DM patients (4/20). SSc patients have a considerable prevalence of pedal peripheral neuropathy as detected by loss of vibratory sensation or inability to sense the 10-g SWME. Further studies are indicated to determine if routine screening for neuropathy and subsequent podiatric care for SSc patients with abnormalities can reduce pedal complications.     

Serum galectin-3 level in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis. Activated fibroblasts are mainly responsible for fibrosis in SSc. Galectin-3, a β-galactoside-binding lectin, plays many important regulatory roles in both physiological and pathological processes including proliferation, apoptosis, inflammation, and fibrosis. The purpose of this study was to assess the serum galectin-3 levels in patients with SSc. Thirty-seven SSc patients, 23 systemic lupus erythematosus (SLE) patients (serving as patient control group), and 28 healthy volunteers were enrolled in this study. Disease activity and severity scores were detected with Valentini disease activity index and Medsger disease severity scale in the SSc group and SLE disease activity index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in the SLE group. The serum levels of galectin-3, vascular endothelial growth factor, transforming growth factor-β, and interleukin-6 were determined. Compared to the control group, the galectin-3 levels were higher in the SSc and SLE groups. The galectin-3 levels were not correlated with the disease activity and severity indexes in both patient groups. But, the serum galectin-3 levels were higher in the active SSc and SLE subgroups than in the inactive SSc (4.6?±?5.8 vs. 1.3?±?1.1 ng/ml, p?=?0.015) and SLE (17.4?±?11.3 vs. 6.5?±?8.9 ng/ml, p?=?0.019) subgroups. These results suggest that galectin-3, which is associated with fibrosis and inflammation by previous studies, may be a prominent biomarker of disease activity in SSc.     

MicroRNAs 103 and 107 link type 2 diabetes and post-menopausal breast cancer

Type 2 diabetes mellitus (T2DM) increases the incidence of post-menopausal breast cancer (PMBC). This study is intended to determine whether microRNA-103/107 (miR-103/107) should be regarded as a potential molecular link between T2DM and PMBC. Samples of serum from 90 patients with T2DM and/or PMBC were collected. Samples of serum from 20 non-diabetic post-menopausal women were used as the control. The body mass index (BMI) of patients with T2DM and PMBC was lower than the BMI of patients with only T2DM or PMBC (p?<?0.05). The expression of miR-103/107 was higher in the serum of T2DM patients compared with that in control samples (2.80?±?0.46/36.29?±?3.41 vs 0.88?±?0.25/8.59?±?1.91, p?<?0.05). The expression of miR-103/107 in the serum of PMBC patients was higher than that in T2DM patients (5.06?±?0.92/49.59?±?6.99 vs 2.80?±?0.46/36.29?±?3.41, p?<?0.05) but lower than that in patients diagnosed with both T2DM and PMBC (7.67?±?0.87/63.24?±?8.58, p?<?0.05). miR-103/107 was positively correlated with the homeostasis model assessment-insulin resistance (HOMA-IR) index (r?=?0.71, 0.685, p?<?0.01). The expression of miR-103/107 was an independent factor of the HOMA-IR index (β?=?0.638, 0.073, p?=?0.02, 0.01). There were higher levels of estradiol (E2) in patients with T2DM and/or PMBC than that in the control group. High expression of miR-103/107 results in insulin resistance and is associated with overweight or obese patients with T2DM and PMBC through elevated levels of E2. miR-103/107 may be a potential molecular link between T2DM and PMBC.     

Metabolic syndrome in Sjögren’s syndrome patients: a relevant concern for clinical monitoring

Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjögren’s syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18–65 years and 71 age-, race-matched control women were enrolled in this case–control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p?>?0.05). MetS (39.4 vs. 16.9 %, p?=?0.005), hypertension (p?=?0.004), and dyslipidemia (p?=?0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p?<?0.05). pSS patients with MetS (n?=?28) had higher BMI, waist circumference, cholesterol, LDL-C, triglycerides, insulin, leptin and HOMA-IR values, and greater hypertension and diabetes rates than pSS patients without MetS (n?=?43) (p?<?0.05). Current and/or previous prednisone use (75.0 vs. 62.8 %, p?=?0.313), current (3.0?±?4.5 vs. 1.6?±?3.2 mg/day, p?=?0.299), and cumulative prednisone doses (p?=?0.495) were similar in both groups. Otherwise, IL-1beta level was higher in MetS patients than in non-MetS patients (p?=?0.012), and this finding was confirmed (p?=?0.048) by multivariate analysis with adjustments for age, ethnicity, prednisone use, current and cumulative prednisone doses, and duration of use. We identified high MetS frequency and abnormal adipocytokine profile in pSS. The association of MetS with elevated IL-1beta level suggests that inflammation plays an important role in its pathogenesis.     

Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: correlation with the Trabecular Bone Score (TBS)

The aim of this research was to determine any correlations between Dickkopf-1 serum levels (Dkk-1, a natural inhibitor of the Wnt signaling pathway promoting osteoclastogenesis) and the Trabecular Bone Score (TBS), in systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. It also aimed at determining any difference in Dkk-1 serum levels between SSc and RA patients and a control group (CNT) of healthy subjects. A prospective study was carried out in 60 SSc and 60 RA patients and 60 CNT. Dkk-1 serum levels were evaluated by the ELISA method (Quantikine Human Dkk-1 Immunoassay, R&D System, Minneapolis, USA). The severity of microvascular damage was evaluated by nailfold videocapillaroscopy (NVC patterns: “Early,” “Active,” “Late”), in the SSc patients. TBS analysis and bone mineral density (BMD, g/cm²) were measured in all patients/subjects. The SSc patients showed higher Dkk-1 serum levels than RA (p?<?0.004) and CNT (p?<?0.0001) patients. SSc patients, showing the “Late” NVC pattern had statistically higher Dkk-1 serum levels than patients with either the “Active” or “Early” (p?<?0.004) patterns. Only in the “Late” NVC pattern group of SSc patients was there a significant negative correlation between Dkk-1 and TBS values (p?<?0.0001). The increased Dkk-1 serum levels and decreased TBS values observed suggest a diffuse bone damage in SSc patients with advanced disease, as demonstrated by the concomitant presence of the “Late” NVC pattern. Moreover, the bone remodeling in SSc seems even higher than that in RA patients.     

The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors

The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene. Aim: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism. Homocysteine levels were measured in a subgroup of 60 patients and 87 controls screened for multiple vascular risk factors. After adjustment for potential confounders, the risk-associated FTO rs9939609 A-allele was associated with raised homocysteine levels (p?=?0.003) in patients diagnosed with MS, but not in controls. Homocysteine levels correlated positively with body mass index (BMI) (p?=?0.045) and total cholesterol levels (p?=?0.048). Both homocysteine (p?=?0.011) and BMI (p?=?0.017) were significantly reduced with higher intake of folate in the diet. Higher BMI also correlated with increased intake of saturated/trans fat (p?<?0.01) and low physical activity (p?<?0.006). Daily intake of at least five fruits and vegetables had a favourable lowering effect on the Expanded Disability Status Scale (EDSS) (p?=?0.035), while smoking increased MS disability (p?<?0.001). This study has shown for the first time that having a diagnosis of MS moderates the effect of the FTO rs9939609 polymorphism on homocysteine levels. This is consistent with the role of FTO in demethylation and epigenetic changes. Identification of FTO rs9939609 reinforces the importance of adequate fruit, vegetable and folate and restriction of saturated/trans fat intake in the diet.     

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.     

Effects of exercise and nutritional intake on sleep architecture in adolescents

Purpose

Few studies have evaluated the relationship between sleep architecture and body mass index (BMI), nutrition, and physical activity in children. This study determined the relationship between sleep architecture and diet and exercise.

Methods

Three hundred nineteen Caucasian and Hispanic children aged 10 to 17 years participated in the follow-up assessment of the Tucson Children’s Assessment of Sleep Apnea study. The children and parents completed several questionnaires on dietary habits, amount of physical activity, and sleep habits. Subjects also underwent a home polysomnogram to characterize their sleep.

Results

Significant bivariate correlations were noted between stage II sleep percentage and the following: BMI (r?=?0.246, p?<?0.01), estimated total recreational energy expenditure (r?=?0.205, p?<?0.01), vigorous activity (r?=?0.130, p?=?0.009), and total estimated activity (r?=?0.148, p?=?0.009). In girls, significant correlations were noted between stage II percentage sleep and BMI score (r?=?0.279, p?<?0.01). Also in girls, significant negative correlation was noted between rapid eye movement (REM) sleep percentage and total fat intake (r?=??0.168, p?=?0.039). In boys, significant correlations were again seen between stage II percentage sleep and the following: BMI score (r?=?0.218, p?=?0.005), estimated total recreational energy expenditure (r?=?0.265, p?=?0.001), vigorous activity (r?=?0.209, p?=?0.008), and total estimated activity (r?=?0.206, p?=?0.010). When controlling for BMI percentile and age, significant bivariate correlation was also noted between REM sleep percentage and total fat intake (r?=?0.176, p?=?0.034) in boys.

Conclusions

BMI and exercise were associated with increases in stage II sleep. In girls, total fat intake was associated with a reduction in REM sleep, while in boys (after controlling for BMI percentile and age), total fat intake correlated with REM sleep.     

Serum β2-microglobulin level is a useful indicator of disease activity and hemophagocytic syndrome complication in systemic lupus erythematosus and adult-onset Still’s disease

This study demonstrates whether serum β₂-microglobulin (β₂-MG) level can be an indicator of the status of systemic lupus erythematosus (SLE) and adult-onset Still’s disease (AOSD), and development of hemophagocytic syndrome (HPS) complication. Serum β₂-MG level was compared between the active and inactive statuses of SLE and AOSD in hospitalized patients. Active status was defined as a state for which a therapy was introduced. Serum β₂-MG level was also compared between patients with and without HPS complication. HPS was diagnosed on the basis of clinical and pathological findings. Laboratory markers of HPS including peripheral blood cell counts and levels of serum lactate dehydrogenase (LDH), serum ferritin, plasma fibrin/fibrinogen degradation product (FDP), and plasma D-dimer were examined to determine their correlations with serum β₂-MG level. Sixteen SLE and seven AOSD patients (all females, aged 39.0?±?16.4) were included. The serum β₂-MG level was high in the active status of underlying diseases and decreased significantly after the therapy (3.5?±?1.4 vs. 2.1?±?0.8 mg/L, p?<?0.001). Among patients with active status, the β₂-MG level was higher in patients with HPS (two with SLE and three with AOSD) than in patients without HPS (4.9?±?1.8 vs. 3.3?±?1.4 mg/L, p?<?0.05). Serum β₂-MG level significantly correlated with the levels of serum LDH (r _s?=?0.42, p?<?0.05), plasma FDP (r _s?=?0.58, p?<?0.05), and plasma D-dimer (r _s?=?0.77, p?<?0.01). Serum β₂-MG level would be a useful indicator of disease activity and development of HPS complication in patients with SLE and AOSD.     

Red blood cell distribution width as a related factor of pulmonary arterial hypertension in patients with systemic sclerosis

The aim of this study was to investigate the utility of red blood cell distribution width (RDW) as a simple and readily available marker of occurrence of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc). One hundred and forty-five consecutive patients with SSc were recruited to the single-center cross-sectional study. Demographic characteristics, hematological parameters, Modified Rodnan Skin Score, and World Health Organization functional classification were determined. Diagnosis of PAH was based on screening by echocardiography and was confirmed by right heart catheterization. Interstitial lung disease (ILD) was diagnosed based on chest high-resolution computed tomography findings. There were no significant differences in gender, age, or disease duration between limited and diffused SSc groups. PAH was detected in 28 of lcSSc (33.3%) and 14 of dcSSc (23.0%) subjects. Patients with higher RDW values were more likely to be men with high anti-u1RNP titers and PAH. A significant correlation was found between RDW and high-sensitivity C-reactive protein (p?=?0.375, p?<?0.01) and the diffusing capacity of the lungs for carbon monoxide (ρ?=???0.396, p?<?0.01). The SSc-PAH group had significantly higher RDW values compared to the SSc group without pulmonary disease (15.7?±?2.2 and 13.7?±?1.0, p?<?0.001). The mean RDW in the SSc-PAH-ILD group was significantly higher than that in the SSc-ILD group (16.3?±?2.2% and 14.0?±?1.5%, p?<?0.001). Besides the recognized risk factors, high RDW was an independent predictor of PAH in patients with SSc (OR?=?3.314 [95%CI 1.038–10.580], p?<?0.05). RDW may be a related factor for identifying the pulmonary arterial hypertension in SSc patients.     

Serum adipokines levels in patients with systemic sclerosis: A meta-analysis

Background: Systemic sclerosis is an chronic inflammatory autoimmune diseases. Adipokine has been reported to play an important role in modulating immune responses. Recent studies suggest that adipokine also plays some roles in the pathogenesis of systemic sclerosis (SSc). However, published data regarding the relationship between plasma/serum adipokine levels and SSc are contradictory. The aim of this study was at performing a meta-analysis to derive a more accurate estimation and further investigate the association of plasma/serum leptin and adiponectin levels with SSc patients.

Methods: PubMed, and Web of Science databases (up to Feb 20, 2016) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle–Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis.

Results: A total of fourteen studies were finally included in this meta-analysis. Among them, six of which were studied for the serum adiponectin levels in SSc patients, six of which were studied for the serum leptin levels in SSc patients, and two of them were studied both for serum adiponectin levels and serum leptin levels in SSc patients. The meta-analysis results showed that the serum adiponectin levels in SSc patients were significantly lower than that in normal controls (SMD = ?0.608?ng/ml, 95% CI = ?1.029 to ?0.186, p?=?0.005). However, there were no significant differences in serum leptin levels between SSc patients and healthy controls (SMD = ?0.990?ng/ml, 95% CI = ?2.340 to 0.359, p?=?0.150). The subgroup analysis showed that Asia SSc patients with age less than 50 years old had lower plasma/serum adiponectin levels when compared with controls.

Conclusion: The serum adiponectin levels, but not serum leptin levels, in SSc patients were significantly lower than that in normal controls.     

Serum adropin level and ENHO gene expression in systemic sclerosis

Adropin, a secreted protein, is encoded by the energy homeostasis associated (ENHO) gene. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. Therefore, the aim of present study was to investigate serum adropin levels and ENHO gene expressions in systemic sclerosis (SSc) characterized by vasculopathy, inflammation, and progressive fibrosis of the skin and internal organs. The study includes 27 patients with SSc, 39 patients with Behçet’s disease (BD), and 20 healthy controls (HC). Serum adropin levels and ENHO gene expressions by peripheral blood mononuclear cells were analyzed by ELISA method and by real-time PCR, respectively. The serum adropin levels were higher in the SSc and BD groups than in the HC group (p?=?0.023 and p?<?0.001, respectively). However, there were no significant differences among the groups in terms of ENHO gene expressions (p _ANOVA?=?0.149). There was no significant difference between the limited and diffuse cutaneous subtypes of SSc in terms of serum adropin level and ENHO gene expression. Moreover, serum adropin level and ENHO gene expression were not associated with the disease activity and severity indexes. ENHO gene expression was correlated with the triglyceride levels in the BD group (r?=??0.426, p?=?0.027). The augmented serum adropin levels may be expected in the chronic inflammatory disease and seem not to be characteristic of only SSc. However, further studies are needed to explain the precise role of adropin in SSc.     

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.     

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.     

Association of biomarkers of inflammation,cartilage and bone turnover with gender,disease activity,radiological damage and sacroiliitis by magnetic resonance imaging in patients with early spondyloarthritis

To assess the association between biomarkers of inflammation, cartilage and bone turnover with gender, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Spondylitis Disease Activity Score (ASDAS) and bone marrow oedema in resonance magnetic imaging (MRI) of sacroiliac joints (SIJs) and radiological damage in early spondyloarthritis (SpA). Cross-sectional study of 60 patients (56.7 % females; mean age, 32.4 years) with early SpA. Sociodemographic data, clinical features, serum matrix metalloproteinase 3 (MMP-3), high sensitivity C-reactive protein (hsCRP), C-terminal cross-linking telopeptides of type I collagen (CTX-I) and urinary deoxypyridinoline, ASDAS, BASDAI, BASFI, BASRI and MRI of the SIJs were collected. The mean (SD) disease duration was 12.4 (6.8 months). Twenty-two (68.7 %) of the 32 patients had active sacroiliitis by MRI. MMP-3 and CTX I correlated with swollen joint (r?=?0.515, r?=?0.386, p?=?0.01). hsCRP correlated with ESR (r?=?0.303, p?=?0.05), with CRP (r?=?0.455, p?=?0.01) and with total BASRI (r?=?0.95, p?=?0.05). Biomarkers were unrelated with the rest of variables. Levels of MMP-3 (44.3?±?52.4 vs 24.7?±?33.4, p?<?0.05) and CTX-I (0.53?±?0.45 vs 0.24?±?0.38; p?<?0.05) were higher in men. Our study shows that CTX-I and MMP-3 are a marker of peripheral disease activity in early SpA. Male gender had higher levels of CTX-I and MMP-3, which may indicate higher disease activity. Higher hsCRP levels trended towards correlation with more baseline radiographic damage. Therefore, these biomarkers may help identify a subgroup of patients who will need closer monitoring and more intensive treatment.     

Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program

Aims/hypothesis

We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP).

Methods

The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n?=?692), intensive lifestyle intervention (n?=?832) or metformin (n?=?887).

Results

At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p?<?0.0001) and WC (p?=?0.0003) but not with BMI (p?=?0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p?<?0.0001); WC decreased in all three groups (p?<?0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p?<?0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p?>?0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p?<?0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI.

Conclusion/interpretation

Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.     

Relationship between the mitochondria-derived peptide MOTS-c and insulin resistance in obstructive sleep apnea

Purpose

The co-occurrence of obstructive sleep apnea (OSA) and obesity are common. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-C) is one of the newly identified mitochondrial derivative peptides that play a role in the regulation of metabolic homeostasis. We aimed to examine the serum levels of MOTS-C to help understand the role of the disease in the pathophysiology, thereby investigating whether it can contribute to the appropriate treatment.

Materials and methods

Seventy patients with OSAS and 20 healthy controls were included. The serum MOTS-C level was measured in all patients. For each participant, demographic features, lipid profile, serum glucose levels, and insulin levels were also evaluated. Homeostatic model assessment indicator of insulin resistance (HOMA-IR) was calculated for all participants.

Results

Patients with OSAS (n?=?70) were grouped as mild (n?=?19), moderate (n?=?19), and severe (n?=?32). Patients with AHI?≤?5 were considered as the healthy control group (n?=?20). Mean age was 50.3 years and 74% (67/90) of the study sample was male. As expected, as the severity of OSA increased, BMI, insulin levels and HOMA-IR increased. MOTS-C levels were significantly lower in patients with OSA compared to healthy controls (p?<?0.000) and we found that MOTS-C levels decreased as OSA severity increased. There was a negative correlation between serum MOTS-C levels and AHI and BMI (r?=???0.492, p?<?0.001, r?=???0.382, p?<?0.001, respectively). Serum MOTS-C levels were independently associated with AHI in BMI and HOMA-IR in linear regression analysis (p?<?0.010, p?<?0.007, p?<?0.007, respectively).

Conclusion

Serum MOTS-C level is related to OSA and BMI. MOTS-C may be a useful new marker for early metabolic disorders in patients with OSA.

     

Induced sputum as a method for detection of systemic sclerosis-related interstitial lung disease

Inducted sputum (IS) is a non-invasive procedure that can be used for collection of airway secretions. The aim of our study is to evaluate the clinical usefulness of IS for detection of airway inflammation in systemic sclerosis (SSc). Bronchoalveolar lavage and IS were performed to 20 patients with SSc. Eighteen patients who were referred to pulmonary medicine for bronchoalveolar lavage due to other reasons were also recruited for cell counts comparisons. Spirometry, echocardiography and thorax CT (HRCT) imaging were also performed to all patients. Mean macrophage and lymphocyte counts were found to be increased in IS of SSc patients compared with that of control (58.4?±?14.5% vs. 31.3?±?16.3%, 30.2?±?15.4% vs. 15.0?±?11.5% P?<?0.001), whereas mean neutrophil count was lower in the SSc patients (4.1?±?4.5% vs. 17.2?±?13.1%, P?<?0.05). Significant correlations were noted between BAL and IS findings for macrophage (r?=?0.55, P?=?0.02) lymphocyte (r?=?0.65, P?<?0.01) and total cell counts (r?=?0.45, P?=?0.06). IS is an easy and reliable method for the detection of alveolitis and can be used for early detection of lung involvement in scleroderma.