RA Group Research Articles

Reveromycin A Inhibits Bone Loss in Ovariectomized Mice

Background and objectives: Reveromycin A inhibits bone metastasis of lung cancer cells in natural killer cell-depleted immunodeficient mice with increasing apoptosis of osteoclasts. This knowledge suggests that reveromycin A is a potent inhibitor for osteoclasts in vivo. To determine the activity of bone loss in acute estrogen deficiency, we studied ovariectomized mice treated with reveromycin A. Materials and Methods: Eight-week-old female C57BL/6 mice were either ovariectomized or sham-operated. Reveromycin A was continuously administered for the first 2 weeks (Group RA) or the last 2 weeks (Group RP) using a subcutaneous mini osmotic pump. Mice were sacrificed 4 weeks after surgery. Inhibition was detected by images as well as serum carboxyterminal telopeptide of type I collagen (CTX). Results: BMD reduction in the RA group was significantly inhibited and was comparable with that in the sham group. In contrast, the RP group failed to inhibit BMD reduction. The plasma CTX level at the 28th day of the experiment was significantly increased in the RP and OVX groups compared with that in the sham group, while the increase was inhibited in the RA group. Morphometric analysis revealed that absorption of trabecular bone was strongly inhibited in the RA group. Conclusion: The inhibitory effects of reveromycin A administered immediately after ovariectomy was the most effective at the early phase of bone loss than at the later stage. A new reagent that inhibits bone loss in acute estrogen deficiency might be a new tool to experimentally study osteoporosis and may have clinical implications.

Cerebral Hemodynamics in Patients with Rheumatoid Arthritis

A total of 22 patients aged 20 to 40-years-old with RA were enrolled in the RA group consecutively. Control group (non-RA group) consisted of 22 age and sex-matched, randomly selected patients without RA who had other diagnosis such as fibromyalgia and did not have risk factors for atherosclerosis (AS).

Urinary albumin excretion in rheumatoid arthritis is not associated with markers of vasculopathy in distal microvascular beds.

Increased UAE is a marker of generalized vascular damage in high-cardiovascular risk patients. However, it remains unknown whether it corresponds to a state of diffuse vasculopathy in high-risk patients with RA. UAE was estimated in 24-hour urine samples in RA and non-RA individuals. Retinal arteriolar and venular diameters were calculated from retinal images with computerized software. SEVR was estimated as an index of microvascular coronary perfusion with applanation tonometry. Dermal capillary density was measured from images obtained with nailfold capillaroscopy, using specifically designed software. In a total of 111 individuals, neither UAE (5.1 [2.8-10.8] vs 6.5 [3.0-11.7]mg/24h) nor prevalence of microalbuminuria (11.0% vs 8.1%) significantly differed between patients (n=74) and controls (n=37). In the RA group, UAE was not significantly associated with inflammation, nor with any of the studied microvascular indices of the retinal microvasculature, the coronary microcirculation, and the dermal capillary network. Among RA patients, UAE was not associated with markers of vasculopathy in distal microvascular beds. Increased UAE in RA might be primarily considered as a manifestation of localized, compromised function of the renal microvasculature, rather than a marker of generalized microvascular impairment.

Effects of acidification pretreatment for respiratory acidosis on the expression of matrix metalloproteinase-9 in rat lung tissues following ischemia/reperfusion

To establish rat model of lung ischemia/reperfusion (IR) in vivo, and to explore the effects of acidification pretreatment for respiratory acidosis on the expression of matrix metalloproteinase-9 (MMP-9) and the possible mechanisms. Methods: A total of 36 male Sprague-Dawley rats were divided into a sham group (S group), a IR group, and an experiment group (RA group) (n=12 in each group). The rat left lung hilum in the S group was dissociated, followed by perfusion without ischemia. After the left lung hilum in the IR group was blocked for 45 min, the rats were followed by reperfusion for 180 min. After left lung hilum in the RA group was dissociated, the respiratory parameters were adjusted so that pressure of end tidal carbon dioxide (PETCO2) reached 56-65 mmHg (1 mmHg=0.133 kPa) for 5 min, then the rats was subjected to IR. Lung tissue wet/dry (W/D) and lung permeability index (LPI) were calculated, while the lung histopathology was observed and the MMP-9 protein expression were measured. Results: Compared with the control group, the W/D and LPI in the IR group and the RA group increased after reperfusion (both P<0.05), and the levels of W/D and LPI in the group RA were lower than that in the IR group (P<0.05). LPI and pathology scores were significantly lower in the RA group than those in the IR group (both P<0.01). After IR, the expression of MMP9 in the lung tissues in the IR group and the RA group increased significantly (both P<0.01). The expression of MMP-9 protein in the RA group was significantly lower than that in the IR group (P<0.01). Conclusion: After lung IR injury, the expression of MMP-9 protein, vascular permeability and inflammatory exudation is increased. The acidification pretreatment for respiratory acidosis can inhibit the expression of MMP-9 protein and reduce inflammatory exudation after lung IR, showing a protective effect on lung IR injury.

Effects of electroacupuncture at different time during reperfusion on the expression of Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury

To compare the effects of electroacupuncture (EA) at different time during reperfusion on the expression of autophagy-related protein Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the autophagy-related mechanism of EA on protecting MIRI. A total of 72 SD rats were randomly divided into a sham operation group, a model group, a RA group, a RB group, a RC group and a RD group, 12 rats in each group. Except the sham operation group, the rats in the remaining groups were treated with ligating the left anterior descending artery (LAD) for 30 minutes followed by reperfusion to establish the model of MIRI. The rats in the sham operation group were treated with crossing a line through the LAD. The rats in the model group did not receive treatment. The rats in the RA group, RB group, RC group and RD group were treated with EA at "Neiguan" (PC 6) for 20 min, starting at 0 h, 0.5 h, 1 h, 2 h after reperfusion. Evans Blue-TTC double-staining was employed to evaluate myocardial infarct size; the serum CK-MB was detected by ELISA and the expression of Bcl-2 and Beclin1 protein in myocardial tissue were detected by Western blot. Compared with the model group, the percentage of myocardial infarct size in the RB group, RC group and RD group was decreased significantly (all P<0.05), and the reduction in the RB group was more significant than that in the RC group and RD group (both P<0.05). Compared with the sham operation group, the expression of CK-MB and Beclin1 in the model group was significantly increased, but the expression of Bcl-2 was significantly decreased (all P<0.01). Compared with the model group, the expression of CK-MB and Beclin1 was decreased significantly in RA group, RB group, RC group and RD group (all P<0.05), but the expression of Bcl-2 was significantly increased (all P<0.05). Compared with the RA group, the expression of CK-MB was decreased in the RB group and RC group (both P<0.05) but the expression of Bcl-2 was increased (both P<0.01); the expression was not significantly different from that in the RD group (P>0.05); the increasing of Bcl-2 in the RB group was more significant than that in RC group (P<0.05). The expression of Beclin 1 in the RB group was significantly lower than that in the RA group (P<0.05), but there was no significant difference among other EA groups (all P>0.05). EA at different time during reperfusion could reduce myocardial infarct size in rats with MIRI, and EA at 0.5 h after reperfusion has best efficacy; this protective effect may be achieved by increasing Bcl-2 expression and reducing Beclin1 expression to inhibit overautophagy during reperfusion.

Radiographic and clinical outcomes of C1-C2 intra-articular screw fixation in patients with atlantoaxial subluxation

BackgroundThe Magerl and Goel-Harms techniques have been reported to produce excellent treatment outcomes in cases of atlantoaxial subluxation, but they also carry a risk of vertebral artery injuries. In order to completely prevent such injuries, we developed a surgical procedure, involving bone grafting between the C1 posterior arch and C2 lamina with clamp- or hook-and-rod-based fixation combined with the insertion of an interference screw into the posterior atlantoaxial joint.MethodsThis was a retrospective single-center study. The subjects were 58 patients in whom atlantoaxial subluxation was treated with the abovementioned procedure after 1995 (33 patients with rheumatoid arthritis (RA group) and 25 patients without rheumatoid arthritis (non-RA group)). The clinical outcomes and imaging findings of anterior subluxation at ≥ 2 years after surgery were compared between the RA and non-RA groups.ResultsNo vertebral artery injuries occurred during surgery. Seven and two patients died during the follow-up period in the RA and non-RA groups, respectively, but none of these deaths were associated with surgery. At ≥ 2 years after surgery, the visual analogue scale score, Japanese Orthopaedic Association score, and Ranawat classification had significantly improved in both groups (p < 0.001). Radiologically, bone fusion was noted in all patients. Significant changes in the atlas-dens interval (ADI) were seen immediately after surgery in both groups (p < 0.001). In the non-RA group, significant changes in the corrected atlantoaxial height were observed immediately after surgery (p < 0.01), and loss of correction was seen at the final follow-up, but it was not significant (p = 0.1965). No significant changes were noted in any other parameter. Regarding the postoperative alignment of the cervical spine, lordosis tended to decrease, but additional surgery was only performed in one patient, who had developmental stenosis at the mid-lower level and belonged to the RA group. No reoperations due to fused adjacent segmental disease or exacerbated curvature were required.ConclusionIn the present study, no vertebral artery injuries occurred during surgery, and no major perioperative complications developed. Favorable clinical outcomes were observed at ≥ 2 postoperative years although the patients’ diseases varied. This procedure produced superior outcomes, especially in terms of spinal correction and the maintenance of the ADI.

Fracture Rate and Overall Survival in mCRPC Patients Treated with Radium-223 and Concomitant Abiraterone

Both radium-223 (Ra) and abiraterone/prednisone (Abi/Pred) prolong overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). Recent prospective randomized data (ERA-223 trial) combining Abi/Pred and Ra (starting simultaneously) in mCRPC patients (pts) indicate that this combination increases fractures and deaths compared to Abi/Pred alone. In ERA-223, risks were partially mitigated by bone health agents (BHA) (i.e denosumab). Herein, we analyzed our institutional pts to assess fractures/OS in pts treated with Ra +/- Abi/steroid (Abi/S). After institutional review board approval, all pts in our institutional database were assessed for fractures/OS provided that they received Ra therapy between 2010 and 2017 and had one or more CT, MRI, or bone scan performed post-Ra. Categorical data were analyzed by chi-square. OS was evaluated using KM and log-rank calculations. Of 82 identified pts, 12 (13%) had radiographically documented fractures. Fracture data is summarized in Table 1. Forty (49%) of the Ra pts were treated with concomitant Abi/S, and 7 (17.5%) had fractures as compared to 5 (12%) pts of the 42 (51%) Ra pts treated with no Abi/S. Of the 82 pts, 34 (41%) also received BHA and 5 (15%) had fractures. There were 48 (59%) pts not receiving BHA and 7 (15%) had fractures. In the Ra group without Abi/S, 10 (12%) pts received BHA and 1 (10%) of these patients had a fracture. Within the Ra + Abi/S group, 10 (12%) pts were started on Ra and Abi/S simultaneously and 3 (30%) of these pts had fractures. Non-simultaneous Ra and Abi/S fracture rates were 4/30 (13%). None of the fracture data were statistically distinct between groups. Overall, pts on Ra and Abi/S had better OS (median 727 days) compared to pts on Ra without Abi/S (353 days, p = 0.0346). Fractures rates are higher in pts with imaging as compared to ALSYMPCA. The highest fracture rates we observed were with pts simultaneously starting Ra and Abi/S. Survival analyses are likely biased when evaluating Abi/S as a univariate factor. Larger data sets are required to provide sample sizes adequate for appropriately powered statistical analyses.Abstract SU_33_2328; Table 1Fracture rate in patients on Ra +/- Abi/S +/-BHACategoryNNumber of patients with fracturesPatients on BHA? (X=All Inclusive)Total patients8212 (15%)XPatients on Ra and Abi/S regardless of BHA status407 (18%)XPatients on Ra, no Abi/S regardless of BHA status425 (12%)XPatients on Ra and Abi/S and BHA244 (17%)YesPatients on Ra and Abi/S and no BHA163 (19%)NoPatients on Ra and Abi/S started simultaneously103 (30%)XPatients on Ra and Abi/S started previously304 (13%)XPatients on Ra, no Abi/S and BHA101 (11%)YesPatients on Ra, no Abi/S and no BHA324 (13%)No Open table in a new tab

9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3 Improve the Differentiation of Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and Wnt Signaling Pathways.

Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways. Cortical neural stem cells were isolated from 14-day-old rat embryos and cultured using the neurosphere assay. The cells were treated in 4 different conditions for 1 week: the negative control group received only the basic fibroblast growth factor, the positive control group received only T3 without growth factors, the RA group was treated with 9-cis-RA, and the Vit D3 group was treated with 1,25(OH)2D3. The effects of 9-cis-RA and 1,25(OH)2D3 on the level of the myelin basic protein (MBP) and the gene expression of the SOX10, MBP gene, HES5, and LRP6 were studied using flow cytometry and real-time PCR. The data were analyzed using one-way ANOVA with GraphPad Prism. A P value less than 0.05 was considered significant. The mRNA expressions of the SOX10, MBP, and MBP gene were significantly increased in the treated groups compared with the negative control group; the increase was similar in the 9-cis-RA group and the positive control group. Furthermore, 9-cis-RA significantly decreased the expression of the HES5 gene, a Notch signaling pathway transcription factor, and 1,25(OH)2D3 significantly reduced the expression of the LRP6 gene, a Wnt signaling pathway co-receptor. It seems that 9-cis-RA and 1,25(OH)2D3 are good candidates to improve the differentiation of OPCs into oligodendrocytes.

Space–time interaction: visuo-spatial processing affects the temporal focus of mind wandering

Our understanding of mind wandering (MW) has dramatically increased over the past decade. Studies have shown that in the vast majority of cases, MW is directed to times other than the present, and a bias toward the future has been reported (prospective bias). The processing of time is not independent of the processing of space: humans represent time along a spatial continuum, on a "mental time line" (MTL). In cultures with a left to right reading/writing system, the MTL expands from left to right. Capitalizing on these findings, here we aimed at investigating the effects of visuo-spatial processing on the temporal orientation of spontaneous MW, and specifically we asked whether we could steer the temporal focus of MW towards the past or the future, by experimentally inducing a leftward and a rightward orienting of attention, respectively. To this aim, we experimentally manipulated the spatial orientation demands associated with the focal task in two independent groups, with a leftward orienting of attention (left-pointing arrows, LA group) and a rightward orienting of attention (right-pointing arrows, RA group). We found that the temporal orientation of MW critically depended on the spatial orientation demands of the task: specifically, the proportion of spontaneous past-oriented MW episodes was higher under the induction of a leftward orienting attention (LA group) than under the induction of a rightward orienting attention (RA group). The opposite pattern was found for spontaneous future-oriented MW episodes. Possible mechanisms involved in this effect and their implications for research on MW and spontaneous cognition are discussed.

Hand strength in patients with RA correlates strongly with function but not with activity of disease

BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints, especially of the hands. The evaluation of handgrip strength (HS) and pinch strength can be useful to detect reduction in hand function in RA patients. The aim of the study was to compare HS and pinch strength between RA patients (RA Group - RAG) and a non-RA control group (CG) and to relate HS and pinch strength to functional capacity, duration and disease activity in the RAG.MethodsA cross-sectional case control study. The RAG was assessed for disease activity by the Disease Activity Score (DAS-28); for functional capacity by the Health Assessment Questionnaire (HAQ), the Cochin Hand Functional Scale (CHFS) questionnaire, and the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire; and for HS and pinch strength (2-point tip-to-tip, lateral or key, and 3-point) using Jamar® and pinch gauge dynamometers, respectively. Associations were analyzed by Pearson and Spearman tests, and groups were compared by the independent samples t test, with a significance level of P < 0.05.ResultsThe convenience sample included 121 rheumatoid patients and a control group matched by age, sex, and body mass index. The RAG showed lower strength values compared with the CG in all measurements (P < 0.01, 95% CI) and these values were associated with worse performance in the functional questionnaires and greater disease activity and duration. There was a strong correlation among the functional assessment instruments.ConclusionsThe decrease in grip and pinch strength, easily measured by portable dynamometers, is a strong indicator of functional disability in RA patients.

RHEUMATOID ARTHRITIS-INCREASED GENE EXPRESSIONS IN MUSCLE ATROPHY ARE RESTORED BACK TO CONTROL AS A RESPONSE TO ACUTE RESISTANCE EXERCISE

This study had as objective to analyze the acute effects of resistance exercise (RE) on the mRNA levels of the following genes (MyoD, myogenin, IGF-1, atrogin-1, MuRF-1, and myostatin) in rheumatoid arthritis (experimental arthritis). Therefore, 26 females rats were randomly allocated into four groups, control (CT, n=7), exercise (Ex, n=6), rheumatoid arthritis (RA, n=6) and RA with exercise (RAEx, n=7). Met-BSA was injected into the tibiotarsal joint in the RA and RAEx groups. After 15 days from injection, the animals were submitted to an acute bout of RE and six hours post protocol the animals were euthanized. We evaluated the joint thickness, inflammation score, cross-sectional area (CSA) of gastrocnemius muscle fibers and mRNA expression of the IGF-1, MyoD, myogenin, myostatin, MuRF-1, atrogin-1 and GAPDH. It was observed that the joint thickness and score strongly increased in arthritic rats (p

Emotional processes and stress in children affected by hereditary angioedema with C1-inhibitor deficiency: a multicenter, prospective study

BackgroundHereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent edema of unpredictable frequency and severity. Stress, anxiety, and low mood are among the triggering factors most frequently reported. Impaired regulation and processing of emotions, also known as alexithymia, may influence outcomes. The aim of this study was to confirm the presence of alexithymia and stress in children with C1-INH-HAE, to determine whether they are also present in children affected by other chronic diseases, and to investigate their relationship with C1-INH-HAE severity. Data from children with C1-INH-HAE (n = 28) from four reference centers in Italy were compared with data from children with type 1 diabetes (T1D; n = 23) and rheumatoid arthritis (RA; n = 25). Alexithymia was assessed using the Alexithymia Questionnaire for Children scale; perceived stress was assessed using the Coddington Life Event Scale for Children (CLES-C).ResultsMean age (standard deviation [SD]) in the C1-INH-HAE, T1D, and RA groups was 11.8 (3.3), 11.7 (2.9), and 11.1 (2.6) years, respectively. Mean C1-INH-HAE severity score was 5.9 (2.1), indicating moderate disease. Alexithymia scores were similar among disease groups and suggestive of difficulties in identifying and describing emotions; CLES-C scores tended to be worse in C1-INH-HAE children. C1-INH-HAE severity was found to correlate significantly and positively with alexithymia (p = 0.046), but not with perceived stress. Alexithymia correlated positively with perceived stress.ConclusionsAlexithymia is common in children with chronic diseases. In C1-INH-HAE, it may result in increased perceived stress and act as a trigger of edema attacks. Comprehensive management of C1-INH-HAE children should consider psychological factors.

Medication Compliance on Glycemic Control in Patients with Elevated HbA1c

The SIMPLE study was a randomized trial comparing two treatment strategies [basal insulin (BI) + GLP-1 RA vs. basal-bolus insulin (BBI)] in patients with T2DM and very elevated HbA1c (&amp;gt;10%). The glucose lowering agents were provided free of charge for the 6-month study. This post-hoc analysis evaluates compliance with the assigned glucose lowering agents, and the effect of compliance on glycemic control. Compliance was assessed by inventory of the returned medication. Optimal compliance was defined as &amp;gt;80% use of the respective agent over the entire duration of the study. Mixed model repeated measures analysis with compliance as a covariate was used to evaluate the treatment effect on HbA1c. The 120 randomized patients had a mean (SD) age 47.4 (9.5) years, BMI 37.2 (10.3) kg/m2, and baseline HbA1c 12.1 (1.4)%. The proportion of patients with optimal compliance with basal insulin was numerically higher in the BI+GLP-1 RA vs. BBI group (p=0.16); optimal compliance with GLP-1 RA was higher compared to bolus insulin (p=0.04) (Table). Compliance was an independent predictor for glycemic improvement (P = 0.008); treatment with BI+GLP-1 RA was superior at lowering HbA1c after adjustment for compliance (P = 0.01). Optimal compliance was low in this patient population. While compliance was a significant contributor to glycemic control, treatment with BI+GLP-1 RA improved HbA1c more than BBI independent of medication compliance.Table. Patients with optimal compliance with glucose lowering agents (&amp;gt;80% over the 6-month study duration) in the two treatment groups (basal insulin + GLP1 RA compared with basal-bolus insulin) and the effect of compliance on glycemic control.Basal-Bolus Insulin Group(BBI, n=56a)Basal Insulin + GLP1 RA Group (BI+GLP1 RA, n=54a)Patients with optimal compliance:Basal Insulin8 (14.3)14 (25.9)Bolus Insulin6 (10.7)NAGLP1 RANA14 (25.9)Change in HbA1c:Adjusted for compliance- 3.1 (-4.0,-2.2)- 4.5 (-5.2,-3.8)Optimal Compliance subgroup-3.2 (-4.8,-1.6)-5.4 (-6.6, -4.2)Low Compliance subgroup-3.0 (-3.7,-2.3)-3.6 (-4.4,-2.8)Data are Least squares means (95%CI) or N (%); NA - Not applicable. acompliance data available for n=110 (intention-to-treat analysis sample). Disclosure A. Elhassan: None. M. Abreu: None. A. Tumyan: None. O. Papacostea: None. K. Peicher: None. P. Dimachkie: None. M.S. Siddiqui: None. B. Adams-Huet: None. X. Li: None. L. Pop: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp &amp; Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S.

Medical, social, and economic consequences of type 2 diabetes therapy with medicinal products from the group of DPP-4i, SGLT-2i, and GLP-1 RA

Medical, social, and economic consequences of type 2 diabetes therapy with medicinal products from the group of DPP-4i, SGLT-2i, and GLP-1 RA

Metabolic syndrome in adults with a history of juvenile arthritis

ObjectiveThe objective of this study was to determine the risk of obesity and metabolic syndrome in adults with a history of juvenile arthritis (JA).MethodsUsing the National Health and Nutrition Examination Survey (NHANES), we compared the characteristics of respondents with arthritis (JA vs rheumatoid arthritis [RA]) to those of the control group without arthritis. We used logistic regression analyses, controlling for age, race, and gender, to determine the ORs for metabolic syndrome.ResultsObesity was increased in the JA group with 67% respondents having body mass index ≥30 kg/m2 vs 55% respondents in the no arthritis cohort (p=0.004). In unadjusted analyses, there was increased odds of metabolic syndrome in JA (OR 6.2, p=0.001) and RA groups compared to those without arthritis (OR 7.7, p=0.001). After adjusting for age, gender, and race, the odds of metabolic syndrome remained increased in JA (OR 5.2, p=0.001) and RA (OR 3.2, p=0.001) groups.ConclusionAdults with a history of JA have a significantly increased risk of metabolic syndrome compared to those without arthritis. These findings are important because metabolic syndrome has been associated with an increased risk of cardiovascular disease and death in other populations.

Dermal capillary rarefaction as a marker of microvascular damage in patients with rheumatoid arthritis: Association with inflammation and disorders of the macrocirculation.

Capillary rarefaction is observed in various cardiovascular diseases, yet it remains understudied in RA, a chronic inflammatory disease accompanied by excess cardiovascular risk. We quantified capillary density in RA patients and explored potential associations with macrocirculatory disorders, inflammation, and cardiovascular risk. Dermal capillary density was assessed with nailfold capillaroscopy in RA and non-RA individuals, using specifically designed semiautomated software. Macrocirculation assessments included large artery stiffening, evaluated with PWV, and myocardial blood flow, calculated as cardiac index from impedance cardiography. Cardiovascular risk score was estimated from the Framingham Heart Study. The number of capillaries per visual field was lower in patients (n=99) compared to controls (n=35) (132.6±30.3 vs 152.9±25.2, P=.001). In the RA group, capillary density negatively correlated with CRP and PWV, and positively with HDL and cardiac index. In the multivariate analysis, CRP independently predicted capillary rarefaction (P=.044). Capillary density significantly correlated with cardiovascular risk, even after adjustment for inflammation (P=.030). Capillary rarefaction appears pronounced in RA and correlates with lower cardiac output, increased arterial stiffness, and cardiovascular risk. However, the associations with macrocirculatory disorders may be obscured by inflammation, which appears as the major contributor to capillary rarefaction in RA.

Lack of significant association between selected STAT3 polymorphisms and rheumatoid arthritis in the Polish population.

ObjectivesRheumatoid arthritis (RA) is the most common systemic inflammatory disease and is of unknown etiology. The altered balance between immunosuppressive and inflammatory T cell subpopulations exerts a huge impact on RA pathogenesis. The STAT3 protein regulates genes involved in the immune responses. It regulates maturation of T and B cells. Its abnormal activity is significantly associated with autoimmune diseases and cancer development. We aimed to evaluate the contribution of three potentially functional single nucleotide polymorphisms (SNPs) within the STAT3 gene to susceptibility and severity of RA in the Polish population.Material and methodsA total of 595 patients with RA and 330 healthy individuals were included in the study. DNA from patients and healthy subjects was obtained from peripheral blood using standard DNA isolating methods. The STAT3 rs1053005, rs1026916 and rs2293152 polymorphisms were genotyped using the TaqMan SNP genotyping assay. The accuracy of SNP genotyping was confirmed using direct DNA sequence analysis.ResultsThe distribution of STAT3 polymorphisms did not differ significantly between cases and controls. Our results revealed a tendency only, where rs1026916 AA genotype occurred more frequently in RA patients compared to healthy controls, in codominant (p = 0.09), dominant (p = 0.06) and recessive (p = 0.09) models. STAT3 rs2293152 polymorphism was associated with higher DAS28 (p = 0.014 codominant model; p = 0.003 dominant model), increased number of swollen joints (p = 0.02), higher VAS (p = 0.01) and higher HAQ score (p = 0.05).ConclusionsWe did not observe a significant association between the three studied STAT3 genetic variants and increased susceptibility to or severity of RA. Only the STAT3 rs2293152 polymorphism was associated with parameters that indicate a more severe course of the disease. However, its distribution did not differ between RA and control groups. According to our observations these 3 studied STAT3 SNPs may not be used as risk factors for developing RA.

Feasibility and clinical outcomes of rotational atherectomy for heavily-calcified side branches of complex coronary bifurcation lesions in the real-world practice of the drug-eluting stent era.

To evaluate the outcomes of rotational atherectomy for heavily-calcified side branches of coronary bifurcation lesions. Side-branch (SB) preservation is clinically important but technically challenging in heavily-calcified non-left main true bifurcation lesions. SB rotational atherectomy (SB RA) is sometimes mandatory but the clinical outcomes are not well studied. We retrospectively studied the outcomes of patients who underwent RA at our institute for heavily calcified, balloon-uncrossable or-undilatable SB lesions over an approximately 5-year period (January 2011 to September 2016). Two hundred and forty-four patients underwent main vessel only RA (SB-MV + RA group) and another 48 patients underwent SB RA (SB + MV ± RA group) for 49 side branches. The demographic variables were comparable between the two groups. However, patients underwent SB RA experienced more SB perforations and greater acute contrast-induced nephropathy (CIN). Among the SB RA patients, 30 (62.5%) underwent RA for both SB and MV (SB + MV + RA subgroup), whereas the other 18 underwent SB only RA (SB + MV-RA subgroup). Patients in these two subgroups could be completed with similar procedural, fluoroscopic durations, and contrast doses. The long-term MACE rate of SB RA was 27.1% over a mean follow-up period of 25.1 months with no differences between the two subgroups. RA for SB preservation in complex and heavily-calcified bifurcation lesions was feasible with high success rate and quite favorable long-term outcomes in the drug-eluting stent (DES) era. Given the higher rates in SB perforation and acute CIN, we recommend that SB RA should be conducted by experienced operators.

DEXAMETHASONE INTRAVITREAL IMPLANT VS RANIBIZUMAB IN THE TREATMENT OF MACULAR EDEMA SECONDARY TO BRACHYTHERAPY FOR CHOROIDAL MELANOMA.

To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma. Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography. The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 μm to 243 ± 58 μm and from 437 ± 71 μm to 254 ± 44 μm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups. Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.

Risk Factors and Early Detection of Diabetes Mellitus in Early Rheumatoid Arthritis Women

Background: Patients with rheumatoid arthritis show predominance of metabolic disorder characterized by overweight, central obesity, dyslipidemia, and impaired glucose tolerance, specifically, few studies have explained insulin resistance in this disease.Objective: The aim of the present study is to examine insulin resistance and the risk of developing diabetes mellitus in middle age Iraqi women with early rheumatoid arthritis.Patients and methods: This work involved seventy female with early rheumatoid arthritis. Who was attending to the National Diabetic Center (NDC) of Al-Mustansiriya University and 35 healthy subjects as a control group. From all subjects blood sample was drawn in fasting state to measure the biochemical parameters which including plasma glucose level and fasting insulin concentrations. Other measurements (RF and anti-CCP) were made by routine methods. Homeostasis model of assessment insulin resistance (HOMA-IR) by using the formula HOMA model Insulin sensitivity was calculated in RA patients and healthy control.Results: Results revealed a highly significant in the level of the rheumatoid factor (RF), anti-CCP and fasting insulin, and HOMA-IR when compared the patient group with the control group. While a significant increase in the level of FBG in the RA group than the control group. Also, there was a positive correlation with high significance among, Anti-CCP, and RF with HOMA-IR in the rheumatoid arthritis group. Conclusions: This study shows that patient with rheumatoid arthritis have abnormal insulin secretion with a high value of IR than a group of healthy control and these patients may be at risk of diabetic mellitus.