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ObjectivesTo compare current all-cause mortality rates in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) versus general population.MethodsIn this population-based, retrospective cohort study, anonymised data on 11 186 586 citizens, including all patients with RA (42 735, 79% female), AS (9707, 43% female), PsA (13 779, 55% female), SLE (10 440, 89% female) and SSc (2277, 88% female), (median age of 64/47/54/53/59 years at study entry, respectively), under prescribed treatment between 2015 and 2019, were extracted from the electronic database covering nearly 99% of the Greek population.ResultsAfter 1:5 (patients:general population) matching for gender/age, we found that survival was worse in SSc, followed by SLE and inflammatory arthritis. Compared with the general population HRs for death increased from the first 3 years to 5 years of observation possibly due to increases in disease duration: RA (from 0.63 to 1.13 (95% CI: 1.05 to 1.22), AS (from 0.62 to 1.01, (95% CI: 0.76 to 1.33)), PsA (from 0.68 to 1.06, (95% CI: 0.88 to 1.28)), SLE (from 1.52 to 1.98, (95% CI: 1.67 to 2.33)) and SSc (from 2.27 to 4.24, (95% CI: 3.19 to 5.63)). In both SLE and SSc mortality was increased in men than women and in patients younger than 50 years.ConclusionsSurvival rates over 5 years in inflammatory arthritis under treatment are currently becoming comparable (AS/PsA) or slightly higher (RA) than those of the general population. However, all-cause mortality is almost twofold and fourfold higher in SLE and SSc, respectively, being even higher for male and younger patients.

ObjectivesDepression and anxiety are linked bi-directionally with inflammatory rheumatic diseases (IRDs) activity, which in turn, depends on subjective patient reported outcomes that can be distorted by comorbid mood disorders. We tested the hypothesis that introduction and/or switching of biologic agents for IRDs are associated with treatment for depression and/or anxiety, by analysing real-world data.MethodsUsing a country-wide electronic prescription database (10 012 604 registered, 99% population coverage), we captured almost all patients with rheumatoid arthritis (n=12 002), psoriatic arthritis (n=5465) and ankylosing spondylitis (n=6423) who received biologic disease modifying anti-rheumatic drugs (bDMARDs) during a 2-year period (8/2016–7/2018). Concomitant antidepressant/anxiolytic medication use was documented in patients who started or switched bDMARDs and compared with those who remained on conventional synthetic (cs)DMARDs or the same bDMARD, respectively, by multivariate regression analysis.ResultsTwo-year data analysis on 42 815 patients revealed that bDMARD introduction was associated with both antidepressant [OR: 1.248, 95% CI 1.153 to 1.350, pConclusionIn real-world settings, both introduction and switching of bDMARDs in patients with IRDs were associated with the presence of mood disorders. Although a causal relationship is uncertain, the impact of depression and anxiety should always be considered by physicians facing the decision to introduce or switch bDMARDs in patients with active IRDs.

Objectives This cross-sectional study aimed: 1) to compare the saliva characteristics and the occurrence of caries in patients with type 2 diabetes mellitus (T2DM) and patients without T2DM, 2) to study the impact of inadequate glycemic control on saliva and caries prevalence. Methods 23 adults with T2DM and 18 controls participated. Patients with T2DM were divided depending on their metabolic control: a) well-controlled (W.C.): HbA1c≤7 %, and b) poorly-controlled (P.C.): HbA1c> 7 %). The examined clinical parameters were: 1) number of natural teeth, 2) DMFT index of coronal caries, 3) saliva pH, 4) saliva flow and buffering capacity, and 5) subjective feeling of dry mouth. Results The groups W.C and P.C showed significant differences in the number of teeth, the saliva flow, and DMFT. The C and P.C groups presented differences in pH, saliva flow, buffer capacity, and DMFT. Finally, the W.C and C groups indicated differences in the buffer capacity, saliva flow, and DMFT. The subjective feeling of dry mouth is related to the duration of the disease. The DMFT value correlated negatively with the status of metabolic regulation. Multiple linear regression revealed that the DMFT value was positively associated with serum HbA1c levels. Conclusions 1) Adults with T2DM present a lower saliva flow rate and buffering capacity, as well as higher caries prevalence than controls; 2) The metabolic control of T2DM is essential for the maintenance of saliva flow rate and buffering capacity, and caries prevalence; 3) The duration of T2DM is of importance for the subjective sense of dry mouth. Clinical significance The duration and metabolic control of T2DM are important clinical parameters for oral complications. Awareness and co-operation of diabetologists and dentists are needed to detect oral lesions in patients with diabetes and be treated timely and effectively.

Purpose: Variation of plasma thyroid hormone levels influences insulin sensitivity and peripheral glucose disposal. High thyroxin dose administration to healthy humans induces insulin resistance, whereas moderate doses increase peripheral glucose disposal. An open-labeled, randomized and placebo-controlled intervention was performed in euthyroid type 2-diabetic patients, to examine the effect of a small thyroxin dose within the euthyroid range on postprandial forearm muscle glucose uptake, insulin sensitivity, in vitro glucose uptake and GLUT4 recruitment in the plasma membrane of monocytes. Methods: A meal was given to eleven euthyroid, treatment-naive, type-2 diabetic patients (aged 43 ± 3.8 yrs, BMI 27.48 ± 1.39 kg/m2, T3 119 ± 5.7 ng/dl, T4 8,13 ± 0.46 μg/dl, TSH 1.51 ± 0.14 μU/ml, FT4 1.272 ± 0.047 ng/dl) before and after administration of 50 μg of thyroxin once daily for 2 months. Similarly, a placebo was given to eleven age, sex and BMI-matched euthyroid, type-2 diabetic patients. Blood was drawn for 300 min from a forearm deep vein and the radial artery for measurements of glucose, insulin, and GLUT4 abundance in peripheral monocytes. Forearm blood flow (BF) was measured with strain-gauge-plethysmography. Forearm glucose-uptake, and insulin sensitivity were assessed. After the first meal-tolerance-test, daily treatment with 50 μg of thyroxin or placebo was initiated for a 2-month period. Then a second identical test was repeated. Results: TSH, glucose, insulin levels and HbA1c reduced significantly in the treatment group. Peak-baseline BF and Glucose-uptake (AUC0-300 min) increased significantly (1.685 ± 0.3 vs. 3.07 ± 0.15 ml/min per 100 cc tissue, p=0.0018) and (587 ± 68 vs. 1015 ± 131 μmol per 100 cc tissue, p=0.0051), respectively. All insulin-sensitivity indices improved post-treatment. Glucose uptake and GLUT4 abundance in monocytes also improved. The placebo group exhibited no change in all variables. Conclusion: Administration of small, subthyrotoxic doses of thyroxin to euthyroid diabetic patients improves peripheral glucose disposal, blood flow responses and overall insulin sensitivity. This could be of therapeutic importance by reducing the burden of hyperglycaemia and possibly the long term complications of diabetes.

Objective A prospective phase II study was conducted to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluoruracil (5-FU) and high-dose leucovorin (LV) (FOLFOX-4) in patients with platinum-resistant, taxane-pretreated recurrent ovarian cancer. Patients and methods Thirty-eight patients, with a median age of 58 years (range 33–77), were treated with oxaliplatin 85 mg m −2 as a 2-h infusion on day 1, LV 200 mg m −2 day −1 as a 2-h infusion followed by bolus 5-FU 400 mg m −2 day −1 and a 22-h infusion of 5-FU 600 mg m −2 day −1 for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. Results The vast majority of patients had performance status 0 or 1 and 76.3% had ≥ 2 metastatic sites. A median number of four cycles per patient (range, 1–8) were administered. Based on an intention-to-treat analysis, 3 patients (7.9%) achieved a complete response (CR) and 8 (21.1%) achieved a partial response (PR), for an overall response rate of 29%. Another 29% of patients had stable disease (SD). The median relapse-free survival was 5.2 months (range 2.5–17), the median time to tumor progression was 4.8 months (range 0.6–19), and the median overall survival was 10.1 months (range 0.2–36). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 29% and 21.1% of patients, respectively. Febrile neutropenia was encountered in 3 patients (7.9%), who were successfully treated. Grade 3/4 neurotoxicity developed in 15.8% of patients; neurotoxicity gradually declined after treatment discontinuation. Alopecia, nausea–vomiting, diarrhea, mucositis, and asthenia were not a serious problem. There were no treatment-related deaths. Conclusion The combination of oxaliplatin and 5-FU/LV (FOLFOX-4) appears to be an effective regimen with a good toxicity profile for the treatment of platinum-resistant, taxane-pretreated ovarian cancer.

Background Adiponectin is an adipose tissue secreted protein known for its insulin sensitising and anti-atherogenic actions. To this date two adiponectin receptors have been discovered, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). The aim of this study was to investigate the association of ADIPOR2 gene variations with coronary artery disease (CAD). Methods Eight common single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR2 locus were chosen to perform association studies with anthropometric and metabolic parameters in a Greek population. They were classified as either CAD (stenosis >50% in at least one main vessel) or non-CAD individuals in accordance with coronary angiography data. Genotyping was performed using a microsphere-based suspension array and the Allele Specific Primer Extension (ASPE) method. Expression of ADIPOR2 protein and mRNA in circulating CD14+ monocytes were determined using flow cytometry and real time Polymerase Chain Reaction assays respectively. Results There was a significant difference in the distribution of genotypes of polymorphism rs767870 of ADIPOR2 between CAD and non-CAD individuals (p = 0.017). Furthermore, heterozygotes of the rs767870 polymorphism had significantly lower Flow Mediated Dilatation (FMD) values, higher values of Intima-Media Thickness (IMT) and increased ADIPOR2 protein levels in peripheral monocytes, compared to homozygotes of the minor allele after adjustment for age, sex, waist to hip ratio and HOMA. Conclusions Our findings suggest that variants of ADIPOR2 could be a determinant for atherosclerosis independent of insulin resistance status, possibly by affecting ADIPOR2 protein levels.