Could serum HMGB1 levels be a predictor associated with psoriatic arthritis?

Background/aim: Psoriasis is a chronic autoimmune disease that predominantly affects the skin and musculoskeletal system. We hypothesized that HMGB1, an inflammatory nuclear protein, may play a role in the musculoskeletal involvement of psoriasis. Methods: Forty patients with psoriasis and 45 with psoriatic arthritis were involved in the study; the results were compared with 22 healthy controls. Serum HMGB1 levels were evaluated from peripheral blood samples. Results: Serum HMGB1 levels were found to be significantly higher in patients with psoriasis regardless of joint involvement (p < 0.001). Also, HMGB1 levels were correlated with the extent of psoriasis. Conclusion: Serum HMGB1 levels may contribute to the progression of psoriasis to psoriatic arthritis and correlate with the severity of skin involvement.

Psoriasis is an autoimmune skin disease that may also affect the joints. Factors leading to the progression of psoriasis to psoriatic arthritis are still a mystery despite an increasing number of animal studies and real-life data. HMGB1 is a nuclear protein that leads to an increase in molecules that increase inflammation (TNF-α, IL-1 and IL-6) in the body. Until now, there was no report about the relationship between psoriatic arthritis and serum HMGB1 levels. Our study aimed to find any difference in HMGB1 levels between healthy and psoriatic patients. Psoriatic arthritis patients had higher levels of serum HMGB1 than patients with psoriasis. Also, HMGB1 levels were correlated with the severity of skin involvement. Our results showed that serum HMGB1 may indicate a high risk for developing psoriasis that involves the joints. Therefore the HMGB1 level in psoriasis patients can potentially serve as a predictor associated with disease severity and the risk of developing psoriatic arthritis.

Unintentional Monotherapy in Rheumatoid Arthritis Patients Receiving Tofacitinib and Drug Survival Rate of Tofacitinib.

OBJECTIVE: To determine the rate of unintentional monotherapy (UM; switching to monotherapy from combination therapy of patients' own volition) in rheumatoid arthritis patients receiving tofacitinib and to evaluate tofacitinib survival rate. METHODS: This national, multicenter study included patients' data from the TURKBIO Registry. Demographics, clinical characteristics, disease duration and activity, comorbidities, and treatments were analyzed. RESULTS: Data of 231 rheumatoid arthritis patients (84.8% female, median age, 56 years) were included; 153 were initially prescribed combination therapy and continued to their therapies; 31 were initially prescribed combination therapy but switched to monotherapy on their own volition (UM); 21 were initially prescribed monotherapy and switched to combination therapy; 26 were initially prescribed monotherapy and continued to their therapies. The rate of comorbidities at the time of data retrieval was higher in the UM group than in the combination group (83.3% vs. 60.3%, p = 0.031). Presence of comorbidities was a significant factor affecting switching to monotherapy ( p = 0.039; odds ratio, 3.29; 95% confidence interval, 1.06-10.18). The combination and UM groups did not differ regarding remission rate assessed by Disease Activity Score 28-joint count C-reactive protein (60.5% and 70%, respectively; p = 0.328). Drug survival rates of the UM and combination groups did not differ. The median drug survival duration of tofacitinib was 27+ months with 1- and 4-year drug survival rates of 89.6% and 60.2%, respectively, in the UM group. CONCLUSIONS: Although 13.4% of the study population started monotherapy unintentionally, drug survival and remission rates of the UM and combination groups were not different. Comorbidity was a factor affecting transition from combination therapy to monotherapy.

Analysis of Slow-Cycling Variants of the Light-Inducible Nuclear Protein Export System LEXY in Mammalian Cells.

The optogenetic tool LEXY consists of the second light oxygen voltage (LOV) domain of Avena sativa phototropin 1 mutated to contain a nuclear export signal. It allows exporting from the nucleus with blue light proteins of interest (POIs) genetically fused to it. Mutations slowing the dark recovery rate of the LOV domain within LEXY were recently shown to allow for better depletion of some POIs from the nucleus in Drosophila embryos and for the usage of low light illumination regimes. We investigated these variants in mammalian cells and found they increase the cytoplasmic localization of the proteins we tested after illumination, but also during the dark phases, which corresponds to higher leakiness of the system. These data suggest that, when aiming to sequester into the nucleus a protein with a cytoplasmic function, the original LEXY is preferable. The iLEXY variants are, instead, advantageous when wanting to deplete the nucleus of the POI as much as possible.

Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia / Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

Corticosteroid-induced sinus bradycardia in a young boy with adrenal insufficiency and sepsis. / Bradicardia sinusal inducida por corticoesteroides en un niño con insuficiencia suprarrenal y septicemia.

The literature does not commonly describe cardiac rhythm disturbances, including bradycardia, in patients who are receiving corticosteroids, and the exact mechanism of such disturbances remains unknown. Herein, we present a case of sinus bradycardia associated with stress-dose corticosteroid therapy. A nine-year-old boy with a history of panhypopituitarism was admitted with gastroenteritis and pneumonia and developed septic shock on the day of admission. Management using intravenous fluids, stress doses of hydrocortisone, and antibiotics resulted in full recovery. However, within 24 hours following treatment, sinus bradycardia was documented, with a heart rate of 45 beats per minute (BPM). The bradycardia resolved after the dose of hydrocortisone was decreased gradually. Corticosteroidinduced sinus bradycardia is an adverse effect that usually resolves after corticosteroid treatment is discontinued. During stress-dose corticosteroid therapy, hemodynamic monitoring should be considered. To our knowledge, this is the first report of sinus bradycardia following the use of hydrocortisone in children who have adrenal insufficiency.

La bibliografía no incluye frecuentemente alteraciones en el ritmo cardíaco de los pacientes que reciben corticoesteroides; se desconoce su mecanismo exacto. En este artículo, presentamos el caso de un paciente con bradicardia sinusal asociada con una dosis de estrés de corticoesteroides. Se ingresó a un niño de 9 años con antecedentes de panhipopituitarismo con gastroenteritis y neumonía y presentó choque septicémico el día de la hospitalización. El tratamiento con líquidos intravenosos, dosis de estrés de hidrocortisona y antibióticos permitió la recuperación. Sin embargo, luego se documentó bradicardia sinusal con una frecuencia cardíaca de 45 latidos por minuto. Esta se resolvió después de reducir gradualmente la hidrocortisona. La bradicardia sinusal inducida por corticoesteroides es un efecto adverso que suele resolverse tras interrumpir el tratamiento. Se debe considerar el monitoreo hemodinámico en estos casos. Este es el primer informe de bradicardia sinusal posterior al uso de hidrocortisona en niños con insuficiencia suprarrenal.

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

Diaphragmatic muscle thickness and diaphragmatic function are reduced in patients with systemic lupus erythematosus compared to those with primary Sjögren's syndrome.

INTRODUCTION: Systemic lupus erythematosus (SLE) is associated with an increased risk of pulmonary infections, as well as a rare condition known as shrinking lung syndrome (SLS). The diaphragm has an important role to play in lung physiology and might also play a role in these adverse events. Here, we aimed to investigate whether SLE patients have impairment in their diaphragmatic muscle thickness and function with respect to another connective-tissue disease: primary Sjögren's syndrome (pSS). METHOD: Patients diagnosed with SLE who were in remission or who had minimal disease activity and had at least one year of follow-up were included in this study. Patients with known lung pathology and smokers were excluded. Patients with pSS constituted the second experimental group. Ultrasonographic evaluation of the diaphragmatic muscle was conducted by an experienced independent sonographer at three time points, diaphragmatic thickness during deep and quiet inspiration and maximum expiration being measured. Diaphragmatic muscle function was evaluated with maximum expiratory pressure (MEP) and maximum inspiratory pressure (MIP). RESULTS: A total of 115 patients were studied (n = 39 SLE; n = 76 pSS). The mean ± standard deviation (SD) thickness of the diaphragmatic muscles during quiet inspiration was significantly reduced in patients with SLE compared to patients with pSS (2.32 mm vs. 2.81 mm; p < 0.05). Similarly, the thickness during deep inspiration and at maximum deep expiration were significantly lower in SLE patients (2.88 mm vs. 3.29 mm and 1.92 mm vs. 2.33 mm, respectively; p < 0.01). MIPs and MEPs, defined as the percentages of expected values, were significantly lower in patients with SLE compared to those with pSS (80% vs. 92% and 76% vs. 120%, respectively; p < 0.05). Diaphragmatic muscle thickness during deep inspiration demonstrated a moderate correlation with MIP (r = 0.434; p = 0.001). CONCLUSION: SLE patients had reduced diaphragmatic muscle thickness compared to those with pSS, which was associated with impaired functional tests. Further prospective studies are needed to investigate whether structural and functional impairments in diaphragmatic muscle play a role in an increased risk of pulmonary infections and SLS in patients with SLE.

Impact of the Charlson Comorbidity Index on dose-limiting toxicity and survival in locally advanced and metastatic renal cell carcinoma patients treated with first-line sunitinib or pazopanib.

BACKGROUND: Anti-angiogenic tyrosine kinase inhibitors, sunitinib and pazopanib, have proven efficacy in advanced renal cell carcinoma, with specific adverse events occurring during treatment process. Comorbidities can reflect functional status and have prognostic value in oncology patients. We aimed to assess the association of the Charlson Comorbidity Index with severe toxicities and mortality in renal cell carcinoma cases treated with front-line sunitinib or pazopanib. METHODS: Files of locally advanced and metastatic renal cell carcinoma patients who received first-line sunitinib or pazopanib were retrospectively examined. Charlson Comorbidity Index of each patient was calculated. Patients were also stratified into Memorial Sloan-Kettering Cancer Center risk groups. Predictors of dose-limiting toxicity were evaluated with binomial logistic regression analysis. Univariate and multivariate Cox regression models were utilized to determine prognostic factors for survival. RESULTS: The study included 102 patients, 64 were treated with first-line sunitinib and 38 with pazopanib. In 42 patients (41.9%), Charlson Comorbidity Index was 9 or more. Dose-limiting toxicities were significantly more frequent in Charlson Comorbidity Index ≥9 group (69% vs. 40%, p = 0.004), and Charlson Comorbidity Index independently predicted dose-limiting toxicity (Hazard ratio (HR) = 4.30, p = 0.002). After adjusting for other variables, a Charlson Comorbidity Index of ≥9 is also a significant prognostic factor for progression-free (HR = 1.76, p = 0.02) and overall survival (HR = 1.75, p = 0.03). CONCLUSIONS: Charlson Comorbidity Index may be a valuable method to estimate prognosis and optimize therapy in patients with advanced renal cell carcinoma receiving first-line sunitinib or pazopanib.

¿El licopeno puede eliminar los efectos perjudiciales de la hiperoxia en los cerebros inmaduros? / Can lycopene eliminate the harmful effects of hyperoxia in an immature brain?

Objetivos: Al ser un antioxidante, el licopeno protege a las células contra el daño causado por los radicales libres, fortalece los enlaces intercelulares y mejora el metabolismo celular. Este estudio analiza los efectos del licopeno sobre los trastornos neurodegenerativos por hiperoxia en ratas recién nacidas a término. Métodos: Estas ratas se dividieron en cuatro grupos: grupo 1 de referencia con normoxia, grupo 2 con normoxia + licopeno, grupo 3 de referencia con hiperoxia y grupo 4 con hiperoxia + licopeno. Los grupos 1 y 2 se supervisaron en condiciones de aire ambiental, y los grupos 3 y 4 se supervisaron con un nivel de oxígeno > 85 % O2. Los grupos 2 y 4 recibieron inyecciones intraperitoneales de licopeno de 50 mg/kg/día; los otros grupos recibieron inyecciones intraperitoneales de aceite de maíz con el mismo volumen. Las ratas se sacrificaron en el día 11, después de 10 días con hiperoxia. Se extrajeron los cerebros, y se evaluaron los parámetros del sistema oxidativo. Resultados: Se detectaron lesiones cerebrales por hiperoxia en sustancia blanca, regiones corticales y tálamo. Aumentó la cantidad de células apoptóticas y disminuyó la cantidad de células PCNA positivas en los grupos 3 y 4, comparados con el grupo 1. No se observó una mejora significativa en la cantidad de células apoptóticas y células PCNA positivas en los grupos 3 y 4; además, aumentó la apoptosis. Conclusión: Se halló que el licopeno no mostró efectos terapéuticos para el daño cerebral en ratas recién nacidas. Además, se demostró que el licopeno podría causar efectos tóxicos.

Objectives. In addition to protecting cells against free radical harm thanks to its anti-oxidant nature, lycopene strengthens the bonds among cells and improves cell metabolism. This study focuses on analyzing therapeutic effects of lycopene in hyperoxia-induced neurodegenerative disorders in newborn rats. Methods. Term newborn rats were divided into four groups as the normoxia control group (group-1), normoxia+lycopene group (group-2), hyperoxia control group (group-3) and hyperoxia+lycopene group (group-4). Group-1 and group-2 were monitored in room air while the group-3 and group-4 were monitored at > 85% O2. The group-2 and group-4 were injected with lycopene intrapertioneally (i.p. ) at 50mg/kg/day while the other groups were injected with corn oil i.p. at the same volume. The rats we sacrificed on the 11th day following the 10-day hyperoxia. The brains were removed and oxidant system parameters were assessed. Results. Injury resulting from hyperoxia was detected in the white matter, cortical regions, and thalamus of the brains. It was observed that the number of apoptotic cells increased and the number of proliferating cell nuclear antigen (PCNA) positive cells decreased in the groups-3 and 4 compared to the group-1. No significant improvement in the number of apoptotic cells and PCNA positive cells was observed in the groups-3 and 4, and apoptosis increased as well. Conclusion. This study found that lycopene, did not show any therapeutic effects for brain damage treatment in newborn rats. In addition, this study demonstrated that lycopene might lead to toxic effects.

Can lycopene eliminate the harmful effects of hyperoxia in an immature brain? / ¿El licopeno puede eliminar los efectos perjudiciales de la hiperoxia en los cerebros inmaduros?

OBJECTIVES: In addition to protecting cells against free radical harm thanks to its anti-oxidant nature, lycopene strengthens the bonds among cells and improves cell metabolism. This study focuses on analyzing therapeutic effects of lycopene in hyperoxia-induced neurodegenerative disorders in newborn rats. METHODS: Term newborn rats were divided into four groups as the normoxia control group (group-1), normoxia+lycopene group (group-2), hyperoxia control group (group-3) and hyperoxia+lycopene group (group-4). Group-1 and group-2 were monitored in room air while the group-3 and group-4 were monitored at > 85% O2. The group-2 and group-4 were injected with lycopene intrapertioneally (i.p. ) at 50mg/kg/day while the other groups were injected with corn oil i.p. at the same volume. The rats we sacrificed on the 11th day following the 10-day hyperoxia. The brains were removed and oxidant system parameters were assessed. RESULTS: Injury resulting from hyperoxia was detected in the white matter, cortical regions, and thalamus of the brains. It was observed that the number of apoptotic cells increased and the number of proliferating cell nuclear antigen (PCNA) positive cells decreased in the groups-3 and 4 compared to the group-1. No significant improvement in the number of apoptotic cells and PCNA positive cells was observed in the groups-3 and 4, and apoptosis increased as well. CONCLUSIONS: This study found that lycopene, did not show any therapeutic effects for brain damage treatment in newborn rats. In addition, this study demonstrated that lycopene might lead to toxic effects.

Objetivos: Al ser un antioxidante, el licopeno protege a las células contra el daño causado por los radicales libres, fortalece los enlaces intercelulares y mejora el metabolismo celular. Este estudio analiza los efectos del licopeno sobre los trastornos neurodegenerativos por hiperoxia en ratas recién nacidas a término. Métodos: Estas ratas se dividieron en cuatro grupos: grupo 1 de referencia con normoxia, grupo 2 con normoxia + licopeno, grupo 3 de referencia con hiperoxia y grupo 4 con hiperoxia + licopeno. Los grupos 1 y 2 se supervisaron en condiciones de aire ambiental, y los grupos 3 y 4 se supervisaron con un nivel de oxígeno > 85 % O2. Los grupos 2 y 4 recibieron inyecciones intraperitoneales de licopeno de 50 mg/kg/día; los otros grupos recibieron inyecciones intraperitoneales de aceite de maíz con el mismo volumen. Las ratas se sacrificaron en el día 11, después de 10 días con hiperoxia. Se extrajeron los cerebros, y se evaluaron los parámetros del sistema oxidativo. Resultados: Se detectaron lesiones cerebrales por hiperoxia en sustancia blanca, regiones corticales y tálamo. Aumentó la cantidad de células apoptóticas y disminuyó la cantidad de células PCNA positivas en los grupos 3 y 4, comparados con el grupo 1. No se observó una mejora significativa en la cantidad de células apoptóticas y células PCNA positivas en los grupos 3 y 4; además, aumentó la apoptosis. Conclusión: Se halló que el licopeno no mostró efectos terapéuticos para el daño cerebral en ratas recién nacidas. Además, se demostró que el licopeno podría causar efectos tóxicos.

Serum heart type fatty acid binding protein levels are not changed in hyperthyroidism.

BACKGROUND: Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels. METHODS: Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay. RESULTS: There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871±66 pg/mL, and 816±66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls. CONCLUSIONS: Serum H-FABP levels are not altered in patients with hyperthyroidism.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study.

OBJECTIVE: Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. METHODS: Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. RESULTS: We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. CONCLUSION: Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Receptor expression discrepancy between primary and metastatic breast cancer lesions.

BACKGROUND: Recent studies have shown that the expression status of hormone receptors and human epidermal growth factor receptor 2 (HER2) in breast cancer may change during disease progression. The aim of this study was to determine and compare the estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status in primary breast cancer and metastatic lesions. METHODS: 58 patients with registered biopsy reports or available samples of the primary tumor and distant metastases were included in the final analysis. Biopsy samples were re-stained using immunohistochemical methods to determine receptor status (if not already recorded in previous reports) and re-examined by 2 independent pathologists. RESULTS: Discordance rates for receptor expression status of the primary tumor and distant metastases for ER, PR, and HER2 were 17.4, 45.4, and 13.3%, respectively. No statistically significant difference in overall survival due to receptor expression discordance between the primary tumor and metastatic sites (p>0.05) was found, although a tendency toward worse survival time was observed in patients with HER2 expression discrepancies. CONCLUSION: This study showed receptor discordance rates between primary and metastatic breast cancer sites for ER, PR, and HER2 of 17.8, 45.4, and 13.3%, respectively. Re-biopsy and IHC evaluation of metastatic sites for receptor status may change treatment decisions in patients with relapsed/progressed BC.

Impact of rheumatoid arthritis in Turkey: a questionnaire study.

OBJECTIVES: Unmet needs of rheumatoid arthritis (RA) patients regarding physician/patient communication, treatment preferences and quality of life issues were investigated in a Turkish survey study. METHODS: The study was conducted with the contribution of 33 rheumatologists, and included 519 RA patients. The study population included patients who had been on biologic therapy for >6 months and were still receiving biologic therapy (BT group), and those who were biologic naive, but found eligible for biologic treatment (NBT group). Of the RA patients, 35.5% initially had a visit to an internal disease specialist, 25.5% to a physical therapy and rehabilitation specialist, and 12.2% to a rheumatology specialist for their RA complaints. The diagnosis of RA was made by a rheumatologist in 48.2% of patients. RESULTS: The majority of RA patients (86.3%) visit their doctor within 15-week intervals. Most of the physician-patient communication focused on disease symptoms (99.0%) and impact of the disease on quality of life (61.8%). The proportion of RA patients who perceived their health status as good/very good/excellent was higher in the BT group than in the NBT group (74.3% vs. 51.5%, p<0.001). However, of those RA patients in the NBT group, only 24.8% have been recommended to start a biologic treatment by their doctors. With respect to dose frequency options, once-monthly injections were preferred (80%) to a bi-weekly injection schedule (8%). CONCLUSIONS: In conclusion, RA patients receiving biologic therapy reported higher rates of improved symptoms and better quality of life and seemed to be more satisfied with their treatment in our study.

Diagnostic dilemma of paraneoplastic arthritis: case series.

OBJECTIVES: Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While presenting the demographic and laboratory features of the patients diagnosed with PA, this study also aims to provide possible appropriate tools to differentiate the PA cases from early rheumatoid arthritis (ERA). METHODS: Sixty-five patients with PA (male/female: 43/22) from 15 different rheumatology clinics and 50 consecutive patients with ERA (male/female: 13/37) fulfilling the 2010 American College of Rheumatology (ACR) criteria for the diagnosis if the RA from Gaziantep Rheumatology Early Arthritis Trial (GREAT) as controls who were diagnosed at least 12 months before, were enrolled into study. RESULTS: Mean ages of the patients with PA and ERA were 50.2 ± 15.3, and 42.7 ± 12.3, respectively, and the mean ages of the patients with PA were significantly higher than the ERA. Unlike the ERA patients, in our case series PA was predominantly observed among males. Oligoarthritis was significantly higher in solid tumors in contrast to ERA (P = 0.001). Polyarthritis and symmetric arthritis were significantly higher in the ERA group in contrast to all malignancies (P = 0.001). Rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) positivity were significantly higher in the ERA group (each P = 0.001). Lactic dehydrogenase levels of hematologic malignancies were significantly higher than other groups (each, P = 0.001). CONCLUSIONS: ERA patients had more symmetric joint involvement than PA; laboratory markers could be also an alternative where there is high RF and anti-CCP positivity with antibody levels among the ERA patients. Finally, the demographic features can be used as differentiating factors; ERA was seen predominantly among females aged 40-59 years which refers to young adults.

Identification of multiple genetic susceptibility loci in Takayasu arteritis.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

Takotsubo syndrome: an underdiagnosed complication of 5-fluorouracil mimicking acute myocardial infarction.

Takotsubo syndrome (TTS)/cardiomyopathy is a syndrome that mimics acute myocardial infarction in the absence of coronary artery disease and is characterized by acute onset of chest pain, electrocardiographic abnormalities, and reversible left ventricular dysfunction. It is usually induced by emotional and physical stress. Fluorouracil is one of the most frequently used chemotherapy agents and a relatively common adverse reaction of fluorouracil is cardiotoxicity. Herein we describe a patient without a history of cardiovascular disorder who developed severe heart failure during infusion of fluorouracil for metastatic gastric cancer. Remarkably, the patient did not develop TTS during prior chemotherapy regimen, which also included fluorouracil. The patient's findings were consistent with the proposed TTS diagnostic criteria and coronary angiography was normal, without obstructive coronary artery disease. With supportive care, the patient's cardiac functions returned to normal. TTS is not a well known syndrome to clinicians and this condition appears to occur more frequently than previously thought. In addition to the presented case, a review of the clinical features and outcome of 10 reported cases of fluorouracil-induced TTS is presented.

Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey.

INTRODUCTION: HLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behçet's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors. METHODS: TAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers. RESULTS: We found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA-B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78). CONCLUSIONS: In this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further.

PDCD1 polymorphisms are not associated with Takayasu's arteritis in Turkey.

OBJECTIVES: Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Based on the associations of programmed death-1 (PD-1) protein encoding gene (PDCD1) with connective tissue diseases and vasculitides, PDCD1 polymorphisms are studied for susceptibility to TA in this study. METHODS: The study group is made up of TA patients (n=229) fulfilling the 1990 ACR classification criteria and compared to 193 healthy controls (HC). PD-1.3, PD-1.5 and PD-1.6 single nucleotide polymorphisms of PDCD1 gene are genotyped by polymerase chain reaction and restriction analysis (PCR-RFLP). RESULTS: The distribution of PD-1.5 polymorphism in TA patients and HC revealed a similar presence of TT genotype in patients and controls (13.3% vs. 11.4%). PD-1.3 and PD-1.6 were less polymorphic and did not differ between the groups. Rare AA genotype of PD-1.3 (1.4% vs. 1.0%) and AG genotype of PD-1.6 was again similarly (22.4% vs. 19.2%) present in TA and HC. CONCLUSIONS: PD-1.3, 1.5 and 1.6 polymorphisms of PDCD1 gene, which were shown to be associated with various autoimmune disorders and vasculitides, are not associated with a susceptibility to TA in Turkish population.

Osteomalacic myopathy associated with coexisting coeliac disease and primary biliary cirrhosis.

OBJECTIVE: To report a patient with coeliac disease (CD) associated with primary biliary cirrhosis (PBC) who presented with myopathy without classical symptoms of CD. CLINICAL PRESENTATION AND INTERVENTION: A 42-year-old woman presented with inability to walk and marked loss of motor function. She had elevated liver enzymes with a cholestatic pattern. Antimitochondrial antibody M2 band, anti-endomysial antibody, antigliadin IgA and IgM were positive. Histopathologic findings of the liver revealed PBC and duodenal biopsy was consistent with CD. She was also found to have osteomalacia. She showed slow response to gluten-free diet, but accelerated full recovery with vitamin D replacement. CONCLUSION: In PBC patients with subclinical CD and myopathy, vitamin D status can provide a basis for treatment.