Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

The Psoriatic Arthritis Registry of Turkey: results of a multicentre registry on 1081 patients.

OBJECTIVE: The aim was to assess the characteristics of PsA, find out how well the disease is controlled in real life, demonstrate the treatments and identify the unmet needs. METHODS: The PsA registry of Turkey is a multicentre Web-based registry established in 2014 and including 32 rheumatology centres. Detailed data regarding demographics for skin and joint disease, disease activity assessments and treatment choices were collected. RESULTS: One thousand and eighty-one patients (64.7% women) with a mean (sd) PsA duration of 5.8 (6.7) years were enrolled. The most frequent type of PsA was polyarticular [437 (40.5%)], followed by oligoarticular [407 (37.7%)] and axial disease [372 (34.4%)]. The mean (sd) swollen and tender joint counts were 1.7 (3) and 3.6 (4.8), respectively. Of these patients, 38.6% were on conventional synthetic DMARD monotherapy, 7.1% were on anti-TNF monotherapy, and 22.5% were using anti-TNF plus conventional synthetic DMARD combinations. According to DAS28, 86 (12.4%) patients had high and 105 (15.2%) had moderate disease activity. Low disease activity was achieved in 317 (45.7%) patients, and 185 (26.7%) were in remission. Minimal disease activity data could be calculated in 247 patients, 105 of whom (42.5%) had minimal disease activity. The major differences among sexes were that women were older and had less frequent axial disease, more fatigue, higher HAQ scores and less remission. CONCLUSION: The PsA registry of Turkey had similarities with previously published registries, supporting its external validity. The finding that women had more fatigue and worse functioning as well as the high percentage of active disease state highlight the unmet need in treatment of PsA.

Prolonged Tpeak-Tend interval in anti-Ro52 antibody-positive connective tissue diseases.

Patients with connective tissue diseases (CTDs) may have prolonged corrected QT interval which indicates increased risk for ventricular arrhythmias. However, a more sensitive measure of ventricular repolarization, T-peak-to-end (Tpe) interval, has not been studied in CTDs. We aimed to investigate the relationship between ventricular repolarization abnormalities and anti-Ro52-positivity in subjects with connective tissue diseases (CTDs). We enrolled patients with anti-Ro52-positive CTDs, ANA-positive CTDs, and healthy subjects in this cross-sectional study. We excluded conditions potentially affecting the QT interval. We compared the ECG measures between the groups and performed analyses to define factors associated with ventricular repolarization measures. 15 ANA and anti-Ro52-positive, 39 ANA-positive and anti-Ro52-negative, and 22 healthy subjects were enrolled. None of the subjects had rhythm or conduction disturbances. Corrected QT intervals were similar between the groups. Tpe (84, 77.3, and 69.4 msn, respectively) and QT-dispersion (40, 27.2, and 20.1 msn, respectively) were higher in anti-Ro52-positive subjects compared with the ANA-positive and healthy subjects. Anti-Ro52 titers were correlated with Tpe and QT-dispersion (r = 0.52 and p < 0.001 for each). ANA and anti-Ro52-positivity were independently associated with higher Tpe (OR = 7.7, p = 0.001 and OR = 6.9, p = 0.001, respectively), corrected Tpe (OR = 11.3, p = 0.001 and OR = 8.4, p = 0.003, respectively), QT dispersion (OR = 7, p = 0.008 and OR = 13, p < 0.001, respectively), and QTc dispersion (OR = 9.1, p = 0.001 and OR = 14.1, p < 0.001, respectively). This study provides evidence that ANA positivity, especially when concomitant anti-Ro52-positivity is present, significantly deteriorates ventricular repolarization. The aforementioned ventricular repolarization abnormalities may render these subjects susceptible to serious rhythm or conduction disorders in the setting of predisposing conditions.

The Effect of the Active Ingredient Thymoquinone on Flap Viability in Random Pattern Flaps in Rats.

Thymoquinone (TQ) is a plant extract that has been shown to have antioxidant, anti-inflammatory, angiogenic, antimicrobial, and anticarcinogenic effects. The aim of this study is to research how the use of TQ affects flap viability. 42 rats were placed into 6 groups, with 7 rats in each. A 3 × 10 cm McFarlane flap model was used on the test animals. The sham group had used neither surgical nor TQ treatment. The control group had surgery but no treatment afterwards. The preoperative TQ group was given oral doses of 2 mg/kg. TQ for 10 days preoperatively with no treatment after the surgical procedure. The postoperative TQ group received oral doses of 2 mg/kg TQ for 10 days after the surgical process. The preoperative + postoperative (pre + postoperative) TQ group was given oral doses of 2 mg/kg TQ for 10 days both preoperatively and postoperatively. Finally, the dimethylsulfoxide group received 10 mg/kg dimethylsulfoxide (DMSO) for 10 days both preoperatively and postoperatively. Ten days after surgery the findings were evaluated. The average rates of necrosis were found to be 29.7 % in the control group, 19.18 % in the preoperative TQ group, 13.05 % in the postoperative TQ group, 8.42 % in the pre + postoperative TQ group, and 29.03 % in the DMSO group. The experimental groups had better area measurement, histopathological, and electron microscopic results than the control group (All; p < 0.05). We believe that, because of its antioxidant, anti-inflammatory, and angiogenic properties, thymoquinone is an agent that can prevent ischemia-reperfusion damage and, therefore, prevent necrosis.

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

Effect of Concentrated Growth Factor on Survival of Diced Cartilage Graft.

BACKGROUND: Diced cartilage grafts are important in rhinoplasty for raising the dorsum and eliminating dorsal irregularities. The most common problems with the use of diced cartilage are wrapping and cartilage resorption. OBJECTIVES: To histopathologically investigate and compare the viability of diced cartilage grafts wrapped with concentrated growth factor, fascia and fenestrated fascia, or blood glue. METHODS: Cartilage grafts were harvested from the ears of 10 New Zealand White rabbits and diced into 0.5 to 1 mm3 pieces. The grafts were divided into five groups for comparison: (1) bare diced cartilage; (2) diced cartilage wrapped with fascia; (3) diced cartilage wrapped with fenestrated fascia; (4) diced cartilage wrapped with concentrated growth factor (CGF); and (5) diced cartilage wrapped with blood glue. Each of the five grafts was autologously implanted into a subcutaneous pocket in the back of each rabbit. Three months later, the rabbits were sacrificed and the implants were harvested and examined histopathologically. RESULTS: Nucleus loss, calcification, inflammation, and giant cell formation differed significantly between the CGF group and both fascia groups. Chondrocyte proliferation was the highest in the CGF group. Nucleus loss rates were similar between the fascia and fenestrated fascia groups. CONCLUSIONS: Our findings suggest that CGF improves the viability of diced cartilage grafts, while fascia hampers it. Punching holes in the fascia does not improve diced cartilage graft viability and neither does blood glue wrapping.

Development and Characterization of Plant-derived Aristatoside C and Davisianoside B Saponin-loaded Phytosomes with Suppressed Hemolytic Activity.

Saponins are glycosides widely distributed in the plant kingdom and have many pharmacological activities. However, their tendency to bind to cell membranes can cause cell rupture, limiting their clinical use. In the previous study, aristatoside C and davisianoside B were isolated from Cephalaria species. Cytotoxicity assays showed that they are more active on A-549 cell lines than doxorubicin but caused hemolysis. In the current research, aristatoside C and davisianoside B were loaded to phytosomes called ALPs and DLPs respectively, and characterized for particle size, zeta potential, encapsulation efficiency, release kinetic, hemolytic activity, and cytotoxicity on A-549 cell line. DLPs maintained the cytotoxic activity of the free saponins against A-549 cells with IC50 of 9,64±0,02 µg/ml but dramatically reduced their hemolytic activity. Furthermore, temperature and time-dependent stability studies based on the size and zeta potential of ALPs and DLPs revealed that the phytosomes have sustained release properties over 2 weeks. Overall, DLPs displayed cytotoxicity against A-549 cells with minimal hemolysis and sustained release, highlighting their potential as nanotherapeutics for clinical applications.

An unexpected long-term complication of genital burn in a child: Secondary cryptorchidism.

Genital and perineal burns are rare and challenging injuries with serious long-term complications. Involvement of the testes is a sign of severity. There is limited knowledge in the literature about the management of complications and testes involvement in genital and perineal burns. In this report, we present the case of an 8-year-old boy with secondary cryptorchidism due to burn contracture who was treated by increasing the scrotal volume by Z-plasties, skin graft, and orchidopexy.

Patients' concerns regarding biological agents in rheumatology.

OBJECTIVE: The potential side effects of biological agents may increase the anxiety levels of patients and influence not only their desire to use these therapies but also their concordance to treatment. This study aimed to determine the level and prevalence of drug-related concern in patients treated with biological agents and to acquire additional information regarding the related causes. MATERIALS AND METHODS: A total of 1134 patients who were using biological agents for at least 3 months with a diagnosis of rheumatic diseases were enrolled. General anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI). RESULTS: The most common cause for drug-related concerns was the potential side effects of the drugs (59.5%). Among the potential side effects, cancer risk was the most common cause for concern (40.1%), followed by the risk of tuberculosis activation (30.7%). Anxiety levels were higher in patients who experienced side effects than in other patients, and this difference was statistically significant (P < 0.05). STAI trait and state scores were moderately correlated with anxiety levels related to the drug (P < 0.001). CONCLUSION: Anxiety related to biological agents may significantly affect the patients' anxiety levels. Awareness regarding the patients' concerns and expectations related to the drug is important to ensure drug adherence and concordance to treatment.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever.

AIM: Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. METHODS: One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. RESULTS: As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p<0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p>0.05). CONCLUSIONS: To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Clinical outcomes and survival in AA amyloidosis patients.

AIM: Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. METHODS: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. RESULTS: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. CONCLUSION: Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Effects of ozone pretreatment on viability of random pattern skin flaps in rats.

BACKGROUND: Medical ozone is a chemical agent that consists of three oxygen atoms and has antioxidant, angiogenic and vasodilator effects. This study evaluated the effects of medical ozone pre-treatment on flap survival. MATERIALS AND METHODS: Rats were divided into four groups of 10 rats each and a 9 × 3 cm McFarlane flap was used. Sham group: Neither surgical nor ozone pretreatment was used. CONTROL GROUP: No pretreatment was used after surgery. Preoperative ozone group: Preoperative 1 mg/kg ozone was given intraperitoneally for 7 days. No pretreatment was used after surgery. Postoperative ozone Group: Postoperative 1 mg/kg ozone was given intraperitoneally for 7 days. After postoperative 1 week, all groups were evaluated by surface area measurement, histopathology and electron microscopy. RESULTS: With the experimental McFarlane flap model, the experimental groups had better surface area measurements, along with histopathological and electron microscopic results when compared with the control group. CONCLUSION: Medical ozone had positive effects on flap survival due to its antioxidant, angiogenic and vasodilator qualities.

Anti-cyclic citrullinated peptide and rheumatoid factor in patients with chronic hepatitis B and hepatitis B carriers.

OBJECTIVE: Rheumatoid factor (RF) positivity that may occur in a number of patients with hepatitis B (HBV) infection poses challenges in terms of differential diagnosis with rheumatoid arthritis (RA). On the other hand, antibodies to cyclic citrullinated peptide (anti-CCP) may prove to be an important marker for differential diagnosis of the two conditions. This study aimed to assess anti-CCP and RF positivity among patients with hepatitis B and rheumatoid arthritis. MATERIAL AND METHODS: Anti-CCP and RF seropositivity was assessed in 61 patients with HBV infection (32 patients with chronic hepatitis, 29 patients with inactive HBV carrier status) and 40 patients with RA as the control group. RESULTS: RF positivity was found in 18.7% and 34.4% of the patients with chronic hepatitis B and inactive HBV carrier status, respectively. On the other hand, only one patient with chronic HBV had low positive anti-CCP. RF was positive in 24 (60%) and anti-CCP was positive in 26 (65%) patients among the 40 patients with RA. CONCLUSION: Anti-CCP may be helpful in the differential diagnosis between RA and chronic HBV infection or inactive HBV carrier status.

Evaluation of the bond strength of resin cements used to lute ceramics on laser-etched dentin.

OBJECTIVE: The purpose of this study was to investigate the shear bond strength (SBS) of two different adhesive resin cements used to lute ceramics on laser-etched dentin. BACKGROUND DATA: Erbium, chromium: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) laser irradiation has been claimed to improve the adhesive properties of dentin, but results to date have been controversial, and its compatibility with existing adhesive resin cements has not been conclusively determined. MATERIALS AND METHODS: Two adhesive cements, one "etch-and-rinse" [Variolink II (V)] and one "self-etch" [Clearfil Esthetic Cement (C)] luting cement, were used to lute ceramic blocks (Vita Celay Blanks, Vita) onto dentin surfaces. In total, 80 dentin specimens were distributed randomly into eight experimental groups according to the dentin surface-etching technique used Er,Cr:YSGG laser and Er:YAG laser: (1) 37% orthophosphoric acid+V (control group), (2) Er,Cr:YSGG laser+V, (3) Er,Cr:YSGG laser+acid+V, (4) Er:YAG laser+V, (5) Er:YAG laser+acid+V, (6) C, (7) Er,Cr:YSGG laser+C, and (8) Er:YAG laser+C. Following these applications, the ceramic discs were bonded to prepared surfaces and were shear loaded in a universal testing machine until fracture. SBS was recorded for each group in MPa. Shear test values were evaluated statistically using the Mann-Whitney U test. RESULTS: No statistically significant differences were evident between the control group and the other groups (p>0.05). The Er,Cr:YSGG laser+A+V group demonstrated significantly higher SBS than did the Er,Cr:YSGG laser+V group (p=0.034). The Er,Cr:YSGG laser+C and Er:YAG laser+C groups demonstrated significantly lower SBS than did the C group (p<0.05). CONCLUSIONS: Dentin surfaces prepared with lasers may provide comparable ceramic bond strengths, depending upon the adhesive cement used.

Comparing female-based contraceptive methods in patients with systemic lupus erythematosus, rheumatoid arthritis and a healthy population.

AIM: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is 10 times more prevalent in women, particularly those of reproductive age. The varying effects of pregnancy on SLE and the differences between available SLE treatments make pregnancy timing and contraceptive methods significant. We aimed to determine the contraceptive methods used by SLE patients in the north-west part of Turkey, and compared them with those used by rheumatoid arthritis (RA) patients and healthy controls. METHOD: The study was comprised of 113 SLE patients, and 84 RA patients at the Rheumatology Outpatient Clinic of Uludag University Medical Faculty. RESULTS: Twenty-three (20.3%) out of 113 SLE patients, 18 (21.4%) out of 84 RA patients and 17 (18.6%) out of 92 healthy controls did not use any contraceptive methods. Use of the withdrawal and condom methods was more common among SLE patients, accounting for 61% (withdrawal 32.7%, condom 28.3%). Moreover, 52% of SLE and 50% of RA patients were neither given information about contraceptive methods nor offered a suggested method, compared to 34% in the health control group. CONCLUSIONS: The prevalence of oral contraceptive use is low in Turkey; notwithstanding the withdrawal and condom methods, which are frequently used despite their high failure risk. Although pregnancy timing is of great importance for SLE patients, necessary information and recommendations concerning contraceptive methods have been ignored and the use of effective methods is not a priority.

Neutrophil lymphocyte ratio can be a valuable marker in defining disease activity in patients who have started anti-tumor necrosis factor (TNF) drugs for ankylosing spondylitis.

OBJECTIVE: Neutrophil lymphocyte ratio (NLR) has emerged as a valuable and reliable method for follow-up of systemic inflammatory disease. We herein aimed to evaluate the role of NLR in the clinical follow-up of inflammation and also to compare its relationship with other measures, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). MATERIAL AND METHODS: A total of 35 active ankylosing spondylitis (AS) and 38 healthy volunteers were included in the study. The patient group was enrolled for treatment with one anti-tumor necrosis factor (TNF) drug. Total blood count, ESR, CRP, and BASDAI score were obtained before and 3 months following the treatment. NLR was found with a mathematical calculation of the ratio of neutrophils with lymphocytes. RESULTS: The mean NLR value of the control group and patients was 1.90±0.89 and 2.67±1.17, respectively (p<0.05). After a 3-month course of treatment, the patient group had a mean NLR value of 1.8±0.7, which was significantly lower than pretreatment values (p<0.001). The post-treatment mean ESR, CRP, and BASDAI scores were significantly lower than mean baseline scores (p<0.001, p=0.007, p<0.001, respectively). Also, NLR was found to be correlated with BASDAI, ESR, and CRP (r=0.388, p<0.001; r=0.455, p<0.0001; and r=0.3389, p<0.005, respectively). CONCLUSION: Neutrophil lymphocyte ratio could be a reliable and easily accessible method for follow-up of patients with AS.

Hairy cell leukemia presenting initially with symptoms of Behçet's disease.

Vasculitis is relatively uncommon in lymphoproliferative disease and may predate the diagnosis of lymphoproliferative disease. Many vasculitides have been associated with hairy cell leukemia (HCL), including polyarteritis nodosa (PAN) and leukocytoclastic vasculitis. We herein report a case whose initial presentation was like Behçet's disease (BD) (arthritis, oral and genital ulcerations, papulopustular skin lesions) in addition to pancytopenia, but turned out to have HCL. Because of the overlap between their symptoms, like oral ulcerations, skin lesions, arthritis and constitutional findings, HCL and BD may mimic each other. We should keep in mind other reasons for vasculitis such as lymphoproliferative disease, especially whose who have hematological abnormalities such as pancytopenia.

Clinical outcomes and survival in AA amyloidosis patients / Desfechos clínicos e sobrevida em pacientes com amiloidose AA

Abstract Aim Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65 ± 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 ± 16 months. Conclusion Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Resumo Objetivo: A amiloidose AA é uma complicação rara de condições inflamatórias crônicas. A maior parte dos pacientes com amiloidose AA apresenta nefropatia, que leva à insuficiência renal e à morte. Estudaram-se as características clínicas e a sobrevida em pacientes com amiloidose AA. Métodos: Analisaram-se retrospectivamente 81 pacientes (51 homens, 30 mulheres) com amiloidose AA comprovada por biópsia renal. Os pacientes foram divididos em grupos de desfecho bom e ruim de acordo com os resultados de sobrevida. Resultados: A maior parte dos pacientes (55,6%) tinha proteinúria na faixa nefrótica no momento do diagnóstico. Os distúrbios subjacentes mais frequentes foram a febre familiar do Mediterrâneo (FFM, 21,2%) e a artrite reumatoide (10,6%) no grupo de desfecho bom e a malignidade (20%) no grupo de desfecho ruim. Somente a pressão arterial diastólica no grupo de desfecho bom e o nível de fósforo no grupo de desfecho ruim foram mais elevados. Os níveis séricos de creatinina aumentaram após o tratamento em ambos os grupos, enquanto a proteinúria diminuiu no grupo de desfecho bom. O aumento na creatinina sérica e a diminuição na TFGe do grupo de desfecho ruim foram mais significativos no grupo de desfecho bom. No momento do diagnóstico, 18,5% e 27,2% de todos os pacientes tinham doença renal crônica avançada (estágios 4 e 5, respectivamente). A duração média da sobrevida renal foi de 65 ± 3,54 meses. Entre todos os pacientes, 27,1% iniciaram tratamento de diálise durante o período de seguimento e 7,4% de todos os pacientes foram submetidos a transplante renal. Níveis elevados de pressão arterial sistólica [taxas de risco (HR) 1,03, intervalo de confiança (IC) de 95%: 1 a 1,06, p = 0,036], creatinina sérica (HR 1,25, IC 95%: 1,07 a 1,46, p = 0,006) e excreção urinária de proteínas (HR 1,08, IC 95%: 1,01 a 1,16, p = 0,027) foram preditores de doença renal terminal. A mediana da sobrevida de pacientes com comprometimento de órgãos foi de 50,3 ± 16 meses. Conclusão: O presente estudo indicou que a FFM constituiu uma grande proporção de casos e crescente quantidade de pacientes com amiloidose AA idiopática. Adicionalmente, observou-se que a sobrevida do paciente não foi afetada pelas diferentes causas etiológicas na amiloidose AA.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever / Investigação de polimorfismos no gene MEFV (G138G e A165A) em pacientes adultos com febre mediterrânica familiar

Abstract Aim: Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. Methods: One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. Results: As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p < 0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p > 0.05). Conclusions: To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Resumo Objetivo: Identificaram-se mutações no gene da febre mediterrânica (MEFV) relatadas como responsáveis pela febre mediterrânica familiar (FMF). Este estudo teve como objetivo determinar a frequência de mutações no MEFV na região sul do mar de Mármara e investigar o impacto dos polimorfismos genéticos G138G (rs224224, c.414A > G) e A165A (rs224223, c.495C > A) nos achados clínicos da doença. Métodos: Foram incluídos neste estudo 116 pacientes com diagnóstico de FMF e 95 indivíduos no grupo controle. Usou-se o método de análise da sequência de DNA para identificar as 10 mutações mais prevalentes localizadas nos éxons 2 e 10 do gene MEFV. Resultados: Como resultado da análise da mutação MEFV, a mutação mais comum foi a mutação alélica M694 V, com uma taxa de frequência de 41,8%. Quando os grupos de pacientes e controles foram comparados em termos de frequência de ambos os alelos polimórficos (alelo polimórfico G, observado no G138G e o alelo polimórfico A, observado no A165A), a variação observada foi estatisticamente significativa (p < 0,001). Verificou-se que os tipos de mutação no MEFV não tinham relação com os achados clínicos nem com a amiloidose (p > 0,05). Conclusões: Que se tem conhecimento, este estudo é o primeiro feito na região sul do mar de Mármara que relata a frequência de mutações no MEFV. Os achados indicam que os polimorfismos G138G e A165A podem ter um impacto sobre o progresso da doença. Acredita-se que são necessários mais estudos que abranjam um maior número de casos e investiguem os polimorfismos do gene MEFV.

Tensile bond strength of indirect composites luted with three new self-adhesive resin cements to dentin.

OBJECTIVE: The aims of this study were to evaluate the tensile bond strengths between indirect composites and dentin of 3 recently developed self-adhesive resin cements and to determine mode of failure by SEM. MATERIAL AND METHODS: Exposed dentin surfaces of 70 mandibular third molars were used. Teeth were randomly divided into 7 groups: Group 1 (control group): direct composite resin restoration (Alert) with etch-and-rinse adhesive system (Bond 1 primer/adhesive), Group 2: indirect composite restoration (Estenia) luted with a resin cement (Cement-It) combined with the same etch-and-rinse adhesive, Group 3: direct composite resin restoration with self-etch adhesive system (Nano-Bond), Group 4: indirect composite restoration luted with the resin cement combined with the same self-etch adhesive, Groups 5-7: indirect composite restoration luted with self-adhesive resin cements (RelyX Unicem, Maxcem, and Embrace WetBond, respectively) onto the non-pretreated dentin surfaces. Tensile bond strengths of groups were tested with a universal testing machine at a constant speed of 1 mm/min using a 50 kgf load cell. Results were statistically analyzed by the Student's t-test. The failure modes of all groups were also evaluated. RESULTS: The indirect composite restorations luted with the self-adhesive resin cements (groups 5-7) showed better results compared to the other groups (p<0.05). Group 4 showed the weakest bond strength (p>0.05). The surfaces of all debonded specimens showed evidence of both adhesive and cohesive failure. CONCLUSION: The new universal self-adhesive resins may be considered an alternative for luting indirect composite restorations onto non-pretreated dentin surfaces.