Tofacitinib therapy for severe pyoderma gangrenosum in a patient with enteropathic arthritis: a case-based review.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that is associated with systemic inflammatory conditions. Currently, there is no universally accepted standard therapy for PG, but immunosuppressive (IS) treatment seems essential. We report a patient here who was successfully treated with tofacitinib despite being PG-refractory to multiple anti-tumor necrosis factor alpha (anti-TNF) therapies and conventional IS. In addition, we performed a comprehensive review of all cases of PG treated with JAK inhibitors. We identified 27 cases treated with JAK inhibitors. Approximately 80% of the patients achieved complete recovery within a median of 12 weeks, even though 17 patients (63%) had received biologics before JAKinib treatment. Notably, this recovery could appear as early as 2 weeks. JAK inhibitors may prove useful in the future, particularly for treating immunosuppressive and steroid-resistant pyoderma gangrenosum, according to recent case reports.

Does obesity affect treatment response to secukinumab and survival in ankylosing spondylitis? Real-life data from the TURKBIO Registry.

OBJECTIVES: The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS). METHODS: We performed an observational cohort study that included AS patients based on the biological drug database in Turkey (TURKBIO) Registry between 2018 and 2021. The patients were divided into three groups: normal [body mass index (BMI) < 25 kg/m2], overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2). Disease activity was evaluated at baseline, 3, 6, and 12 months. Drug retention rates at 12 months were also investigated. RESULTS: There were 166 AS patients using secukinumab (56.6% male, mean age: 44.9 ± 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (P = .003). There was no statistically significant difference in Bath Ankylosing Spondylitis Disease Activity Index 50, Assessment of SpondyloArthritis international Society 20 (ASAS20), ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, and ASDAS clinically important improvement responses between the three groups at 3, 6, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (P > .05). CONCLUSIONS: This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.

SAPHO syndrome: current clinical, diagnostic and treatment approaches.

This review provides an overview of SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), a rare autoinflammatory disease that primarily affects bones, skin, and joints. We conducted a search on Medline/PubMed using keywords such as SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms. SAPHO syndrome is rare, with a reported frequency of 1 in 10,000 in the Caucasian population. However, the actual incidence of SAPHO syndrome is unknown, and the incidence of the disease is likely higher. The pathogenesis of SAPHO syndrome remains incompletely understood. Current evidence suggests that SAPHO results from a complex interplay between immune dysregulation, genetic susceptibility, and environmental factors. It's not clear if SAPHO syndrome is an autoimmune disease or an autoinflammatory disease, but current evidence suggests that it's more likely an autoinflammatory disease because of things like neutrophil hyperactivity, fewer natural killer (NK) cells, high levels of interleukin (IL)-1, and a good response to treatments that block IL-1. Osteo-articular (OA) involvement is a key clinical feature of SAPHO. It affects the anterior chest wall, axial skeleton, peripheral joints, mandible, long bones of the extremities, and pelvis. Dermatological involvement is a common target in SAPHO, with lesions observed in 60-90% of cases. Common skin lesions include psoriasis and acne, with hidradenitis suppurativa and neutrophilic dermatoses being less commonly seen. Other clinical findings include constitutional symptoms caused by systemic inflammation, such as fever, weight loss, and fatigue. There is no specific laboratory finding for SAPHO syndrome. However, during active disease, there may be an increase in positive acute phase markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels, mild leukocytosis, and thrombocytosis. Diagnosis is crucial for SAPHO syndrome, which lacks a specific diagnostic finding and is often underrecognized. A comprehensive evaluation of a patient's medical history and physical examination is crucial. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional and synthetic disease-modifying agents (cDMARDs and sDMARDs), biological therapies, bisphosphonates, and antibiotics. Biological treatments have emerged as a viable alternative for SAPHO patients who do not respond to conventional treatments.

Quantitative analysis of JAK/STAT signaling pathway in patients of inflammatory skin disorders.

BACKGROUND: Inflammatory skin diseases (ISDs), are characterized by dysregulated activation of innate and adaptive immune systems, with inflammatory cytokines playing a crucial role in their pathogenesis. OBJECTIVES: This study aimed to investigate the involvement of Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway in the pathogenesis of ISDs. METHODS: The study analyzed a total of 117 skin biopsies, comprising 31 from pyoderma gangrenosum (PG), 25 from hidradenitis suppurativa (HS), 35 from psoriasis patients, and 26 from control subjects. To assess the expression levels of JAK/STAT pathway components, immunohistochemical staining was performed on both the dermal and epidermal layers of the skin. The Histo score (H score) was utilized as the immunoexpression score to evaluate the staining intensity. RESULTS: The results indicated that all components of the JAK/STAT signaling pathway, except JAK2 and STAT6 in PG, JAK1, STAT4, and STAT6 in HS, and JAK1 in psoriasis, were overexpressed in the dermal skin compared to the control group (p < 0.05). Psoriatic skin had higher expression of STAT6 than both PG and HS and higher expression of JAK2 than PG (p < 0.05). Additionally, HS biopsies had higher expression of JAK2 and STAT6 compared to PG (p < 0.05). JAK1 expression was higher in PG than in HS, psoriasis, and the control group (mean H score was 265.8, 184.8, 191.4, and 113.1, p < 0.05, respectively). CONCLUSIONS: This study provides new insights into the potential contribution of the JAK/STAT pathway to the pathogenesis of ISDs. The findings suggest that targeting this pathway could be a promising therapeutic strategy for treating these disorders.

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.

COVID-19 in familial Mediterranean fever: Clinical course and complications related to primary disease.

OBJECTIVES: To evaluate the impact of familial Mediterranean fever (FMF) features on the clinical course and outcomes of coronavirus disease 2019 (COVID-19) and clinical course of FMF after COVID-19. METHODS: Consecutive FMF patients with COVID-19 were enrolled from three referral hospitals. Clinical features of FMF and detailed COVID-19 information were obtained from patient interviews and medical records. RESULTS: Seventy-three FMF patients were included in the study. 94.5% of patients had clinical symptoms of COVID-19. We found 24.7% hospitalization, 12.3% respiratory support, 4.1% intensive care unit admission, 6.8% complication, and 1.4% mortality rate in patients. The risk factors of hospitalization for respiratory support were male gender [OR: 7.167 (95% CI: 1.368-37.535)], greater age [OR: 1.067 (95% CI: 1.016-1.121)], and non-adherence to colchicine treatment before the infection [OR: 7.5 (95% CI: 1.348-41.722)]. One-third of patients had reported attacks after COVID-19. The patterns of triggered attacks were fever, peritonitis, pleuritis, transient arthritis, chronic knee mono-arthritis, and protracted febrile myalgia. CONCLUSIONS: FMF characteristics were not associated with worse outcomes of COVID-19. Colchicine non-adherence was the risk factor of hospitalization for oxygen support. The rate of FMF attacks after COVID-19 is prominently increased, with some of them being protracted and destructive.

A Significant Association Between rs2295190 Polymorphism of the ESR1 Gene and Fibromyalgia Syndrome.

Fibromyalgia syndrome (FMS) is a multifactorial disease characterized by chronic diffuse pain. Genetic factors are also involved in the etiology. However, there is not enough information on the genetic factors that play a role in the pathogenesis of FMS. The aim of this study is to investigate the relationship between estrogen receptor 1 gene (ESR1) 594G>A (rs2228480) and 325C>G (rs2295190) polymorphisms and fibromyalgia syndrome (FMS). A total of 294 women, 146 of who were FMS patients and 148 of whom were healthy controls, were enrolled in the study. The instruments used to collect data from patients included patient follow-up form, Visual Analogue Scale (VAS), and Fibromyalgia Impact Questionnaire (FIQ). Genotyping of ESR1 594G>A and 325C>G polymorphisms in the extracted DNA samples was performed using an RT-PCR device and TaqMan hydrolysis probes. It was found that, for rs2295190 polymorphism, patients with CG and GG genotypes versus CC genotypes showed a decreased risk for FMS (OR: 0.442; 95% CI: 0.234-0.833). But there were no significant differences were found in the genotype distribution of  rs2228480 polymorphism between the FMS patients and controls. The intragroup evaluation of FMS patients revealed no significant association between symptoms, pain score, FIQ score, and polymorphisms (p>0.05). We are of the opinion that there is a significant association between ESR1 rs2295190 polymorphism and FMS and that this polymorphism may be protective against FMS. However, there is a need for comprehensive studies on different populations to obtain clearer data as well as further studies to elucidate the possible mechanism of association.

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1ß, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10(-13)). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10(-8)). Serum IL-1ß, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1ß and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1ß function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

Rheumatologic manifestations in a cohort of patients with Vogt-Koyanagi-Harada disease.

OBJECTIVES: Vogt-Koyanagi-Harada Disease (VKHD) is a systemic autoimmune disorder characterized by granulomatous panuveitis. Inflammatory rheumatic diseases (IRDs) are among the differential diagnosis of VKHD. However, current knowledge on the rheumatological aspects of VKHD is still limited. We aimed to investigate the prevalence of rheumatic conditions in VKHD patients. METHODS: VKHD patients were included in the study and they were reviewed in terms of the presence of any rheumatological manifestations. RESULTS: There were 18 patients with a female preponderance (83.3%, female). Inflammatory type of peripheral joint pain (11%) and sicca symptoms (33%) were the most common rheumatological findings. The frequency of spondyloarthritis-related features such as inflammatory back pain and HLA-B27 rate was not increased. None of the patients had radiographic sacroiliitis. Anti-nuclear antibody was positive in high titres nearly in 30% of the patients and three patients had antibodies against extractable nuclear antigens. Nailfold capillaroscopy was abnormal in about one-third of the patients. Pathergy test was negative in all cohorts. While angiotensin-converting enzyme was elevated in nearly 20% of the patients, there were no abnormalities on chest X-rays. CONCLUSION: VKHD shares some features with IRDs. The common features were mostly suggestive of connective tissue disease rather than SpA or rheumatoid arthritis.

The effect of COVID-19 pandemic in a large series of patients with Takayasu arteritis.

BACKGROUND: Patients with inflammatory rheumatic diseases faced several challenges during the COVID-19 pandemic. Uncertainties such as the lack of evidence regarding the use of immunosuppressive (IS) therapies and deferred patient care because of limited health resources affected negatively on many aspects of treatment decisions and routine follow-up of the patients. In this study, we aimed to investigate the prevalence and severity of SARS-CoV-2 infection, the impact of the pandemic on delays in routine clinical follow-up, changes in IS treatment, and COVID-19 vaccination status of patients with Takayasu arteritis (TAK). METHODS: The study was performed between July and September 2021. TAK patients who registered in our database were investigated with regards to the COVID-19 infection and vaccination status, delays in routine clinical visits, changes in their IS treatments, and flares during the pandemic. Physical examination, laboratory tests, and imaging of the patients were performed and ITAS2010 scores were calculated. RESULTS: There were 56 adult TAK patients (87.5% female and median age 47 years). A total of 44 (78.6%) patients experienced a delay with routine follow-up visits to their physicians and about 20% of patients stopped their antirheumatic treatments without consulting their physicians. Compared to the pre-COVID-19 pandemic, 16 (28.5%) patients flared. In total group, 13 (23.2%) patients had a mild COVID-19 infection and about 90% of the patients had received the COVID-19 vaccine. DISCUSSION: Deferred patient care and disease flares are the most significant problems in TAK patients during the pandemic. The risk of TAK flares may outweigh the risk of COVID-19 infection.

Validation and cross-cultural adaptation of the Turkish version of the revised Leeds Disability Questionnaire in patients with ankylosing spondylitis.

BACKGROUND: The revised Leeds Disability Questionnaire (RLDQ) is a unique assessment tool for patients with ankylosing spondylitis (AS); its comprehensive structure includes posture and neck flexibility parameters. The aim of the study was to determine the psychometric properties of the Turkish RLDQ in patients with AS. METHODS: A total of 100 AS patients were enrolled in the study. In the first evaluation, patients filled out the Dougados Functional Index (DFI) and Bath Ankylosing Spondylitis Functional Index (BASFI), Stanford Health Assessment Questionnaire (HAQ) in addition to RLDQ. Then, patients were refilled the revised RLDQ in the second assessment. RESULTS: The mean age of the patients (40 women, 60 men) was 48.3 ± 12.6 years. The test-retest reliability and internal consistency of the RLDQ total score were excellent. ICC score and Cronbach's alpha score were calculated as 0.853 and 0.905, respectively. The SEM and MDC values calculated for the RLDQ total score were 2.74 and 7.60, respectively. RLDQ had degrees of correlation with DFI, HAQ, and BASFI of 0.814, 0.742, and 0.852, respectively. Construct validity was excellent (r > 0.50, p < 0.01). DISCUSSION: The Turkish version of the RLDQ was found to be valid and reliable in patients with AS. It should be emphasized that the RLDQ is a distinctive and valuable tool that focuses separately on neck, posture, or other mobility parameters in the clinical assessment of AS.

Inflammatory rheumatic diseases in patients with ochronotic arthropathy.

BACKGROUND: Ochronotic arthropathy (OcA) refers to excessive homogentisic acid (HGA) deposition in the musculoskeletal system. Our current understanding of OcA is limited, as there are less than a thousand alkaptonuria (AKU) cases reported in the literature. Herein, we investigated the rheumatological manifestations of OcA in a group of adult AKU patients. METHODS: Adult AKU patients with symptoms suggestive of OcA were included. Patients underwent a detailed rheumatological assessment. Laboratory testing, including autoantibodies and radiological investigations such as conventional X-rays, and magnetic resonance imaging (MRI) were performed. RESULTS: Eight out of 12 (66%) patients had symptoms consistent with OcA. The median age at OcA symptoms was 36 (27-48) years, and the presenting symptom was back pain in 87.5% of the patients. All patients had chronic back pain, and three (37.5%) had an inflammatory type of pain character. Radiographic sacroiliitis based on X-rays was present in 2 (25%) cases. MRI of the sacroiliac joints documented bone marrow edema in five (62.5%), and spinal MRI identified corner inflammatory lesions in three patients (37.5%). One patient (12.5%) had rheumatoid arthritis. Extra-articular involvement, including enthesitis (n = 1; 12.5%), interstitial lung disease (n = 1; 12.5%), and scleritis (n = 1; 12.5%), was also noted. CONCLUSION: The frequent occurrence of OcA-related inflammatory manifestations in our patients contradicts the conventional concept of OcA as a non-inflammatory disorder. The activation of inflammatory pathways, possibly by the HGA products, may responsible for this condition.Significance and innovationsAbout three-fourths of adult ochronotic arthropathy (OcA) patients in our group had associated inflammatory disease.OcA associated inflammatory diseases were showing a severe phenotypeNearly half of the OcA patients required early prosthesis operations compared to their healthy counterparts.

Identification of potential microRNA markers related to Crimean-Congo hemorrhagic fever disease.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future.

The Turkish experience with therapeutic plasma exchange: A national survey.

Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE.

The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia

Background/aim: The distribution of Mediterranean fever (MEFV) gene mutations in Turkish familial Mediterranean fever (FMF) patients varies according to geographic area of Turkey. There is a need for highly representative data for Turkish FMF patients. The aim of our study was to investigate the distribution of the common MEFV mutations in Turkish FMF patients in a nationwide, multicenter study. Materials and methods: Data of the 2246 FMF patients, from 15 adult rheumatology clinics located in different parts of the country, were evaluated retrospectively. The following mutations have been tested in all patients: M694V, M680I, M694I, V726A, and E148Q. Results: There were 1719 FMF patients with available genetic testing. According to the genotyping, homozygous M694V, present in 413 patients (24%), was the most common mutation . One hundred and fifty-four (9%) of patients had no detectable mutations. Allele frequencies of common mutations were: M694V (n = 1529, 44.5%), M680I (n = 423, 12.3%), V726A (n = 315, 9.2%), E148Q (n = 214, 1%), and M694I (n = 12, <1%). Conclusion: In this large-scale multicenter study, we provided information about the frequencies of common MEFV gene mutations obtained from adult Turkish FMF patients. Nearly half of the patients were carrying at least one M694V mutations in their alleles.

Radiographic Progression in Ankylosing Spondylitis: From Prognostication to Disease Modification.

PURPOSE OF REVIEW: Pain, functional limitation, and spinal damage are the three main domains that have significant impact on various aspects of axial spondyloarthritis (axSpA). RECENT FINDINGS: Several randomized controlled trials (RCTs) showed a beneficial effect of non-steroid ant-inflammatory drugs (NSAIDs) and biologic treatments on pain and function. The effect of available treatments on spinal damage is still of interest and is being studied. In this article, we review the literature on radiographic progression in axSpA. We discuss the natural course of spinal progression, predictors of spinal damage, and the effect of lifestyle changes and medications on radiographic progression in axSpA.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Effects of vitrification and transplantation on follicular development and expression of EphrinB1 and PDGFA in mouse ovaries.

The aim of this study was to assess the follicular development and the patterns of EphrinB1 and PDGFA immunostaining in vitrified mouse ovarian tissue (OT) with and without transplantation. Histological evaluation was performed on fresh and vitrified OTs, whether transplanted or not. RT-PCR was performed on fresh and vitrified ovarian samples (OSs) and vitrified OS graft. Vitrification alone did not significantly reduce the normal primordial, primary, and secondary follicles except antral ones (p > 0.05). However, transplantation decreased all the follicle types. The EphrinB1 immunoexpression showed high intensity in all follicular types in vitrified OT and the significant increased was detected in secondary and antral follicles (p < 0.05). PDGFA protein immunoexpression of primordial and primary follicles was decreased in vitrified OT (p < 0.05). However, the lowest immunoexpression of EphrinB1 and PDGFA was detected after transplantation (p < 0.05). The levels of ephrinb1 and pdgfa mRNA expressions in vitrified OS and vitrified OS grafts were found as comparable to the fresh OS. In conclusion, vitrification has no detrimental effect on the follicles at the different developmental stages, majority of ovarian follicular loss takes place after transplantation rather than vitrification. Overall, vitrification and grafting do not change the ephrinb1 and pdgfa gene expressions. In addition, EphrinB1 and PDGFA are expressed during different stages of folliculogenesis in a different manner in fresh, vitrified, or grafted OTs. Vitrification and/or grafting appear to affect the follicular expression of EphrinB1 and PDGFA. These findings suggest that these proteins could have several functions related to the development of follicles and angiogenesis after transplantation.

Analysis of dedicated sacroiliac views to improve reliability of conventional pelvic radiographs.

Objective: To compare the antero-posterior (AP) pelvis view with the Ferguson view of the SI joint in order to resolve whether one modality has a clear advantage for grading of sacroiliitis. Methods: One hundred and nine patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) criteria for axial spondyloarthritis who had AP pelvis and Ferguson views on the same day were identified from an axial spondyloarthritis clinic registry. Two rheumatologists independently scored the AP pelvis and Ferguson views according to modified New York (NY) criteria. Intra- and inter-reader agreements were obtained for both evaluations by using the kappa statistic and intraclass correlation coefficient (ICC). Any change in diagnostic category dictated by the Ferguson vs the AP pelvis views was also evaluated. Results: A total of 266 radiographs were read from 109 patients. Intra-observer reliability of the observers showed similar ICC scores; this was also reflected in the kappa for diagnosis of AS fulfilling modified NY criteria between the observers. The inter-rater agreement showed similar kappa values between the two modalities. When separately evaluating SI joints with score grading of 0-2, grade 2 showed the lowest kappa, reaching a low of 0.1 and 0.19 for the right SI joint for Ferguson and AP pelvis views, respectively. Both modalities were concordant diagnostically; reclassification from AS to non-AS and vice versa was in the range 5-11%. Conclusion: There was general agreement between the Ferguson and AP pelvis X-ray ICC and kappa scores. Either modality can be employed to evaluate the SI joint for sacroiliitis with the Ferguson view showing no clear superiority over the standard AP pelvis view.