Discrepancies between clinical and pathological findings seen at renal biopsy in rheumatological diseases.

OBJECTIVE: Renal biopsy contributes to the diagnosis, follow-up, and treatment of many rheumatic conditions. This study assessed the diagnostic role and safety of renal biopsies in a tertiary rheumatology clinic. METHODS: Renal biopsies performed between June 2020 and December 2022 were screened, and demographic, clinical, histopathological, and safety data were collected from patient records. RESULTS: In this study, 33 males and 38 females were included. Except for 1 patient who received acetylsalicylic acid, antiaggregant, and/or anticoagulant drugs were stopped before the biopsy. Complications included a decrease of hemoglobin in 8 patients (11.3%) and microscopic hematuria in 40 patients (56.3%). Control ultrasonography was performed in 16 patients (22.5%), and a self-limiting hematoma was found in 4 of them (5.6%) without additional complications. While less than 10 glomeruli were obtained in 9 patients (9.9%), diagnosis success was 94.4%. Histopathological data were consistent with one of the pre-biopsy diagnoses in 54 of 67 cases (80.6%) but showed discrepancies in 19.4% (n=13) of patients. A repeat biopsy was performed in 7 patients for re-staging or insufficient biopsy. CONCLUSIONS: Renal biopsy significantly contributes to rheumatology practice, especially in patients with complex clinical and laboratory findings or in whom different treatments can be given according to the presence, severity, and type of renal involvement. Although the possibility of obtaining insufficient tissue and the need for re-staging and repeat biopsy in the follow-up might be expected, complication risk does not seem to be a big concern. Renal biopsy often evidenced discrepancies between pre-biopsy diagnosis and histopathological findings.

Dermatomyositis associated with thymoma: A case report and literature review.

Abstract: Thymoma can present with paraneoplastic-autoimmune neuro-muscular disorders, including polymyositis, dermatomyositis, and granulomatous myositis. Rarely, concomitant subclinical myasthenia gravis (MG) can be a diagnostic dilemma and cause deleterious outcomes regarding missed or delayed diagnosis. We report a Turkish patient presented with thymoma associated dermatomyositis and positive acetylcholine receptor antibody without evident MG clinic.

Inflammatory rheumatic diseases developed after COVID-19 vaccination: presentation of a case series and review of the literature.

OBJECTIVE: An increasing number of new on-set autoimmune-inflammatory rheumatic diseases (AIRD) after COVID-19 vaccination has begun to be reported in the literature. In this article, we present our patients with new-onset AIRD after vaccination for COVID-19 and review the literature on the subject. PATIENTS AND METHODS: We investigated the clinical characteristics and laboratory parameters of previously described "newly developed AIRD in individuals recently vaccinated for COVID-19", in 22 cases vaccinated with one of the COVID-19 vaccines (BNT162b2 or CoronaVac) approved in our country. RESULTS: We collected 22 cases (14 female, 63.6%) that developed an AIRD after COVID-19 vaccination. Mean age was 53±14.4 (24-87) years. The interval between the last dose of vaccination and the development of the first complaint was 23.9±19.5 (4-90) days. CoronaVac was administered to four patients, and the BNT162b2 to 18 patients. AIRD-related symptoms developed in 12 patients after the first dose, in 8 patients after the second dose, and in two patients after the third dose. Twelve out of the 22 (54.5%) cases were diagnosed with rheumatoid arthritis, two with SLE, and the remaining eight patients each with leukocytoclastic vasculitis, Sjogren's syndrome, psoriatic arthritis, ankylosing spondylitis, systemic sclerosis, mixed connective tissue disease, eosinophilic granulomatosis with polyangiitis, and inflammatory myositis, respectively. Six patients had a history of documented antecedent COVID-19 infection. CONCLUSIONS: Autoimmune/inflammatory rheumatic diseases may develop after COVID-19 vaccinations. In the era of the COVID-19 pandemic, vaccination should be questioned carefully in newly diagnosed AIRD patients.

Coexistence of relapsing polychondritis and eosinophilic granulomatous with polyangiitis: A rare entity.

Abstract: Relapsing polychondritis (RP) is a a rare multisystemic disease and it affects cartilaginous tissue and proteoglycan rich organs. The spectrum of clinical features are intermittent inflammation involving especially the auricular and nasal regions. In some patients with RP, systemic vasculitis, autoimmune diseases or malignancy may accompany. Although rare, any of the ANCA-associated vasculitis have been reported in patients with RP. Eosinophilic granulomatous with polyangiitis (EGPA) is a multisystem small vessel vasculitis associated with asthma and eosinophilia. Here we present a case of coexistence of RP and EGPA.

Efficacy of anticytokine treatments added to corticosteroids in patients with COVID-19-associated pneumonia and hyperinflammation: a single center experience.

OBJECTIVE: Pneumonia and hyperinflammatory state related to COVID-19 infection are fatal clinical conditions without definite treatment modalities. Interleukin-6 and Interleukin-1 targeted therapies have been proposed as treatment options. This study was conducted to investigate the efficacy of anakinra and tocilizumab added to corticosteroids in patients with COVID-19-associated pneumonia and hyper-inflammatory syndrome in our tertiary clinical center. PATIENTS AND METHODS: Patients with COVID-19-associated pneumonia and hyperinflammatory state who did not respond to initial treatments, including corticosteroids, were included in the study. The patients' electronic records were reviewed retrospectively and recorded according to a standardized data table. Univariate and multivariate regression analyses were used to identify risk factors associated with intubation. RESULTS: 388 patients were included in the study. 197 patients were intubated and most of them died (n=194/197, 98%). 67 patients received tocilizumab, and 97 patients received anakinra. Anakinra [OR: 0.440, 95% CI=0.244-0.794, p=0.006] and tocilizumab [OR: 0.491, 95% CI=0.256-0.943, p=0.033] were both associated with a decreased risk for intubation. However, having a neutrophil/lymphocyte ratio ≥ 10 [OR: 2.035, 95% CI=1.143-3.623, p=0.016], serum lactate dehydrogenase (LDH) level ≥ 400 [OR: 3.160, 95% CI=1.937-5.156, p<0.001] and age ≥ 50 [OR: 4.048, 95% CI=2.037-8.043, p < 0.001] was associated with an increased risk for intubation. CONCLUSIONS: Both anakinra and tocilizumab, added to initial standard COVID-19 treatments (including glucocorticoids) reduced the need for intubation in patients with COVID-19-associated severe pneumonia and hyperinflammatory syndrome. Given the high mortality rate of intubated patients with COVID-19, both treatments may have added benefits on mortality.

Relapsing Polychondritis in a Patient with Ankylosing Spondylitis under Two Different Tumor Necrosis Factor Alpha Inhibitors Treatment.

Abstract: Relapsing polychondritis (RP) is a rare autoimmune disease char-acterized by multi-systemic involvement characterized by recurrent and progressive inflammation of the cartilaginous tissue. Auricular inflammation is a characteristic finding of RP. Anti-tumor necrosis fac-tor alpha (anti-TNF) is a highly effective drug used in the treatment of inflammatory arthritis. There are several case reports showing potential relationship between the RP development and anti-TNF treatment. Here, we present a case of RP in a patient with ankylosing spondylitis under the two different tumor necrosis factor alpha inhibitors therapy.

Atherosclerosis assessment and rheumatoid arthritis.

BACKGROUND AND AIM: Rheumatoid arthritis is associated with increased morbidity and mortality due to atherosclerotic cardiovascular diseases. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme of phospholipase A2; it plays an important role in inflammation and atherosclerosis. Herein we aimed to investigate whether Lp-PLA2 activity is associated with atherosclerosis in patients with rheumatoid arthritis and compare the Lp-PLA2 activity with carotid intima media thickness (CIMT). PATIENTS AND METHODS: 25 patients with rheumatoid arthritis and 40 controls (20 patients with type 2 diabetes mellitus [DM] and 20 healthy controls) were included in the study. Frozen serum samples were used for analyzing Lp-PLA2 activity. Disease activity was calculated with DAS28 (Disease Activity Score 28) in the rheumatoid arthritis group. The mean CIMT was calculated in all participants. RESULTS: Lp-PLA2 activity was significantly higher in the DM group (p = 0.006) and LDL (Low density cholesterol levels) were lower in rheumatoid arthritis and healthy control groups compared with diabetics (p = 0.001 and p = 0.029, respectively). The mean CIMT was significantly higher in patients with type 2 DM (p = 0.047). CONCLUSION: Lp-PLA2 activity was not increased in the rheumatoid arthritis group when compared with healthy controls and the DM group. This result may be associated with low disease activity scores in patients with rheumatoid arthritis.

Massive lower gastrointestinal bleeding associated with solitary rectal ulcer in a patient with Behçet's disease.

Solitary rectal ulcer syndrome is a rare benign disorder that has a wide range of clinical presentations and variable endoscopic findings which makes it difficult to diagnose and treat. The clinical and endoscopic picture in this condition can also mimic malign ulceration, malignancy or Crohn's disease. Behçet's disease can affect the gastrointestinal tract. However to the best of our knowledge, no case with solitary rectal ulceration has been reported so far in literature. We herein present a patient diagnosed with Behçet's disease admitted to our clinic with rectal bleeding due to solitary rectal ulceration.

Parkinsonism in elderly rheumatoid arthritis patients.

OBJECTIVE: The incidences of extrapyramidal symptoms and Parkinson's disease were reported to be increased in patients with rheumatoid arthritis (RA). In this study we aimed to explore the frequency of the symptoms of Parkinsonism among RA patients older than 60 years. PATIENTS AND METHODS: 30 (6 males, 24 females) consecutive RA patients, followed at a rheumatology outpatient clinic, who were 60 years of age or older; 23 patients who were diagnosed as PD and 50 sex and age matched healthy controls were included to the study. All participants were examined for the motor and non-motor findings of Parkinsonism including bradykinesia, rigidity, tremor, postural abnormality, upper limb sway abnormality, gait impairment, decrease in facial expression, seborrhea, slowing of speech and impairment in the self care. RESULTS: When the RA, PD cases and healthy control group were compared for bradykinesia, rigidity, tremor, posture, upper limb sway, gait impairment, facial expression, seborrhea, speech and self care; highly significant differences were seen for all parameters. Two out of the 30 RA cases (6,7%) were diagnosed as Parkinson's disease. CONCLUSIONS: The signs of Parkinsonism and Parkinson's disease were found more frequent in elderly RA cases as compared to healthy controls.

Thyroid autoimmunity in patients with Familial Mediterranean Fever: preliminary results.

AIM: We investigated whether there was a significant increase in thyroid autoimmunity in patients with Familial Mediterranean fever (FMF). PATIENTS AND METHODS: In total, 220 patients, consisting of 42 with FMF, 75 with rheumatoid arthritis (RA), and 103 healthy controls, were enrolled. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid autoantibodies (anti-thyroid peroxidase and anti-thyroglobulin) were measured in all participants. RESULTS: After adjustment for age, gender, and smoking status, statistically significant differences between serum levels of anti-thyroglobulin antibody, anti-thyroid peroxidase antibody, and fT3 were found between the groups (all p < 0.001). Serum TSH level did not differ between the groups (p > 0.05). The frequency of autoimmune thyroiditis in FMF group is higher than control group. However, this difference did not reached the level of statistical significance (p > 0.05). CONCLUSIONS: Although statistically not significant, thyroid autoimmunity was observed more frequently in patients with FMF than in healthy controls. Thyroid autoantibodies were significantly higher in patients with FMF. Studies with greater number of patients are required for evaluating the frequency of the autoimmune thyroiditis in patients with FMF.

A case of propylthiouracil-induced antineutrophilic cytoplasmic antibody-positive vasculitis successfully treated with radioactive iodine.

Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis is one of the rare complications of propylthiouracil treatment. Having a variable clinical spectrum, it may be presented with both skin limited vasculitis and life-threatening systemic vasculitis. In this study, we present a case that developed ANCA-positive vasculitis with skin and kidney involvement (hematuria and proteinuria) six months after propylthiouracil treatment was initiated for toxic nodular goiter. Proteinuria recovered dramatically subsequent to radioactive iodine treatment following ceasing the drug.

Lack of an effect of CYP3A4 and MDR1 gene polymorphisms on colchicine pharmacogenetics in the treatment of Familial Mediterranean fever.

The P-gp/MDR1 multidrug transporter mediates detoxification of numerous drugs, including colchicine, and CYP3A4 is key to the biotransformation of colchicine. We investigated the effects of CYP3A4 and P-gp/MDR1 polymorphisms on bioavailability of colchicine in patients with Familial Mediterranean fever (FMF). Forty-eight Turkish patients with FMF treated with colchicine were genotyped for 3435C>T, (-)1A>G, 61A>G, 1199G>A, 1236C>T, 2677G>A, 2677G>T polymorphisms in the P-gp/MDR1 gene and 3435C>T, 1B(-392A>G), 2(15713T>C), 3(23171T>C), 12(21896C>T), 17(15615T>C) polymorphisms in the CYP3A4 gene. Doses of colchicine administered to patients did not differ with respect to P-gp/MDR1 or CYP3A4 gene polymorphism. We also determined the genotype distributions of CYP3A4 and P-gp/MDR1 genes among FMF patients. There was no significant gender difference in the P-gp/MDR1 polymorphism, whereas there were significant gender differences in the frequencies of 15713T>C and 15615T>C polymorphisms in the CYP3A4 gene. No significant relationship was found between colchicine doses that would introduce optimal clinical response and affect the therapeutic dose and CYP3A4 and P-gp/MDR1 gene polymorphisms in these FMF patients.

An adult-onset still's disease with autoimmune thyroiditis.

Adult-onset Still's disease is a rare inflammatory disorder of unknown etiology and has same clinical characteristics of the systemic form of juvenile rheumatoid arthritis. A 17 years old white female had arthralgias of multiple joints including small joints of hands. She had fever, rash, hepatosplenomegaly, and CRP-122mg/dl, ESR-91mm in 1st hour. She had also TSH - 6.24µIU/mL, fT3 - 2.1pg/mL, fT4 - 1.36ng/dL and diagnosed as Adult-onset Still's disease with autoimmune thyroiditis. It is an inherited condition and is more common in women than in men.

Familial Mediterranean fever without cardinal symptoms and role of genetic screening.

Familial Mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Successful treatment response was achieved by colchicine.

Copper phytoextraction in tandem with oilseed production using commercial cultivars and mutant lines of sunflower.

Use of sunflower (Helianthus annuus L.) for Cu phytoextraction and oilseed production on Cu-contaminated topsoils was investigated in afield trial at a former wood preservation site. Six commercial cultivars and two mutant lines were cultivated in plots with and without the addition of compost (5% w/w) and dolomitic limestone (0.2% w/w). Total soil Cu ranged from 163 to 1170 mg kg(-1). In soil solutions, Cu concentration varied between 0.16-0.93 mg L(-1). The amendment increased soil pH, reduced Cu exposure and promoted sunflower growth. Stem length, shoot and capitulum biomasses, seed yield, and shoot and leaf Cu concentrations were measured. At low total soil Cu, shoot Cu mineralomass was higher in commercial cultivars, Le., Salut, Energic, and Countri, whereas competition and shading affected morphological traits of mutants. Based on shoot yield (7 Mg DW ha(-1)) and Cu concentration, the highest removal was 59 g Cu ha(-1). At high total soil Cu, shoot Cu mineralomass peaked for mutants (e.g., 52 g Cu ha(-1) for Mutant 1 line) and cultivars Energic and Countri. Energic seed yield (3.9 Mg air-DW ha(-1)) would be sufficient to produce oil Phenotype traits and shoot Cu removal depended on sunflower types and Cu exposure.

Development of novel protein scaffolds as alternatives to whole antibodies for imaging and therapy: status on discovery research and clinical validation.

Recent advances in combinatorial protein engineering have made it possible to develop antibody-based and non-Ig protein scaffolds that can potentially substitute for most whole antibody-associated properties. In theory, many different natural human protein backbones are suitable to be used as recombinant templates for engineering : antibody-derived scaffolds, carrier proteins that display a single binding interface, backbones that provide a rigid core structure suitable for grafting loops or protein scaffolds allowing the incorporation of variable loops in a favorable 3D configuration. In practice however, only a few have yielded the necessary properties to be translated into 'druggable Biologicals'. Amongst these properties, potential broad specificities towards any kind of target, ease of production, small size, good tolerability and low immunogenicity are essential and will be discussed in this review. Intellectual property is another key issue for the development of these protein scaffolds; although circumventing antibody-associated patents is often a major if not primary goal, clear advantages compared to whole antibodies must be presented to translate scaffold discovery into successful therapeutic drug candidates. In this review, a particular emphasis will be given to the most validated scaffolds that have reached the clinical development phase. Although the question of their immunogenicity is still open, preliminary clinical data do not point to any particular adverse immunogenic reactions although these are highly dependent on dosage, administration route and therapeutic indication. Finally, some of the emerging Biotechs developing protein scaffolds have been associated during the last two years with successful acquisitions by Big Pharmas and we will speak on the perspective positions of these proteins within the global Biologicals market.

Remediation of copper-contaminated topsoils from a wood treatment facility using in situ stabilisation.

Five organic matters, three phosphate compounds, zerovalent iron grit (ZVIG, 2% by soil weight), two alkaline compounds, and two commercial formulations were incorporated, singly and some combined with ZVIG, into a highly Cu-contaminated topsoil (Soil P7, 2600 mg Cu kg(-1)) from a wood treatment facility. Formulations and two composts were also singly incorporated into a slightly Cu-contaminated topsoil (Soil P10, 118 mg Cu kg(-1)) from the facility surrounding. This aimed to reduce the labile pool of Cu and its accumulation in beans cultivated on potted soils in a climatic chamber. Lowest Cu concentration in soil solution occurred in P7 soils amended with activated carbon (5%) and ZVIG, singly and combined. Basic slag (3.9%) and compost of sewage sludge (5%) combined with ZVIG promoted shoot production and limited foliar Cu accumulation. For amended P10 soils, no changes occurred in soil solution and foliar Cu concentrations, but one compost increased shoot production.

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[Dependence and necessities of non-covered services for the elderly in a health sector of Zaragoza]. / Dependencia y necesidades de cuidados no cubiertas de las personas mayores de una zona de Salud de Zaragoza.

BACKGROUND: Dependency to carry out the activities of daily living (ADL) and home care needs of older adults depend upon factors which are not well understood. Caregiving is mainly provided by the family. The aim of this study is to estimate the prevalence of ADL dependence and associated factors among older adults and to identify associated factors with unmet home care needs in people over age 75 in Zaragoza (Spain). METHOD: A cross-sectional study was conducted on a representative sample of the community dwelling population over age, 75 in one Health Care District in Saragossa in 1998 (n = 351). Data were collected during a personal interview. ADL dependency was assessed by the Katz index. Home care needs were assessed using prevalent norms for desired frequency of care. Sources of informal care, socio-demographic characteristics, self-rated health and depression (Yesavage Geriatric Depression Scale) were considered independent variables. Logistic regression was used to identify factors associated with both ADL dependency and unmet home care needs. RESULTS: Prevalence of ADL dependence is 37.3%. The variables predicting ADL dependence are the perception of poor health, depression, being a female and being over 85 years of age. The prevalence of unmet care needs among ADL dependent individuals is 22.1%. Sources of help are limited to the families. Being a woman and living alone are the stronger risk factors for unmet needs. CONCLUSIONS: A high percentage of older adults are dependent. Informal support is insufficient and confined to the family. The social and health care system in Spain should provide to the family, emotional, financial and social support and special care for disabled people living alone and with limited material resources.

Dependencia y necesidades de cuidados no cubiertas de las personas mayores de una zona de salud de Zaragoza / Dependency and Unmet Need of Care in Older People in a Health Area of Saragossa, Spain

Fundamento: El nivel de autonomía para las actividades del cuidado personal en personas mayores y la necesidad de apoyo no cubiertas dependen de diferentes factores poco conocidos en nuestro medio. Los cuidados en la dependencia se facilitan principalmente por el sistema informal de cuidados. El propósito del estudio es estimar la prevalencia de dependencia para las actividades del cuidado personal y los factores asociados, e identificar los factores asociados con las necesidades de cuidados no cubiertas en personas dependientes, en población mayor de 75 años de Zaragoza. Método: Se realizó un estudio transversal en una muestra representativa de la población no institucionalizada mayor de 75 años, en una Zona de Salud de Zaragoza, en el año 1998 (n=351). Los datos se cumplimentaron a través de una entrevista directa. Se utilizó el índice de Katz para valorar la capacidad funcional para las actividades del cuidado personal y un cuestionario ad hoc para el apoyo informal y el resto de variables. El apoyo informal, las características sociodemográficas, autopercepción de salud y depresión (Escala de Depresión de Yesavage) se consideraron como variables independientes. Se aplicó la regresión logística para identificar los factores asociados a la dependencia y necesidades de cuidados no cubiertas. Resultados: La prevalencia de dependencia para las actividades del cuidado personal es de un 37,3 per cent. Las variables que predicen la dependencia para las actividades del cuidado personal son una mala percepción de salud, depresión establecida, ser mujer y ser mayor de 85 años. La prevalencia de necesidades de apoyo no cubiertas en personas dependientes para las actividades del cuidado personal es de 22,1 per cent. El apoyo informal lo presta la familia. Ser mujer y vivir sola se presenta como un factor de riesgo para no tener las necesidades cubiertas, así como también no estar deprimido. Conclusiones: El porcentaje de personas mayores con dependencia es elevado. El apoyo informal es insuficiente y limitado a la familia. El modelo de atención a las personas mayores en España debería desarrollar servicios de apoyo emocional, económicos y sociales a la familia y establecer una especial atención sobre las personas con dependencia que viven solas y con escasos recursos materiales (AU)