[Comparative assessment of sensitivity and specificity of three variants of classification criteria for systemic lupus erythematosus in a cohort of Russian patients].

BACKGROUND: The clinical and serologic heterogeneity of systemic lupus erythematosus (SLE) presents challenges for diagnosis, particularly in the earliest stages of the disease when there are insufficient signs to make a reliable diagnosis. AIM: To make a comparative assessment of sensitivity and specificity of various classification criteria of SLE on a cohort of patients of Nasonova Research Institute of Rheumatology. MATERIALS AND METHODS: A total of 252 patients were included in the study; 152 (60%) of 252 patients had reliable SLE (mean age 36 [29.5-46] years, duration of disease 9 [3.4-19] years). Of 252 patients, 26 (11%) had PAPS (mean age 36.5 [31-42] years, duration of disease 4.6 [1-10.4] years). Systemic sclerosis was diagnosed in 74/252 (29%) patients, (mean age 51.5 [42-59] years, duration of disease 9 [5-16] years). The quality of the classification function of the criteria was assessed by ROC analysis. RESULTS: SLE was diagnosed in 131 (86%) of 152 patients using the American College of Rheumatology - ACR)-1997 criteria, in 145 (95%) using the The Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, and in 144 (94.7%) using the European League Against Rheumatism (EULAR)/ACR 2019 criteria. ANF positivity was the least statistically significant of all signs in relation to the diagnosis of SLE. The area under the curve (AUC) for ANF≥1/160 titers was AUC 0.654 for the ACR-97 criteria, AUC 0.616 for the SLICC-12 SLE criteria, and AUC 0.609 for the 2019 EULAR/ACR criteria. ROC analysis of the relationship between the number of criteria/points and a reliable diagnosis of SLE revealed a high diagnostic accuracy - the AUC for all SLE criteria was greater than 0.940. In the ROC analysis of patients with SLE and PAFS, indicating the number of diagnostic criteria, sensitivity was 86% for ACR-1997, 95% for SLICC-2012, 95% for EULAR/ACR 2019, and specificity was 100, 62 and 62%, respectively. CONCLUSION: The classification criteria SLICC-2012 and EULAR/ACR 2019 are more sensitive for the diagnosis of SLE in the Russian population, and the criteria ACR-1997 are more specific. All three variants of the SLE classification criteria have sufficient sensitivity and specificity for their use in real clinical practice.

Global Antiphospholipid Syndrome Score (GAPSS) in Patients with Systemic Lupus Erythematosus.

The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) SLE patients with aPL, and 50 (44%) patients with SLE. There was a history of thrombosis in 58 (50%) out of 115 patients; of them, 14 (24%) had arterial thrombosis, 29 (50%) had venous thrombosis, and 15 (26%) had combined thrombosis. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17 ± 5.64 versus 4.48 ± 4.55 without these manifestations (p = 0.0003). There was a significant association between GAPSS levels and thrombosis: patients with thrombosis had a GAPSS of 7.31 ± 5.70, those without thrombosis-4.00 ± 4.81 (p = 0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40 ± 25.30 versus 5.82 ± 5.28, p = 0.01). GAPSS levels  ≥ 6 and  ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.

Thermal, mechanical and biodegradation studies of biofiller based poly-3-hydroxybutyrate biocomposites.

Biodegradable poly-3-hydroxybutyrate [P(3HB)] and natural fillers - clay, peat, and birch wood flour - were used to prepare powdered composites to form pellets and granules. Pellets were produced by cold pressing of polymer and filler powder whereas granules were produced from the powders wetted with ethanol. Characterization techniques like IR spectroscopy, differential scanning calorimetry, X-ray analysis, mechanical analysis and electron microscopy were employed to study the properties of the initial P(3HB) and fillers and the composites. Analysis of the IR spectra of the composites showed the absence of chemical bonds between the components, i.e. the composites were physical mixtures. Young's moduli of the pellets prepared from initial materials varied considerably, and the highest value was obtained for P(3HB) pellets (350 MPa). Studies of biodegradation of composite pellets and granules in the soil for 35 days showed that the residual mass of the pellets had decreased to 68% for P(3HB); 56.4% for P(3HB)/peat; 67% for P(3HB)/wood flour, and 64% for P(3HB)/clay; granules exhibited a similar mass loss, residual mass of the granules of P(3HB) was 68.4%, P(3HB)/peat 46.4%; P(3HB)/wood flour 77%, and P(3HB)/clay 74%. This shows the significance of the material as an eco-friendly composite without sacrificing its mechanical properties.

Biotechnological wound dressings based on bacterial cellulose and degradable copolymer P(3HB/4HB).

Hybrid wound dressings have been constructed using two biomaterials: bacterial cellulose (BC) and copolymer of 3-hydroxybutyric and 4-hydroxybutyric acids [P(3HB/4HB)] - a biodegradable polymer of microbial origin. Some of the experimental membranes were loaded with drugs promoting wound healing and epidermal cells differentiated from multipotent adipose-derived mesenchymal stem cells. A study has been carried out to investigate the structure and physical/mechanical properties of the membranes. The in vitro study showed that the most effective scaffolds for growing fibroblasts were composite BC/P(3HB/4HB) films loaded with actovegin. Two types of the experimental biotechnological wound dressings - BC/P(3HB/4HB)/actovegin and BC/P(3HB/4HB)/fibroblasts - were tested in vivo, on laboratory animals with model third-degree skin burns. Wound planimetry, histological examination, and biochemical and molecular methods of detecting factors of angiogenesis, inflammation, type I collagen, and keratin 10 and 14 were used to monitor wound healing. Experimental wound dressings promoted healing more effectively than VoskoPran - a commercial wound dressing.

[The study of effectiveness of polyhydroxyalkanoates based biodegradable stents in ureteropelvic segment pyeloplasty].

INTRODUCTION: Among urologic diseases, ureteropelvic segment stenosis with hydronephrosis is a common indication for instrumental or surgical correction. The restriction of urine flow with dilatation proximal to obstruction develops in 6.5-37% of cases at different times after the ureteral reconstruction. All this urges to develop and improve stents and search for effective ways to place stents and control their function. AIM: To investigate the effectiveness of polyhydroxyalkanoates based biodegradable stent compared with a commercial analogue in upper urinary tract drainage after ureteropelvic segment pyeloplasty. MATERIALS AND METHODS: Morphological and functional changes in the stented ureter were investigated in 45 male rabbits of "Soviet chinchilla" breed weighing 4550-5200 g that underwent stenting of ureteropelvic segment (UPS). The study used polymeric stents based on poly-3-hydroxybutyrate, poly-4-gidroksibutirotom P (3GB/4GB) and a mixture of poly-3-hydroxybutyrate with polycaprolactone II (3GB)/PCL with the inclusion of PCL 75%; the control material was polyurethane stents. Morphologic evaluation was conducted on ureteral fragments and UPSs in the area of the stent placement at 7, 14 and 28 days after operation. RESULTS: Throughout the experiment, excretory urography and spiral tomography in experimental groups showed no changes in the pelvicalyceal system after placing polymeric stents. The morphologic examination in the experimental group at day 28 after surgery revealed preserved longitudinal folding of ureteral mucosa and absence of muscle hypertrophy. Transitional epithelium had no signs of atrophy and desquamation, its mean thickness was 112.4+/-8.5 mm, whereas in the control group a productive inflammation resulting in sclerosis was found to develop. CONCLUSIONS: We conducted a comparative study of morphologic and functional changes in rabbit ureters after stenting using polyurethane stents (control group) and polymeric stents made of poly-3-hydroxybutyrate, poly-4-hydroxybutyrate II (3GB /4GB) and a mixture of poly-3-hydroxybutyrate with polycaprolactone II (3Gb)/PCL (experimental group). Despite the difference in physical and mechanical properties of biodegradable PGA-based stents, the tissue response to both types of stent was comparable. Ureteral wall preserved longitudinal folds, there was no muscle layer hypertrophy, and mucous membrane had smooth contours with a uniform thickness of the transitional epithelium, whereas in the control group a productive inflammation resulting in sclerosis was found to develop.

Porous 3D implants of degradable poly-3-hydroxybutyrate used to enhance regeneration of rat cranial defect.

The study describes preparation and testing of porous 3D implants of natural degradable polymer of 3-hydroxybutyric acid P(3HB) for regeneration of bone tissue defects. The ability of the P(3HB) implants to favor attachment and facilitate proliferation and directed differentiation of mesenchymal stem cells (MSCs) was studied in the culture of MSCs isolated from bone marrow and adipose tissue. Tissue-engineered hybrid systems (grafts) constructed using P(3HB) and P(3HB) in combination with osteoblasts were used in experiments on laboratory animals (n = 48) with bone defect model. The defect model (5 mm in diameter) was created in the rat parietal bone, and filling of the defect by the new bone tissue was monitored in the groups of animals with P(3HB) implants, with commercial material, and without implants (negative control). Computed tomography (CT) and histologic examination showed that after 120 days, in the group with the osteoblast-seeded P(3HB) implants, the defect was completely closed; in the group with the cell-free P(3HB) implants, the remaining defect was no more than 10% of the initial one (0.5 mm); in both the negative and positive controls, the size of the defect was about 1.0-1.2 mm. These results suggest that P(3HB) has good potential as osteoplastic material for reconstructive osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 566-577, 2017.

Laser processing of polymer constructs from poly(3-hydroxybutyrate).

CO2 laser radiation was used to process poly(3-hydroxybutyrate) constructs - films and 3D pressed plates. Laser processing increased the biocompatibility of unperforated films treated with moderate uniform radiation, as estimated by the number and degree of adhesion of NIH 3T3 mouse fibroblast cells. The biocompatibility of perforated films modified in the pulsed mode did not change significantly. At the same time, pulsed laser processing of the 3D plates produced perforated scaffolds with improved mechanical properties and high biocompatibility with bone marrow-derived multipotent, mesenchymal stem cells, which show great promise for bone regeneration.