Results of open prospective study of clinical assessment of efficacy and safety of Nifuratel during exacerbations of recurrent cystitis

The article presents the results of an open prospective study of the clinical assessment of the efficacy and safety of the use of nifuratel during exacerbations of recurrent cystitis. The aim of the program was to assess the change in the duration of the relapse-free course of recurrent cystitis and the effectiveness of the course treatment with Nifuratel-SZ in the treatment of recurrent cystitis. During a non-interventional program, Nifuratel-SZ has been shown to be an effective and well-tolerated drug for the treatment of recurrent uncomplicated lower urinary tract infection.

556. Ruxolitinib for the Management of Severe Pneumonia Caused by SARS-CoV-2. Exploring the Combination with dexamethasone

Background Mexico is one of the top five countries with a higher mortality rate of hospitalized patients of 30.1%. Since COVID-19 has been associated with immune dysregulation and hyper inflammation, JAK-12 inhibitors have been tested to reduce IL6 production. Studies have shown improvements when using ruxolitinib (rxb) in severely hospitalized patients with COVID-19. These have included patients in combination with corticosteroids such as dexamethasone (dxm). This work aims to test the response of hospitalized patients with severe or critical COVID-19 treated with rxb with or without dxm. Methods An experimental, open, prospective study in a single third-level hospital in Mexico was performed. The primary outcome was favorable clinical response defined as withdrawal or decline of supplementary oxygen. Secondary outcomes such as mean hospital stay, improvement in systemic inflammatory response parameters, and mortality were also evaluated. Statistical differences for baseline and final measure and the use and not use of dxm were estimated. The study included adults with SARS-CoV-2 infection confirmed with polymerase chain reaction, radiological pneumonia, and oxygen saturation less than 90%. Rxb was administered 5mg/12hrs/15days, IV dxm 6mg/day/10days. Results The final sample was 108 adults with complete information and informed consent. Sixty-two patients (57%) received only rxb. There were no differences between groups for any parameter at the beginning of treatment, and all patients were receiving supplemental oxygen. After 28-day follow-up, 70% reduce supplemental oxygen requirement (74% rxb and 71% rxb+dxm; p=0.628), 18% remained, and 2% increases support (1% with rxb, and 5% rxb+dxm; p< 0.001); 87% of patients were discharged (89% rxb and 85% rxb+dxm; p=0.603). In both groups, there was a significant reduction of CRP, LDH, and Ferritin on day 15. The mortality rate was 9% (no difference in groups; p=0.453), and a higher proportion died for Pseudomonas aeruginosa superinfection in the rxb+dxm group (p< 0.001). Differences for support oxygen at baseline and discharge Final health outcomes of patients with severe or critical COVID-19 in a third-level hospital in Mexico Conclusion The use of rxb could be considered as a treatment helping clinical improvement in hospitalized patients with severe COVID-19. Combination with dxm apparently did not add clinical benefits. It should be further evaluated. Disclosures All Authors: No reported disclosures

Periostin as a predictor of uncontrolled asthma and lung function decrease in patient of different age groups

Introduction. Uncontrolled bronchial asthma (BA) increases risk of hospitalizations, future exacerbations and decreases quality of life; factors improving the probability to achieve BA control are under study.Methods and materials. The open prospective study included 104 patients of three groups: children (6—11 years, n=38), adolescents (14—17 years, n = 35) and adults (25 — 50 years, n = 31). Inclusion criteria: BA duration >12 month, uncontrolled asthma, absence of acute respiratory infection for 14 days. Clinical history, respiratory function and sampling (serum and nasal brushings) for periostin assay were performed on Visit 1. Maintenance therapy correction and triggers avoiding recommendations were made. Two further visits 6 months apart were done. Statistical processing included ANOVA (Kruskall — Wallis test) and Pearson correlation test. Differences were considered significant when p<0.05.Results. 75 % of «Children» group,70.6 % of «Adolescents» and 53.6 % of «Adults» had achieved BA control. Obesity, non-atopic phenotype, FEV1 <65 % of predicted were risk factors of uncontrolled BA. Serum periostin levels were highest in uncontrolled BA subgroup, Me [Q25; Q75] =32.9 [28.6; 39.1] ng/ml. Nasal periostin levels were highest in «Adolescent» group: 9.8 [4.8; 11.2] ng/ml. Nasal periostin and low FEV1 had moderate reverse correlation (r=—0.61).Conclusion. Serum and nasal periostin levels could indicate treatment efficacy and prognose future risks of BA control loss.

Long-Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cell Injections in Patients With Progressive Forms of Multiple Sclerosis

Background: Mesenchymal stem cells (MSC) were shown to possess immunomodulatory and neurotrophic effects. Our previous trials, have shown that intrathecal (IT) and intravenous (IV) administration of MSCs were safe and provided indications of beneficial clinical effects.Methods: This is an open prospective study to evaluate the safety and the long-term clinical and immunological effects of multiple injections of autologous MSCs in 24 patients with active-progressive MS. At inclusion, the mean age of the patients was 47.0 ± 9.22, and the mean EDSS score was 6.75 ± 0.68 (range: 5.5–7.5). Patients were initially treated with 1 ×106 MSCS/kg of body weight (IT + IV) and subsequently with up to additional eight courses of MSCs, at intervals of 6–12 months. The duration of the trial was 4 years.Results: No serious, treatment-related adverse events were observed during the follow-up period. Twenty-two of the 24 patients were either stable or improved at the last follow-up visit. Ten patients had a lower than baseline EDSS at the last follow-up (nine were among those who received &gt;2 treatments and one in the subgroup of ≤ 2 treatments, p = 0.04). The mean EDSS score reduced from 6.75 ± 0.68 at baseline to 6.42 ± 0.84 at the last visit, during a median follow-up period of 27.8 months (p = 0.028). Immunological follow-up showed a transient upregulation of CD4+CD25+FoxP3+ cells and downregulation of the proliferative ability of lymphocytes.Conclusions: Repeated MSC treatments in patients with progressive MS were shown safe at the short/intermediate term and induced clinical benefits (especially in patients treated with &gt;2 injections) that lasted for up to 4 years, paralleled by short-term immunomodulatory effects.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04823000.

The role of occupational factors in the development and course of respiratory sarcoidosis

Aim. The aim of the study was to study the frequency of occurrence of exposure to harmful occupational factors in patients with sarcoidosis of the respiratory organs, depending on the course of the disease. Materials and methods. An open prospective study included 121 patients with sarcoidosis of the respiratory system from the age of 21 to 66 years, from 20072019. The diagnosis was histologically confirmed in all patients. Patients underwent a set of laboratory and instrumental examinations, studied profane history. The presence of a history of contact with harmful and dangerous production factors was clarified. To determine the effect of a harmful production factor on the course of sarcoidosis, patients were divided into 2 clinical groups: the first group consisted of 85 (70.2%) patients with a favorable course of the disease, the second group included 36 (29.8%) patients with an unfavorable course sarcoidosis (standardization coefficient between groups 2.4:1). Results and discussion. Among the examined patients of working age prevailed (87%). Patient groups were comparable by age, but statistically differed by gender (chi2=9.75, p=0.0018). Frequency analysis of the occurrence of harmful occupational factors in sarcoidosis of the respiratory organs showed that the most frequently encountered factors in all the studied groups were contact with chemical hazards. Conclusion. The presence of contact with harmful production factors increases the risk of an unfavorable course of sarcoidosis by more than 2 times.

An open prospective study on the efficacy of Navina Smart, an electronic system for transanal irrigation, in neurogenic bowel dysfunction

Background Transanal irrigation (TAI) has emerged as a key option when more conservative bowel management does not help spinal cord injured (SCI) individuals with neurogenic bowel dysfunction (NBD). Aim To investigate the short-term efficacy and safety of an electronic TAI system (Navina Smart) in subjects with NBD. Design We present an open, prospective efficacy study on Navina Smart, in individuals with NBD secondary to SCI, studied at three months. Population Eighty-nine consecutive consenting established SCI individuals (61 male; mean age 48, range 18–77) naïve to TAI treatment were recruited from ten centres in seven countries. Subjects had confirmed NBD of at least moderate severity (NBD score ≥10). Methods Subjects were taught how to use the device at baseline assisted by the Navina Smart app, and treatment was tailored during phone calls until optimal TAI regime was achieved. The NBD score was measured at baseline and at three months follow up (mean 98 days). Safety analysis was performed on the complete population while per protocol (PP) analysis was performed on 52 subjects. Results PP analysis showed a significant decrease in mean NBD score (17.8 to 10, p<0.00001). In subjects with severe symptoms (defined as NBD score ≥14), mean NBD scores decreased (19.4 to 10.9, p<0.0001). The number of subjects with severe symptoms decreased from 41 (79%) subjects at baseline to 16 (31%) at three months follow-up. Device failure accounted for the commonest cause for loss of data. Side effects possibly related to the device developed in 11 subjects (12%). Discontinuation due to failure of therapy to relieve symptoms was reported by 5 subjects (6%). Conclusion Navina Smart is effective for individuals with NBD, even those with severe symptoms; long-term data will follow. Whilst there were some device problems (addressed by the later stages of subject recruitment) the treatment was generally safe. Clinical trial (ClinicalTrials.gov number NCT02979808)

The Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease According to Polysystemic Ultrasound of the Arteries and Hepatic Steatometry

Introduction. Coronary heart disease (CHD) remains the most common cause of death and disability in Ukraine and around the world. CHD is caused by atherosclerosis. Non-alcoholic fatty liver disease (NAFLD) is considered an independent predictor of CHD. Aim. To identify the relationship between atherosclerosis and NAFLD according to polysystemic ultrasound (ps-US) of the arteries and liver steatometry. Materials and methods. We conducted an open prospective study in 2019 of 93 people, including 58 women and 35 men aged 22 to 79 years. Chronic CHD was detected in 36 patients and 57 apparently healthy individuals. US was performed by Soneus P7 (Ultrasign, Ukraine). We determined condition of the abdominal organs in the B-mode as well as the amount extent of hepatic steatosis – through steatometry by attenuation coefficient (AC) measurement – ACM) for the diagnosis of NAFLD. Atherosclerosis of the abdominal aorta and common carotid arteries (atherosclerotic plaques and the thickness of the intima-media complex) was detected. Results and discussion. There was an increase in AC (a sign of NAFLD) in 36 patients with CHD. The presence of carotid atherosclerosis confirms a higher percentage of patients with signs of hepatosis in the CHD group. Conclusions. An innovative method of quantitative ultrasound of hepatosteatosis (steatometry) can be used as a screening for the detection of NAFLD in population studies. The relationship between markers of atherosclerosis and NAFLD has been revealed according to the data of ps-US of the arteries and hepatic steatometry which allows to prescribe comprehensive treatment and evaluate its effectiveness. NAFLD can be a predictor of atherosclerosis and the formation of CHD, which gives grounds for the primary prevention of the latter.

AB0875 HYBRID COOPERATIVE COMPLEXES OF SODIUM HYALURONATE + SODIUM CHONDROITIN NON-SULFATED (HA-SC) IN THE TREATMENT OF HIP OA: CLINICAL RESULTS

Background:Hip Osteoarthritis (OA) is a widespread disease characterized by pain and functional impairment, which, particularly in the elderly, may compromise overall health and quality of life. In the last decades, Intra-articular (I.a.) injections of hyaluronic acid (HA) gained more space among the conservative treatment of OA because of their beneficial effects and positive outcomes without relevant complications. (1,2). An innovative and patented formulation containing hybrid cooperative complexes of sodium hyaluronate 2.4% + sodium chondroitin non-sulfated 1.6% of biotechnological origin (HA-SC) has been recently developed for the I.a. treatment of hip OA and evaluated in a pilot study (3).Objectives:1) Primary aim: Evaluation of the safety of HA-SC in the treatment of symptomatic hip OA; 2) Secondary aim: Evaluation of the efficacy of HA-SC in terms of pain reduction (VAS) and function improvement (Lequesne) of the affected hip joint.Methods:This is a pilot, multicentric, open, prospective study. The following inclusion criteria were established: Patients (both genders) aged ≥ 40 years suffering for primary hip OA confirmed by X-Ray; Grade I-II-III according to K&L grading scale; Basal VAS pain at the target hip > 40 mm; Failure of at least two lines of conservative treatments. All patients underwent a single I.a. hip injection of a 3mL vial of HA-SC and followed-up for six months.Results:48 patients have been enrolled and completed the study. The treatment was generally well-tolerated, with only ten patients out of 48 (20.8%) reporting local effects mainly consisting of injection site pain and arthralgia localized in the treated area. All these patients completed the study. The treatment with HA-SC was associated with a statistically significant decrease of VAS scale from a basal value of 67.5 (mean) to 22.8 (mean, p<0.0001) at the end of the observation period at six months, with a statistically significant decrease at seven days of follow-up evaluation (29.3, mean, p<0.0001). The mean Lequesne’s Index total score after the single injection of HA-SC decreased from a baseline value of 10.4 (mean) to 5.1 (mean, p<0.0001) at six months. The decrease was marked and significant also at any of the other evaluated time point (p<0.0001).Conclusion:A single I.a. injection of the innovative formulation containing hybrid cooperative complexes of sodium hyaluronate + sodium chondroitin non-sulfated (HA-SC) showed to be well tolerated and safe in the treatment of symptomatic hip OA. A rapid and significant decrease in hip pain (VAS) and Lequesne’s Index was also observed starting immediately after the I.a. injection and lasting until the end of the follow-up period. However, conservative treatment of hip OA is still challenging. This new formulation could represent a promising, long-lasting, and effective I.a. treatment.References:[1]Papalia R. et al. J. Biol. Regul. Homeost. Agents 2017; 31 (4 Suppl. 2): 103-109.[2]Abate M. et al. Int. J. Immunopathol.Pharmacol. 2017; 30 (1): 89-93.[3]IBSA Data on file.Acknowledgments:The author thanks all the investigators of the study: Costantino Cosimo, UO Medicina Riabilitativa, Azienda Ospedaliero-Universitaria di Parma, Italy; Fortina Mattia, Unità di Ortopedia Universitaria, AOU Senese Policlinico Santa Maria alle Scotte, Italy; Sadile Francesco, II Ortopedia - Ortopedia Infantile, Università degli studi di Napoli Federico II, Italy; Salini Vincenzo, Clinica Ortopedica e Traumatologica, Ospedale SS Annunziata di Chieti, Italy; Voglino Nicola, UO Ortopedia e Traumatologia, Ospedale Alto Tevere Città di Castello Azienda USL Umbria 1, ItalyDisclosure of Interests:Rocco Papalia Speakers bureau: Speaker for IBSA