Doses Of Glucocorticosteroids Research Articles

BCD020 rituximab bioanalog compared to standard treatment in juvenile systemic lupus erythematosus: The data of 12 months case-control study.

Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. To compare the benefits of RTX above SOCT. The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.

Catastrophic Antiphospholipid Syndrome.

Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a "thrombotic storm". CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates.

Update on Adult-Onset Still's Disease: Diagnosis, Therapy and Guideline

Adult-onset Still's disease (ASOD) is an autoinflammatory disease of unknown etiology which is pathogenetically characterized by an involvement of the innate immune response with activation of neutrophils and an increased secretion of IL-1, IL-6, IL-18, type 1 interferons. Still's disease may occur at any age with distinct variability in signs and symptoms. Recently, the German Society of Rheumatology (DGRh) has issued an AOSD guideline which recommends diagnosing AOSD based on a characteristic combination of symptoms including intermittent fever, rash, arthralgia, and arthritis after exclusion of infections, neoplasms and other rheumatological conditions. Classification criteria according to Yamaguchi may support the clinical diagnosis. Therapy is recommended to include glucocorticosteroids and methotrexate or ciclosporin, at higher activity levels IL1-receptor antagonist anakinra, IL-1β antibody canakinumab, or IL6-receptor antibody tocilizumab. At a high disease activity, anakinra or canakinumab may be employed primarily. Local drug licensing policies may have to be considered, as these substances are not universally approved in these scenarios. Important complications to consider consist in perimyocarditis, a multi-faceted pulmonary involvement, and macrophage activation syndrome (MAS). MAS features multi-organ involvement and cytopenias. Besides supportive measures often requiring intensive care, high dose glucocorticosteroids as well as above named biologics, and if necessary, also etoposide based therapeutic regimen are used.

Experience of successful laparoscopic sleeve resection of the stomach and treatment of morbid obesity in a patient with a classic form of congenital adrenal dysfunction

The article presents a clinical observation of a patient with congenital adrenal dysfunction (CHD), a salt-losing form of 21-hydroxylase enzyme deficiency (homozygous mutation I 172N), and also with morbid obesity, due to long-term use of high doses of glucocorticosteroids, who underwent bariatric surgery - laparoscopic sleeve resection of the stomach. A feature of the presented case is the elimination of one of the causes of decompensation of the disease, namely, overweight, as well as insulin resistance, which requires the intake of large doses of glucocorticoids, which in turn leads to a worsening of the course of obesity, thereby causing a vicious circle. 7 months after surgical treatment, the goal was achieved - a reduction in the dose of Prednisolone by 25%, with a decrease in body weight by 72.1% of overweight.The presented case clearly demonstrates the possibility of performing bariatric surgery for the treatment of morbid obesity in patients with CAH with the participation and control of a specialized multidisciplinary team. If there are indications for bariatric intervention, VDKN should not be an absolute contraindication to such operations, and the ratio of the safety profile and the efficacy profile testifies in favor of the need for their implementation.

Relapses of pain syndrome in patients with polymyalgia rheumatica during reduction of glucocorticoid therapy

An analysis of causes leading to pain recurrence in patients with polymyalgia rheumatica (PR) after tapering down the dose of glucocorticosteroids (GCS) is presented. True exacerbations resulting from the main disease recurrence and pseudo-exacerbations when the resumption of pain syndrome is not due inflammation but because of other causes – steroid myopathy or chronic adrenal insufficiency (AI) are identified. The experience of using tocilizumab, an inhibitor of interleukin-6 receptors, as steroid-sparing agent in patients with PR is considered. The factors contributing to pain syndrome development, which can mimic exacerbations of PR (associated myofascial pain, vitamin D deficiency, etc.) are indicated. The methodology for AI diagnosis in patients receiving GCS therapy is discussed in detail. Recommendations for the rational AI therapy including acute cases are given.

Predictors of Bone Mineral Density Reduction in Patients with Hodgkin’s Lymphoma Associated with Pathogenetic Therapy

Hodgkin’s lymphoma is more common in the younger patient population. An increase in overall and recurrence-free survival increases the likelihood of developing post-cytostatic complications in the form of a decrease in bone mineral density and associated low-energy fractures.The aim of the work is to evaluate risk factors for bone mineral density decrease in patients with Hodgkin’s lymphoma after standard polychemotherapy and autologous hematopoietic stem cell transplantation.Material and Methods: The study included 118 people, of which 88 people were patients with Hodgkin’s lymphoma and 30 people were the control group. The study group of patients with Hodgkin’s lymphoma was divided into 2 groups: patients who received standard polychemotherapy and patients who received standard polychemotherapy and autologous hematopoietic stem cell transplantation. For all patients, measurements of bone mineral density were performed using the HologicDiscovery QDR scanner (USA) in the lumbar spine (L2–L4) and in the thigh region (total area of t he thigh and femoral neck). The minimum measurements of bone mineral density and T-scores in the hip and femoral neck were selected, and the Z-score was calculated for young patients.Results: According to the results of densitometry in both study groups, there was no decrease in bone mineral density below the age norm. In 13 patients (30 %) who received autologous hematopoietic stem cell transplantation, a decrease in T-score was found, which corresponds to osteopenia and osteoporosis. In the standard PCT group, a decrease in the T-criterion was observed in 6 patients (14 %): to stagnation — in 3 patients (7 %), to osteoporosis — in 3 patients (7 %). All patients with Hodgkin’s lymphoma included in the study received high doses of glucocorticosteroids. There was no correlation between the decrease in BMD, Z-criterion and the risk of low-energy fracture on the stage and variant of the disease.Conclusion: The high incidence of bone density reduction, taking into account a favorable prognosis for the life of patients with Hodgkin’s lymphoma, indicates the need to develop schemes for the prevention of osteoporosis and osteopenia.

Cмертельный альянc двух пандемий: COVID-19 и сахарный диабет

Objective: to study the features of the course of viral pneumonia in patients with diabetes mellitus. Materials and methods. A random sampling method was used to conduct a retrospective analysis of 300 archival medical records of inpatients with laboratory-instrumentally confirmed COVID-associated pneumonia for the period 2020-2022. Results. As a result of the study, two groups were formed - the main and control. The main group included 150 patients diagnosed with diabetes mellitus; the control group consisted of 150 patients without diabetes mellitus. The average number of bed-days spent by the main group in the hospital was 12.4 days, the control group - 10.5 days (р˂0.001). Significantly more often, the main group of patients is diagnosed with a serious condition at the time of hospitalization, as well as unilateral localization of the pathological process in the lungs. Conclusion. In patients with diabetes mellitus and pneumonia caused by a new coronavirus infection, a dependence of the volume fraction of lung tissue damage on the level of hyperglycemia was revealed. In patients with DM, anticoagulant therapy was carried out longer during inpatient treatment, combinations of several groups of antibacterial drugs were used more often, and the starting dose of glucocorticosteroids was also higher.

Эффективность ритуксимаба в терапии системного ювенильного идиопатического артрита

Эффективность ритуксимаба в терапии системного ювенильного идиопатического артрита

Efficacy and Safety of Belimumab in Lupus Nephritis Patients: A Real-World Observational Study in China

Background: This study aimed to describe disease activity, clinical outcome, and overall patterns of lupus nephritis care in patients who received belimumab in a real-world clinical setting in China. Materials and Methods: This observational cohort study included lupus nephritis patients who received belimumab as adjunct therapy. We deeply investigated the characteristics of those patients including clinical response to belimumab and safety. Results: All 61 lupus nephritis patients were included with a median follow-up period of 9 months (6, 19). Prevalence of proteinuria (52.5–24.6%) and hematuria (33.3–9.8%) was decreased with a stable level of eGFR at last visit. The percentage of patients achieved complete or partial renal response increased from 47.5% to 78.7% and the proportion of complete or partial renal response in patients with proliferative lupus nephritis was higher than those with membranous lupus nephritis (75 vs. 50%) at last visit. The median SLEDAI score decreased from 6 to 2, and there was an increase in patient of LLDAS from 17 to 33 at last visit. A notable dose reduction was seen for glucocorticosteroid dose, with a median change from 10 to 5 mg/d. The proportion of patients receiving >7.5 mg/d steroids reduced from 52.5% at baseline to 23.0% at last visit. The discontinuation of belimumab was rare (3/61) for drug-induced fever, hyperthyroidism, and uveitis. Conclusions: Lupus nephritis patients with belimumab demonstrated improvements in clinical response and a reduction in glucocorticosteroids, which provided evidence of effectiveness and safety in real-world clinical practice in China.

РЕФРАКТЕРНИЙ САРКОЇДОЗ ЛЕГЕНЬ: ПЕРСПЕКТИВИ ЗАСТОСУВАННЯ КОМБІНОВАНОЇ ТЕРАПІЇ МЕТОТРЕКСАТОМ ТА ГІДРОКСИХЛОРОХІНОМ

Refractory sarcoidosis is a variant of sarcoidosis course when glucocorticosteroids (GCS) used in maintenance dose not less than 10 mg daily (prednisolone equivalent) and methotrexate (MTX), including combined use, are not effective enough to achieve clinical remission. Aim — to evaluate the feasibility of combination use of MTX and GCS in patients with refractory pulmonary sarcoidosis. Mаtеrials and methods. There were enrolled 7 patients with refractory sarcoidosis: 4 females, 3 males; age – from 32 to 62 years. In 1 patient the diagnosis of refractory sarcoidosis was jastified by low effectiveness of MTX monotherapy 15 mg weekly for not less than 3 months, prescribed due to contraindications for use of GCS (history of manifest mental disturbance in response to short course of GCS, prescribed for other indication). In 5 patients the refractoriness was defined by low effectiveness of MTX, prescribed due to relative resistance to GCS (initial response to GCS followed by progression of the disease during dose tapering). In 1 patient there was a combination treatment failure (methylprednisolone 12 mg daily with MTX 15 mg weekly) used for at least 3 months. In addition to clinical evaluation all patients were examined using high resolution computed tomography (CT) of lungs using multi-slice CT scanner Aquilion TSX-101A (Toshiba). CT scans were assessed using criteria described by M. Veltkamp, J. C. Grutters (2014). Lung function was assessed using flow-volume curve analysis, whole bodypletysmography, and spirometry by means of spirometry system MasterScreen («Viasys Healthcare GmbН») equipped by appropriate modules. For patients, who failed to respond to MTX monotherapy, combination therapy MTX 10 mg weekly with hydroxychloroquine (HCQ) 200 mg daily was prescribed. For patients, failed to respond to MTX/GCS therapy, we recommended tapering GCS dose until complete discontinuation, followed by MTX/HC combination therapy in above mentioned doses. To assess treatment tolerance before the initiation of combination treatment, 2 weeks after initiation and later on, once per month a laboratory workup including total blood count and blood chemistry (WBC, PLT, creatinine, alanineaminotransferase (ALT)) was done. Additionally, before the start of combination therapy all patients underwent ophthalmological examination. Results are presented in form of clinical series case report. Considering limited number of cases, a level of statistical significance (p) of prior treatment and combination MTX and HCQ treatment was determined using Fisher’s exact test. Combination therapy with MTX (15 mg/week) with HCQ (200 mg daily) for at least 3 months was quite effective in 5 out of 7 patients with refractory pulmonary sarcoidosis (Fisher’s exact test was 0,011, р < 0,05)) with overall satisfactory tolerability of treatment. Serious adverse reactions resulted in discontinuation of combination therapy were observed in 2 cases. Those patients were switched on GCS therapy. Conclusion. Despite successful use of combination therapy (MTX+HCQ) in majority of patients with refractory pulmonary sarcoidosis, high frequency of adverse reactions (almost in 1/3 of patients) requires justified personal treatment with regular monitoring of blood cellular composition and functional liver and kidney parameters. Key words: refractory pulmonary sarcoidosis, methotrexate, hydroxychloroquine, combination therapy, effectiveness, tolerability.

Clinical case of rhino-orbital mucormycosis in a convalescent COVID-19 patient: diagnostic and treatment tactics

According to current data, SARS-CoV-2 virus has the ability to cause multi-organ pathology, leading to acute damage of various organs and systems and long-term consequences characterized by polymorphic symptoms. Recently, a high incidence of invasive mycoses, particularly mucormycosis COVID-M, has been noted among the COVID-19 complications. The predisposing factor for the development of this pathology is diabetes mellitus, immunodeficiency states, and prolonged use of high doses of glucocorticosteroids. Mucormycosis is characterized by severe clinical manifestations and high lethality, and timely diagnostics of this pathology often represents a difficult problem. The aim of this study was to analyze a clinical case of rhino-orbital mucormycosis in convalescent COVID-19 patient. In the study, there was used mucopurulent nasal discharge from the patient previously hospitalized with a severe novel coronavirus infection. Here, we describe the methodology allowing to isolate and identify a pure mold fungus culture from the biomaterial using methods of routine bacteriology and MALDI-ToF mass spectrometry. Direct microscopy examination of nasal cavity discharge revealed branched non-septic hyphae with a characteristic branching angle, allowing to preliminarily diagnose invasive mucormycosis. Growth of mycelial fungus colony was observed by using Sabourauds medium with potassium tellurite. Microscopy of the pure culture revealed branching mycelium without septa, broad, with irregular thickness, unsegregated hyphae, and sporangia with a typical column specific to mucormycetes. Analysis of the obtained mass spectra allowed to establish the microbial species identity as Lichtheimia corymbifera. The latter along with other members of the order Mucorales, are known to cause mucormycosis. As a result of antifungal treatment (Amphotericin B) and timely surgical intervention, the patient was discharged from the hospital with prominent clinical improvement and no complaints during further outpatient follow-up period. The analysis of this clinical case showed the lack of alertness in some clinical diagnostic laboratories to detect pathogens of invasive mycoses. To avoid errors, while making a diagnosis, attention should be paid not only to detection of fungal spores in clinical material, but also take into account the structure of mycelium underlying major difference between yeast-like fungi, higher and lower molds. The isolation and identification of a pure pathogen culture allows to confidently verify the diagnosis, timely correct the treatment tactics and monitor circulation of mycotic agents to prevent occurrence of mycoses in most vulnerable patients cohorts.

Secondary Immunodeficiency in Rheumatology

Secondary Immunodeficiency in Rheumatology Abstract. For the treatment of autoimmune and autoinflammatory diseases an immunosuppressive therapy with conventional, small molecule or biological disease modifying anti-rheumatic drugs (DMARDS) plays a key role. This may lead to secondary immunodeficiency with an increased risk for infections, which we discuss in the present article. The risk for reactivation of chronic hepatitis B increases particularly with glucocorticoid dosages of ≥ 20mg/d for longer than four weeks, with B-cell-depleting therapies, followed by anti-TNF-α-inhibitors. The latter also represent a risk for the reactivation of latent tuberculosis. High doses of glucocorticosteroids for prolonged periods increase the risk for pneumonia with Pneumocystis jirovecii, especially if combined with other DMARDs. An elevated risk for Herpes zoster exists for B-cell depletion, TNF-α-inhibition and for JAK blockade. Severe immunosuppression (B-cell depletion, cyclophosphamide, mycophenolate mofetil, JAK inhibitors, prednisone ≥ 20mg/d or combination therapy) increase the risk for severe COVID-19 infections.

Mucormycosis in patients with COVID-19 in Russia: the results of a prospective multi-center study

We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation.The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011–2020.In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (≥100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially ≥10 days (OR=25,4). The main localization of mucormycosis in patients with COVID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of ≥2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%).90-days overall survival of patients with mucormycosis and COVID-19 – 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and ≥ 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046).

Pulse dose glucocorticosteroid therapy in COVID-19 pneumonia patients in an intensive care unit

Pulse dose glucocorticosteroid therapy in COVID-19 pneumonia patients in an intensive care unit

Symptomatic melanoma metastases in the brain: are we using all therapy options?

In recent years, significant advances have been made in systemic therapy for patients with metastatic melanoma of the skin, resulting in an increase in one-year overall survival (OS) from 25 to 85% and 5-year OS from less than 10 to 60% in certain patient subgroups. Approximately 50% of patients with metastatic skin melanoma are diagnosed with metastatic brain lesions in the course of the disease. Modern drug therapy for metastatic brain lesions is slowly but surely proving to be effective. Thus, in the presence of a mutation in the BRAF gene, BRAF inhibitor monotherapy provides an intracranial objective response rate (iORR) of 25 to 40%, whereas BRAFi + MEKi combined targeted therapy (CTT) achieves already 58% iORR, including in patients with symptomatic metastases to the brain. However, the duration of responses achieved on targeted therapy (TT) is shorter than for extracranial disease prevalence. On the other hand, regardless of the presence of a BRAF mutation, immunotherapy (PD-1 monotherapy) achieves a response in approximately 20-22% of patients, but these responses are more durable, although fewer than on TT. The combination of CTLA-4 + PD-1 checkpoint inhibitors produces long-lasting responses with a iORR of 51-54%. However, the achievement of these results and an overall increase in life expectancy with immunotherapy is mostly possible in symptom-free patients and in patients receiving low or no doses of glucocorticosteroids (10 mg or less on prednisolone). Therefore, for symptomatic patients, especially those whose tumors have been identified with a BRAF mutation, a combination of targeted therapy, which would quickly achieve an objective response in 58%, and anti-PD1/PDL1 immunotherapy, which is likely to increase the duration of the response achieved and give a chance for a sustained remission, looks promising. This article provides an overview of key studies and our own experience with the triple combination in metastatic brain lesions.

Combination therapy of tacrolimus, high doses of glucocorticosteroids, and cyclophosphamide against existing historical treatment for patients in severe conditions of interstitial lung diseases complicated with dermatomyositis: A retrospective analysis.

The high-dose glucocorticosteroid (GC) treatment is the first choice for dermatomyositis complicated with interstitial lung disease (DM-ILD) but patients are resistant to the high-dose GC monotherapy. Besides, the high dose of GC, the secondary immunosuppressive agent(s) is necessary but there is controversy for the selection of immunosuppressive agent(s). The objectives of the study were to analyze the efficacy of different therapeutic options for DM-ILD to identify the optimal therapy. A total of 60 patients had received intravenous 1.0–2.0 mg/ kg/day prednisolone for DM-ILD. In severe conditions, patients had received oral 1 to 3 mg/day tacrolimus (TAC), 500 mg/ m2/month cyclophosphamide (CY), and/or 1 g/ day methylprednisolone pulse (TI cohort, n = 24). In severe conditions, patients had received 1 g/day methylprednisolone pulse and 2–3 mg/ kg/day cyclosporine A (CsA) and/or 500 mg/ m2/month CY (existing historical treatment; CT cohort, n = 36). Patients of the TI cohort did not receive CsA. Patients in the CT cohort were received CY in significantly fewer numbers than those of the TI cohort during treatment (P = .0112). A total of 11 (46%) patients from the TI cohort and 14 (39%) patients from the CT cohort were developed relapsed. At the end of the 30-months, higher numbers of patients of the TI cohort had an event(s) free survival than those of the CT cohort (7 (29%) vs 2 (6%), P = .0229). Also, higher numbers of patients of the TI cohort had survived irrespective of an event(s) than those of the CT cohort (21 (87%) vs 22 (61%), P = .0399). Patients of the TI cohort had developed herpes zoster (2 (8%)) and cytomegalovirus (4 (17%)) infections. Patients of the CT cohort developed renal dysfunction (10 (28%)). Hyperglycemia, hyperlipidemia, and fracture (GC-related toxicities) were also reported in both cohorts and these toxicities were fever in the TI cohort. The addition of TAC to high doses GC with CY is an ideal treatment for severe conditions of DM-ILD (Level of Evidence: III; Technical Efficacy Stage: 4).

Дерматомиозит, осложненный аспирационной пневмонией

Dermatomyositis is an autoimmune disease characterized by damage to proximal symmetrical muscle groups, skin in the form of erythema, as well as other systems. With timely diagnosis, dermatomyositis responds well to therapy with high doses of glucocorticosteroids. However, serious complications may develop during the course of the disease, for example, aspiration pneumonia, which significantly affect the patient's management tactics and the course of the disease. This article presents a clinical case of aspiration pneumonia on the background of dermatomyositis, which significantly limited the arsenal of therapy used.

Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists as of February 23, 2022.

The first Polish recommendations regarding the management of patients with COVID-19 were published by the Polish Society of Epidemiologists and Infectiologists (PTEiLChZ) on March 31, 2020, and the last annex was dated November 12, 2021. The ongoing state of pandemic, the emergence of new variants of the virus, and the availability of new drugs necessitate their updating. Changes introduced in the current version of recommendations for the management of COVID-19 comprised the possibility of using remedesivir in an outpatient setting, previously reserved for inpatient treatment, as well as other antiviral drugs-molnupiravir and nirmatrelvir / ritonavir. We revised the possibility of using monoclonal antibodies due to the resistance of the currently dominant Omicron variant. Anakinra, an antagonist of interleukin 1 receptors, has been added as a treatment option in advanced stages of the disease, and the recommended daily dose of glucocorticosteroids used in the most severe forms of COVID-19 has been increased. Information on vaccination and pre-exposure prophylaxis in specific populations has also been updated.

Сложность ведения пациента с инфекционным эндокардитом при васкулите, ассоциированном с антинейтрофильными цитоплазматическими антителами

The article presents a clinical case of a 27-year-old woman with infectious endocarditis in vasculitis associated with antineutrophil cytoplasmic antibodies. Difficulties in the management of the patient are described, consisting in verifying the nature of changes in the heart (vegetation), as well as in determining the treatment tactics. Changes in the heart were regarded as infectious endocarditis. Adequate antibacterial therapy was carried out with a positive clinical and laboratory effect, with a significant decrease in vegetations on the valves, a decrease in the size of the formation in the aorta sinus, and a decrease in aortic regurgitation. The therapy of infectious endocarditis in granulomatosis with polyangiitis is difficult due to the need for a correct combination of adequate antibacterial therapy of infectious endocarditis and high doses of glucocorticosteroids and immunosuppressive drugs for autoimmune disease.

Cyclosporine A but Not Corticosteroids Support Efficacy of Ex Vivo Expanded, Adoptively Transferred Human Tregs in GvHD.

Reshaping the immune balance by adoptive transfer of regulatory T-cells (Tregs) has emerged as a promising strategy to combat undesired immune reactions, including in Graft-versus-Host Disease (GvHD), which is the most lethal non-relapse complication of allogeneic hematopoietic stem cell transplantation. Currently however, little is known about the potentially inhibitory in vivo effects of conventional immunosuppressive drugs, which are routinely used to treat GvHD, on adoptively transferred Tregs. Here we demonstrate drug-specific effects of the conventional immunosuppressive drugs Cyclosporine A, Mycophenolate mofetil and methylprednisolone on adoptively transferred Tregs in a humanized NOD/SCID/IL2Rgamma-/- GvHD mouse model. The clinical course of GvHD and postmortem organ histology, including cellular organ infiltration, showed that co-administration of Cyclosporine A and Tregs is highly beneficial as it enhanced Treg accumulation at inflammatory sites like lung and liver. Similarly, co-administration of Mycophenolate mofetil and Tregs improved clinical signs of GvHD. In contrast, co-administration of methylprednisolone and Tregs resulted in reduced Treg recruitment to inflammatory sites and the fast deterioration of some animals. Consequently, when clinical trials investigating safety and efficacy of adjunctive Treg therapy in GvHD are designed, we suggest co-administering Cyclosporine A, whereas high doses of glucocorticosteroids should be avoided.