Third Month Of Therapy Research Articles

Selamerex: regional real-world practice and perspective of therapy optimisation

Перенести в английский вариант BACKGROUND. Hyperphosphatemia in CKD is spread widely, represents as independent factor of mortality at all stages of CKD, after transplantation, reduces the effectiveness of nephroprotection, leads to vascular calcification, stimulates hyperparathyroidism. Achieving the phosphatemia target is a difficult task and is based on a combination of a hypophosphate diet, effective dialysis, the antihyperparathyroidic measures and the phosphate-binders (PBs). THE AIM. The aim is to evaluate the effectiveness of sevelamertherapy in real clinical practice as part of a hypophosphatemic strategy with clarification of the conditions and measures under which it is optimal. PATIENTS AND METHODS. In an eight-month study in a region where there are no restrictions on access to calcium-free PBs, 127 patients were included in the study after the "washing period ": the of sevelamer doses were titrated until phosphatemia reaches below 1.58 mmol/l in parallel with individual measures of four-component hypophosphatemic strategy. RESULTS. From the starting dose of 3-6 tablets/day, 38 patients experienced either dose increase (+ 1016 ± 760 mg) or in 28 patients– decrease (- 1427 ± 1059 mg). By the third month of therapy, the proportion of patients with phosphatemia < 1.58 mmol/l reached 70 %, < 1.78 mmol/l – 90 %. The decrease magnitude depended on the initial phosphatemia, the level of PTH (maximum in the range of 150-600 pg/ml), occurs more slowly in men. During therapy, there was a decrease in the need for antihyperparathyroid therapy in the absence of dynamics in the parathyroid hormone level. In multiple regression analysis models, the independent factors associated with phosphatemia during treatment were sevelamer dose, dialysis dose, baseline phosphate and parathyroid hormone levels; the magnitude of phosphatemia reduction was independently associated with sevelamer dose, dialysis dose, baseline parathyroid hormone level, and assessment of treatment compliance. CONCLUSION. Sevelamer in a moderate well–tolerated doses as part of an individualized hyperphosphatemia correction strategy is able to achieve target phosphatemia (< 1.58 mmol/L) in 70 % of cases, and relatively safe level (< 1.78 mmol/L) – in 90 %.

Myeloid-Derived Suppressor Cells (MDSC) in Melanoma Patients Treated with Anti-PD-1 Immunotherapy.

Myeloid-derived suppressor cells (MDSC) are a subset of immature myeloid cells with suppressive activity well described in the context of cancer. They inhibit anti-tumour immunity, promote metastasis formation and can lead to immune therapy resistance. In a retrospective study, blood probes of 46 advanced melanoma patients were analysed before the first administration of anti-PD-1 immunotherapy and in the third month of treatment for MDSC, immature monocytic (ImMC), monocytic MDSC (MoMDSC) and granulocytic MDSC (GrMDSC) by multi-channel flow cytometry. Cell frequencies were correlated with response to immunotherapy, progression-free survival (PFS) and lactate dehydrogenase (LDH) serum level. Responders to anti-PD-1 therapy had higher MoMDSC levels (4.1 ± 1.2%) compared to non-responders (3.0 ± 1.2%) (p = 0.0333) before the first administration of anti-PD-1. No significant changes in MDSCs frequencies were observed in the groups of patients before and in the third month of therapy. The cut-off values of MDSCs, MoMDSCs, GrMDSCs and ImMCs for favourable 2- and 3-year PFS were established. Elevated LDH level is a negative prognostic factor of response to the treatment and is related to an elevated ratio of GrMDSCs and ImMCs level compared to patients' LDH level below the cut-off. Our data may provide a new perspective for more careful consideration of MDSCs, and specially MoMDSCs, as a tool for monitoring the immune status of melanoma patients. Changes in MDSC levels may have a potential prognostic value, however a correlation with other parameters must be established.

PS-BPC05-7: HEMODYNAMIC MANAGEMENT OF RESISTANT HYPERTENSION

Background: Hypertension is the most prevalent chronic disease worldwide and is related to a high probability of cardiac disease, kidney disease and cerebrovascular events. Blood pressure measurement was used in the last decades to diagnose and guide antihypertensive therapy; however blood pressure is the result of the interaction of more complex hemodynamic parameters previously reserved for experimental studies or critical care patients management using invasive methods. Since 1996 few studies have proposed the use of hemodynamic parameters to classify and guide hypertension therapy with good results. Purpose: The present study's purpose was to measure hemodynamic parameters in patients with non-controlled resistant hypertension and use it to guide pharmacologic treatment to archive control blood pressure values according to the European Society of Cardiology guidelines. Methods: A total of 84 patients between 32 and 95 years old diagnosed with non-controlled primary resistant hypertension were recruited and after previous therapy washout hemodynamic parameters were measured using noninvasive Methods: preload by central venous pressure (CVP) using inferior vena cava diameter, cardiac index and systemic vascular resistance using Lyljestrand & Zander modified formula. Patients were classified into 3 basic groups depending on which parameter was above normal value: hyperdynamic (HD) for high cardiac index > 3.5 L/min/m2, fluid overload (FO) for CVP > 8cmH2O and high systemic vascular resistance index (HSVRi) > 2500 dynes/sec/m2/cm5, also 3 combined groups were a patient had 2 simultaneous hemodynamic alterations (HD+FO, HD+HSVRi and FO+HSRVi), according to this classification pharmacotherapy was guided indicating Bisoprolol in HD group, Amlodipine to HSVR patients and Hydrochlorothiazide to FO patients, in combined groups, combined therapy was given. Patients were observed for 6 months period taking as primary endpoint blood pressure control, acute cardiovascular events and hypotension. Results: A significant reduction of hemodynamic parameters and blood pressure was observed in the first month of treatment obtaining a 100% hemodynamic and blood pressure goals in all patients in the third month of therapy without hypotension or acute cardiovascular event during this period, the HD+FO group reach goals at the 6th month of treatment without reported complications. Conclusions: In this preliminary study we observed that hemodynamic guided high blood pressure control may be a valuable tool for a better understanding, classification and treatment in patients with resistant hypertension; however larger outcome studies confirm this hypothesis.

Оценка эффективности и комплаентности применения Вожея® у женщин на этапе прегравидарной подготовки и в ранние сроки беременности

Aim: to assess the clinical efficacy, safety and tolerability of Vojea® in the prevention of iron-deficiency anemia and folic acid deficiency in women during the preconception (pregravid) period and early stages of pregnancy, as well as to evaluate patient compliance with this product. Patients and Methods: this prospective multi-center observational study was performed in 2022 in four medical centers and women's health clinics of Ekaterinburg. The study included 87 women with latent iron deficiency (mean ferritin level below 15 ng/ml). The first group consisted of 37 women during the pregravid preparation period, and the second group consisted of 50 pregnant patients with up to 12 weeks of pregnancy. Patients received the Vojea® once daily for three months. Clinical and laboratory efficacy (the absence of objective anemia signs and the changes in hemoglobin level, folate and ferritin blood tests over time), as well as tolerability (the rate of adverse events, tolerability of the taken product evaluated using the visual analog scale) was assessed at days 30, 60 and 90 after the beginning of treatment. Results: beginning from the first month of treatment with the studied complex, some positive changes in clinical symptoms and laboratory findings were reported in both groups. By the third month of therapy, the increment of hemoglobin level in the pregravid preparation group was 17 (13.9%) units, the level of ferritin increased by 6.3 times (clinically significant after two months of the product intake), and the level of blood serum folates increased by 4.6 times. In group 2, the increment of hemoglobin level, as pregnancy was progressing, in three months of the product intake reached 19 units (17%), the level of ferritin increased by 5.9 times (clinically significant after two months of treatment), and the level of blood serum folates increased by 3.9 times. In group 1, adverse events were reported only in 2/37 (5.4%) patients who had dark stool color on the 2nd month of follow-up. In group 2, such adverse events as nausea were reported in 3/50 (6%) patients during the 1st month of product intake. All patients informed that the product was well tolerated which ensured high patient compliance. Conclusion: maintaining iron and folic acid homeostasis by oral intake of the Vojea® complex during three months in the preconception period and early stages of pregnancy is a feasible option based on its high efficacy and good tolerability with the minimal risk of side effects, encouraging high patient compliance. KEYWORDS: ferric pyrophosphate, folic acid, pregravid preparation, pregnancy, active metabolite of folic acid, methyltetrahydrofolate, glucosamine salt, Quatrefolic, micronized microencapsulated ferric iron, Vojea, compliance. FOR CITATION: Kononova I.N., Kareva E.N., Stebenyaeva E.V. et al. Assessment of the efficacy and compliance with Vojea® in women during the pregravid preparation and the early stages of pregnancy. Russian Journal of Woman and Child Health. 2023;6(2):95–104 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-95-104.

Astımlı Hastalarda D Vitamini Düzeyinin Astım Kontrolü Üzerine Etkisi

The aim of this study is to evaluate the effects of serum vitamin D level on asthma control and pulmonary functions in asthmatic patients. 35 healthy controls and 60 asthma patients were included. Demographic characteristics, ACT and PFT were recorded and laboratory tests were measured. 53 asthmatic patients and 32 controls with decreased vitamin D levels were referred to the Endocrinology Department for vitamin D replacement therapy. In asthmatic patients, ACT and PFT were repeated at third month of therapy. In terms of age, sex, sociodemographic characteristics, smoking status, daily sun exposure, calcium-containing diet, and menopausal status, there was no significant difference between asthmatics and controls, and laboratory test findings were similar. Vitamin D levels were low in about 90%. While 71,7% of asthmatic patients were uncontrolled at initial admission, the rate of uncontrolled patients decreased to 13,2% after the post-replacement evaluation. There was a significant increase of ACT with vitamin D replacement. There was also significant increase in FVC, FEV1 and FEV1/FVC after replacement therapy. The mean BMI were high in both groups (≥30 kg/m²). The mean ACT score was lower in obese asthmatics than in non-obese patients, but the difference was not significant. Presence of controlled or uncontrolled disease was similar between the obese and non-obese. According to our findings, vitamin D replacement therapy has a positive effect on asthma control and pulmonary function.

MO230: De Novo Double Glomerulopathy (Membranous Nephropathy, Mn and Collapsing Focal Segmental Glomerulosclerosis, CFSGS) Associated to Positive Myeloperoxidase-O (MPO) Antibody Following Pfizer-Biontech MRNA Vaccination Covid 19

Abstract BACKGROUND AND AIMS In the COVID 19 pandemic era, anti SARS-CoV-2 vaccination showed high efficacy at preventing the infection and its most severe complications. The aim of this report is to describe an unusual double glomerulopathy related to anti SARS-CoV-2 vaccination and the good results obtained with the immunosoppressive treatment. METHOD An 80-year-old caucasian woman developed a nephrotic syndrome, progressive renal insufficiency and microhematuria. The patient presented a medical history of thrombocytopenic purpura treated and resolved by steroids in 2013, hypothyroidism, hypertension, ischaemic heart disease treated with surgical bypass in 2019 and pacemaker in 2020 for atrial ventricular block. Due to pandemic COVID 19 status, she received two doses of the Pfizer BioNTech mRNA COVID-19 vaccine in March 2021. Two weeks after the second dose her weight increased of 23 kg. The family physician added furosemide to her therapy for generalized edema with no diuretic effect. In April, creatinine was 1.38 mg/dL (versus 0.8 mg/dL 1 year before); urinalysis showed proteinuria (300 mg/dL) and microscopic hematuria; serum total cholesterol level was 218 mg/dL and triglycerides 178 mg/dL; then it was suggested to increase the doses of furosemide. In May 2021, creatinine resulted 2 mg/dL, serum albumin 2 g/dL, and urinalysis confirmed proteinuria and microscopic hematuria; proteinuria was 10 g/day. Abdomen ultrasound showed normal liver, kidneys and spleen, not ascites. Lower limb eco-Doppler showed right superficial femoral artery stenosis of 60% and absence of venous thrombosis. The physical examination evidenced anasarca. The patients were admitted to the nephrology unit; hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antigen and antibody were negative. Both complement C3 and C4 levels resulted within the normal range. Cryoglobulins were absent. Urinary Bence Jones, antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA), anti-double stranded DNA (nDNA) antibodies were negative. Antineutrophil cytoplasm antibodies (ANCA) were 1:2560 with Perinuclear pattern and anti-MPO positivity (716 UA/mL); anti-proteinase-3 antibodies (PR3) were negative. Anti-phosholipase A2 receptor antibody (PLA2R Ab) was positive with high titre. A kidney biopsy was performed showing a double nephropathy: a focal segmental glomerulosclerosis (FSGS) with some collapsing features, superimposed on membranous glomerulonephritis (Fig. 1). RESULTS We started the Ponticelli regimen (alternate months steroids and cyclophosphamide). After the first month of therapy, blood tests revealed creatinine 1.7 mg/dL, haemoglobin 11.7 g/dL; serum albumin 2.7 g/dL and urinalysis without microscopic haematuria. At the third month of therapy, the patient developed atrial fibrillation and started anticoagulation; blood tests were as follows: creatinine 1.1 mg/dL, serum albumin 3.0 g/dL, Ab anti-MPO 7 UA/mL and PLA2R Ab was absent. A left ocular, frontal and parietal herpes zoster induced a short discontinuation of therapy and responded well to Acyclovir; then we concluded the fourth month of therapy. At the fifth month, a SARS CoV 2 RT PCR unexpectedly resulted positive; the patient remained asymptomatic, but we stopped definitively the therapy. One month later, blood tests showed: creatinine 1 mg/dL, serum albumin 4 g/dL, proteinuria 0.7 g/die, MPO 2 UA/mL and PLA2R Ab absent. CONCLUSION To our knowledge, this is the first case of nephrotic sindrome secondary to a de novo MN and FSGS, associated with positive MPO antibody, following Pfizer–BioNTech mRNA vaccination COVID 19; the patient responded well to immunosoppression going in remission and regaining renal function.

Effect of vitamin D on myocardial remodeling and inflammatory status in children with congenital heart disease.

Vitamin D insufficiency is a common public health problem that is often unrecognized in children with congenital heart disease, and is not generally evaluated at congenital heart disease (CHD) follow-up. Recent studies have suggested that inadequate vitamin D status may have an adverse effect on cardiovascular health. This study investigates the relationship between vitamin D levels and hemodynamic parameters in children with CHD. Included in the study 40 patients (25 females, 15 males) with CHD, who were evaluated for Ross heart failure score, vitamin D, parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase (ALP), whole blood count (WBC) and echocardiographic measurements, and all measurements were repeated in the third month of the therapy. The mean vitamin D level was 16.4 ± 6.6 ug/L before and 27.5 ± 9.9 μg/L in the third month of therapy, while the mean PTH level was 53.3 ± 34.9 pg/mL before and 43.8 ± 21.4 pg/mL in the third month of therapy. The mean WBC was 8084 ± 2324/µL before and 7378±1893/µL in the third month of the therapy, and the mean platelet (PLT) count was 280,897 ± 80,119/µL before and 307,179 ± 60,202/µL in the third month of the therapy. The mean ejection fraction (EF) was 64% ± 7.2% before and 66.7% ± 6.2% in the third month of therapy, while the right ventricle (RV) myocardial performance index (MPI) was 32.1% ± 6.7% before and 28.9% ± 6.5% in the third month of the therapy. IL10 level was increased in four patients in the third month of therapy. A statistically significant decrease in PTH level and WBC, and an increase in PLT number and IL-10 level were detected by the therapy. Furthermore, echocardiographic findings revealed a statistically significant increase in EF and a decrease in RVMPI attributable to the therapy. The decreased levels of PTH, which is a proinflammatory marker, the increases in IL-10, which is an antiinflammatory cytokine, and the decreases in the number of WBC resulting from vitamin D treatment demonstrate the antiinflammatory effects of vitamin D. An improvement in EF means improvement in left ventricular contractility, while a decrease in RV MPI has been shown to improve the systolic and diastolic function of the right ventricle. These results suggest that vitamin D therapy has a positive effect on the heart, and so vitamin D levels should be evaluated during the routine follow-up of congenital heart disease.

The first experience of using upadacitinib in the treatment of rheumatoid arthritis in real clinical practice (results of the multicenter project “RACURS”)

Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice.Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice.Materials and methods. The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder.Results. During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (p<0.001). The goals of therapy (remission or low disease activity) by the 3rd month of therapy according to the combined indices of activity DAS28-ESR and DAS28-CRP reached 44.8 and 63.4% of patients, respectively, according to the SDAI index – 56.7%, according to the CDAI index – 25.9%. A pronounced improvement in joint function (70% improvement according to the criteria of the American College of Rheumatology) was noted by 33.3% of patients, population indicators of functional state (HAQ≤0.5) had 15.8% of patients. The difference in the HAQ index by the 3rd month of therapy compared to the indicator before treatment was –0.60 points. The quality of life, assessed by patients using the EQ-5D questionnaire, improved in 98.5% of patients, with a 70% improvement noted in more than a third of them (41.7%). The drug was well tolerated, no adverse reactions were registered by the 3rd month of therapy, all patients continued treatment.Conclusions. The first results of the use of UPA in RA patients with insufficient efficacy of previous therapy with DMARDs or GEBDs in real clinical practice indicate its efficacy and safety, an improvement in the functional state and quality of life of patients by the 12th week of the study.

Zadovoljstvo terapijom kod bolesnika sa dijabetesom melitusom tip 1 lečenim intenziviranom insulinskom terapijom analozima insulina

The outcome of diabetes treatments can and should be evaluated through the patients' treatment satisfaction. The aim of this study was to examine the patients' satisfaction with the therapy with human insulin analogues compared with previous treatment with human insulin. We evaluated patient satisfaction in patients with T1DM in our institution who were currently on IIT with human insulins. We performed testing with standard World Health Organization Diabetes Treatment Satisfaction Questionnaire (WHO DTSQ) before and after the therapy with insulin analogs. The overall DTSQ score in forty-nine patients after the third month of therapy and after the sixth month of therapy is higher than before the initiation of therapy (p < 0.001). The results of the responses on the perception of hyperglycaemia were lower after three months of therapy (p < 0.05) and after the six months of treatment than before the onset of therapy (p < 0.01). There were no differences in the perception of hypoglycaemia after three months; however, perception of hypoglycaemia after the sixth month of treatment was lower than before the onset of therapy (p < 0.001) and compared to the score after the third month of therapy (p < 0.01). Therapy of T1DM patients with insulin analogue aspart over three months led to an increase in satisfaction with therapy and a reduction of the perception of hyperglycaemia. Therapy of T1DM patients with insulin analogues (aspart and glargine) over three months led to an increase in satisfaction with therapy and a reduction of the perception of both hyperglycaemia and hypoglycamia.

Molecular response in long-term monitoring of patients with chronic myelogenic leukemia (CML) on nilotinib therapy

Targeted therapy with tyrosine kinase inhibitors (TKIs) was introduced for the suppression of BCR-ABL fusion protein in chronic myelogenic leukemia (CML) more than 50 years ago. The introduction of TKI was an elegant way to gain control over the disease and opened a horizon to the development of new and safer drugs to better manage the disease progression in CML patients. Although Imatinib (the first TKI) was highly effective for the treatment of CML, the lack of response in some patients and the development of resistance led to the introduction of a second-generation TKI, like Nilotinib (Tasigna®). This study aimed to show the molecular response to Nilotinib after a long-term monitoring of CML patients. We analyzed the molecular response rate of twenty-seven CML patients admitted to the Hematology Ward. All of them were subjected to multiple control measurements of Philadelphia chromosome once in at least three months’ period between January 2017 and March 2020. All patients showed a remarkable decrease in the level of the fusion gene’s expression. The highest drop in the expression level was detected after the first dose admission. Some of the patients even reached an expression of BCR-ABL below the detection limit and it was maintained stably low during further examinations. In our patients with CML, Nilotinib resulted in prolonged and deep molecular response. The expression level of BCR-ABL fusion gene showed a substantial decrease immediately after Nilotinib treatment, revealed as early as the third month of therapy.

The impact of medical therapy for benign prostatic obstruction on the health-related quality of life at tertiary hospital: A prospective study

Benign prostatic obstruction (BPO) is a common condition in older men that often result in lower urinary tract symptoms (LUTS). LUTS associated with Benign Prostate Enlargement (BPE) may have significant negative impact on patients’ health-related quality of life as can certain treatments for the condition. This study aimed to determine the impact of medical therapy on health-related quality of life among patients on treatment for BPO.This was a hospital based descriptive study carried out in urology public and private clinics from April to December 2017. All diagnostic and treatment options of patients were decided by attending clinicians of which Patients aged ≥40 years on medical treatment for BPO were included. Symptom and Health Related Quality Life (HRQL) were measured at baseline and at 3 months using the International Prostate Symptom Score (IPSS) and the Benign Prostatic Hyperplasia Impact Index score (BII) tools. A total 150 patients were included in the analysis with a mean age of 54), mean PSA of 4.45ng/ml and a mean prostate volume 54.62cc. Majority, 144(96.5%) had moderate and severe LUTS and 94(63%) men received a combination of tamsulosin and finasteride and 44(29%) men received tamsulosin alone: Medical therapy was associated with overall improvement of quality of life (p<0.001). A combination of tamsulosin and finasteride was associated with more adverse effects. Improvements in Quality of life (QoL) and symptoms were noted across the medical treatments most widely used in real-life practice at MNH to manage patients with BPO. Tamsulosin showed an equivalent efficacy to a combination of tamsulosin and finasteride at third month of therapy with fewer adverse effects.

P4558Hemodynamic management of resistant hypertension

Abstract Background Hypertension is the most prevalent chronic disease worldwide and is is related with high probability of cardiac disease, kidney disease and cerebrovascular events. Blood pressure measurement was used in the last decades to diagnose and guide antihypertensive therapy; however blood pressure is the result of interaction of more complex hemodynamic parameters previously reserved to experimental studies or critical care patients management using invasive methods. Since 1996 few studies has proposed the use of hemodynamic parameters to classify and guide hypertension therapy with good results. Purpose The present study purpose was to measure hemodynamic parameters in patients with non-controlled resistant hypertension and use it to guide pharmacologic treatment in order to archive control blood pressure values according to the European Society of Cardiology guidelines. Methods A total of 84 patients between 32 and 95 years old diagnosed with non-controlled primary resistant hypertension were recruited and after previous therapy washout hemodynamic parameters were measured using noninvasive methods: preload by central venous pressure (CVP) using inferior vena cava diameter, cardiac index and systemic vascular resistance using Lyljestrand & Zander modified formula. Patients were classified in 3 basic groups depending on which parameter was above normal value: hyperdynamic (HD) for high cardiac index >3.5 L/min/m2, fluid overload (FO) for CVP >8cmH2O and high systemic vascular resistance index (HSVRi) >2500 dynes/sec/m2/cm–5, also 3 combined groups were a patient had 2 simultaneous hemodynamic alterations (HD+FO, HD+HSVRi and FO+HSRVi), according to this classification pharmacotherapy was guided indicating Bisoprolol in HD group, Amlodipine to HSVR patients and Hydrochlorothiazide to FO patients, in combined groups, combined therapy was given. Patients were observed for 6 months period taking as primary endpoint blood pressure control, acute cardiovascular events and hypotension. Results A significant reduction of hemodynamic parameters and blood pressure was observed since the first month of treatment obtaining a 100% hemodynamic and blood pressure goals in all patients at the third month of therapy without hypotension or acute cardiovascular event during this period, the HD+FO group reach goals at the 6th month of treatment without reported complications. Conclusions In this preliminary studied we observed that hemodynamic guided high blood pressure control may be a useful tool to a better understanding, classifications and treatment in patients with resistant hypertension; however a larger outcome studies to confirm this hypothesis.

Двойное слепое рандомизированное плацебо-контролируемое исследование эффективности и безопасности комплекса ацетил-L-карнитина, L-карнитина фумарата и альфа-липоевой кислоты (СпермАктин® Форте) в лечении мужского бесплодия

Oxidative stress of sperm is a common pathologic condition, which can be detected in 30-80% infertile men. It is established that dietary consumption of antioxidants and microelements contributes to an increase of conception probability in subfertile couples, and also reduces the risk of reproductive losses. Drug complexes influencing various factors of spermatogenesis disturbance (oligo-, astheno-, teratozoospermia), oxidative stress and the level of sperm DNA fragmentation are of greatest and reasonable interest.To study the effects of complex acetyl-l-carnitine, l-carnitine fumarate and alpha-lipoic acid (SpermActin Forte) on oxidative stress, ejaculate quality and sperm DNA fragmentation in men with infertility.A total of 80 infertile men aged 25-40 years with increased level of sperm DNA fragmentation and oxidative stress were included in open-label, prospective, randomized study. In Group A (n=20) patients received a placebo for 180 days, and in Group B patients were prescribed to SpermActin Forte, 1 sachet of 10 g once a day. The criteria for the efficiency of therapy included sperm analysis, the level of sperm DNA fragmentation, the level of sperm oxidative stress, as well as information about achievement of pregnancy, obtained by interviewing all participants.In patients taking antioxidant complex SpermActin Forte there were significant positive changes in the main parameters of sperm analysis, including sperm mobility and morphology starting from the third month of therapy. The level of free oxygen radicals (as indicator of oxidative stress) in Group B also significantly decreased (by 86%). A more profound decrease in DNA fragmentation was seen in Group B compared to Group A (21.5% vs. 3.6%). Pregnancy was achieved in 1 and 13 cases in Group A and B, respectively.The use of the SpermActin Forte antioxidant complex allowed to improve sperm analysis in most patients, and these changes were significant starting from the third month of therapy. Stimulation of spermatogenesis using the antioxidant complex SpermActin Forte is an effective and safe method of treating male infertility.

Двойное слепое рандомизированное плацебо-контролируемое исследование эффективности и безопасности комплекса ацетил-L-карнитина, L-карнитина фумарата и альфа-липоевой кислоты (СпермАктин® Форте) в лечении мужского бесплодия

Oxidative stress of sperm is a common pathologic condition, which can be detected in 30-80% infertile men. It is established that dietary consumption of antioxidants and microelements contributes to an increase of conception probability in subfertile couples, and also reduces the risk of reproductive losses. Drug complexes influencing various factors of spermatogenesis disturbance (oligo-, astheno-, teratozoospermia), oxidative stress and the level of sperm DNA fragmentation are of greatest and reasonable interest. To study the effects of complex acetyl-l-carnitine, l-carnitine fumarate and alpha-lipoic acid (SpermActin Forte) on oxidative stress, ejaculate quality and sperm DNA fragmentation in men with infertility. A total of 80 infertile men aged 25-40 years with increased level of sperm DNA fragmentation and oxidative stress were included in open-label, prospective, randomized study. In Group A (n=20) patients received a placebo for 180 days, and in Group B patients were prescribed to SpermActin Forte, 1 sachet of 10 g once a day. The criteria for the efficiency of therapy included sperm analysis, the level of sperm DNA fragmentation, the level of sperm oxidative stress, as well as information about achievement of pregnancy, obtained by interviewing all participants. In patients taking antioxidant complex SpermActin Forte there were significant positive changes in the main parameters of sperm analysis, including sperm mobility and morphology starting from the third month of therapy. The level of free oxygen radicals (as indicator of oxidative stress) in Group B also significantly decreased (by 86%). A more profound decrease in DNA fragmentation was seen in Group B compared to Group A (21.5% vs. 3.6%). Pregnancy was achieved in 1 and 13 cases in Group A and B, respectively. The use of the SpermActin Forte antioxidant complex allowed to improve sperm analysis in most patients, and these changes were significant starting from the third month of therapy. Stimulation of spermatogenesis using the antioxidant complex SpermActin Forte is an effective and safe method of treating male infertility.

Assessment of potential predictive value of peripheral blood inflammatory indexes in 26 cases with soft tissue sarcoma treated by pazopanib: a retrospective study.

PurposeThe aim of this study was to evaluate the prognostic and predictive value of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (DNLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in soft tissue sarcoma (STS) cases treated with pazopanib.Materials and methodsThe study population included 26 STS cases treated with pazopanib for at least 3 months. NLR, DNLR, LMR, and PLR were evaluated at baseline, and at third month of therapy and also compared with response to pazopanib. Median measurements were taken as cutoff for NLR (4.8), DNLR (3.1), LMR (3.6), and PLR (195). The associations between these cutoff values and survival times (progression-free survival [PFS] and overall survival [OS]) were assessed by Kaplan–Meier curves and Cox proportional models.ResultsPatients with low pretreatment NLR and DNLR had longer OS (P=0.022, P=0.018), but low PLR was found to be associated only with longer OS. Additionally, decrease in NLR and DNLR after 3 months of therapy as compared with pretreatment measurements was found to be associated with an advantage for OS (P=0.021, P=0.010, respectively) and PFS (P=0.005, P=0.001, respectively). Response to pazopanib; changes in NLR, DNLR, LMR, and PLR; and >3 metastatic sites were found to be independent risk factors in univariate analysis, but NLR was the only independent risk factor in multivariate analysis.ConclusionLow pretreatment and decrease in NLR and DNLR values, and regression/stable disease after 3 months of pazopanib are predictive factors for longer OS and PFS.

Persistence and outcomes of non-vitamin K antagonist oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation.

To compare persistence and outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in Chinese patients with non-valvular atrial fibrillation (AF). Given the unpredictable warfarin response and the costliness of NOACs, more research is needed to clarify which drug enjoys better persistence and outcomes, helping to provide personalised care for patients. A prospective cohort study. Chinese patients taking NOACs or warfarin from March 2016-April 2018 were followed up by telephone or outpatient visit at 3, 6months and half a year thereafter. Anticoagulant persistence and outcomes including stroke and bleeding were collected. We used Cox regression to analyse data. This study was reported according to the STROBE guideline. A total of 344 patients were enrolled; 146 patients received NOACs including dabigatran and rivaroxaban, and 198 patients received warfarin. Persistence with anticoagulants was low and dropped sharply at the third month. Patients on NOACs had worse persistence at 3, 6 and 12months than those on warfarin. There was no difference in the incidence of ischaemic stroke and bleeding between groups, although ischaemic stroke and major bleeding occurred less frequently in the NOACs group. Paroxysmal AF, no heart failure and no stroke were predictors of NOACs non-persistence. Prior catheter ablation and no diabetes were associated with poor persistence of warfarin. The main reason for anticoagulant cessation was patient preference. Chinese patients taking NOACs had lower persistence, similar rate of ischaemic stroke and bleeding compared with those on warfarin. Further inventions are needed to improve persistence in Chinese patients on NOACs. Anticoagulation should highlight both persistence and outcomes emphasising personalised care of different drugs. Further interventions to improve persistence should be developed based on causes and risk factors and carried out in the third month of therapy.

Unique Experience of Cherubism Targeted Therapy

The family form of giant cell reparative granuloma or cherubism is a rare benign lesion of the jaws which causes face deformation reminiscent of the cherubs portrayed in Renaissance art. Radical surgery, especially in children before puberty, is impossible or irrational, because it leads to disablement. For four years, a child with cherubism was undergoing an outpatient supervision in the Department of Maxillofacial Surgery in Russian Children Clinical Hospital. During the observation period it was noted that tumor masses were slowly progressing leading to exoorbitism. The child had a diagnosis histological verification; a treatment using human monoclonal antibodies to RANKL was developed, adapted and approved by the ethical committee. The clinical effect was observed from the third month of therapy - jaws corners sharpened, the volume reduced. The control biopsy material taken at the end of the 6-month course did not reveal any giant cells which meant complete pathomorphism. Computed tomography showed that at the end of the therapy bone density increased by 6-7 times in the affected zones and was additionally growing over the next 6 months of observation. Such dynamics allowed making effective contouring surgery of excessive bone tissues. Inoperable and early stages of cherubism require a combined treatment which includes a course of monoclonal antibodies followed by alendronic acid therapy that increases osteoblasts survival. After the treatment, if it is necessary to improve the appearance, contouring surgery of excessive bone tissue is performed.

The Polycomb BMI1 Protein Is Co-expressed With CD26+ in Leukemic Stem Cells of Chronic Myeloid Leukemia.

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells). We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors. To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1, and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed. At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib. The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation. In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients.

The Efficacy of Cerebrolysin in Improvement of Spasticity in Children with Cerebral Palsy: A Clinical Trial

Background: Cerebral Palsy (CP) constitutes a heterogeneous group of developmental disorders resulting from damage to the brain which affects motor system. Cerebrolysin, as a neurotrophic peptide has been used for improving symptoms of patients suffering from neurodegenerative disorders. Objectives: Due to the presence of limited information about the usefulness of Cerebrolysin in CP, this study was performed for the evaluation of Cerebrolysin in the management of spasticity in children with CP. Methods: 26 Spastic CP patients aged between 2 and 6 years entered this study. At the first visit, Modified Ashworth scale for assessment of spasticity was used. Then Cerebrolysin was administered at a dose of 0.1 cc/kg intramuscularly (IM) for 3 months. In the first month, the medication was injected 5 times per week. In the second month of therapy, injections were performed as follows: 4 injections in the first week, 3 injections in the second week, 2 injections in the third week and a single one in the fourth week. In the third month of therapy, Cerebrolysin was continued as weekly injections. The spasticity of the patients was evaluated at the end of the first and third month of therapy. Results: Modified Ashworth score at baseline was 20.62 ± 9.65 which reached 15.19 ± 7.30 after 1 month of treatment. This figure was 14.81 ± 3.77 at month 3. Total decline in Modified Ashworth Scale was 5.42 ± 5.33 at the first month and 5.81 ± 2.74 at the third month in comparison to baseline. The difference between Modified Ashworth Scale at baseline and 1 month after therapy was significant (P = 0.000) but there was no significant difference between first month and third month of therapy. (P = 0.755). Also analysis indicates that there was an association between absolute reduction of Modified Ashworth score and the age at beginning of treatment (P = 0.037). Conclusions: Using Cerebrolysin as a neurotrophic peptide may improve spasticity of children with CP and should be considered as a possible useful treatment in CP cases. © 2018, Iranian Journal of Pediatrics.

Evaluation of the effect of 3-month bladder basic advice in children with monosymptomatic nocturnal enuresis

Advice (BBA) into the standards of patients' care in both monosymptomatic and non-monosymptomatic nocturnal enuresis. Although the idea of this recommendation was clear and reflects clinical experience, duration and efficacy have not been definitely established. Recent data have demonstrated the lack of efficacy of BBA and a fierce discussion has ensued. The present study was aimed to assess the efficacy of BBA in a group of previously untreated children with primary monosymptomatic nocturnal enuresis (MNE). The study was a prospective interventional multicenter trial in a cohort of previously untreated MNE patients. Forty-nine children (36 males, 13 females, mean age 7.2 years) were included in the analysis. The treatment efficacy was assessed at the 30th, 60th, and 90th days of BBA. We discovered that the mean number of wet nights decreased significantly (p<0.001) only after 3 months of BBA from 8.9 to 5.9 episodes every 2 weeks. BBA was fully successful in 2% o the children after 30 day, 12% after 60 days, and 18% after 90 days (Figure). Partial response (by ICCS) was assessed for 8%, 20%, and 34% of the patients. We noted a relatively high rate of non-responders that decreased from 90% to 47% after 90 days. We detected no differences in BBA efficacy between children with night-time polyuria or decreased maximal voided volume. A lower number of wet nights initially predicted the response to the BBA. Our study confirmed rather limited efficacy of BBA, similarly to previous observations, but provided more information on isolated MNE, because of a more specific study group and longer period of observation. The limitation of the study was lack of randomization. Our study revealed that in treatment-naïve children with monosymptomatic enuresis basic bladder training had a low (18%) and late effect, mostly pronounced after the third month of therapy. It seems that only if the patient presents with a favorable profile of bedwetting, occasionally and with a high maximum voided volume, it is worth maintaining BBA for a longer period of up to 3 months before initiating second-line therapy. In an unfavorable initial profile desmopressin or an alarm may be introduced much earlier.