Onset Of Remission Research Articles

T(11;14) with multiple myeloma: Standard risk survival but slow and poor response.

We described 790 patients with newly diagnosed multiple myeloma, including 224 (28.4%) standard risk (SR) patients without t(11;14), 99 (12.5%) patients with t(11;14)alone, 58 (7.3%) with t(11;14) + HR, and 409 (51.8%) in the high-risk cytogenetic abnormality (HRCA) group including t(4;14), t(14;16), t(14;20), C1A1 and/or del(17p) but without t(11;14), to evaluate the impact of t(11;14) in NDMM patients on response rate, response kinetics and survival. Our study showed that NDMM patients in the t(11;14)alone group had similar PFS (49.3 vs. 50.7months; P = 0.392) and OS (112.4 vs. NR months; P = 0.982) as those in the SR group. However, the t(11;14)alone group exhibited a significantly poorer depth of response compared to the SR group, particularly with a lower MRD negativity rate (60.0% vs. 76.0%, P = 0.009). In the t(11;14)alone group, MRD status did not significantly impact PFS or OS, which was in contrast to the other groups. Response kinetics analyses showed that the t(11;14)alone group had a slower response rate than the other subgroups (t(11;14)alone vs. SR vs. HRCA: median time to MRD negativity = 9.19 vs. 4.25 vs. 4.27 months; P < 0.001). Our study showed that t(11;14)alone was characterized by survival comparable to standard risk cytogenetics despite exhibiting the slowest timing of response onset and lowest plateau of remission, which suggested a relatively indolent clinical course.

Pleiotropicity of immunomodulating effects of synthetic thymic hexapeptide in chronic infectious and inflammatory diseases of the genital tract in immunocompromized women

A reason for a protracted course and frequent recurrence of pelvic inflammatory diseases (PID) is dysfunction of the immune system, which dictates the need of effective immunotherapeutic approaches. Objective: to clarify the features of immune system functioning, the interferon system, the profile of cytokines during the period of exacerbation of PID in women; to develop targeted immunotherapy using hexapeptide with assessment of its effectiveness. The studied immunocompromised women 20-40 years old with exacerbation of PID were divided into study groups (SG): SG1 (n = 22), SG2 (n = 70) before treatment; SG1a, SG1 receiving standard therapy; SG2a, SG2, receiving standard therapy and hexapeptide (HP, Imunofan®). The parameters of cellular and humoral immunity, levels of serum interferons, cytokines were determined. During exacerbation of PID, a decrease in IFNα was in both groups and IFNγ, more pronounced in SG1. In SG1, the levels of IL-6, TNFα were increased, the level of IL-8 was decreased. In SG2, the level of IL-6 was increased. An increase in IL-4, IL-10 was noted in both groups. Against the background of IFNα, IFNγ deficiency and cytokine imbalance, a significant decrease in T lymphocytes, T helper cells, B lymphocytes was observed in both study groups. After standard treatment, there was no recovery of IFNα, IFNγ. Only TNFα decreased, the levels of IL-1β, IL-6 were increased at the end of treatment, there was no increase in IL-4, IL-10 and restoration of cellular and humoral immunity. It leads to maintaining chronic inflammation and exacerbation of PID within 3 months after treatment. After immunotherapy including fHP, IFNα was restored in 50% cases. There was a decrease in IL-1β, TNFα without significant changes in the levels of IL-8, IL-18. Resolution of inflammation was accompanied by an increase in IL-10. The modulating effect of fHP on interferons and cytokines contributed to the restoration of T cell and humoral immunity, which is related to the onset of clinical remission of PID at an earlier time and an increase in the duration of the inter-relapse period. The positive effectiveness of immunotherapy with Imunofan® is due to its pleiotropic effects, which provides significant advantages compared to the use of standard therapy only.

The long shadow of early-change patterns: a 3-year follow-up after the use of a web-based intervention for mild to moderate depressive symptoms

ABSTRACT Web-based interventions can be effective in treating depressive symptoms. Patients with risk not responding to treatment have been identified by early change patterns. This study aims to examine whether early changes are superior to baseline parameters in predicting long-term outcome. In a randomized clinical trial with 409 individuals experiencing mild to moderate depressive symptoms using the web-based intervention deprexis, three latent classes were identified (early response after registration, early response after screening and early deterioration) based on early change in the first four weeks of the intervention. Baseline variables and these classes were included in a Stepwise Cox Proportional Hazard Multiple Regression to identify predictors associated with the onset of remission over 36-months. Early change class was a significant predictor of remission over 36 months. Compared to early deterioration after screening, both early response after registration and after screening were associated with a higher likelihood of remission. In sensitivity and secondary analyses, only change class consistently emerged as a predictor of long-term outcome. Early improvement in depression symptoms predicted long-term outcome and those showing early improvement had a higher likelihood of long-term remission. These findings suggest that early changes might be a robust predictor for long-term outcome beyond baseline parameters.

#2988 Use of rivaroxaban for prevention of thrombotic events in patients with nephrotic syndrome

Abstract Background and Aims Patients with nephrotic syndrome are at increased risk of thrombotic events. The risk of thromboembolism is particularly high in patients with primary membranous nephropathy, elderly patients and patients with severe hypoalbuminemia. Although increased incidence of thrombosis is a well reported complication associated with nephrotic syndrome, management strategies are not well established. Use of aspirin seems to be insufficient to prevent venous thromboembolism. Use of warfarin and low-molecular-weight heparins is inconvenient for outpatients. The aim of the trial was to evaluate effectiveness and safety of rivaroxaban in venous thromboembolism prophylaxis in patients with nephrotic syndrome. Method The randomized single-center trial was performed from October 2020 to November 2023. 30 adult patients with nephrotic syndrome due to primary glomerular diseases and glomerular filtration rate more than 60 ml/min were divided into two groups. The treatment group (n = 15) received 10-20 mg of rivaroxaban daily. The control group (n = 15) had no anticoagulation therapy. Thrombotic events and bleedings were recorded. Results Patients in both groups received immunosuppressive treatment of nephrotic syndrome according to primary disease. Rivaroxaban was prescribed for the entire treatment period until the onset of remission. Patients with membranous nephropathy were equally represented in both study groups (4 per group). No thromboembolic events were recorded in both groups. As well as there were no bleeding complications in patients who received rivaroxaban. Conclusion Rivaroxaban might be a possible alternative to warfarin and low-molecular-weight heparins in prevention of thrombosis in nephrotic syndrome. However, indications for anticoagulant prophylaxis, its duration and discontinuation are still not clear. Future studies should address the question regarding the utility of primary thromboprophylaxis.

A Real-Life 208 Week Single-Centred, Register-Based Retrospective Study Assessing Secukinumab Survival and Long-Term Efficacy and Safety Among Greek Patients with Moderate to Severe Plaque Psoriasis, Including Difficult-to-Treat Manifestations Such as Genitals and Scalp.

Psoriasis is a chronic inflammatory disease with multiple skin manifestations, and in case of lesions affecting the genital area, sexual health impairment and psychological distress can furthermore impair the patients quality of life. Secukinumab is a fully humanized immunoglobulin G1 kappa antagonist of IL-17A and is indicated for the treatment of moderate-to-severe psoriasis, since it shows a significant efficacy in clinical outcomes, with rapid onset of remission, prolonged treatment response rate, advantageous safety profile and a valuable improvement of the patients quality of life. This study was conducted in order to gather retrospective real-world data regarding the efficacy of secukinumab in treating patients with moderate-to-severe plaque psoriasis in Greece. To fill the relevant literature gap, we included difficult-to-treat manifestations in our analysis, specifically regarding the efficacy in the genital area and on the skin folds where relevant data are missing both from the drug clinical program as well as from the real-world setting. All adult patients receiving 300 mg secukinumab and attending follow-up visits on a regular basis, according to routine medical practice were included. The timeline of the study was from 2015 to 2020. Primary endpoint of the study was the percentage of patients who achieved a psoriasis area and severity index (PASI) 75 response rate at week 16 and week 52 post baseline. Secondary endpoints were the evaluation at baseline (week 0), week 4 (±1), week 16 (±1), week52 (±1), and week 104 (±1), week 156 (±1), week 208 (±1) of clinical outcomes, incidence of adverse events and potential predictive variables influencing response rate. Ninety-nine patients were included in the study population, from whom sixty six patients (66.67%) were bio-naive, whereas 33 patients had never received systemic treatment. Regarding difficult-to-treat manifestations, we recorded scalp involvement in 74.74% (74/99) of our patients, genital psoriasis in 27.27% (27/99) and skin folds involvement (psoriasis inversa) in 17% (17/99). At week 16, PASI75/PASI90/PASI100 were observed in 87.5%/69.8%/49%, respectively. At week 4 lesions affecting the genital area and patients with skin fold involvement experienced a rapid regression and 84.1% of patients achieved sPGA 0/1 (Physician Global Assessment). Treatment with secukinumab during the 208 weeks of observation did not reveal any major adverse event or systemic infection and generally it was well tolerated. According to our outcomes secukinumab is an effective treatment choice for treating chronic plaque psoriasis, but, additionally, it can be efficacious in the subgroups of patients with difficult-to-treat manifestations, as our patients experienced great improvement starting even 5 weeks after treatment initiation. This real-life study offers information about clinical efficacy, retention and safety profile of secukinumab in patients from everyday clinical practice over a long-term, 4-year, follow-up period in Greece.

Increased Th17 and Treg levels in peripheral blood positively correlate with minimal residual disease in acute myeloid leukaemia.

Immune dysregulation plays a key role in acute myeloid leukemia (AML). We aimed to explore the correlation between T helper cell 17 (Th17) and the regulatory cells (Tregs) in the peripheral blood of patients with newly diagnosed (ND) AML and bone marrow blast cells, as well as minimal residual disease (MRD) before and after treatment. Changes in Th17 and Treg cells in the peripheral blood of 32 patients with ND AML were observed before and after induction chemotherapy with cytarabine for seven days and anthracycline for three days. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. Correlation analysis between bone marrow blast cells and Th17 and Treg cell frequencies was performed using the Pearson's correlation test. Frequencies of Th17 and Treg cells and MRD were assessed using flow cytometry. IL-6, IL-10, IL-17A, and GM-CSF levels gradually increased in patients with ND AML and CR and NR patients. The percentages of Th17 and Treg cells positively correlated with those of blast cells. In addition, the frequencies of Th17 and Treg cells in MRD-positive patients were higher than those in MRD-negative patients at the initial induction and after three months of chemotherapy. The frequencies of Tregs and Th17 cells positively correlated with MRD onset. Increased Th17 and Treg cell levels were positively correlated with onset of AML, poor remission, and MRD.

The natural course of idiopathic cervical dystonia.

Idiopathic cervical dystonia (ICD) is by far the largest subgroup of dystonia. Still, its natural course is largely unknown. We studied the natural course of 100 ICD patients from our botulinum toxin clinics (age at ICD onset 45.8 ± 13.5years, female/male ratio 2.0) over a period of 17.5 ± 11.5years with follow-ups during botulinum toxin therapy and with semi-structured interviews. Two courses of ICD could be distinguished by symptom development of more or less than 6months. ICD-type 2 was less frequent (19% vs 81%, p < 0.001), had a more rapid onset (8.7 ± 8.0weeks vs 3.8 ± 3.5years), a higher remission rate (92% vs 5%, p < 0.001) and a higher prevalence of excessive psychological stress preceding ICD (63% vs 1%, p < 0.001). In both ICD-types, the plateau phase was non-progressive. Significant differences in patient age at ICD onset, latency and extent of remission, female/male ratio and prevalence of family history of dystonia could not be detected. ICD is a non-progressive disorder. ICD-type 1 represents the standard course. ICD-type 2 features rapid onset, preceding excessive psychological stress and a high remission rate. These findings will improve prognosis, treatment strategies and understanding of underlying disease mechanisms. They contradict the widespread fear of patients of a constant and continued decline of their condition. Excessive psychological stress may be an epigenetic factor triggering the manifestation of genetically predetermined dystonia.

Remission of type 2 diabetes mellitus in a patient with obesity and hypogonadism

Currently, obesity is the main risk factor for the development of type 2 diabetes mellitus (type 2 diabetes) as a key link in the emergence of insulin resistance. Traditionally, the basic strategy for controlling type 2 diabetes is to normalize blood glucose levels by correcting lifestyle and lifelong use of oral and/or injectable hypoglycemic therapy. However, in recent years, doctors and researchers are increasingly turning to the possibility of remission of type 2 diabetes. Remission of diabetes mellitus is the preservation of normal values of glycemia with the complete abolition of hypoglycemic therapy (tablet or injection). Many studies reflect that lifestyle changes, such as weight loss, dieting and increased physical activity, contribute to the onset of remission of type 2 diabetes in a significant number of people. In this clinical case, we demonstrate the possibility of achieving remission of diabetes mellitus with a multifactorial approach to the treatment of type 2 diabetes mellitus, which causes stabilization of blood glucose levels, prevention of complications and improvement of quality of life, and thus, we exhibit new prospects in the treatment of this disease.

Trajectories of remitted psychotic depression: identification of predictors of worsening by machine learning.

Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory. One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics. Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model. Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Optimization of treatment of vulvar scleroatrophic lichen with using modern laser technologies

Background. Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis, which is characterized by focal skin atrophy of the vulva and mucous membranes. It leads to deformation of the perineum. The prevalence of VLS in children is up to 0.1%, among the adults — 3%. The average age of the first symptoms appearance in girls is 5.4 years, in women — 55.1 years. The diagnosis of VLS is made on the base of anamnesis, assessment of pubertal development, physical examination of the external genitalia, advanced vulvoscopy and vaginoscopy, bacteriological, bacterioscopic and cytological studies of vaginal wet mount, assessment of the hormonal profile. The treatment methods include high-potency steroids as the initial treatment, usage of diode, fractional CO2 and erbium lasers with different wavelengths and injections of platelet-rich plasma to improve the regeneration processes of the affected tissue by improving collagenogenesis, vasculogenesis, production of proteoglycans and glycoproteins.&#x0D; The aim of the study is to compare the effectiveness of photodestruction with a manual diode laser of the Dornier Medilas D LiteBeam, wavelength of 940 nm, minimum power in pulsed mode on the girls’ vulva mucosa with various types of VLS during neutral and preadolescent age. To obtain the results there were analyzed criteria including the size of the lesion after photodestruction therapy, the disappearance of cracks and angiomatosis in the LS area. The objectives of the complex therapy of VLS in girls were elimination of itching, decrease of the inflammatory changes, improvement of the skin and mucosa blood supply, and stimulation of local immunological mechanisms.&#x0D; Materials and methods. The study was conducted on the base of the gynecological department of Russian Children’s Clinical Hospital. The effectiveness of the laser-induced thermotherapy with a wavelength of 940 nm, minimum power in pulsed mode on the vulva of VLS girls of neutral and preadolescent periods as a part of the complex therapy was evaluated. Ninety 5 to 13 year VLS patients took part in the trial. They were divided into 3 groups. The first group included 30 patients (average age 7.5 ± 1.1) with atrophic form of lichen treated with a laser with a wavelength of 940 nm. The second group consisted of 30 patients (average age 6.8 ± 1.3) with erythematous-edematous lichen, who were treated with a laser with a wavelength of 635 nm. The third group included 30 patients (average age 7.3 ± 1.2) with erosive and ulcerative form of VLS, who received high-potency corticosteroids therapy. &#x0D; Results. The treatment results in the three subgroups of VLS patients show a diode laser with a wavelength of 940 nm therapy to be the most effective. After the first treatment course 27 (90%) patients in the first group showed a positive trend with a decrease in itching and burning, pink-color presence in vulva mucousа, a decrease of the skin pigmentation area and an increase in the elasticity of the skin. After 2 courses, 29 (96.7%) patients had positive trend. The second most effective method of treatment is photodestruction with a 635 nm wavelength laser. After the 4 courses (two hospitalisations), 25 (83,3%) patients noted a decrease in itching and in a “tightening” feeling. In 24 (80%) patients there was an improvement in the condition of the mucous membranes of the vulva. Reduction of edema was observed in 23 (76.7%) patients by the time of an examination in 3 weeks after the last therapy course. However, it was not possible to completely restore the mucous membranes of the vulva in patients of this group. The least effective — drug therapy with high-potency steroids. 8 (26.7%) patients noted positive dynamics only by the 4th day therapy, 11 (36,7%) by the time of the 3 weeks after the initial application of the ointment, 12 (40%) by the 2nd month. In 5 (16.7%) patients, the visible condition of the mucous membranes did not change, the number of bleeding ulcers decreased minimally.&#x0D; Conclusions. The results of the trial indicate the high efficiency of laser therapy of VLS in children compared with the topical glucocorticoids treatment. The duration of the therapy and condition of the external genitalia after treatment depends on the histological form and stage of VLS. According to our study, laser therapy contributes to the remission onset in pediatric patients with different types of VLS in the shortest possible time after the photodestruction procedure.

415 Efficacy of 2% crisaborole ointment in 49 patients of atopic dermatitis with chronic hyperplasia lesions: a real-world study

Abstract Asian Atopic dermatitis (AD) presents as a mixed phenotype between the European American (EA) AD and psoriasis phenotypes, with highly atypical features for AD, including clearer demarcation of lesions, with more prominent scaling, lichenification, parakeratosis, hyperplasia and a unique cytokine profile with coactivation of the TH2 and TH17 axes. The cutaneous immune dysregulation in Chinese patients with AD usually exhibit remarkable increase in epidermal hyperplasia and parakeratosis, frequently observed in areas such as the hands, feet, knees and elbows. Currently, the response of chronic hyperplastic lesions to various conventional treatment modalities, including topical corticosteroids and topical calcineurin inhibitors, is not optimistic and often accompanied by various complications. As a Phosphodiesterase 4 (PDE4) inhibitor, crisaborole broadly inhibits inflammatory signaling pathways, and has demonstrated definite efficacy in AD partly due to its smaller molecular weight and higher transdermal absorption efficiency. This study aims to find the clinical efficacy of 2% crisaborole ointment monotherapy for chronic hyperplastic lesions of AD in real-world research in China. We retrospectively enrolled 49 patients with AD aged 12 years or older with chronic hyperplastic lesions and an Investigator’s Static Global Assessment (ISGA) score of mild or moderate. The patients were administered with 2% crisaborole ointment for twice-daily application until the complete clearance of lesion. The efficacy endpoints comprised the onset time of pruritus and lesion remission, and the time of complete lesion clearance. A 1-grade or more improvement of the VAS scores from baseline was defined as the pruritus remission. An improvement of 1 point or more of the ISGA scores was indicative of improved skin lesions. The ISGA score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline indicated complete remission of skin lesions. After subgrouping the patients by age and AD duration, we further compared differences in efficacy endpoints to explore potential influencing factors on the effectiveness of crisaborole. Two percent crisaborole ointment showed good efficacy for treating chronic hyperplasia lesions in Asian patients with AD, with minor irritation, early remission of pruritus [7.0 ( 3.0, 10.0) days] and lesions [7.0 (5.0, 10.0) days]. The median time for complete lesion clearance was 30 days. Two percent crisaborole ointment showed different efficacy in the different age. The onset of pruritus remission appeared to be more rapid in the elderly [2.0 (1.0, 10.0)] compared with the adolescents [4.0 (2.3, 6.5)] and the adults [7.0 (3.5, 10.0)], but with no statistically significant difference (P = 0.072). The adolescents had an earlier onset of lesion remission by approximately 3 days compared with the adults and the elderly (P = 0.044). Although the onset of pruritus remission for the adolescents and the adults was similar to their onset of lesion remission, the elderly seemed to experience significantly earlier pruritus remission compared with their lesion remission onset. There was no statistical difference in complete lesion clearance time among different age groups (P = 0.019). Commonly seen in Asian patients with AD, chronic hyperplasia lesions generally do not respond well to other topical medications. Two percent crisaborole ointment monotherapy is an effective treatment for chronic hyperplasia lesions in patients with AD of all age groups, and onset of pruritus and lesion remission is different in the different age group.

АКТУАЛЬНЫЕ ВОПРОСЫ ДИАГНОСТИКИ И ЛЕЧЕНИЯ АТИПИЧНОГО ГЕМОЛИТИКО-УРЕМИЧЕСКОГО СИНДРОМА: ОПЫТ ВЕДЕНИЯ ПАЦИЕНТОВ В ЧЕЛЯБИНСКОЙ ОБЛАСТИ

Atypical hemolytic-uremic syndrome (aHUS) is a rare systemic life-threatening disorder with an unfavorable prognosis and progressive course and is based on chronic uncontrolled overactivation of the alternative complement pathway of hereditary (gene mutations with loss of function of complement regulators/activators) or acquired nature (antibodies to factor H), which leads to the development of a systemic complement-mediated form of thrombotic microangiopathy (TMA). The pathomorphological essence of TMA is the development of endotheliosis, which in its turn triggers the activation of the coagulation cascade with the formation of platelet-fibrin thrombi, partially or completely occluding the lumen of the vessels of the microvasculature (small arteries and arterioles). The therapeutic approach to aHUS has been improved with the introduction of eculizumab, a humanized monoclonal antibody, into clinical practice. Eculizumab has a high affinity for the C5 component of complement and, by binding to it, completely blocks the splitting of C5 into C5a and C5b. As a result, the formation of pro-inflammatory cytokines is inhibited by blocking the formation of C5a and the membrane attack complex (MAC) by blocking the formation of C5b. This therapy improves the prognosis of the disease and reduces the risk for development of the life-threatening conditions, including end-stage chronic kidney disease (CKD). The Article represents the analysis of the Authors’ own clinical experience with aHUS in the region of the Chelyabinsk Oblast of Russia. The diagnosis of aHUS was based on a combination of microangiopathic non-immune hemolytic anemia, thrombocytopenia, and acute kidney injury, after excluding other forms of TMA. Most often, aHUS in the form of clinical manifestations of TMA was diagnosed in pediatric patients during the first 3 years of life (67%). Both pathogenic and possibly-pathogenic mutations associated with the development of aHUS were detected in 56% of cases. These included mutations in the CFH, CFI, C3 genes, heterozygous deletion of CFHR1/CFHR3. Eculizumab had demonstrated its high efficiency accompanied by the restoration of diuresis, a decrease in the severity of arterial hypertension, a rapid suppression of hemolysis activity and the signs of active TMA. Throughout the course of treatment, all patients maintained hematological remission coupled with the absence of necessity for continuing extracorporeal therapy. Conclusion: the onset of remission of aHUS against the background of complement blocking therapy with eculizumab confirmed the correctness of the established diagnosis and the chosen treatment tactics.

Non-invasive assessment of ulcerative colitis activity when choosing a treatment regimen

In recent decades, there has been a steady increase in the incidence of ulcerative colitis worldwide. The purpose of the work was to analyze the literature data on modern features of the treatment of ulcerative colitis, as well as to present our own results and cases from practice. Mesalazine remains the mainstay of remission and often its induction in patients with ulcerative colitis. Currently, the nature of the treatment of ulcerative colitis is determined by the target level of remission. The fact of the onset of endoscopic remission is known to occur much later than subjective clinical improvement. In recent years, this provision has been supplemented by evidence of a delay in histological, laboratory (fecal calprotectin) and transmural remission from endoscopic. There is increasing evidence that the duration and quality of remission depends on the depth of remission. When using ultrasound, it is not difficult to urgently assess the activity and prevalence of inflammation by the parameters of the intestinal wall. Together with the level of fecal calprotectin, this information may be key to the choice of induction, escalation, maintenance or de-escalation treatment options. Of course, endoscopic examination with colon biopsy remains a necessary planned component of the management of a patient with ulcerative colitis. There are 3 cases from practice in which the achievement of transmural remission was carried out during the treatment with mesalazine. The possibility of monitoring the activity of the inflammatory process and its prevalence in the colon with the help of ultrasound examination of the intestinal wall has been clearly demonstrated. According to the results of our study, it was found that with a high activity of the disease according to the scale of Doppler mapping of the colon wall (Limberg 4), an erosive-ulcerative process was recorded in all patients according to the results of endoscopic examination (Mayo 3). Detection of the normal intestinal wall on the echogram in all cases was accompanied by the absence of endoscopic activity (Mayo 0) or its minimal manifestations (Mayo 1).

Acute Myeloid Leukemia Causes Serious and Partially Irreversible Changes in Secretomes of Bone Marrow Multipotent Mesenchymal Stromal Cells.

In patients with acute myeloid leukemia (AML), malignant cells modify the properties of multipotent mesenchymal stromal cells (MSCs), reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the role of MSCs in supporting leukemia cells and the restoration of normal hematopoiesis by analyzing ex vivo MSC secretomes at the onset of AML and in remission. The study included MSCs obtained from the bone marrow of 13 AML patients and 21 healthy donors. The analysis of proteins contained in the MSCs-conditioned medium demonstrated that secretomes of patient MSCs differed little between the onset of AML and remission; pronounced differences were observed between MSC secretomes of AML patients and healthy donors. The onset of AML was accompanied by a decrease in the secretion of proteins related to ossification, transport, and immune response. In remission, but not at the onset, secretion of proteins responsible for cell adhesion, immune response, and complement was reduced compared to donors. We conclude that AML causes crucial and, to a large extent, irreversible changes in the secretome of bone marrow MSCs ex vivo. In remission, functions of MSCs remain impaired despite the absence of tumor cells and the formation of benign hematopoietic cells.

The effectiveness of two-stage surgical treatment of children with complicated Crohn’s disease

Introduction. Crohn’s disease (CD) is an inflammatory disease of the digestive tract of unknown etiology with segmental transmural inflammation of various parts of the gastrointestinal tract. The annual increase in the number of children with newly diagnosed CD, late diagnosis and untimely surgical treatment is one of the urgent problems due to the lack of a single algorithm of surgical treatment.&#x0D; The aim: to determine the effectiveness of surgical treatment of CD in children.&#x0D; Materials and methods. The study included thirty six patients with complicated CD Over the period from 2018 to 2022, a re­trospective and prospective analysis of children who received medical care for CD with two-stage surgical treatment (resection of the affected area with enterostomy and subsequent restoration of gastrointestinal continuity) was carried out. &#x0D; Results. Clinical activity according to Pediatric Crohn’s Disease Activity Index (PCDAI) in 23 (63.8%) children before treatment was recorded as high (30.0–75.2 points), in 15 (36.2%) children had average activity (11–29 points). After the staged surgical treatment, there was a change in the indicators — the onset of remission in 2 (5.5%) children and in 34 (94.5%) mild course &#x0D; (p &lt; 0.05). Statistical analysis of anthropometric indicators revealed positive changes (HAZ p &lt; 0.05 and BAZ p &lt; 0.001) with increase in weight and height criteria. Assessment of laboratory dynamics revealed positive changes (p &lt; 0.001) — the absence of anemia, hypoalbuminemia and relief of bacterial inflammation. CD debuted before the age of 10 years in 7 children (19.4%), aged 10 to 16 years — in 29 (80.5%). In 24 (66.7%) children, genetic engineering biological therapy (GEBT) at the time of the development of surgical complications was not performed, from them 15 (62.5%) received hormonal and immunomodulatory therapy while it was not effective, while for 9 (37.5%) patients the timely verification was diagnosed at the stage of development of CD complications. However, the development of surgical complications was noted in 12 (33.3%) children, despite the timely verification and appointment of treatment for genetic engineering biologic therapy (GEBT). Biological therapy was continued for 7 (58.3%) children who received GEBT before surgery, and in 5 (41.7%) patients, treatment was continued with a change of GEBT. The period of stay with a stoma was found to be from 7 to 31 months (Me = 8).&#x0D; Conclusions. In complicated forms of CD in children, despite drug therapy, including GEBT, the development of complications requiring surgical treatment was noted, which indicates an aggressive and progressive course of CD. However, the use of stage-by-stage surgical treatment showed efficiency due to the positive dynamics of anthropometric indicators, laboratory markers, the potency of surgical treatment, and made it possible to achieve stable remission against the background of specific therapy and improve the quality of life in CD children.

Complete remission in children and adolescents with type 1 diabetes mellitus—prevalence and factors

Little is known about complete remission in Type 1 diabetes mellitus (T1D) with the discontinuance of insulin treatment for a period of time. In this retrospective study we analysed the frequency and factors of onset and duration of 1. remission and 2. complete remission in children and adolescents with T1D from the Children Diabetes Centre in Bratislava, Slovakia. A total of 529 individuals with T1D, aged < 19 years (8.5 ± 4.3 years) at diabetes onset were included in the study. Remission was defined by HbA1c < 7.0% (53 mmol/mol) and an insulin daily dose < 0.5 IU/kg (and 0 IU/kg for complete remission). Remission occurred in 210 (39.7%) participants, and 15 of them had complete remission (2.8% from all participants). We have identified a new independent factor of complete remission onset (higher C-peptide). Complete remitters had a longer duration of remission compared with other remitters and also differed in lower HbA1c levels. No association was seen with autoantibodies or genetic risk score for T1D. Thus, not only partial but also complete remission is influenced by factors pointing toward an early diagnosis of T1D, which is important for better patient outcome.

Three-stage surgical treatment for colon lesions in children with Crohn's disease. Retrospective-prospective study

Background. Crohn's disease (CD) in children is characterized by a more severe and progressive course, with the development of a form that is not susceptible to drug therapy, and the development of surgical complications. Up to 50% of cases, inflammation is localized in the ileocecal region. Isolated inflammation of the colon is diagnosed in the smallest number of patients with Crohn's disease, in adults from 18.1 to 28.3%, in pediatric patients from 5.1 to 24.4%.&#x0D; Aim. To substantiate the effectiveness of three-stage surgical treatment in children with colon lesions in CD.&#x0D; Materials and methods. From 2018 to 2022, 75 children with complicated Crohn's disease underwent surgical interventions in the National Medical Research Center for Children's Health. A single-stage retrospective-prospective study of 7 (9.3%) children with isolated colon lesion was conducted. Four (57%) children stenosis in the left colon; 3 (43%) children continuously recurrent inflammation of the colon, not amenable to drug therapy. The effectiveness of staged surgical treatment was evaluated after 6, 12, 18, 24 months based on statistical analysis of clinical, endoscopic and laboratory activity of CD, changes in anthropometric indicators.&#x0D; Results. In 4 children, the onset of remission was noted, and in 3 children, clinical activity was mild (p0.05). The onset of endoscopic (p0.05) and laboratory remission (p0.05) was noted in all children. The assessment of the growth-to-age ratio also showed statistically significant positive dynamics, however, when assessing the ratio of body mass index to age, no statistically significant changes were detected (p=0.066).&#x0D; Conclusion. Isolated colon lesion is the rarest phenotype in children with CD. The formation of colon stricture requires surgical treatment, but predicting the volume of surgical treatment at the preoperative stage is a difficult task. The chosen tactics of conducting surgical treatment in three stages, with the correction of drug therapy after disconnecting the colon from the digestive tract, allowed not only to avoid postoperative complications associated with the formation of an anastomosis on the affected intestinal wall, but also to achieve remission of the disease.

Лікувально-профілактичні підходи до хворих на псоріаз після перенесеної коронавірусної інфекції

The results of preliminary observations indicate that the SARS-COV-2 virus can also affect the skin and affect the course of chronic diseases, including dermatoses. The cause and pathogenesis of skin manifestations have not yet been established and are under study, but they are most likely caused by infectious and allergic damage to blood vessels, as well as a high level of pro-inflammatory cytokines. The subject is to increase the effectiveness of the therapy of patients with psoriasis after suffering from the coronavirus disease by using drugs that affect the state of the endothelium of blood vessels and the blood coagulation system. Materials and methods. 69 patients with psoriasis associated with COVID-19 infection were under observation. The patients were divided into two clinical and therapeutic groups, which were representative in terms of age, sex, and severity of the disease: The first experimental group (36 patients) in complex treatment received drugs that had an effect on the normalization of endothelial dysfunction and the blood coagulation system. Patients of the II group (33 persons) received treatment according to the protocols. The control group consisted of 20 practically healthy persons, representative in terms of age and sex. Control of the treatment was carried out on the basis of clinical and laboratory data. Subjective and objective signs of the disease were evaluated, clinical and biochemical indicators were determined, including a general blood test, the state of the coagulation system using modern standardized laboratory tests. The degree of inflammatory reaction was assessed by the level of C-reactive protein and IL-6. Statistical processing of data was carried out using methods of variational statistics. Significance of differences was assessed using Student’s test for independent samples. The results. When using drugs that had an effect on the normalization of endothelial dysfunction and the blood coagulation system, in the complex treatment of patients of the 1st group, a significant improvement in the general condition was noted, a decrease in the subjective symptoms of the disease: itching, dryness, soreness in the foci of inflammation, which decreased 3–4 days earlier, than in patients from the comparison group who received traditional therapy. Clinical remission in patients of the I group occurred in (22.3 ± 2.7) days, while in patients in the II group – in (29.2 ± 3.5) days, that is, 6.9 days earlier (p &lt; 0, 05). The use of the proposed treatment-prophylactic approach improved the parameters of the blood coagulation system in patients with psoriasis who suffered a coronavirus infection, which was manifested by the normalization of AChT, PTI, fibrinogen content and a significant decrease in D-dimer, which indicates a probable reduction in the risk of thrombotic complications. At the same time, there was a significant decrease in inflammation indicators – PSA and IL-6. Conclusions. The use of the proposed treatment-prophylactic approach contributed to an earlier onset of clinical remission: the subjective and objective signs of the disease stopped almost 7 days earlier than in patients treated only by traditional methods, normalization of indicators of the state of the coagulation system, endothelial dysfunction, which prevented development of complications from the cardiovascular system.

Psychological predictors of favorable and unfavorable disease course of prostate cancer: results of a pilot study.

The statistical data on the incidence and mortality rates from prostate cancer leavegaps in understanding the causal risk factors for the unfavorable course of the disease determined the relevance of this work, determined the purpose of the study: to identify psychological predictors of favorable and unfavorable courses of prostate cancer. Basic beliefs, coping, quality of life, level of subjective control, resilience, life orientation, as well as socio-demographic characteristics were analyzed in 124 men with different courses of the disease. Firstly, the psychological characteristics of men with prostate cancer with a favorable or unfavorable course were compared, and secondly, psychological predictors were identified and their contribution to the course of prostate cancer was assessed. It has been established that high involvement as an indicator of resilience, externality in the sphere of failures, the absence of restrictions on daily life due to physical condition, and a low value of belief about control is associated with a favorable course of the disease. The involvement of a man in his own life and ongoing events, interest in his own activities, the conviction that not all events can be controlled, as well as the localization of control outside, contribute to a faster onset of remission or stabilization of the disease. The psychological features determine the behavior of men with prostate cancer, including the implementation of doctor's recommendations and compliance with treatment requirements, timely visits to the doctor, taking medications, which in turn determines the course of the disease and the success of treatment.

Brestfeeding and Genetic Features of Juvenile Rheumatoid Arthritis

The article describes the clinical and genetic features of juvenile rheumatoid arthritis and the consequences of the disease after treatment with chronotherapy. The clinical features of the disease, the results of laboratory analysis are important when choosing an effective treatment method. An effective treatment method is characterized by a faster onset of remission, an extension of its duration and a decrease in the side effects of drug treatment. The benefits of breastfeeding for babies are well known, but there is growing evidence that breastfeeding has a positive impact on a mom's health as well. Research shows that breastfeeding lowers a risk for juvenile rheumatoid arthritis.