Prospective Open-label Study Research Articles

No evidence for an association of voxel-based morphometry with short-term non-motor outcomes in deep brain stimulation for Parkinson’s disease

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson’s disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Preoperative morphometry-based metrics have recently received increasing attention to explain treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. Forty-nine PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating volume loss of the superior frontal cortex with subpar motor outcomes. Overall non-motor burden, however, was not significantly associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling.

A study of potency determination of 3C antimuonium crudum in the treatment of corn

Background: Planter skin is anatomically different from the normal skin of the body due to prominence of keratin filaments such as k6, k7, k9, k16 and k17. As per Hahnemann statement in chronic disease, Antimuonium crudum is basically the native ore (persulphuric of antimony) found in blocks of parallel block needle with a metallic lustre and are composed of twenty-eight parts of sulphur combined with 100 parts of metallic antimony. Methods: An observational comparative prospective open label study was conducted from September 2019 to September 2020. 32 patients were included in the study. Follow up of the cases were done after every 15 days where the size of the corn was measured using a vernier caliper. Height, width and diameter of the corn was also measured pre and post-treatment to analyse the results. Results: A total of 32 patients were studied. The size of the corn was considerably reduced after taking the medication. There was a significant reduction in the intensity of the pain due to corn after medication as well. Conclusions: There is a significant reduction of disease intensity score, after the homoeopathic treatment. Which shows the efficacy and potency of 3C Antimuonium crudum in the treatment of corn.

A prospective open-label study to evaluate the effectiveness of intravenous ketamine as an adjunct in treating severe depression

BackgroundKetamine, an emerging pharmacotherapeutic agent for depression, has demonstrated rapid and substantial improvement in mood and suicidal ideation, particularly in severe cases. While previous studies have established its efficacy, the current study aims to delve into the effectiveness of intravenous ketamine in treating severe depression.MethodsAn open-label prospective study enrolled 49 consecutive patients with severe depression. Baseline assessments using the Hamilton Depression Rating Scale (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Modified Scale for Suicidal Ideation (MSSI) were conducted. Intravenous (IV) ketamine, administered at 0.5 mg/kg in 100-ml normal saline over 40 min, was given during sessions spaced on alternate days. Each patient received at least five sessions alongside their regular antidepressants. Close monitoring occurred during the infusion, and disease rating scale scores were recorded. Data was analyzed; employed paired Student t-test and graphical were used for visual clarity.ResultsFollowing the initiation of IV ketamine, a significant reduction in scores was observed from baseline. Response rates were achieved in over half of the patients by the third session and in nearly all by the end of fifth session. Remission rates were attained in nearly half of the patients by the fourth session and in almost all by the fifth session.ConclusionsIV ketamine could be considered as an adjunct to antidepressants in treating severe depression especially among those with suicidal ideations to obtain rapid improvement. However, the need for long-term studies is emphasized to determine the duration of its effect.

Oxygen-ozone therapy for pain relief in patients with trapeziometacarpal osteoarthritis: a proof-of-concept study

Purpose Trapeziometacarpal osteoarthritis (TMC-OA) is a prevalent hand disorder affecting a growing number of people worldwide. While a multidisciplinary approach might provide additional advantages, the analgesic and anti-inflammatory role of intra-articular oxygen-ozone (O2O3) injections combined with physical therapy is still unknown. To assess the impact of a multimodal therapeutic approach combining O2O3 injections with physical therapy in patients with TMC-OA. Materials and methods A prospective open-label study conducted in the Physical and Rehabilitation Medicine Unit of the "Renato Dulbecco" University Hospital of Catanzaro. We assessed patients with TMC-OA who had not responded to standard medical therapy. Participants received O2O3 therapy and targeted physical therapy for 4 weeks. Pain relief, muscle strength, and physical functioning were assessed at baseline and after 4, 12 and 24 weeks (respectively T0, T1, T2, and T3) Results Seventeen patients with a mean age of 67.1 ± 6.1 years were included in the study. Short-term improvements in pain intensity were observed (T0: 6.221 ± 1.514; T1: 3.172 ± 1.1451; p < .001) and were maintained over a 24-week follow-up period (T0: 6.221 ± 1.514; T3: 4.393 ± 1.438; p: 0.006). Significant changes were reported also in terms of muscle strength and physical functioning. O2O3 therapy was well-tolerated with no adverse effects. Conclusions A combination of O2O3 injections and physical therapy might be considered in patients with TMC-OA. Further investigation is warranted to assess the effectiveness of O2O3 therapy in managing TMC-OA.

Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen

To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H2<4% in the gas mixture), the control group (n=17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p<0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p<0.001), and the date in oxidative damage (p<0.001) and antioxidant activity (p=0.03) parameters in the blood serum. The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

The advent of the first electric driven EUS-guided 17 gauge core needle biopsy – A pilot study on subepithelial lesions

Background and aims This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument. Methods An investigator-led prospective open label, performance and safety control study, including seven patients (female n = 4, median 71 y, range 28–75) with a determined SEL (median size 30 mm, range 17–150 mm) in the upper digestive tract (stomach n = 6, duodenum n = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill® 17-G passes with three fanning strokes. Results Quality of samples as ‘visible pieces’ (>5 mm): FNB (n = 5/7) (fragmented/blood imbibed n = 1, poor tissue quantity n = 1) compared with 17-G CNB (n = 7/7). Histological result which led to final diagnosis (leiomyoma n = 2, adenocarcinoma n = 1, schwannoma n = 1, neuroendocrine tumour n = 1, desmoid tumour n = 1 and gastrointestinal stromal tumour (GIST) n = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded. Conclusions By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor

Introduction. Natalizumab (NTZ) is a humanized monoclonal antibody (mAb) that selectively inhibits α4-integrin adhesion molecule located on the surface of lymphocytes and prevents their trafficking into the central nervous system (CNS).&#x0D; The aim of this study was to identify characteristics of lymphocyte population and subpopulation pattern in the peripheral blood (PB) of multiple sclerosis (MS) patients who discontinued NTZ due to an increased risk of developing developing progressive multifocal leukoencephalopathy.&#x0D; Materials and methods. We conducted an open-label prospective observational study in 26 MS patients. Of those, 6 patients had rapidly progressive MS, 10 patients discontinued NTZ and had confirmed relapses afterwards, and 10 patients received NTZ and had no relapses during the washout period. Ten apparently healthy individuals were used as controls. Cell-mediated immunity parameters were evaluated by flow cytometry using a panel of mAbs to differentiation antigens of PB lymphocytes.&#x0D; Results. Patients who discontinued NTZ had significantly decreased absolute lymphocyte counts in PB, decreased T-cytotoxic, NKT and B1 lymphocyte subpopulation levels, and decreased activated T-cell (CD3+HLA–DR+) levels, which may be related to their redistribution, passing through the blood-brain barrier, and trafficking into the central nervous system. CD20+ В-cell levels did not differ from normal. Additional immune predictors of MS relapses after NTZ discontinuation can include decreased absolute count of PB lymphocytes and decreased percentage of CD3+CD8+ T-cell, NKT-cell, and B1-cell (CD19+CD5+) subpopulations. Significantly increased levels of CD25+- and CD38+-activated B-cells compared with the normal levels in naïve patients and subjects without relapses after NTZ discontinuation may suggest a high activation potential of the circulating B-cell pool and, therefore, a high risk of MS relapses.&#x0D; Conclusions. The changes in the lymphocyte subpopulation pattern in the PB of MS patients after NTZ discontinuation may have a prognostic value for assessing the risk of relapses; they justified switching patients to anti-B-cell therapy.

Long-term effect of antiretroviral therapy on mortality among HIV-positive children and adolescents in China

IntroductionHighly active antiretroviral therapy (HAART) was piloted in 2002 and was scaled up in 2003 in mainland China. The aim of this study was to evaluate the mortality and its possible predictors based on the long-term initial antiretroviral therapy (ART) cohort among HIV positive children and adolescents. MethodsThis prospective open-labeled multicenter cohort study was conducted from January 2008 to July 2021. The participants were recruited from six representative sites in mainland China. A total of 609 participants with an HIV-positive serostatus and <18 years old were recruited and each participant was informed consent at the time of enrollment. Mortality and annual hazard were calculated, and predictors for death were analyzed using Cox regression models generating hazard ratios (HR). ResultsThe results showed that the mortality was 0.721 per hundred person-years, and the annual hazard was less than 0.10 over time. Both CD4+T cell count and CD4+T cell percentage declined in the death group during the follow-up. The Cox regression model showed that the baseline low CD4+T cell count level (Low vs. High: aHR = 8.309, 95% CI: (1.093, 63.135)) and age >5 years old at HIV diagnosis (6–12 vs. 0–5: aHR = 3.140, 95%CI: (1.331, 27.411)); 13–18 vs. 0–5: aHR = 5.451, 95%CI: (1.434, 20.724)) were possible risk factors for death. ConclusionThe longitudinal cohort study demonstrated the efficacy of China's ART program among HIV-positive children and adolescents which could be beneficial to other countries with limited resources.

Beyond Pain Relief: Unveiling the Multifaceted Impact of Anti-CGRP/R mAbs on Comorbid Symptoms in Resistant Migraine Patients.

The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief.

Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. ClinicalTrials.gov; identifier, NCT06019273.

Melatonin and melatonin receptor agonists in the treatment of nocturia: A systematic review.

Causes of nocturia may extend beyond primary bladder pathology and it has been commonly associated as a side effect of sleep disorders. This has led to the study of melatonin and melatonin receptor agonists as a primary treatment for nocturia hypothesized to be secondary to sleep disorders. We aim to systematically review the efficacy and reported safety of melatonin and melatonin receptor agonists in the treatment of nocturia. A search strategy of EMBASE and Pubmed/Medline databases was utilized to identify eligible studies. Two thousand and twenty-eight unique references were identified in concordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines for systematic reviews, of which nine papers met the inclusion criteria. The Cochrane Collaboration risk of bias criteria in the open label and nonplacebo studies was used to assess bias. The nine studies identified included 3 randomized double-blinded placebo-controlled trials, 2 randomized non-placebo trial, and 4 prospective open-label trials. Three utilized the melatonin-receptor agonist ramelteon (8 mg) and six utilized melatonin (four 2 mg extended release, two 2 mg normal release). Nocturia improved in 8 studies varying from moderate to low efficacy related to reduction in nocturia episodes. Five studies evaluated sleep parameters finding improvement in both nocturia and sleep quality. Male subjects represented 76.8% of 371 total subjects in prospective and randomized trials. Ramelteon and melatonin were both reported as well tolerated during nocturia treatment. A meta-analysis was not able to be performed due to the heterogeneity of bladder diagnoses. At this time, there is insufficient evidence to routinely recommend melatonin as an effective treatment for nocturia given the limitations of current clinical studies. Randomized placebo-controlled trials and prospective open label studies in non-neurogenic populations report a trend towards nocturia improvement with good tolerability and rare side effects. Therefore, further larger scale randomized trials with focused urologic diagnoses in well-characterized patient populations are warranted.

Ostomy Belt Use Improves Quality of Life in Patients with a Stoma

Ostomy formation is a vital component in the treatment of advanced gastrointestinal diseases, including colorectal cancer and inflammatory bowel disease. It usually involves externalizing a part of the colon or small bowel to the skin surface. Thus, the creation of an ostomy can often have a major negative impact on quality of life. This study aimed to evaluate whether the use of an ostomy belt could improve quality of life measures in stoma patients through a prospective interventional open-label study of 17–80-year-old English- and Spanish-speaking patients with stomas who were using an ostomy belt for 8 weeks. Changes in quality of life were assessed using the Stoma Quality of Life Scale questionnaire at baseline, at 4 weeks, and at 8 weeks post ostomy belt use. A total of 45 patients enrolled (20 female, mean age 48) in the study. The ostomy belt significantly improved quality of life scores from baseline to 4 weeks regarding overall life satisfaction (F(2, 76) = 14.77, p &lt; 0.001) and in the domains of work/social function (F(2, 72) = 30.32, p &lt; 0.001), sexuality/body image (F(2, 68) = 3.34, p = 0.04), and stoma function (F(2, 72) = 8.72, p &lt; 0.001). These improvements were sustained at the 8-week follow-up. No significant differences were observed in the domains of financial impact and skin irritation. This study represents the first prospective interventional study that provides evidence for the simple low-cost intervention of ostomy support belt use in improving quality of life in patients with a stoma.

(193) Low Intensity Shockwave Therapy in Combination with Phosphodiesterase-5 Inhibitors is an Effective and Safe Treatment Option in Patients with Vasculogenic ED who are PDE5i Nonresponders: A Multicenter Single-Arm Clinical Trial

Abstract Introduction Low-intensity shockwave therapy (Li-ESWT) has been shown to be an effective and safe treatment for vasculogenic erectiledysfunction (ED) Objective We aim to evaluate the effectiveness and safety of LiESWT in treating patients affected from vasculogenic ED who did not respond to oral treatment with Phosphodiesterase 5 inhibitors (PDE5-i) Methods It is a multicentric open-label prospective study, in a cohort of patients non-responders to PDE-5i. Li-ESWT was performed in an outpatient setting by using the following schedule: 3000 shockwaves with an energy of 0.25 mJ/mm2 and a frequency of 4–6 Hz, twice a week for 3 weeks. International Index of Erectile Function, Erection Hardness Score and Sexual Quality of Life-Male questionnaires, and penile doppler ultrasound (PDU) are the outcome measurements. Results The Student t-test or Wilcoxon signed-rank test were applied to compare variables, with results considered statistically significant at p &amp;lt; 0.05. 106 (97.2%) completed treatment and performed follow-up visit after 4 weeks. At follow up visit, the mean IIEF-EF increased by 8.6 points (13.47 ± 4.61 vs 22.07 ± 5.27; p &amp;lt; 0.0001). A clinically significant improvement of IIEF-EF was achieved in 75 patients (70.7%). An EHS score ≥ 3, sufficient for a full intercourse, was reported by 72 patients (67.9%) at follow-up visit. 37 (34.9%) patients reported a full rigid penis (EHS = 4) after treatment. Li-ESWT treatment was also able to improve quality of life (SQOL-M: 45.56 ± 8.00 vs 55.31 ± 9.56; p &amp;lt; 0.0001). Li-ESWT significantly increased mean PSV (27.79 ± 5.50 vs 41.66 ± 8.59; p &amp;lt; 0.0001) and decreased mean EDV (5.66 ± 2.03 vs 1.93 ± 2.11; p &amp;lt; 0.0001) in PDU. Conclusions Combination of Li-ESWT and PDE5-i represents an effective and safe treatment for patients affected from ED who do not respond to first line oral therapy Disclosure No.

Bilastine in Refractory Chronic Spontaneous Urticaria: Disease Control and Cytokine Modulation in an Open-label Prospective Study.

The treatment options for chronic spontaneous urticaria (CSU) primarily include second generation non-sedative antihistamine (SGAHs). Bilastine is a newer, nonsedating SGAH approved for urticaria in February 2019 by the Drugs Controller General of India. Its major advantages are in terms of superior efficacy, lack of drug interactions and adverse effects, including sedation, compared to conventional SGAHs. The role of cytokines in the pathogenesis of CSU is well known. However, there is a shortage of data regarding the change in serum levels of proinflammatory cytokines following H1 antihistamines. We conducted this trial to evaluate the role of bilastine in cytokine modulation and autoimmunity, thereby explaining its role in modifying the disease process in CSU. This prospective study was conducted in a tertiary institute in Kolkata on patients aged 12 years and above with a CSU >6 months. These patients had an unsatisfactory response, as per the Urticaria Activity Score 7 (UAS7), to previous antihistamine therapies in standard doses. Treatment effectiveness was determined by comparing the UAS7 at baseline with that at weeks 4, 8 and 12. Also, baseline serum interleukin-6 (IL-6) and IL-17 were compared with those at the end of the study, that is, 12 weeks. Thirty patients who matched the inclusion criteria and signed informed consent were included in the study. At the end of 12 weeks, 10% of patients (n = 3) achieved a complete treatment response (UAS = 0), whereas 43.33% of patients (n = 13) were labelled as having well-controlled urticaria (UAS <6). At 12 weeks, the mean UAS7 score (6.47 ± 4.45) was statistically significant compared to the baseline score (25.47 ± 7.74). The mean values of serum IL-6 (pg/ml) and IL-17 (pg/ml) at baseline were 5.96 ± 5.24 pg/ml and 6.96 ± 5.97 pg/ml, respectively. At the end of treatment, that is, 3 months, the mean values were reduced to 4.61 ± 4.56 pg/ml and 5.08 ± 3.87 pg/ml. The reduction was statistically significant for both serum IL-6 (P < 0.001) and IL-17 (P < 0.0001). We conclude that bilastine at a once-daily continuous dose of 40 mg for 3 months is safe and effective in CSU patients who are refractory to treatment at the standard doses of SGAHs. Improved symptomatic control with bilastine was also associated with better control over the inflammatory process, as suggested by the lowering of mean cytokine levels in our study.

Serious Game with Electromyography Feedback and Physical Therapy in Young Children with Unilateral Spastic Cerebral Palsy and Equinus Gait: A Prospective Open-Label Study.

The clinical effects of a serious game with electromyography feedback (EMGs_SG) and physical therapy (PT) was investigated prospectively in children with unilateral spastic cerebral palsy (USCP). An additional aim was to better understand the influence of muscle shortening on function. Thirty children with USCP (age 7.6 ± 2.1 years) received four weeks of EMGs_SG sessions 2×/week including repetitive, active alternating training of dorsi- and plantar flexors in a seated position. In addition, each child received usual PT treatment ≤ 2×/week, involving plantar flexor stretching and command strengthening on dorsi- and plantar flexors. Five-Step Assessment parameters, including preferred gait velocity (normalized by height); plantar flexor extensibility (XV1); angle of catch (XV3); maximal active ankle dorsiflexion (XA); and derived coefficients of shortening, spasticity, and weakness for both soleus and gastrosoleus complex (GSC) were compared pre and post treatment (t-tests). Correlations were explored between the various coefficients and gait velocities at baseline. After four weeks of EMGs_SG + PT, there was an increase in normalized gait velocity from 0.72 ± 0.13 to 0.77 ± 0.13 m/s (p = 0.025, d = 0.43), a decrease in coefficients of shortening (soleus, 0.10 ± 0.07 pre vs. 0.07 ± 0.08 post, p = 0.004, d = 0.57; GSC 0.16 ± 0.08 vs. 0.13 ± 0.08, p = 0.003, d = 0.58), spasticity (soleus 0.14 ± 0.06 vs. 0.12 ± 0.07, p = 0.02, d = 0.46), and weakness (soleus 0.14 ± 0.07 vs. 0.11 ± 0.07, p = 0.005, d = 0.55). At baseline, normalized gait velocity correlated with the coefficient of GSC shortening (R = -0.43, p = 0.02). Four weeks of EMGs_SG and PT were associated with improved gait velocity and decreased plantar flexor shortening. A randomized controlled trial comparing EMGs_SG and conventional PT is needed.

Evaluation of Post-Vaccination Immunity in Children and Adolescents after Viral Hepatitis B Vaccine

Vaccination against viral hepatitis B is an effective method of protection against this infection. There is multiple decrease in the hepatitis B incidence. However, there was increase in chronic hepatitis B by 42.5%, 15 cases of acute viral hepatitis B in children and 2 deaths from this infection were registered according to the state report “On the sanitary and epidemiological wellbeing of the population of the Russian Federation for 2022”. The criteria for evaluating protection against viral hepatitis B are the anti-HBs level and the duration of post-vaccination immunity.Objective. The aim of the study is to evaluate the duration of postvaccination immunity in temporal aspect in children and adolescents vaccinated against viral hepatitis B.Methods. Prospective open-label study was conducted to assess post-vaccination immunity against viral hepatitis B in 143 children and adolescents. The study of anti-HBs was implemented via the immunoenzyme test system “Vectohep B-HBs-antigen”. Microsoft Office Excel 2010 package and the Prism9 program (GraphPad, USA) were used for statistical analysis.Results. It has been shown that hepatitis B vaccine provides 100% seroconversion. However, decrease in anti-HBs levels was revealed already 6 months after vaccination in 15.07% of cases of seronegative individuals, after 1 year their number has increased up to 28.77% of cases. On average, every fourth person had low protective level of anti-HBs. Almost two-thirds of adolescents became seronegative by the age of 14.Conclusion. Vaccination against viral hepatitis B ensures the maximum production of anti-HBs 1 month after the completed vaccination in 100% of cases. Antibody level begins to decrease 6 months after the third completed vaccination against hepatitis B, and in 14 years, 72.74% of those immunized become seronegative. All of these dictates the need to consider a booster dose in adolescents at the age of 14 years.

Assessment of specificity of immunologic tests for detection of tuberculosis infection in children with juvenile idiopathic arthritis

Introduction. The use of genetic engineering biological agents (GEBA) in the treatment of rheumatic diseases over the past decades has led to a significant improvement in the prognosis in this group of patients. However, against the background of anti-tumor necrosis factor α therapy (anti TNF-α), the risk of developing tuberculosis increases tenfold.Aim. To evaluate the specificity and safety of Mantoux test, recombinant tuberculosis allergen (RTA) test, IGRA tests: TB-Feron IGRA, T-SPOT.TB, QuantiFERON-TB GIT in patients from 5 to 18 years of age, who are at risk for the development of tuberculosis, due to the use of immunosuppressive therapy, including GEBP.Materials and methods. This clinical trial is a prospective single-center open-label study with 120 patients under observation. Girls predominated among the patients – 71 (59.2%), the average age was 12 years (95% CI [5.2–17.4]). As part of the treatment of the underlying disease, patients in the vast majority of cases (78.3%) received iFNO-α drugs: etanercept (67 people), adalimumab (25 people), golimumab (2 people).Results and discussion. According to the results of a comprehensive medical examination, including CT scan of the chest organs, the presence of active tuberculosis was not established in any of the patients. A positive result of the RTA sample was registered in 0.8% of the subjects, Mantoux test in 46.6%, T-SPOT.TB – 1.7%, TB-Feron IGRA and QuantiFERON-TB GIT – 0.8% each. During the safety assessment, it was noted that within 28 days after the study, none of the 120 patients had any adverse events. Patients need appropriate screening before starting treatment and regular follow-up examinations.Conclusions. The Mantoux test with 2 TE has low specificity (0.49), and the sample with RTA (0.99), TB-Feron IGRA (0.99), T-SPOT.TB (0.98) and QuantiFERON-TB GIT (0.99) are highly specific and safe as tests for detecting tuberculosis infection in children with juvenile idiopathic arthritis.

Radiological Progression and Predictors of Radiological Progression in Early Rheumatoid Arthritis Treated with Conventional Synthetic Disease-modifying Agents

Aim: To study the clinical and serological predictors of radiological progression at one year in a cohort of Indian patients with early rheumatoid arthritis (RA). Methods: In this prospective open-label observational study, consecutive patients with early RA (&lt;six months) were examined at baseline and at each visit (0, 3, 6, 9 and 12 months) for disease activity, DAS ESR 28 and European League Against Rheumatism response. Radiography of the hands and feet was performed at baseline and at one year of treatment, and radiologic progression was assessed using van der Heijde’s Sharp score. The prognostic factors were evaluated using a logistic regression model. Results: Fifty-one eligible patients were analysed for disease outcomes, whereas 43 were eligible for radiographic progression. The mean duration of RA was 3.4 ± 1.85 months. At baseline, 96% of the patients had moderate to high disease activity. The proportion of patients with erosions increased from 16.3% to 37.2% at one year, whereas that of patients with joint space narrowing (JSN) increased from 21% to 39.5%. At one year, the mean increase in total Sharp’s score was 1.67, while 32.5% of patients had radiological progression. Age of onset, presence of erosions, JSN, anticitrullinated protein antibody (ACPA) titre and tender joint counts at baseline were associated with radiographic progression at one year. However, in the multivariate analysis, none of the variables predicted radiographic damage. Only JSN was positively associated with progression at one year. Conclusion: Age at onset, presence of erosions, JSN, ACPA titre and tender joint counts at baseline were associated with radiographic progression at one year, but further studies are required to confirm these results.

A Review of Olanzapine in the Treatment of Cancer Anorexia-Cachexia Syndrome.

Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS. A comprehensive search was conducted to identify the primary literature that involved olanzapine for anorexia and cachexia in cancer patients between 2000 and 2023. Seven articles were identified and are discussed here, including two randomized double-blinded placebo-controlled studies, one randomized comparative study, two prospective open-label studies, one retrospective chart review, and one case report. Low dose olanzapine (2.5-5 mg once daily) may be useful in the treatment of CAS for increasing appetite, reducing nausea and vomiting, and promoting weight gain. Further large-scale multi-center randomized placebo-controlled studies will be needed to investigate the impact of olanzapine on weight change in CAS patients.

Clinical efficacy of plasmid encoding p62/SQSTM1 (Elenagen) in combination with gemcitabine in patients with platinum-resistant ovarian cancer: a randomized controlled trial.

The purpose of this trial is to evaluate the safety and efficacy of ELENAGEN, a novel anticancer therapeutic DNA plasmid encoding p62/SQSTM1 protein, as an adjuvant to chemotherapy with gemcitabine (GEM) in patients with advanced platinum-resistant ovarian cancer. This open-label prospective randomized study with two arms. GEM (1000 mg/m2) on days 1 and 8 every 3 weeks was administered in both arms: in the Chemo arm (n = 20), GEM was the only treatment, and in the ELENAGEN arm (n = 20), GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1, and criteria safety was assessed according to NCI CTCAE version 5.0. According to the cutoff data, the median follow-up was 13.8 months. There were no serious adverse events related to ELENAGEN treatment. The median PFS was 2.8 and 7.2 months in the Chemo and ELENAGEN arms, respectively (p Log-Rank = 0.03). Notably, at the time of cutoff, 9 patients (45%) in the ELENAGEN arm did not progress, with the longest PFS recorded thus far being 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of ELENAGEN in patients with worse prognostic factors: high pretreatment levels of CA125 and progression after platinum-free interval <3 months. The addition of ELENAGEN to gemcitabine is effective in patients with platinum-resistant ovarian cancer, including those with a worse prognosis. https://www.clinicaltrials.gov/study/NCT05979298, identifier NCT05979298, 2023-08-07.