Etiological factors and treatment of chylothorax in paediatric patients - a systematic review

Chylothorax is an accumulation of chyle in the pleural cavity. It is a relatively rare cause of pleural effusion in children and its annual incidence is 14 cases per 100 000 children in Europe.  The pleural fluid triglyceride level greater than 110 mg/dl with a cholesterol level lower than 200 mg/dl confirms the diagnosis of chylothorax. Medical imaging are also necessary such as a non-invasive and easily accessible lung ultrasound. Symptoms of this disease are tachypnea, dyspnea, and in some cases dry cough. This review aims to summarize the current literature regarding chylothorax in children, analyze its possible etiologies and treatments. The causes of chylothorax are varied. It may appear after surgical interventions, traumas, infections and also be congenital. Iatrogenic factors are the most common cause of chylothorax in children with cardiothoracic surgeries. Management of chylothorax can be quite complex and highly variable, depending on patient’s condition and their response to the introduced treatment. Conservative treatment consisting of nutrition therapy, chest drain, and pharmacotherapy is typically a first-line of treatment. Diet modification consist in dietary supplements enriched with medium chain triglycerides (MCT) or starting the patient on a total parenteral nutrition (TPN). In most of the analyzed cases the conservative treatment alone proved sufficient in the management of chylothorax. In case of its failure, surgical treatment was a secondary therapy choice. One of the most common surgical procedures for pleural effusion is a thoracic duct ligation (TDL) or pleurodesis and both of these methods are highly effective therapy for chylothorax. This review of the literature reveals a wide variety of causes and methods of treatment of chylothorax. There are no clear standards of management and the therapy is adjusted to the clinical condition of the patient

Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis

Evobrutinib; Multiple sclerosis; Receptors in B cells; Receptors in myeloid cellsEvobrutinib; Esclerosis múltiple; Receptores en células B; Receptores en células mieloidesEvobrutinib; Esclerosi múltiple; Receptors en cèl·lules B; Receptors en cèl·lules mieloidesBACKGROUND: Bruton's tyrosine kinase (BTK) regulates the functions of B cells and myeloid cells that are implicated in the pathogenesis of multiple sclerosis. Evobrutinib is a selective oral BTK inhibitor that has been shown to inhibit B-cell activation both in vitro and in vivo. METHODS: In this double-blind, randomized, phase 2 trial, we assigned patients with relapsing multiple sclerosis to one of five groups: placebo, evobrutinib (at a dose of 25 mg once daily, 75 mg once daily, or 75 mg twice daily), or open-label dimethyl fumarate (DMF) as a reference. The primary end point was the total (cumulative) number of gadolinium-enhancing lesions identified on T1-weighted magnetic resonance imaging at weeks 12, 16, 20, and 24. Key secondary end points included the annualized relapse rate and change from baseline in the score on the Expanded Disability Status Scale (EDSS). RESULTS: A total of 267 patients were randomly assigned to a trial group. The mean (±SD) total number of gadolinium-enhancing lesions during weeks 12 through 24 was 3.85±5.44 in the placebo group, 4.06±8.02 in the evobrutinib 25-mg group, 1.69±4.69 in the evobrutinib 75-mg once-daily group, 1.15±3.70 in the evobrutinib 75-mg twice-daily group, and 4.78±22.05 in the DMF group. The baseline adjusted rate ratios for the total number of lesions over time as compared with placebo were 1.45 in the evobrutinib 25-mg group (P = 0.32), 0.30 in the evobrutinib 75-mg once-daily group (P = 0.005), and 0.44 in the evobrutinib 75-mg twice-daily group (P = 0.06). The unadjusted annualized relapse rate at week 24 was 0.37 in the placebo group, 0.57 in the evobrutinib 25-mg group, 0.13 in the evobrutinib 75-mg once-daily group, 0.08 in the evobrutinib 75-mg twice-daily group, and 0.20 in the DMF group. There was no significant effect of trial group on the change from baseline in the EDSS score. Elevations in liver aminotransferase values were observed with evobrutinib. CONCLUSIONS: Patients with relapsing multiple sclerosis who received 75 mg of evobrutinib once daily had significantly fewer enhancing lesions during weeks 12 through 24 than those who received placebo. There was no significant difference with placebo for either the 25-mg once-daily or 75-mg twice-daily dose of evobrutinib, nor in the annualized relapse rate or disability progression at any dose. Longer and larger trials are required to determine the effect and risks of evobrutinib in patients with multiple sclerosis.Funded by EMD Serono; ClinicalTrials.gov number, NCT02975349

Influence of environmental factors and diet on inflammatory bowel diseases – a review of the literature

Introduction and objectiveInflammatory bowel disease (IBD), leading to inflammation in the gastrointestinal tract, causes a number of bothersome symptoms that contribute to the deterioration of patients' quality of life both physically and psychologically. Therapy methods based on pharmacotherapy in IBD often remain insufficient in the treatment of these disorders, so other factors affecting the course of IBD are being sought. The purpose of this review is to present risk and prevention factors for the development of inflammatory bowel disease based on diet and environmental factors. Abbreviated description of the state of knowledgeThe review has identified a number of factors that influence IBD. One of these is smoking, which shows a commonly detrimental effect on CD, while it has a protective effect in UC patients. Antibiotic therapy, by disrupting the composition of the endogenous intestinal microflora, contributes to an increased risk of IBD exacerbations. A review of the literature on surgical interventions does not allow a clear conclusion. Stress and psychiatric disorders increasing the production of pro-inflammatory cytokines, inhibiting the anti-inflammatory action of the vagus nerve increase the risk of IBD exacerbations. A healthy and balanced diet is an important aspect in the treatment of UC and CD. Scientific societies unanimously recognize breastfeeding and its effect on the development of the intestinal microflora as an important protective factor. On the other hand, introducing an elimination diet without a food intolerance confirmed by a blood test is unjustified and harmful. SummaryAwareness of the risk factors for development and exacerbations in IBD patients is crucial. Further research into the impact of diet and environmental factors may support pharmacological treatment in achieving therapeutic success in patients with inflammatory bowel disease

Drought-related secondary metabolites of barley (Hordeum vulgare L.) leaves and their metabolomic quantitative trait loci

Determining the role of plant secondary metabolites in stress conditions is problematic due to the diversity of their structures and the complexity of their interdependence with different biological pathways. Correlation of metabolomic data with the genetic background provides essential information about the features of metabolites. LC-MS analysis of leaf metabolites from 100 barley recombinant inbred lines (RILs) revealed that 98 traits among 135 detected phenolic and terpenoid compounds significantly changed their level as a result of drought stress. Metabolites with similar patterns of change were grouped in modules, revealing differences among RILs and parental varieties at early and late stages of drought. The most significant changes in stress were observed for ferulic and sinapic acid derivatives as well as acylated glycosides of flavones. The tendency to accumulate methylated compounds was a major phenomenon in this set of samples. In addition, the polyamine derivatives hordatines as well as terpenoid blumenol C derivatives were observed to be drought related. The correlation of drought-related compounds with molecular marker polymorphisms resulted in the definition of metabolomic quantitative trait loci in the genomic regions of single-nucleotide polymorphism 3101-111 and simple sequence repeat Bmag0692 with multiple linkages to metabolites. The associations pointed to genes related to the defence response and response to cold, heat and oxidative stress, but not to genes related to biosynthesis of the compounds. We postulate that the significant metabolites have a role as antioxidants, regulators of gene expression and modulators of protein function in barley during drought

Systematic review and network meta-analysis (NMA) for cladribine tablets in achieving sustained disability improvement (SDI) in multiple sclerosis

Introduction. This study was performed to compare probabilities of SDI on the Expanded Disability Status Scale (EDSS) in patients with relapsing-remitting multiple sclerosis (RRMS), treated with cladribine tablets (CT) or fingolimod (FTY), natalizumab (NAT), alemtuzumab (ALE) and ocrelizumab (OCR). Clinical rationale for the study. Progression of neurological disability as measured by the EDSS has been a common endpoint in multiple sclerosis (MS) trials. Novel therapies can not only slow this process, but in some patients even reverse it. This effect can be measured by the sustained disability improvement (SDI) — an endpoint that seems to continuously gain importance in clinical practice. Despite that, SDI has rarely been explored as an outcome in MS clinical studies, mostly as post-hoc analyses from randomised trials or as retrospective analyses based on patient registry records. Material and methods. A systematic review was conducted in Medline, Embase and Cochrane to identify clinical trials (RCT or non-RCT) evaluating 6-month SDI. An indirect comparison via network meta-analysis (NMA) was performed. Bayesian inference with Markov chains Monte Carlo methods were applied. Results. Eight trials presenting SDI results and applicable for NMA were included: six non-RCTs, with control groups selected by propensity score matching, and two RCTs. NMA results revealed that probability of achieving 6-month SDI with CT was significantly higher compared to all other high efficacy disease-modifying drugs with available data — HR (95% Crl - Bayesian Credibility Interval) vs. FTY: 4.98 (2.11–11.79); vs. NAT: 3.12 (1.31–7.27); vs. ALE: 9.29 (3.40–25.21). The main results were confirmed in the sensitivity analyses. Conclusions. Of all considered therapies, treatment with cladribine tablets was associated with a higher probability of sustained disability improvement in RRMS patients. As this conclusion is based on available clinical data of limited quality, future studies, as well as real-world data, would be valuable to provide further evidence regarding the comparative effectiveness of RRMS therapies

Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic

Introduction. Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. Material and methods. We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. Results. We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. Conclusions. Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort

Strengthening the resources of inmates with gambling disorders in the perspective of a solution focused approach

Artykuł stanowi próbę spojrzenia na proces resocjalizacji w sposób komplementarny, uwzględniający zarówno identyfikację i oddziaływania mające na celu ograniczanie czynników ryzyka powrotu do przestępczości, jak i wzmacniania czynników chroniących przed ową powrotnością. W praktyce penitencjarnej w trakcie prowadzenia oddziaływań skierowanych do osób osadzonych istnieje tendencja do koncentracji na identyfikacji deficytów oraz planowaniu oddziaływań mających na celu ich ograniczenie. Równie istotne jest jednak wydobywanie i wzmacnianie zasobów osób pozbawionych wolności oraz wykorzystywanie tychże zasobów do ograniczania lub korygowania deficytów. Ta druga perspektywa jest rozważana przez autorki w świetle podejścia skoncentrowanego na rozwiązaniach.The article is an attempt to look at the resocialization process in a complementary way, taking into account both the identification and interventions aimed at reducing the risk factors for a return to crime, as well as strengthening the factors protecting against return. In penitentiary practice, when conducting interventions aimed at inmates, there is a tendency to focus on identifying deficits and planning interventions aimed at reducing them. However, it is equally important to obtain, strenghten and use the resources of persons deprived of their liberty and their use in reducing or correcting deficits. The latter perspective is considered by the authors in light of the solution-focused approach and its usefulness for penitentiary practice

Evaluation in the prevention and treatment of behavioral disorders

Bibliogr. przy rozdz