Cholesin receptor signalling is active in cardiovascular system-associated adipose tissue and correlates with SGLT2i treatment in patients with diabetes.

BACKGROUND: Recently deorphanized G protein-coupled receptor 146 (GPR146) was shown to respond to signal from a newly identified hormone-cholesin-and to play a role in hepatic lipid metabolism. However, the importance of its biological activity in human organism remains elusive, mainly due to the lack of studies on human tissues up to this point. This study aimed to identify the cholesin receptor-associated genes and clinical factors linked with their expression in cardiovascular system and associated adipose tissues. METHODS: Right cardiac auricle, aortic wall, saphenous vein, and adipose tissue (periaortic-PAT, epicardial-EAT, thymic-TAT) samples were collected during coronary artery bypass grafting. Clinical records of the study participants were assessed for the presence of diabetes, medications taken and serum cholesterol levels. GPR146 mRNA expression in all gathered tissues was assessed with qPCR, and RNA seqencing was performed in selected tissues of 20 individuals to identify pathways associated with GPR146 expression. RESULTS: We included 46 participants [37 male, 23 with type 2 diabetes, median age 68.50 (Q1-Q3: 63.00-72.00) years, BMI 28.39 (26.06-31.49) kg/m2]. GPR146 expression in adipose tissues significantly correlated with BMI, c-peptide, total cholesterol, and LDL concentrations. Selected metabolic pathways were significantly and positively enriched in GPR146-dependent manner. GPR146-coexpressed genes contained key regulators of lipid metabolism involved in such pathways as fatty acid metabolism, tricarboxilic acid cycle and peroxisomal metabolism. Those genes correlated positively with serum concentrations of LDL, HDL, and total cholesterol. SGLT2i treatment was associated with inversion of GPR146-related signature in EAT, suggesting potential impact on cholesin-GPR146 network. CONCLUSIONS: GPR146 expression is associated with serum lipids and metabolically-relevant transcriptomic changes in EAT similar to SGLT2i-associated ones.

Retrospective analysis of treatment, including access to breast reconstructions, of breast cancer patients - war refugees from Ukraine in Poland - the experience of a single tertiary care institution.

<b>Introduction:</b> Following the Russian invasion, more than 3600000 refugees have fled Ukraine and settled down in Poland; this group includes a growing number of breast cancer patients whose treatment had been started in Ukraine and hence required urgent therapy in Poland.</br></br> <b>Aim:</b> The aim of the study was to analyze the treatment of breast cancer patients from Ukraine, who entered Poland as war refugees - the experience of a single tertiary care institution.</br></br> <b>Material and methods:</b> The treatment of 25 consecutive breast cancer patients, war refugees from Ukraine was reviewed retrospectively.</br></br> <b>Results:</b> Patients were treated according to subtype and staging, e.g. surgery, endocrine, anti-HER2 therapy, chemotherapy, radiotherapy. 7 patients received an immediate implant, mesh-based breast reconstruction. In 2 cases, the patients refused breast reconstruction.</br></br> <b>Conclusions:</b> Nearly 5.5 million refugees across Europe who have fled the combat zones in Ukraine; of these, the vast majority sought shelter in Poland, and many of whom are women. It is expected that breast cancer mortality rates may rise and progress in oncology may slow as the war in Ukraine disrupts routine patient care, clinical trials and research. Hence, support from neighboring countries is mandatory.

Safety of the COVID-19 vaccination in children with juvenile idiopathic arthritis-A observational study from two pediatric rheumatology centres in Poland.

Introduction: The safety of COVID-19 vaccines in children with juvenile idiopathic arthritis (JIA) is the concern of patients and their parents and doctors in the current pandemic reality. The main objective of the study was to evaluate the safety of COVID-19 vaccine in patients with JIA. Method: A cohort study based on short clinical follow-up of 43 children with JIA was conducted in the years 2021-2022 in two centres of paediatric rheumatology in Poland. All patients received mRNA COVID-19 vaccine. The patients' data were collected using appropriate validated questionnaire. Disease activity was evaluated using Juvenile Arthritis Disease Activity Score 27-joint count (JADAS-27). Results: Ten (22.7%) children had COVID-19 infection before getting COVID-19 vaccine. After first dose of COVID-19 vaccine 25/43 (58.1%) patients presented typical adverse events: arm pain or oedema at the application side or weakness. Also, twenty five (58.1%) children had side effects after second dose of this vaccine, however the spectrum of the symptoms was wider (additionally: headache, fever, lymphadenopathy, arrhythmia). Thirteen out of 43 (30.2%) patients had active disease before and 8/43 (18.6%) after COVID-19 vaccination, while the degree of JADAS-27 activity was higher in the study group before COVID-19 vaccination (p = 0.047). Conclusions: Our study found out that children and adolescents with JIA with remission without treatment or on the long-term treatment-cDMARDs or even bDMARDs, can be safely vaccinated for COVID-19. Moreover, the study found that COVID-19 vaccination does not interfere with the JIA treatment and does not exacerbate symptoms of the disease and that vaccination protected against developing COVID-19 in children with JIA even on treatment.

Putative molecular targets for vitamin A in neutralizing oxidative stress in acute and chronic pancreatitis - a systematic review.

Acute pancreatitis (AP) and chronic pancreatitis (CP) are debilitating diseases of gastrointestinal tract and constitute great threat for human health in high-income countries. Recent studies emphasize the impact of oxidative stress on development of these pathologies, and numerous authors evaluate the effect of the antioxidant therapy on the course of AP and CP. Though several antioxidative agents were discovered in the past decades, vitamins remain canonical antioxidants. Despite the fact that vitamin A is known for its antioxidative effect, there is little data about the impact of vitamin A on oxidative stress in the pathogenesis of AP and CP. The scope of the review is to evaluate molecular targets for vitamin A, which may be involved in oxidative stress occurring in the course of AP and CP. Our research of available literature revealed that several mechanisms are responsible for attenuation of oxidative stress in AP and CP, including Nrf2, MAPK, AMPK, TLR3, and TLR4. Furthermore, these factors are at least partially expressed in vitamin A-dependent manner, though further investigations are required for elucidating in detail the role of vitamin A in defense against reactive oxygen species. Our review revealed that vitamin A might influence the expression of several molecular pathways involved in antioxidative defense and cytoprotection; thus, its administration during AP and CP may change the course of the disease.

Management of Pelvic Pain in Patients with Crohn's Disease-Current Overview.

Crohn's disease (CD) is a subtype of chronic inflammatory bowel diseases (IBD) with characteristic skip lesions and transmural inflammation that may affect the entire gastrointestinal tract from the mouth to the anus. Persistent pain is one of the main symptoms of CD. This pain has multifactorial pathogenesis, but most often arises from intestinal inflammation itself, as well as from gut distention or partial intestinal obstruction. Some current evidence also suggests sensitization of sensory pathways, as well as modulation of those signals by the central nervous system, which highlights the impact of biopsychosocial factors. To date, most studies have focused only on the pain located in the abdomen, while pelvic pain has rarely been explored, despite it being a common symptom. The aim of this study is to provide an abbreviated summary of the current state of knowledge on the origins and treatment of pelvic pain in CD.