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.

Safe and effective use of a passive safety needle by healthcare professionals in a simulated environment, including perceptions and preferences.

BACKGROUND: Needlestick injuries (NSIs) may potentially expose healthcare professionals (HCPs) to bloodborne pathogens. Safety needles are designed to protect against NSIs. We evaluated whether a new fully passive safety needle could be used safely by HCPs. RESEARCH DESIGN AND METHODS: The passive safety needle was tested by physicians, nurses, and pharmacists in subcutaneous or intramuscular injection scenarios in simulation studies (1-3). Data collected included successes, close calls, difficulties, use errors, and failures. In study 4, HCPs rated the device safety (21-item questionnaire). RESULTS: Overall, 104 participants completed 4772 simulated tasks, including 932 injections. 915 injections (98.18%) were performed successfully and no NSIs (0%) were observed in any of the studies. Studies 1 & 2: 84.15% tasks and 96.06% injections were completed successfully, but use errors occurred, mostly arising from the participants' mental model. There were no failures in Study 3. In Study 4, >98% of participants responded positively to every question, while all felt that the passive safety feature could eliminate NSIs and would better protect against bloodborne pathogens than other existing devices with active or semi-passive safety mechanisms. CONCLUSIONS: The passive safety needle was used successfully by HCPs, did not lead to any NSIs, and was rated as the safest compared to similar devices.

The impact of single nucleotide polymorphisms in MTHFR and MTRR genes on disease activity and the presence of methotrexate treatment side effects in children with juvenile idiopathic arthritis.

Introduction: To determine the impact of single nucleotide polymorphisms (SNPs) in MTHFR and MTRR genes on disease activity and the presence of MTX therapy adverse events in Polish children with juvenile idiopathic arthritis (JIA). Methods: SNP genotyping was performed using genomic DNA isolated from peripheral blood samples. Results: Patients with MTHFR rs1801133 CT/TT variant had higher values of inflammatory markers, number of joints with active arthritis, and JADAS-71 value at the baseline of MTX treatment. Children with MTRR rs1801394 AG/AA variant presented higher inflammatory marker values at JIA diagnosis. Conclusions: MTHFR rs1801133 and MTRR rs1801394 polymorphisms are associated with higher disease activity at the moment of JIA diagnosis.

Acute kidney injury as the most important predictor of poor prognosis after interventional treatment for aortic stenosis.

BACKGROUND: Aortic stenosis (AS) is the most common acquired valvular disease. There are two methods of interventional treatment: surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). The choice between SAVR and TAVI depends on the assessment of individual perioperative risk and long-term treatment outcomes. It is essential to identify factors that may influence the outcomes of the treatment to minimize their negative effects. AIMS: The study aimed to identify the most important risk factor which affects treatment outcomes in patients with AS undergoing SAVR/TAVI. METHODS: This study reviewed retrospectively patients with AS who underwent SAVR or TAVI. The primary outcomes included incidences of major adverse cardiovascular events (MACE) defined as cardiovascular death, stroke, and hospitalization for cardiovascular issues assessed over a one-year follow-up period. An occurrence of postprocedural AKI (acute kidney injury) was identified as an independent predictor of MACE. RESULTS: The study included 78 patients, with the same number of subjects in each group (SAVR/TAVI [n = 39]). Twenty-nine patients developed AKI. It was similar in both groups (SAVR [n = 15]; TAVR [n = 14]). In the SAVR group, 13 (33%) patients developed at least one MACE compared to 5 (13%) patients in the TAVI group. AKI and the type of procedure (SAVR) were shown to be significantly and independently associated with the development of MACE (P = 0.01 and P = 0.03, respectively) as shown in the Cox multivariable regression model. CONCLUSIONS: Our study demonstrated that AKI is the strongest predictor of major adverse cardiovascular events after using both methods of aortic valve replacement (SAVR/TAVI).

The impact of single nucleotide polymorphisms in ADORA2A and ADORA3 genes on the early response to methotrexate and presence of therapy side effects in children with juvenile idiopathic arthritis: Results of a preliminary study.

AIM: Methotrexate (MTX) administered at the dose 10-15 mg/m2 is recommended as the first-line therapy in most juvenile idiopathic arthritis (JIA) subtypes. The disease-modifying effect of methotrexate is associated with release of adenosine and mediated via binding to adenosine receptor A2A (ADORA2A) and 3 (ADORA3). The aim of our study was to determine the association between single nucleotide polymorphisms in ADORA2A (rs2236624, rs2298383) and ADORA3 (rs3393) receptor genes on the disease activity and presence of MTX therapy side effects in patients with JIA. METHODS: One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months after starting MTX. Single nucleotide polymorphism genotyping was performed using genomic DNA isolated from peripheral blood samples. RESULTS: The polymorphic variant of ADORA2A rs2236624 was associated with ~3.5 times higher odds of gastrointestinal side effects occurrence (odds ratio: 3.59, 95% CI: 1.15-11.22, P = 0.0282). Children with the ADORA3 rs3393 polymorphic variants (CT/CC) after 6 months of MTX treatment had significantly lower number of joints with active arthritis (median: 0.00 vs 1.00, P = 0.0400) and value of C-reactive protein (0.60 vs 2.40, P = 0.0242) in comparison to TT variant. CONCLUSION: Although future studies are needed to verify our findings, polymorphisms in ADORA2A and ADORA3 genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.

Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes-Time for Translational Studies or Back to the Basics?

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.