Effects of Dapagliflozin in Patients with Membranous Nephropathy.

Introduction: Despite the provision of renin-angiotensin-aldosterone-system inhibitors and immunosuppressive therapies, membranous nephropathy often progresses to end-stage kidney disease (ESKD). The objective of this prespecified analysis was to assess the safety and efficacy of dapagliflozin in patients with membranous nephropathy enrolled in the DAPA-CKD trial. Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 200-5,000 mg/g were randomized to dapagliflozin 10 mg once daily or placebo, along with standard-of-care and followed for median 2.4 years. The primary endpoint was a composite of ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Exploratory efficacy endpoints included eGFR slope and UACR. Results: Among DAPA-CKD participants with membranous nephropathy, 19 were randomized to dapagliflozin and 24 to placebo. The mean (SD) age was 59.9 ± 12.1 years, the mean eGFR was 45.7 ± 12.1 mL/min/1.73 m2, and the median UACR was 1,694.5 (25%, 75% range 891-2,582.5) mg/g. Two of 19 (11%) patients randomized to dapagliflozin and five of 24 (21%) randomized to placebo experienced the primary composite endpoint. Total and chronic mean eGFR slopes for dapagliflozin and placebo were -3.87 and -4.29 and -2.66 and -4.22 mL/min/1.73 m2/year, respectively; corresponding between-group mean differences were 0.42 and 1.57 mL/min/1.73 m2/year. Dapagliflozin reduced geometric mean (SEM) UACR relative to placebo (-29.3% ± 1.2% vs. -3.6% ± 1.1%; between-group mean difference [95% CI] -26.7 [-50.4, 8.3]). Four (21%) patients randomized to dapagliflozin and seven (29%) randomized to placebo experienced a serious adverse event. Conclusion: In membranous nephropathy, the effects of dapagliflozin on kidney disease progression and albuminuria were generally favorable; there was insufficient power to justify formal inference testing.

Stress granule-mediated sequestration of EGR1 mRNAs correlates with lomustine-induced cell death prevention.

Some chemotherapy drugs modulate the formation of stress granules (SGs), which are RNA-containing cytoplasmic foci contributing to stress response pathways. How SGs mechanistically contribute to pro-survival or pro-apoptotic functions must be better defined. The chemotherapy drug lomustine promotes SG formation by activating the stress-sensing eIF2α kinase HRI (encoded by the EIF2AK1 gene). Here, we applied a DNA microarray-based transcriptome analysis to determine the genes modulated by lomustine-induced stress and suggest roles for SGs in this process. We found that the expression of the pro-apoptotic EGR1 gene was specifically regulated in cells upon lomustine treatment. The appearance of EGR1-encoding mRNA in SGs correlated with a decrease in EGR1 mRNA translation. Specifically, EGR1 mRNA was sequestered to SGs upon lomustine treatment, probably preventing its ribosome translation and consequently limiting the degree of apoptosis. Our data support the model where SGs can selectively sequester specific mRNAs in a stress-specific manner, modulate their availability for translation, and thus determine the fate of a stressed cell.

Evaluation of Prostate-Specific Membrane Antigen (PSMA) Immunohistochemical Expression in Early-Stage Breast Cancer Subtypes.

Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels (p < 0.0001, RSpearman 0.42) and tumor cells (p = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels (p = 0.0053, R Spearman -0.26 and p = 0.00026, R Spearman -0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer.

Tackling the challenge of cardiovascular diseases and diabetes across Europe: a joint action by more than 300 public health professionals. Commentary.

Cardiovascular diseases (CVD) and diabetes pose significant health challenges in Europe, affecting millions and burdening healthcare systems. The recent EU4Health Programme places reducing the burden of non-communicable diseases (NCD) at the forefront, through a Joint Action focused on CVD and diabetes (JACARDI, Joint Action on CARdiovascular diseases and DIabetes). This initiative unites 21 European countries, including Ukraine, and over 300 experts. Employing an innovative approach and standardised methodology, JACARDI implements 142 pilot projects covering the entire "patient" journey. Particular focus will be given to improvement of data availability and quality. Additionally, JACARDI will emphasise transversal and intersectional aspects, such as health equity, determinants of health, and social, cultural, and ethnic diversity, while pioneering gender-transformative leadership. Committed to evidence-based interventions, JACARDI aims to harmonise strategies and disseminate knowledge for enhanced CVD and diabetes prevention and management. The goal is to identify effective strategies for wider implementation, fostering cross-national collaboration and fortifying Europe's health resilience.

The impact of GLP-1 receptor agonist liraglutide on blood pressure profile, hydration, natriuresis in diabetic patients with severely impaired kidney function.

Chronic treatment with GLP-1R agonists may moderately lower blood pressure due to increased natriuresis and RAAS inhibition. Short-term effect of these drugs on blood pressure may be opposite and its mechanism remains unclear. We investigated the effect of a single dose of liraglutide on diurnal blood pressure profile, natriuresis, hydration and serum concentration of renin, aldosterone and atrial natriuretic peptide (ANP) in diabetic kidney disease (DKD). 17 patients with eGFR < 30 ml/min/1.73 m2 and 17 with > 60 ml/min/1.73 m2 received in a random order a single subcutaneous dose 1.2 mg liraglutide and placebo with subsequent 24 h blood pressure and natriuresis monitoring. Before and after each medication thoracic fluid index and plasma renin, aldosterone and ANP were also assessed. The blood pressure load in the daytime and nighttime were significantly increased after liraglutide compared to placebo in patients with eGFR < 30 ml/min/1.73 m2. In patients with eGFR > 60 ml/min/1.73 m2 the changes of arterial pressure were comparable, while the morning surge was significantly reduced after liraglutide compared to placebo. After liraglutide 24 h urine sodium excretion increased in both groups vs. placebo (p < 0.001), the effect was greatest in subjects with eGFR > 60 ml/min/1.73 m2. Plasma ANP increased after liraglutide in both groups, most in patients with eGFR < 30 ml/min/1.73 m2 group. Plasma aldosterone (p = 0.013) and thoracic fluid index (p = 0.01) decreased after liraglutide compared to placebo (p = 0.013 and p + 0.01, respectively. Plasma renin concentration remained unchanged. In severe chronic kidney disease liraglutide induces a transient increase of blood pressure due to reduced natriuresis. The natriuretic effect of liraglutide in DKD may be related to increased ANP and decreased aldosterone secretion.

A review and recommendations for oral chaperone therapy in adult patients with Fabry disease.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding the enzyme α-galactosidase A. FD-affected patients represent a highly variable clinical course with first symptoms already appearing in young age. The disease causes a progressive multiple organ dysfunction affecting mostly the heart, kidneys and nervous system, eventually leading to premature death. Disease-specific management of FD includes enzyme replacement therapy with agalsidase α and ß or pharmacological oral chaperone migalastat. Migalastat is a low-molecular-mass iminosugar, that reversibly binds to active site of amenable enzyme variants, stabilizing their molecular structure and improving trafficking to the lysosome. Migalastat was approved in the EU in 2016 and is an effective therapy in the estimated 35-50% of all patients with FD with amenable GLA gene variants. This position statement is the first comprehensive review in Central and Eastern Europe of the current role of migalastat in the treatment of FD. The statement provides an overview of the pharmacology of migalastat and summarizes the current evidence from the clinical trial program regarding the safety and efficacy of the drug and its effects on organs typically involved in FD. The position paper also includes a practical guide for clinicians on the optimal selection of patients with FD who will benefit from migalastat treatment, recommendations on the optimal selection of diagnostic tests and the use of tools to identify patients with amenable GLA mutations. Areas for future migalastat clinical research have also been identified.

The Plasma Neurofilament Light Chain, Brain-Derived Neurotrophic Factor, and Risk of Depression in Chronic Hemodialysis Patients.

INTRODUCTION: Depression is highly prevalent among hemodialysis patients. Understanding the relationship between the plasma neurofilament light chain (NfL) and brain-derived neurotrophic factor (BDNF) may help us to better understand the mechanisms of depression. This study determined their impact, alongside that of other factors, on the risk of depression in hemodialysis patients. METHODS: The study enrolled 82 patients undergoing chronic hemodialysis. Serum NfL, BDNF, uric acid, urea, potassium, calcium, phosphorus, intact parathyroid hormone, and C-reactive protein (CRP) levels were measured. The patients completed the Beck Depression Inventory (BDI). Blood pressure values, body mass before and after hemodialysis, and weekly duration of hemodialysis in hours were assessed. For 19-month survival analysis, the patients were stratified according to baseline BDI scores. RESULTS: Based on the BDI score, 18.3% of the patients had an increased risk of depression. Lower scores were associated with significantly longer duration of hemodialysis treatment (37.5 (25-57) 24 (14-37) months, p = 0.01). Within the 19-month survival analysis, 31.7% of patients died. The patients with BDI scores above the median had significantly lower survival than those below the median (log-rank test p = 0.02). No significant differences in serum BDNF levels (192.7 [125.2-278.2]; 207.7 [142.8-265.8] pg/mL, p = 0.40), or NfL concentrations (1431.5 [1182.6-1625.7]; 1494.6 [1335.7-1667] kDa, p = 0.52) were found between patients with lower and higher risk of depression. Patients with BDI scores above the median had significantly higher levels of CRP (9.6 [4.4-14]) than those with scores below the median (3.6 [2.2-7.5], p = 0.01). A significant positive correlation was found between the BDI score and serum CRP level (r = 0.38, p = 0.01). A significant negative correlation was observed between the BDI score and URR% value (r = -0.36, p = 0.02). CONCLUSIONS: Patients with lower BDI scores had a longer dialysis duration, indicating a potential negative association between depression risk and length of dialysis treatment. Neither serum NfL nor BDNF levels can serve as markers of depression risk in the dialysis population.

The Two-Domain Model Utilizing the Effective Pinning Energy for Modeling the Strain-Dependent Magnetic Permeability in Anisotropic Grain-Oriented Electrical Steels.

This paper presents a newly proposed domain wall energy-based model of the 2D strain dependence of relative magnetic permeability in highly grain-oriented anisotropic electrical steels. The model was verified utilizing grain-oriented M120-27s electrical steel sheet samples with magnetic characteristics measured by an automated experimental setup with a magnetic yoke. The model's parameters, identified in the differential evolution-based optimization process, enable a better understanding of the interaction between stress-induced anisotropy and magnetocrystalline anisotropy in electrical steels. Moreover, the consequences of the simplified description of grain-oriented magnetocrystalline anisotropy are clearly visible, which opens up the possibility for further research to improve this description.

Expression of semaphorin 3A (SEMA3A) in breast cancer subtypes.

Breast cancer is a major health concern, and its accurate diagnosis and management depend on identifying its histological type and biological subtype. Semaphorin-3A (SEMA3A) is a membrane protein with diverse roles in cellular processes, including cancer progression and angiogenesis regulation. However, its role in breast cancer remains poorly understood. This study aimed to evaluate SEMA3A expression in breast cancer and investigate its distribution across breast cancer subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Immunohistochemical evaluation was performed on 98 breast cancer patients' tumor specimens, and SEMA3A expression was assessed in tumor cells and vessels. The study included the analysis of the Ki67 proliferation index, estrogen receptor (ER) expression, progesterone receptor (PR) expression, and HER2 status in conjunction with SEMA3A expression. Analysis indicated positive expression of SEMA3A in breast cancer cells in 60 out of 98 cases. SEMA3A expression correlated positively with Ki67 levels in tumor cells (p = 0.0005, R Spearman 0.338). Notably, a negative correlation was found between SEMA3A expression and ER and PR levels in tumor cells (p = 0.04, Spearman's R = - 0.21 and p = 0.016, Spearman's R = - 0.25 respectively). HER2 status did not significantly influence SEMA3A expression. The study demonstrated positive SEMA3A expression in tumor vessels across all subtypes in 91 out of 98 cases, suggesting its involvement in endothelial cell function. However, no significant differences in SEMA3A expression were observed between breast cancer subtypes either in vessels or tumor cells. These findings suggest that elevated SEMA3A expression may be associated with worse prognosis in breast cancer, especially in ER- and PR-negative tumors. Further investigations are warranted to fully comprehend the role of SEMA3A in breast cancer biology, which may lead to the identification of novel therapeutic targets and personalized treatment strategies for breast cancer patients.

Continuous Erythropoietin Receptor Activator for the Treatment of Chronic Dialysis Patients with Renal Anemia in Daily Clinical Practice in Poland: A Non-Interventional, Multi-Center, Pragmatic NAVIGO Trial.

BACKGROUND: Renal anemia is one of the most common complications of chronic kidney disease (CKD). This real-life study assessed the effectiveness of methoxy polyethylene glycol-epoetin beta, a continuous erythropoietin receptor activator (C.E.R.A.), for the treatment of CKD-associated anemia in patients receiving dialysis in daily clinical practice. METHODS: 247 patients receiving chronic intermitted dialysis in 26 centers in Poland with CKD-associated symptomatic anemia, ESA-naïve, and with balanced iron stores in the investigators' opinion were enrolled this real-life study. Over 12 months, the following data were collected: hemoglobin (Hb) concentration and dosage, route of administration and dosing scheme of C.E.R.A., dialysis adequacy, adverse events, iron therapy, and blood transfusions. RESULTS: During the treatment, a Hb concentration of ≥10 g/dL was noted in 90.9% of hemodialysis patients (n = 224) and 96.0% of peritoneal dialysis patients (n = 23). At baseline, 7.8% of patients had a Hb concentration of 10-12 g/dL, which increased to 63.3% after 12 months. The median time when Hb concentration was maintained within 10-12 g/dL was 115.2 (interquartile range 49.1-188.7) days. A Hb concentration ≥12 g/dL was observed after 7 months of treatment in a maximum of 24.1% of hemodialysis patients, and 31.8% of peritoneal dialysis patients. The median time elapsed between the start of treatment and the first Hb concentration >10 g/dL was 42.0 (21.0-78.2) days. C.E.R.A. was well tolerated. CONCLUSIONS: C.E.R.A. corrects CKD-associated anemia in dialysis patients, and maintains Hb levels within the recommended target range. The study also confirmed the acceptable safety profile of the drug.

Kidney Transplant Recipients Show Limited Lung Diffusion Capacity but Similar Hydrogen Peroxide Exhalation as Healthy Matched Volunteers: A Pilot Study.

Patients with end-stage chronic kidney disease show higher systemic oxidative stress and exhale more hydrogen peroxide (H2O2) than healthy controls. Kidney transplantation reduces oxidative stress and H2O2 production by blood polymorphonuclear leukocytes (PMNs). Kidney transplant recipients (KTRs) may be predisposed to an impairment of lung diffusing capacity due to chronic inflammation. Lung function and H2O2 concentration in the exhaled breath condensate (EBC) were compared in 20 KTRs with stable allograft function to 20 healthy matched controls. Serum interleukin eight (IL-8) and C-reactive protein (CRP), blood cell counts, and spirometry parameters did not differ between groups. However, KTRs showed lower total lung diffusing capacity for carbon monoxide, corrected for hemoglobin concentration (TLCOc), in comparison to healthy controls (92.1 ± 11.5% vs. 102.3 ± 11.9% of predicted, p = 0.009), but similar EBC H2O2 concentration (1.63 ± 0.52 vs. 1.77 ± 0.50 µmol/L, p = 0.30). The modality of pre-transplant renal replacement therapy had no effect on TLCOc and EBC H2O2. TLCOc did not correlate with time after transplantation. In this study, TLCOc was less reduced in KTRs in comparison to previous reports. We suggest this fact and the non-elevated H2O2 exhalation exhibited by KTRs, may result perhaps from the evolution of the immunosuppressive therapy.

Physical Activity, Body Composition, Serum Myokines and the Risk of Death in Hemodialysis Patients.

Background and Objectives: The aim of this study was to assess the relationship between habitual physical activity, body composition, serum myokine concentration, and all-cause mortality in chronic hemodialysis patients. Materials and Methods: A prospective cohort study with a 7-year follow-up was conducted in a group of 38 patients (24 men, 14 women, mean age 65.6 ± 13.9 years, dialysis vintage 1.17 ± 1.25 years). Baseline serum concentrations of myokines-follistatin and myostatin-were assessed along with a measurement of physical activity with multidimensional accelerometery, body composition, and the force of forearm muscle contraction. Survival analysis was performed using the Kaplan-Meier method for tertiles of follistatin, serum myostatin, body composition, and physical activity expressed in metabolic equivalents (MET). Results: The mean physical activity among patients was 81 min/24 h (median 38.5 min), and the mean weekly 3MET activity was 493 min (median 218 min). The probability of survival of patients was significantly lower in the subgroup with 3MET/24 h less than 26 min/24 h and 3METt less than 148 min per week compared to the other subgroup (p = 0.006 and p = 0.006, respectively). During the 70-month follow-up, the subgroup with the lowest baseline follistatin concentration showed a significantly lower risk of death (p = 0.02). Baseline myostatin levels were not significant risk factors for mortality, nor were BMI or lean and fat tissue index categories. Conclusions: Physical activity and low plasma follistatin, but not body composition indexes or plasma myostatin, could serve as predictors of all-cause mortality in hemodialysis patients.

Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).

The TGFBI gene and protein expression in topotecan resistant ovarian cancer cell lines.

PURPOSE: The primary limiting factor in achieving cures for patients with cancer, particularly ovarian cancer, is drug resistance. The mechanisms of drug resistance of cancer cells during chemotherapy may include compounds of the extracellular matrix, such as the transforming growth factor-beta-induced protein (TGFBI). In this study, we aimed to analyze the TGFBI gene and protein expression in different sensitive and drug-resistant ovarian cancer cell lines, as well as test if TGFBI can be involved in the response to topotecan (TOP) at the very early stages of treatment. MATERIALS AND METHODS: In this study, we conducted a detailed analysis of TGFBI expression in different ovarian cancer cell lines (A2780, A2780TR1, A2780TR2, W1, W1TR, SKOV-3, PEA1, PEA2 and PEO23). The level of TGFBI mRNA (QPCR), intracellular and extracellular protein (Western blot analysis) were assessed in this study. RESULTS: We observed upregulation of TGFBI mRNA in drug-resistant cell lines and estrogen-receptor positive cell lines, which was supported by overexpression of both intracellular and extracellular TGFBI protein. We also showed the TGFBI expression after a short period of treatment of sensitive ovarian cancer cell lines with TOP. CONCLUSION: The expression of TGFBI in ovarian cancer cell lines suggests its role in the development of drug resistance.

Pharmacological Nephroprotection in Non-Diabetic Chronic Kidney Disease-Clinical Practice Position Statement of the Polish Society of Nephrology.

Chronic kidney disease (CKD) is a modern epidemic worldwide. Introducing renin-angiotensin system (RAS) inhibitors (i.e., ACEi or ARB) not only as blood-pressure-lowering agents, but also as nephroprotective drugs with antiproteinuric potential was a milestone in the therapy of CKD. For decades, this treatment remained the only proven strategy to slow down CKD progression. This situation changed some years ago primarily due to the introduction of drugs designed to treat diabetes that turned into nephroprotective strategies not only in diabetic kidney disease, but also in CKD unrelated to diabetes. In addition, several drugs emerged that precisely target the pathogenetic mechanisms of particular kidney diseases. Finally, the role of metabolic acidosis in CKD progression (and not only the sequelae of CKD) came to light. In this review, we aim to comprehensively discuss all relevant therapies that slow down the progression of non-diabetic kidney disease, including the lowering of blood pressure, through the nephroprotective effects of ACEi/ARB and spironolactone independent from BP lowering, as well as the role of sodium-glucose co-transporter type 2 inhibitors, acidosis correction and disease-specific treatment strategies. We also briefly address the therapies that attempt to slow down the progression of CKD, which did not confirm this effect. We are convinced that our in-depth review with practical statements on multiple aspects of treatment offered to non-diabetic CKD fills the existing gap in the available literature. We believe that it may help clinicians who take care of CKD patients in their practice. Finally, we propose the strategy that should be implemented in most non-diabetic CKD patients to prevent disease progression.

The response and resistance to drugs in ovarian cancer cell lines in 2D monolayers and 3D spheroids.

Ovarian cancer is the most common type of gynecologic cancer. One of the leading causes of high mortality is chemoresistance, developed primarily or during treatment. Different mechanisms of drug resistance appear at the cellular and cancer tissue organization levels. We examined the differences in response to the cytotoxic drugs CIS, MTX, DOX, VIN, PAC, and TOP using 2D (two-dimensional) and 3D (three-dimensional) culture methods. We tested the drug-sensitive ovarian cancer cell line W1 and established resistant cell lines to appropriate cytotoxic drugs. The following qualitative and quantitative methods were used to assess: 1) morphology - inverted microscope and hematoxylin & eosin staining; 2) viability - MTT assay; 3) gene expression - a quantitative polymerase chain reaction; 4) identification of proteins - immunohistochemistry, and immunofluorescence. Our results indicate that the drug-sensitive and drug-resistant cells cultured in 3D conditions exhibit stronger resistance than the cells cultured in 2D conditions. A traditional 2D model shows that drug resistance of cancer cells is caused mainly by changes in the expression of genes encoding ATP-binding cassette transporter proteins, components of the extracellular matrix, "new" established genes related to drug resistance in ovarian cancer cell lines, and universal marker of cancer stem cells. Whereas in a 3D model, the drug resistance in spheroids can be related to other mechanisms such as the structure of the spheroid (dense or loose), the cell type (necrotic, quiescent, proliferating cells), drug concentrations or drug diffusion into the dense cellular/ECM structure.

Supporting the Diagnosis of Fabry Disease Using a Natural Language Processing-Based Approach.

In clinical practice, the consideration of non-specific symptoms of rare diseases in order to make a correct and timely diagnosis is often challenging. To support physicians, we developed a decision-support scoring system on the basis of retrospective research. Based on the literature and expert knowledge, we identified clinical features typical for Fabry disease (FD). Natural language processing (NLP) was used to evaluate patients' electronic health records (EHRs) to obtain detailed information about FD-specific patient characteristics. The NLP-determined elements, laboratory test results, and ICD-10 codes were transformed and grouped into pre-defined FD-specific clinical features that were scored in the context of their significance in the FD signs. The sum of clinical feature scores constituted the FD risk score. Then, medical records of patients with the highest FD risk score were reviewed by physicians who decided whether to refer a patient for additional tests or not. One patient who obtained a high-FD risk score was referred for DBS assay and confirmed to have FD. The presented NLP-based, decision-support scoring system achieved AUC of 0.998, which demonstrates that the applied approach enables for accurate identification of FD-suspected patients, with a high discrimination power.

Nephro-oncology: clinical and biochemical aspects of kidney disease and cancer.

Onco-nephrology is a new field of medicine which combines many aspects of kidney injury in cancer patients and cancers in patients with kidney disease. This connection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, numerous paraneoplastic syndromes and an increased rate cancers in dialysis and transplanted patients. The appropriate laboratory assessment of the kidney function allows to optimize chemotherapy and thus minimizes the risk of complications. This article focuses on acute kidney injury (AKI), chronic kidney disease (CKD), various electrolyte and acid-base disorders, the most common cancers after kidney transplantation and the kidney disorders associated with HSCT (hematopoietic stem cell transplantation). The possibility of the application of novel cancer therapy, such as cancer immunotherapy and proton therapy in transplant recipients was also discussed.