Publications by authors named "Leszek Paczek"

Oxidative stress (OS), defined as an imbalance between pro-oxidant and antioxidant mechanisms, contributes to DNA and protein oxidation as well as cellular injury, and plays a pivotal role in the pathogenesis of chronic kidney disease (CKD). Peroxiredoxins (PRDXs) are key antioxidant enzymes that regulate intracellular peroxide levels and maintain redox homeostasis. Beyond its renal implications, OS is closely intertwined with hypertension and atherosclerosis, both common comorbidities that accelerate CKD progression.

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Emerging treatments for antibody-mediated rejection (ABMR, NEJM391(2):122-132) have increased the importance of ABMR detection when donor-specific antibody (DSA) is negative. We addressed this issue in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703) using three centralized tests in 690 kidney transplant biopsies: DSA (One Lambda Inc.

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Background/objectives: The risk of post-transplantation lymphoproliferative disorder (PTLD) varies according to the type of transplanted organ. To investigate the factors contributing to PTLD development and treatment outcomes, we established a multicenter registry that included patients diagnosed with PTLD within a population of 13,263 kidney, liver, and lung transplant recipients (KTRs, LTRs, and LngTRs, respectively), observed in a period between 2000 and 2023.

Methods: The chi-squared test was used to analyze differences in group composition.

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Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a rising global health issue. Chronic intestinal inflammation is an important risk factor for colorectal cancer (CRC). Despite significant progress in IBD and CRC treatment, numerous patients remain resistant to standard pharmacotherapy or experience severe side effects that prevent them from continuing treatment.

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: microRNAs are small non-coding RNAs that regulate gene expression by inducing mRNA degradation or inhibiting translation. A growing body of evidence suggests that miRNAs may be utilized as anti-cancer therapeutics by targeting expression of key genes involved in cancerous transformation and progression. Renal cell cancer (RCC) is the most common kidney malignancy.

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Background: Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely underexplored.

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Background: Prevalence of type 2 diabetes increases with age. Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) promote the enrollment of older patients to randomized controlled trials (RCTs) in diabetes. The objective of this study was to assess the eligibility criteria limiting the inclusion of older adults to RCTs in type 2 diabetes.

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Article Synopsis
  • IgA vasculitis (IgAV) is a pediatric disease characterized by skin and systemic symptoms, and researchers conducted comprehensive studies involving genome, transcriptome, and proteome analyses on a large cohort of IgAV patients and controls to better understand the disease mechanisms.* -
  • Significant associations were found with specific genetic risk factors, including two novel non-HLA loci linked to IgA receptor functioning, which may contribute to disease development through altered immune responses.* -
  • Systems biology approaches helped identify key regulatory networks and master regulators in myeloid cells, along with 21 genetic loci that overlap with IgA nephropathy, suggesting shared pathways in these related conditions.*
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Although therapies based on mesenchymal stromal cells (MSCs) are being implemented in clinical settings, many aspects regarding these procedures require further optimization. Domestic dogs suffer from numerous immune-mediated diseases similar to those found in humans. This study aimed to assess the immunomodulatory activity of canine (c) Wharton jelly (WJ)-derived MSCs and refer them to human (h) MSCs isolated from the same tissue.

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  • Xanthine oxidase inhibitors like allopurinol and febuxostat are primary treatments for high uric acid levels, known as hyperuricemia.
  • A meta-analysis of 11 studies found that these therapies had no overall impact on all-cause mortality, but showed potential benefits for patients with chronic kidney disease and hyperuricemia, resulting in a 14% lower risk of death.
  • However, the treatment may actually increase mortality by 28% in heart failure patients, suggesting it should be avoided in this group.
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Background: Long-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunologic deterioration. Pretransplant C-reactive protein (CRP) and albumin (ALB) levels impact kidney transplantation. We evaluated the effects of preoperative CRP, ALB, neutrophils (NEU), and platelet (PLT) counts on 1- and 5-year recipient survival after simultaneous pancreas and kidney transplantation (SPK).

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Obesity is a risk factor for many diseases, diagnosed by calculating body mass index (BMI). To find an association between BMI and mortality in adults, we searched PubMed for articles published in the 21st century. Our review included 82 original studies, comprising 2.

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Background: Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications.

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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of malignant and non-malignant disorders. CARs are synthetic transmembrane receptors expressed on genetically modified immune effector cells, including T cells, natural killer (NK) cells, or macrophages, which are able to recognize specific surface antigens on target cells and eliminate them. CAR-modified immune cells mediate cytotoxic antitumor effects via numerous mechanisms, including the perforin and granzyme pathway, Fas and Fas Ligand (FasL) pathway, and cytokine secretion.

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Assessing inorganic phosphate levels seems crucial in deciphering the biochemical state of organisms or tissues. The concentration of inorganic phosphate in blood is an order of magnitude smaller than in tissues and, on top of that, it is dynamically used to fill temporary gaps in tissues. This is the reason blood inorganic phosphate level is considered a poor proxy for tissue levels.

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BACKGROUND Hypertension is a risk factor for graft failure and mortality among kidney transplant recipients (KTRs). The aim of the study was to examine blood pressure (BP) as a factor that contributes to graft failure or death during a 10-year observation period. MATERIAL AND METHODS The study group comprised 70 KTRs who were treated according to their clinical state.

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Article Synopsis
  • This study focuses on the role of Neutrophil Extracellular Traps (NETs) in the development of thoracoabdominal aortic aneurysms and how they are influenced during surgery involving stent-graft implantation.
  • It involved 20 patients and assessed NETosis markers (dsDNA, ssDNA, and Cit-H3) before and after surgery to evaluate inflammation and coagulation responses.
  • The results indicated an increase in NET markers after surgery, highlighting their significance in the inflammatory response, and introduced ssDNA as a new marker for NETosis.*
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Immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly limited the spread of coronavirus disease 2019 (COVID-19) and reduced the associated complications, especially mortality. To prolong immunity, an immune booster was implemented. We evaluated the role of SARS-CoV-2 infection history in the vaccination schedules of kidney and liver transplant recipients and patients with chronic kidney disease (CKD).

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Background: Advanced renal cell carcinoma (RCC) is therapeutically challenging. RCC progression is facilitated by mesenchymal stem/stromal cells (MSCs) that exert remarkable tumor tropism. The specific mechanisms mediating MSCs' migration to RCC remain unknown.

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  • IgA nephropathy (IgAN) is a serious kidney disease linked to IgA buildup, and a large study identified 30 genetic risk factors associated with it.
  • Fourteen new loci were discovered that suggest a connection between genetic influences and abnormal IgA levels.
  • The research highlights inflammation-related pathways and potential drug targets, revealing that higher genetic risk scores are tied to earlier kidney failure.
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Chronic kidney disease (CKD) is associated with increased levels of creatinine and other uremic toxins (UTs), which impaired kidneys cannot filtrate. Typically, CKD is diagnosed by calculating the estimated glomerular filtration rate using serum creatinine or cystatin C levels. In pursuit of more sensitive and reliable biomarkers of kidney dysfunction, scientific attention has turned towards other UTs, such as trimethylamine N-oxide (TMAO), successfully quantified in standard matrices, blood and urine.

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BACKGROUND Carbapenems are the primary treatment for urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae. However, the recurrence rate is high, and patients often require rehospitalization. We present the results of an observational study on patients with recurrent UTIs who were treated in an outpatient setting with maximal therapeutic oral doses of amoxicillin with clavulanic acid.

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During the last decade, thanks to omics technologies, new light has been shed on the pathogenesis of many diseases. Genomics, epigenomics, transcriptomics, and proteomics have helped to provide a better understanding of the origin and heterogeneity of several diseases. However, the risk factors for most autoimmune diseases remain unknown.

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