Repurposing FDA-approved drugs to target G-quadruplexes in breast cancer.

Breast cancer, a leading cause of cancer-related mortality in women, is characterized by genomic instability and aberrant gene expression, often influenced by noncanonical nucleic acid structures such as G-quadruplexes (G4s). These structures, commonly found in the promoter regions and 5'-untranslated RNA sequences of several oncogenes, play crucial roles in regulating transcription and translation. Stabilizing these G4 structures offers a promising therapeutic strategy for targeting key oncogenic pathways.

The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit.

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials.

Emerging role of genetics in kidney transplantation.

The advent of more affordable genomic analytical pipelines has facilitated the expansion of genetic studies in kidney transplantation. Advances in genetic sequencing have allowed for a greater understanding of the genetic basis of chronic kidney disease, which has helped to guide transplant management and address issues related to living donation in specific disease settings. Recent efforts have shown significant effects of genetic ancestry and donor APOL1 risk genotypes in determining worse allograft outcomes and increased donation risks.

Identification and analysis of reference-independent movement event-related desynchronization.

Characterization of the electroencephalography (EEG) signals related to motor activity, such as alpha- and beta-band motor event-related desynchronizations (ERDs), is essential for Brain Computer Interface (BCI) development. Determining the best electrode combination to detect the ERD is crucial for the success of the BCI. Considering that the EEG signals are bipolar, this involves the choice of the main and reference electrodes.

The Janus-faced nature of complement in hemodialysis: interplay between complement, inflammation, and bioincompatibility unveiling a self-amplifying loop contributing to organ damage.

In hemodialysis (HD), complement activation, bioincompatibility, and inflammation are intricately intertwined. In the 1970s, as HD became a routine therapy, the observation of complement pathway activation and transient leukopenia by cellulosic dialysis membranes triggered the bioincompatibility debate and its clinical relevance. Extensive deliberations have covered definitions, assessment markers, scope, and long-term clinical consequences of membrane-dependent bioincompatibility reactions.

Post-transplant glomerular diseases: update on pathophysiology, risk factors and management strategies.

In recent years, advancements in immunosuppressive medications and post-transplant management have led to a significant decrease in acute rejection rates in renal allografts and consequent improvement in short-term graft survival. In contrast, recent data have shown an increased incidence of post-transplant glomerular diseases, which currently represent a leading cause of allograft loss. Although pathogenesis is not fully understood, growing evidence supports the role of inherited and immunological factors and has identified potential pre- and post-transplant predictors.

Metastasis-directed stereotactic radiotherapy and systemic treatment continuation for patients with oligoprogressive metastatic breast cancer.

Background: About 15-20 % of patients with metastatic breast cancer (mBC) can experience oligoprogressive disease (OPD) in ≤ 5 sites of disease. Patients with OPD may benefit from metastasis-directed stereotactic radiotherapy (SBRT) to all sites of cancer progression while maintaining the same systemic treatment, aiming to prolong the time to next systemic treatment (NEST). This study aims to assess the outcomes provided by this multimodal strategy.

Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study.

Background: Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown.

Patients And Methods: We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers.

[What's New in the CKD-BMD Therapy?].

The important advances in scientific knowledge have led to a notable enrichment of therapeutic offers in the field of CKD-MBD, which have allowed better control of the related biochemical parameters compared to the past. However, this has not corresponded to a tangible improvement in the clinical outcomes, both bone and cardiovascular, associated with CKD-MBD, nor has there been a significant drop in the number of pills that nephropathic patients must take, to keep the parameters controlled biochemicals, with the therapeutic cost of these interventions remaining high. All these unsatisfied needs continue to stimulate research to find new solutions that can improve one or more of these objectives not yet achieved.

Changes in 24-hour blood pressure profile after 12 weeks of dapagliflozin treatment in patients with diabetic kidney disease: an Italian multicenter prospective study.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) lower ambulatory blood pressure (ABP) in patients with type 2 diabetes mellitus; whether the same holds true in diabetic kidney disease (DKD) is unknown. This information is critical to the knowledge of mechanisms of nephroprotection and safety of this therapy.

Methods: This multicenter prospective study evaluates the changes in ABP after 12 weeks of dapagliflozin 10 mg/day in a cohort of patients with type 2 DKD and glomerular filtration rate (GFR) >25 mL/min/1.

Fresh Frozen Plasma in Orthotopic Liver Transplant: Friend or Foe?

Background: Traditionally, the administration of large volumes of fresh frozen plasma (FFP) was common during liver transplant surgery, with no improvement in the results in terms of bleeding and blood-saving. Moreover, this hydric overload caused by FFP may be harmful, leading to an increase in hospital stays and patient morbidity.

Methods: The objective is to assess the morbidity associated to the use of FFP in the intraoperative period of patients undergoing orthotopic liver transplantation.

Proceedings of a membrane update symposium: advancements, scientific insights, and future trends for dialysis membranes for enhanced clinical outcomes in end stage kidney disease patients.

Purpose Of Symposium: From September 6 - 8 2022, the Life/2022 Membrane Symposium was held in Frankfurt, Germany, and transmitted live to a worldwide internet audience. The event was part of the Life/Nephrology Campus initiative, a continuous educational platform for the nephrology community to expand knowledge and share expertise on contemporary topics in chronic kidney disease. We describe recent questions and advances in the field, and we underline challenges in the care of dialysis patients and opportunities for integration of new findings into clinical practice to improve patient outcomes in end stage kidney disease patients.

The role of gene-environment interactions in social dysfunction: Focus on preclinical evidence from mouse studies.

Human and animal research has demonstrated that genetic and environmental factors can strongly modulate behavioral function, including the expression of social behaviors and their dysfunctionalities. Several genes have been linked to pathologies characterized by alterations in social behaviors, e.g.

Developing combination therapies with biologics in triple-negative breast cancer.

Introduction: Novel compounds have entered the triple-negative breast cancer (TNBC) treatment algorithm, namely immune checkpoints inhibitors (ICIs), PARP inhibitors and antibody-drug conjugates (ADCs). The optimization of treatment efficacy can be enhanced with the use of combination treatments, and the incorporation of novel compounds. In this review, we discuss the combination treatments under development for the treatment of TNBC.

Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19] years.

Native vitamin D in CKD and renal transplantation: meaning and rationale for its supplementation.

Chronic kidney disease (CKD) poses a significant epidemiological challenge, necessitating effective patient management strategies. Nutritional intervention, particularly vitamin D supplementation, has garnered attention for its potential therapeutic utility in CKD. Despite widespread acknowledgment of the importance of vitamin D, particularly in bone and mineral metabolism, its supplementation in CKD patients for non-skeletal purposes remains contentious due to limited evidence.

Hepatitis C virus infection is associated with proteinuria according to a systematic review with meta-analysis.

Introduction And Aim: Hepatitis C virus infection and chronic kidney disease are major public health issues all over the world. It has been suggested a role of HCV as a risk factor for the development and progression of chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) in the general population but conflicting findings have been given.

Material And Methods: A systematic review of the published medical literature was conducted to assess whether positive HCV serologic status is associated with greater rate of proteinuria in the adult general population.

Germline BRCA pathogenic variants in patients with ovarian cancer and post-poly (ADP-ribose) polymerase inhibitor myeloid neoplasms.

Background: Among patients with advanced high-grade ovarian carcinoma (aHGOC) treated with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis), the presence of a germline BRCA pathogenic variant (gBRCA-PV) may increase the risk of bone marrow mutagenesis resulting in postcytotoxic therapy myelodysplastic neoplasms (MDS-pCT) or acute myeloid leukemia (AML-pCT), as it is expressed in heterozygosity also by hematopoietic progenitors. We aimed to investigate the occurrence of post-PARPi MDSs/AMLs-pCTs according to gBRCA-PV status.

Patients And Methods: We conducted a retrospective single-center study to evaluate MDS/AML-pCT in patients with aHGOC and a known gBRCA-PV status receiving at least 8 weeks of maintenance PARPi, in any line of therapy, from February 2017 to December 2022.

Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients.

Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1).

Clinical Factors and Biomarkers Associated with Depressive Disorders in Older Patients Affected by Chronic Kidney Disease (CKD): Does the Advanced Glycation End Products (AGEs)/RAGE (Receptor for AGEs) System Play Any Role?

Depressive disorders are highly prevalent among subjects suffering from chronic kidney disease (CKD). The aim of the present study is to evaluate clinical and biochemical factors associated with depressive disorders in a sample of older CKD patients, with a focus on advanced glycation end products (AGEs) and their soluble receptors (sRAGEs). A total of 115 older subjects affected by CKD (stages 3 to 5, not in dialysis) were selected for this study.

Recognition patterns of acute kidney injury in hospitalized patients.

Background: Acute kidney injury (AKI) during hospitalization is associated with increased complications and mortality. Despite efforts to standardize AKI management, its recognition in clinical practice is limited.

Methods: To assess and characterize different patterns of AKI diagnosis, we collected clinical data, serum creatinine (sCr) levels, comorbidities and outcomes from adult patients using the Hospital Discharge Form (HDF).