Polymeric scaffolds as building blocks for nanomaterials with biomedical applications

Functional polymers are emerging as strong candidates for a variety of biomedical applications, but progress in this field is slow due to the difficulties associated with the synthesis of libraries of polymers. Polymeric scaffolds facilitate the rapid synthesis of such functional polymers by employing click chemistries as a tool for post-polymerisation modification. Acrylic and acetylene based polyhydrazides have been explored as potential scaffolds for the in situ screening of functionalised polymers for biomedical applications. Poly(acryloyl hydrazide) was prepared from commercially available starting materials using RAFT polymerisation in a three step synthesis, and its postpolymerisation modification using a variety of hydrophilic and hydrophobic aldehydes was investigated. Biocompatible solvents and reaction conditions were determined such that the postpolymerisation modification could be achieved with good yields or better. The applicability of the scaffold was shown during the in situ screening of functional polymers for siRNA delivery, which required no isolation or purification of candidate polymers. Poly(4-ethynylbenzohydrazide) was synthesised using rhodium catalysed polymerisation conditions, towards achieving a helical polymer scaffold. Despite the lack of solubility in aqueous solvents, the stability and post-polymerisation modification was analysed in a variety of conditions, opening the possibility of synthesising biodegradable mimics to naturally occurring helical moieties

SERUM LIPIDOMIC BIOMARKERS FROM PATIENTS WITH PROSTATE PATHOLOGY, IDENTIFIED BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED WITH MASS SPECTROMETRY

Introduction: Lipidomics can offer an instant picture of the lipophilic metabolites from tissues and biofluids and can indicate the evolution of different pathologies, such as hyperplasia or different types of cancers. Related to these pathologies, Prostate Serum Antigen (PSA), proved to have a low grade prediction for an accurate diagnosis. Meanwhile, untargeted or targeted metabolomics became a useful advanced technology to discover new biomarkers for a better diagnosis.Aims: To  realize an adequate procedure based on liquid chromatography coupled with mass spectrometry (HPLC-MS) to determine the profile of lipids from blood serum, followed by adequate biostatistics.Materials and Methods: Blood samples, obtained from healthy men and patients with prostate benign hyperplasia,  post-biopsy cancer and post-surgery cancer were processed for lipid extraction and subjected to HPLC-ESI(+)QTOF-MS measurements, followed by the multivariate analysis (PCA and Cluster Analysis) with Unscrambler 10.1 software. TofControl 3.2 and Data Analysis 4.2 software (BrukerDaltonics) were used for the control of the instrument and data processing.Results: The molecules responsible for such discriminations were identified to be mainly represented by lyso-phospatidylcholines. By Cluster Analysis, the dendograms showed good statistical clustering of samples, especially for cancer patients agains controls and less clustered for hyperplasia.Conclusion: One can consider that molecules belonging to phospholipid family and diacyl /triacylglycerides or ceramides or carnitines can be considered potential biomarkers for hyperplasia and prostate cancer

Software Components for Signal Fishing based on GA Element Position Optimizer

Long-term adaptation solutions do not receive much attention in the design phase of a wireless system. A new approach is proposed, where the antenna takes an active role in characterising and learning the operation environment. The proposed solution is based on a signal fishing mechanism. Several software components, among which a genetic optimizer, implement the processing stages of autonomous design of the antenna array during operation

Salvage radical prostatectomy after external beam radiation therapy: A systematic review of current approaches

Background: Radical external beam radiotherapy (EBRT) is a standard treatment for prostate cancer patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. For these patients, local salvage therapy such as radical prostatectomy, cryotherapy, and brachytherapy may be indicated. Objective: The objectives of this review were to analyze the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. Methods: A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. Results: Most studies demonstrated that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. Conclusions: Our results suggest that for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis. An improvement in selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological outcome and least comorbidity

Molecular basis and therapeutic targets in prostate cancer: A comprehensive review

Prostate cancer is one of the most significant causes of morbidity and mortality in male patients. The incidence increases with age, and it is higher among African Americans. The occurrence of prostate cancer is associated with many risk factors, including genetic and hereditary predisposition. The most common genetic syndromes associated with prostate cancer risk are BRCA-associated hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. Local-regional therapy, i.e., surgery is beneficial in early-stage prostate cancer management. Advanced and metastatic prostate cancers require systemic therapies, including hormonal inhibition, chemotherapy, and targeted agents. Most prostate cancers can be treated by targeting the androgen-receptor pathway and decreasing androgen production or binding to androgen receptors (AR). Castration-resistant prostate cancer (CRPC) usually involves the PI3K/AKT/mTOR pathway and requires targeted therapy. Specific molecular therapy can target mutated cell lines in which DNA defect repair is altered, caused by mutations of BRCA2, partner and localizer of BRCA2 (PALB2), and phosphatase and tensin homolog (PTEN) or the transmembrane protease serine 2-ERG (TMPRSS2-ERG) fusion. Most benefits were demonstrated in cyclin dependent-kinase 12 (CDK12) mutated cell lines when treated with anti-programmed cell death protein 1 (PD1) therapy. Therapies targeting p53 and AKT are the subject of ongoing clinical trials. Many genetic defects are listed as diagnostic, prognostic, and clinically actionable markers in prostate cancer. Androgen receptor splice variant 7 (AR-V7) is an important oncogenic driver and an early diagnostic and prognostic marker, as well as a therapeutic target in hormone-resistant CRPC. This review summarizes the pathophysiological mechanisms and available targeted therapies for prostate cancer

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes

Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy

To investigate the prognostic role of neutrophil percentage-to-albumin ratio (NPAR) in muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC)

Evaluation of predictive factors for i-CLARAS (intraoperative complications in laparoscopic renal and adrenal surgery): a multicentre international retrospective cohort study

The laparoscopic approach represents the standard of treatment for renal and adrenal diseases, and its use is increasing even outside referral centres. Although most procedures are routinely performed, intraoperative complications do not occur, and the rate and predictive factors of these complications have not been established. The aim of this study was to evaluate the incidence and type of intraoperative complications and to identify predictive factors in patients undergoing laparoscopic renal and adrenal surgery. This was a cohort, multicentre, international retrospective study. Patients who underwent laparoscopic renal and adrenal surgeries between April 2017 and March 2022 were included in the study. Bivariate analysis was performed using contingency tables and the χ2 test for independent samples to compare qualitative variables and the T test and Mood test for continuous variables. Multivariate analysis was performed using a logistic regression model to obtain adjusted odds ratios. A total of 2374 patients were included in the study. Intraoperative complications were reported for 8.09% of patients who underwent renal surgery, with the most common complications reported being hollow viscus and vascular complications, and for 6.75% of patients who underwent adrenal surgery, with the most common complication reported being parenchymatous viscous complications. Multivariate analysis revealed that both adrenal and renal surgery radiological preoperative factors, such as invasive features during adrenalectomy and the RENAL score during nephrectomy, are predictive factors of intraoperative complications. In contrast to existing data, surgeon experience was not associated with a reduction in the incidence of perioperative complications

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years