No abstract

Infection stones-which account for 10-15% of all urinary calculi-are thought to form in the presence of urease-producing bacteria. These calculi can cause significant morbidity and mortality if left untreated or treated inadequately; optimal treatment involves complete stone eradication in conjunction with antibiotic therapy. The three key principles of treating struvite stones are: removal of all stone fragments, the use of antibiotics to treat the infection, and prevention of recurrence. Several methods to remove stone fragments have been described in the literature, including the use of urease inhibitors, acidification therapy, dissolution therapy, extracorporeal shockwave lithotripsy, ureteroscopy, percutaneous nephrolithotomy (PCNL), and anatrophic nephrolithotomy. PCNL is considered to be the gold-standard approach to treating struvite calculi, but adjuncts might be used when deemed necessary. When selecting antibiotics to treat infection, it is necessary to acquire a stone culture or, at the very least, urine culture from the renal pelvis at time of surgery, as midstream urine cultures do not always reflect the causative organism.

Ureteral stents are one of the most commonly used devices in the treatment of benign and malignant urological diseases. However, they are associated with common complications including encrustation, infection, pain and discomfort caused by ureteral tissue irritation and possibly irregular peristalsis. In addition, stent migration and failure due to external compression by malignancies or restenosis occur, albeit less frequently. As these complications restrict optimal stent function, including maintenance of adequate urine drainage and alleviation of hydronephrosis, novel stent materials and designs are required. In recent years, progress has been made in the development of drug-eluting expandable metal stents and biodegradable stents. New engineering technologies are being investigated to provide stents with increased biocompatibility, decreased susceptibility to encrustation and improved drug-elution characteristics. These novel stent characteristics might help eliminate some of the common complications associated with ureteral stenting and will be an important step towards understanding the behaviour of stents within the urinary tract.

Heparin-based anticoagulant drugs have been widely used for the prevention of blood clotting during surgical procedures and for the treatment of thromboembolic events. However, bleeding risks associated with these anticoagulants demand continuous monitoring and neutralization with suitable antidotes. Protamine, the only clinically approved antidote to heparin, has shown adverse effects and ineffectiveness against low-molecular weight heparins and fondaparinux, a heparin-related medication. Alternative approaches based on cationic molecules and recombinant proteins have several drawbacks including limited efficacy, toxicity, immunogenicity, and high cost. Thus, there is an unmet clinical need for safer, rapid, predictable, and cost-effective anticoagulant-reversal agents for all clinically used heparins. We report a design strategy for a fully synthetic dendritic polymer-based universal heparin reversal agent (UHRA) that makes use of multivalent presentation of branched cationic heparin binding groups (HBGs). Optimization of the UHRA design was aided by isothermal titration calorimetry studies, biocompatibility evaluation, and heparin neutralization analysis. By controlling the scaffold's molecular weight, the nature of the protective shell, and the presentation of HBGs on the polymer scaffold, we arrived at lead UHRA molecules that completely neutralized the activity of all clinically used heparins. The optimized UHRA molecules demonstrated superior efficacy and safety profiles and mitigated heparin-induced bleeding in animal models. This new polymer therapeutic may benefit patients undergoing high-risk surgical procedures and has potential for the treatment of anticoagulant-related bleeding problems.