Radical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest

IntroductionPatients with renal cell carcinoma (RCC) with level 3 or 4 caval thrombus have a poor prognosis, with reported five-year survival rates of 30–40%. The aim of this study was to assess the perioperative morbidity and long-term oncological outcomes for radical nephrectomy with resection of vena cava thrombus using a combined surgical approach, including extracorporeal circulation and deep hypothermic circulatory arrest.MethodsA retrospective review was performed of the institutional case log to identify all radical nephrectomies with caval thrombus performed from January 2006 to May 2020.ResultsTwenty-five patients were identified with level 2 thrombus in one (4%), level 3 thrombus in eight (32%), and level 4 in 16 (64%). The median followup was 20.6 months (range 0.2–133.3). The median age at surgery was 68.4 years (range 44.2–85.5). Twenty-one (84%) patients were symptomatic at presentation. Six (24%) patients had distant metastases at diagnosis. The median circulatory arrest time was 15 minutes (range 6–35). The 30-day grade ≥3 complication rate was 8%. The 30-day mortality rate was 8%. The one-year, two-year, three-year, and five-year recurrence-free survival (RFS) rates were 53%, 18%, 10%, and 10%, respectively. The median time to systemic treatment was 7.7 months (range 1.2–25.7). The one-year, two-year, three-year, and five-year overall survival (OS) rates were 70%, 43%, 36%, and 31%, respectively.ConclusionsRadical nephrectomy with resection of vena cava thrombus using extracorporeal circulation and deep hypothermic circulatory arrest is associated with some morbidity and mortality but remains a safe and effective strategy for advanced RCC patients who would otherwise be managed palliatively.     

A good ligand is hard to find: Automated docking methods

Summary Many approaches have been developed for solving the docking problem: Predict the structure and binding free energy of a ligand-receptor complex given only the structures of the free ligand and receptor. We review major approaches for docking small-molecule ligands to receptors and focus on the successes and limitations of their application to drug design.     

Growth factor antagonists for the treatment of diabetic vascular complications

Diabetic vascular disease is characterised by altered vascular reactivity and blood flow, hyperpermeability, hyperproliferative responses, and increased extracellular matrix deposition in tissues that are sites of complications. These vascular functional and structural changes have been linked to excessive glucose metabolism in target organs via at least three pathophysiological mechanisms, including increased sorbitol (polyol) pathway activity, increased nonenzymatic glycation of vascular wall proteins, and increased protein kinase C (PKC) activity. These potential mechanisms of glucose toxicity remain the subject of intense scientific investigation, and therapies targeting each of them are being evaluated in clinical trials. It is becoming increasingly clear that excessive production of growth factors provides a common denominator linking these diverse mechanisms of glucose toxicity to the functional and structural vascular alterations associated with diabetes. Increased expression of vascular endothelial growth factor (VEGF) has been linked to increased metabolism of glucose via the sorbitol pathway, to nonenzymatic glycation, and to increased PKC activity, and appears to modulate the hyperpermeability and hyperproliferative responses of diabetes. Consequently, because of the unmet medical need and market size, numerous pharmaceutical and biotechnology companies have initiated research programmes evaluating growth factor antagonists as a potential therapeutic approach for treating complications associated with diabetic vascular disease. However, before growth factor antagonists can enter clinical testing, a number of important issues must be clarified, including the physiological effect of chronic growth factor inhibition, which appears to be necessary for ameliorating chronic vascular deterioration of diabetes, and administration routes, especially for protein-based therapies.     

Exacerbation of postdural puncture headache after epidural blood patch

The purpose of this report is to describe a new complication of epidural blood patch for inadvertent dural puncture. A dural tap in an obstetric patient was managed initially with a prophylactic blood patch via the epidural catheter. Despite this, 48 hr later, she developed post-dural puncture headache, neck, and shoulder pain, and was given a second epidural blood patch. This was followed by an immediate and severe exacerbation of her symptoms, which later resolved after the administration of diclofenac. There were no further sequelae. Although severe complications of epidural blood patch are rare, they are alarming. Exacerbation of the original symptoms of post-dural puncture headache caused by, or following, epidural blood patching has not previously been reported.     

Mechanical properties of a light-polymerizing provisional restorative material with and without reinforcement fibers

Interim restorations are vulnerable to inadvertent fracture during mastication. Autopolymerizing acrylic resins have traditionally been selected for fabrication of provisional restorations. Triad light-polymerizing tooth-colored acrylic resin was recently introduced as an alternative material for this procedure. This material does not contain methyl methacrylate monomer and permits an increased working time. Heavy occlusal forces may initiate cracks within these restorations, and propagation of these cracks may ultimately lead to failure. Various forms of reinforcement fibers are available and are marketed for strengthening dental resins used for provisional restorations. Investigators have demonstrated that the mechanical properties of acrylic resins may be improved with the incorporation of reinforcing fibers, but a published evaluation of fiber-reinforced light-polymerizing provisional restorative materials is lacking. This investigation recorded and compared two mechanical properties of one light-polymerizing provisional restorative material with and without incorporation of vertically and horizontally oriented woven, matted, polyethylene fibers. No significant difference in modulus of rupture was recorded between groups with and without fibers. The mean flexural elastic modulus of the group with the horizontally oriented fibers was significantly greater than the mean flexural elastic modulus of the specimens without incorporated fibers.