Optimal conduit choice for open lower extremity bypass in chronic limb-threatening ischemia.

Open bypass surgery remains a major tool for limb salvage in chronic limb-threatening ischemia (CLTI). Although rest pain and tissue loss both fall into the category of CLTI, goals of revascularization are markedly different for each context. Rest pain mandates long-term patency considerations. Tissue loss, however, requires consideration of infection risks and patency enough to heal the wound. Of the major conduit options, autologous saphenous vein graft continues to be the conduit of choice, given both superior patency and low risk of infection. When saphenous vein graft is not available or not available in appropriate length, arm vein, small saphenous vein, and spliced combinations of these have acceptable patency rates. Heparin-bonded polytetrafluoroethylene and Dacron grafts are prosthetic conduits with excellent patency rates when vein is not available. For infected wounds without other options, cryovein continues to provide acceptable patency for limb salvage. Creation of a bypass is only part of CLTI management. Appropriate postoperative surveillance with noninvasive studies, including ankle-brachial index and duplex ultrasound, can alert to impending graft failure, with a drop in ankle-brachial index of 0.15 and velocity ratios of 3 or more suggestive of significant stenoses. Anticoagulation has only been found in limited contexts (such as poor conduit or poor outflow) to offer some patency benefit, however, findings from the VOYAGER PAD (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial were a major breakthrough, showing a reduction in the composite outcome of major adverse limb, cardiac, and cerebrovascular events in revascularized patients taking low-dose rivaroxaban in conjunction with aspirin, without a substantial increase in bleeding risk.

A Quality Improvement Initiative to Improve Medication Management in an Acute Care for Elders Program Through Integration of a Clinical Pharmacist.

PURPOSE: To describe the implementation and impact of integrating a clinical pharmacist into interdisciplinary Acute Care for Elderly (ACE) rounds at a teaching hospital. METHODS: Pre- and postanalyses were performed 6 months before and 12 months after the intervention. We report the total number, type, and frequency of recommendations made by the clinical pharmacist, the acceptance rate by the physician, and interventions on potentially inappropriate medications (PIM). RESULTS: Among the 588 patients who met the ACE inclusion criteria, mean age was 81.2 years, 54.9% were female, and 79.8% were of white race. A total of 1243 pharmacy recommendations were recorded. The median number of recommendations per patient increased from a median of 1 (range: 1-7) in the preintervention to 2 (1-13) in the postintervention period, resulting in an incidence rate ratio of 1.25 (95% confidence interval [CI]: 1.10-1.40). The main categories of recommendations were dose adjustment, avoidance of inappropriate therapy, and prevention of adverse drug events. In the postintervention period, there was an increase in recommendations among analgesics (from 3.7% to 7.5%), PIMs (from 12% to 14%), and, in particular, antidepressant/antipsychotics (from 1.9% to 6.0%). The acceptance rate of the recommendations remained roughly the same (86.5% vs 84.4%). CONCLUSION: Proactive involvement of a clinical pharmacist in ACE rounds resulted in a substantial increase in recommendation for medication changes, most notably for PIMs. These recommendations generally were accepted by physicians. The integration of a clinical pharmacist requires significant dedicated time but leads to increased recognition of drug-related problems in the acute-care setting, resulting in improved patient outcomes.

Coacervation and precipitation in polysaccharide-protein systems.

Precipitation poses a consistent problem for the growing applications of biopolymer coacervation, but the relationship between the two types of phase separation is not well understood. To clarify this relationship, we studied phase separation as a function of pH and ionic strength, in three systems of proteins with anionic polysaccharides: ß-lactoglobulin (BLG)/hyaluronic acid (HA); BLG/tragacanthin (TG); and monoclonal antibody (mAb)/HA. We found that coacervation and precipitation are intrinsically different phenomena, responsive to different factors, but their simultaneity (for example with changing pH) may be confused with transitions from one state to another. We propose that coacervate does not literally turn into precipitate, but rather that both coacervate and precipitate are in equilibrium with free protein and polyanion, so that dissolution of one and formation of the other can overlap in time. While protein-polyanion complexes must achieve neutrality for coacervation, precipitation only requires tight binding which leads to the expulsion of counterions and water molecules. The pH-dependence of phase separation, considered in terms of protein and polyion charge, revealed that the electrostatic magnitude of the protein's polymer-binding site ("charge patch") plays a key role in the strength of interaction. These findings were supported by the inhibition of precipitation, seen when the bulky side chains of TG impede close protein-polymer interactions.

Complex equilibria, speciation, and heteroprotein coacervation of lactoferrin and ß-lactoglobulin.

There has been a resurgence of interest in complex coacervation, a form of liquid-liquid phase separation (LLPS) in systems of oppositely charged macroions, but very few reports describe the somewhat anomalous coacervation between acidic and basic proteins, which occurs under very narrow ranges of conditions. We sought to identify the roles of equilibrium interprotein complexes during the coacervation of ß-lactoglobulin dimer (BLG2) with lactoferrin (LF) and found that this LLPS arises specifically from LF(BLG2)2. We followed the progress of complexation and coacervation as a function of r, the LF/BLG molar ratio, using turbidity to monitor the degree of coacervation and proton release and dynamic light scattering (DLS) to assess the stoichiometry and abundance of complexes. Isothermal titration calorimetry (ITC) showed that initial complex formation is endothermic, but a large exotherm related to coacervate formation obscured other regions. On the basis of turbidimetry, proton release, and DLS, we propose a speciation diagram that presents the abundance of various complexes as a function of r. Although multiple species could be simultaneously present, distinct regions could be identified corresponding to equilibria among particular protein pairs.