In vivo evaluation of temperature-responsive antimicrobial-loaded PNIPAAm hydrogels for prevention of surgical site infection.

Surgical site infections (SSIs) are a persistent clinical challenge. Local antimicrobial delivery may reduce the risk of SSI by increasing drug concentrations and distribution in vulnerable surgical sites compared to what is achieved using systemic antimicrobial prophylaxis alone. In this work, we describe a comprehensive in vivo evaluation of the safety and efficacy of poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ], an injectable temperature-responsive hydrogel carrier for antimicrobial delivery in surgical sites. Biodistribution data indicate that PNDJ is primarily cleared via the liver and kidneys following drug delivery. Antimicrobial-loaded PNDJ was generally well-tolerated locally and systemically when applied in bone, muscle, articulating joints, and intraperitoneal space, although mild renal toxicity consistent with the released antimicrobials was identified at high doses in rats. Dosing of PNDJ at bone-implant interfaces did not affect normal tissue healing and function of orthopedic implants in a transcortical plug model in rabbits and in canine total hip arthroplasty. Finally, PNDJ was effective at preventing recurrence of implant-associated MSSA and MRSA osteomyelitis in rabbits, showing a trend toward outperforming commercially available antimicrobial-loaded bone cement and systemic antimicrobial administration. These studies indicate that antimicrobial-loaded PNDJ hydrogels are well-tolerated and could reduce incidence of SSI in a variety of surgical procedures.

Serum Lactate and Mortality in Emergency Department Patients with Cancer.

INTRODUCTION: Patients with malignancy represent a particular challenge for the emergency department (ED) given their higher acuity, longer ED length of stay, and higher admission rate. It is unknown if patients with malignancies and hyperlactatemia are at increased risk of mortality. If serum lactic acid could improve detection of at-risk patients with cancer, it would be useful in risk stratification. There is also little evidence that "alarm" values of serum lactate (such as >/=4 mmol/L) are appropriate for the population of patients with cancer. METHODS: This was a continuous retrospective cohort study of approximately two years (2012-2014) at a single, tertiary hospital ED; 5,440 patients had serum lactic acid measurements performed in the ED. Of the 5,440 patients in whom lactate was drawn, 1,837 were cancer patients, and 3,603 were non-cancer patients. Cumulative unadjusted mortality (determined by hospital records and an external death tracking system) was recorded at one day, three days, seven days, and 30 days. We used logistic regression to examine the risk of mortality 30 days after the ED visit after adjusting for confounders. RESULTS: In an unadjusted analysis, we found no statistically significant difference in the mortality of cancer vs. non-cancer patients at one day and three days. Significant differences in mortality were found at seven days (at lactate levels of <2 and 4+) and at 30 days (at all lactate levels) based on cancer status. After adjusting for age, gender, and acuity level, 30-day mortality rates were significantly higher at all levels of lactic acid (<2, 2-4, 4+) for patients with malignancy. CONCLUSION: When compared with non-cancer patients, cancer patients with elevated ED lactic acid levels had an increased risk of mortality at virtually all levels and time intervals we measured, although these differences only reached statistical significance in later time intervals (Day 7 and Day 30). Our results suggest that previous work in which lactate "cutoffs" are used to risk-stratify patients with respect to outcomes may be insufficiently sensitive for patients with cancer. Relatively low serum lactate levels may serve as a marker for serious illness in oncologic patients who present to the ED.

Relationship between the timing of preoperative medical visits and day-of-surgery glucose in poorly controlled diabetes.

BACKGROUND: This study evaluated referral patterns for preoperative evaluations of patients with poorly controlled diabetes mellitus (DM) and determined whether intervals between evaluations and surgery day were associated with preoperative glucose levels. RESULTS/METHODOLOGY: In this retrospective analysis of DM patients with a hemoglobin A1c level greater than 8.0%, of the 163 patients who underwent preoperative medical evaluation, only 45% were evaluated by endocrinology. Patients who had surgery earlier than 10 days after the preoperative medical evaluation had preoperative glucose levels 18% higher than those of patients who waited more than 10 days. Preoperative outpatient contact with endocrinology was not associated with preoperative glucose level (p = 0.90). CONCLUSION: For poorly controlled DM, more than 10 days are needed to achieve preoperative glycemic control.

Analysis of Benign Prostatic Hyperplasia Patients' Perspective Through a Third Party-administered Survey.

OBJECTIVE: To assess patient-reported functional and quality-of-life (QoL) outcomes associated with various surgical treatments for benign prostate hyperplasia (BPH). MATERIALS AND METHODS: An independent third-party survey was sent to all patients who underwent any surgical treatment for BPH at our institution from January 2007 through January 2013. Overall satisfaction and urinary and sexual outcomes were evaluated using Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS) for urinary function, and International Continence Society-Short Form (ICSmaleSF) questionnaires. RESULTS: Four hundred and seventy-nine respondents (response rate, 55.6%) had undergone holmium laser enucleation of the prostate (HoLEP; n = 214), transurethral resection of the prostate (n = 210), holmium laser ablation of the prostate (n = 21), photoselective vaporization (n = 18), transurethral incision of the prostate (n = 9), and open simple prostatectomy (n = 7). Postoperatively, Sexual Health Inventory for Men scores were not different. However, total IPSS varied significantly among surgical techniques (P < .001). Mean (standard deviation) IPSS was lowest for open simple prostatectomy (4.0 [2.6]), followed by HoLEP (5.8 [5.4]). For individual domains, significant differences were in intermittency (P < .001), weak stream (P = .003), straining (P < .001), and QoL (P = .001). In all these domains, HoLEP had the lowest scores. Regarding International Continence Society-Short Form, we observed a significant difference favoring transurethral resection of the prostate in incontinence (P < .001) and favoring HoLEP in voiding (P = .02) and QoL domains (P = .03). Most patients were satisfied with their surgical intervention, independent of the procedure type. Regret was least in patients who underwent HoLEP (P = .02). CONCLUSION: Patients generally expressed satisfaction with various interventions for BPH. However, those who underwent HoLEP had the best outcomes.

In situ forming, resorbable graft copolymer hydrogels providing controlled drug release.

In situ forming hydrogels are promising drug delivery vehicles due to their ease of delivery as liquids and their ability to be used in sites with irregular geometries. In this work, we report on in situ forming, resorbable hydrogels based on N-isopropylacrylamide (NIPAAm) as a fluid-like controlled release gel. These gels are the first resorbable NIPAAm-based gels providing controlled release without relying on affinity between the drug and device. Therefore, these gels provide a more flexible delivery system which can be used to deliver any drug at a controlled rate. The polymers contain repeat units of NIPAAm with (R)-α-Acryloyloxy-ß,ß-dimethyl-γ-butyrolactone (DBLA) and varying amounts of hydrophilic Jeffamine® M-1000 acrylamide (JAAm) grafts. The graft copolymer architecture allows the water content of the hydrogels to be tuned over a wide range while keeping the initial gelation temperature below body temperature. Incorporation of JAAm in the polymers led to greater water content, faster gel degradation, and reduced burst release. Sustained release of the antimicrobial drugs cefazolin and vancomycin (over about 5 and 7 days, respectively) was observed from gels containing an intermediate amount of grafts which combined reduced phase separation with a degradation time of 40 days. The degradation byproducts of one hydrogel formulation were cytocompatible to NIH 3T3 fibroblasts at concentrations up to 2.5 wt %. This class of terpolymer hydrogels is a promising local delivery system for a wide variety of drugs, particularly for applications involving irregular geometries such as implant interfaces.