Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.

Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.

Peripheral Nerve Blocks Causing Increased Risk for Fall and Difficulty in Ambulation for the Hip and Knee Joint Replacement Patient.

A systematic review of the literature was completed by the Evidence-Based Practice Group for the Patient population, Intervention/Issue, Comparison Intervention, Outcomes, Timing (PICOT) question: "Does the use of a peripheral nerve block increase the risk for falls and difficulty ambulation in patients after lower extremity surgery through postoperative day 2?" A search of multiple databases using specified key terms resulted in 258 articles for total knee arthroplasty or total hip arthroplasty. These were reduced to 13 with exclusion criteria and became primary evidence. Numbers Needed to Harm and Numbers Needed to Treat (NNT) were calculated. Numbers Needed to Harm supported the PICOT question. Further research of postoperative falls and nursing interventions to reduce or prevent falls is suggested before creation of a Clinical Practice Guideline.

Simultaneous occurrence of a single coronary artery and persistent left superior vena cava.

We present a case of simultaneous occurrence of 2 rare congenital anomalies. A 57-year-old woman undergoing evaluation of dyspnea was found to have a single coronary artery and persistent left superior vena cava. The incidence of single coronary artery is 0.024% to 0.066% in the general population. Persistent left superior vena cava occurs in 0.3% of those without other congenital anomalies and in up to 5% when other anomalies are present. The likelihood of both anomalies occurring as a random event in 1 patient is approximately 1 in 10 million. Patient characteristics and data are presented, with a discussion on the epidemiology, incidence, diagnosis and pathologic implications of each anomaly.

A prospective randomized clinical trial of the use of fluoroscopy in obtaining femoral arterial access.

BACKGROUND: There is no consensus on the utility of fluoroscopy in obtaining common femoral artery (CFA) access. METHODS: Patients weighing < 136.4 kg (300 lbs) with palpable femoral pulses undergoing coronary angiography were randomized to arterial access with or without the use of fluoroscopy (using the center of the femoral head as the optimal site to enter the artery). RESULTS: 208 patients were enrolled with 110 randomized to the palpation group and 98 were randomized to the palpation +fluoroscopy group. Mean age (+/- SD) was 60 +/- 11 years, 61% were male, 35% had diabetes, and 40% had a body mass index (BMI) > 30 kg/m(2). Clinical characteristics and procedural factors were similar among the two groups with the exception that fewer needle passes were required and access was achieved faster in the palpation group. Arterial puncture over the femoral head occurred in 91% of the palpation group versus 95% of the palpation + fluoroscopy group (p = 0.27). Successful CFA puncture occurred in 85% of the palpation group versus 90% of the palpation + fluoroscopy group (p = 0.49). Cannulation of the external iliac artery occurred in 1 patient in each group, whereas arterial puncture distal to the CFA bifurcation occurred in 16 (15%) of the palpation group and in 9 (9%) of the palpation + fluoroscopy group (p = 0.33). CONCLUSION: In this single-center, randomized trial, the use of fluoroscopy did not increase the probability of arterial puncture over the femoral head or the rate of successful CFA cannulation.

The contrast media iohexol causes vasoconstriction of the proximal left anterior descending coronary artery: implications for appropriate stent sizing.

The effect of the contrast agent iohexol on reference vessel size in patients with proximal left anterior descending disease is unknown. Quantitative coronary angiography and intravascular ultrasound were performed in 15 patients with atherosclerotic disease of the proximal left anterior descending. Mean proximal reference vessel diameter was 2.95 +/- 0.59 mm with quantitative coronary angiography and 4.65 +/- 0.66 mm with intravascular ultrasound (P < .05). Intracoronary injection of iohexol resulted in a significant decrease in intravascular ultrasound-measured proximal reference vessel diameter from 4.65 +/- 0.66 mm to 4.47 +/- 0.68 mm (P = .002). Vasoconstrictive response to iohexol in the proximal reference vessel ranged from -0.04 mm to 0.5 mm with a mean of 0.18 +/- 0.16 mm. This study shows that iohexol can cause significant vasoconstriction of the proximal reference vessel in patients with severe disease involving the proximal left anterior descending.

Measuring and treating serum lipids in patients in a chest pain observation unit.

We evaluated opportunities to initiate statin therapy in 574 consecutive subjects admitted to a chest pain observation unit (CPOU). Ten-year Framingham risk scores were retrospectively calculated for all patients according to the National Cholesterol Education Program and Adult Treatment Panel III 2001 recommendations. Subjects were then stratified according to (1) recommendations for initiation of a lipid-lowering medication and (2) whether they received lipid-lowering drug therapy at discharge. Of 574 subjects, we excluded 50 with previously established coronary heart disease or who were already taking a statin medication on presentation, 23 with missing data, and 80 who did not have a low-density lipoprotein (LDL) measurement at admission. Of the remaining 421 subjects, the mean age was 47 years, 40% were men, 57% were white, 31% had hypertension, 27% were current smokers, and 6% had diabetes. Ten-year risk calculation classified 47% (n=199) at low risk (<2 risk factors), 32% (n=134) at moderate risk (>or=2 risk factors and <10% risk), 11% (n=48) at moderate-high risk (10% to 20% risk), and 10% (n=40) at high risk (>20% risk). Of the entire cohort, 23% of subjects (n=96) had hypercholesterolemia, of which 52% (n=50) met indications for initiation of lipid-lowering medication. Only 6% of patients with an indication for treatment (n=3) were prescribed a lipid-lowering medication on discharge, leaving 94% (n=47) untreated for their hypercholesterolemia. In conclusion, patients admitted to a CPOU have a high prevalence of hypercholesterolemia, and therefore, an increased long-term risk for cardiovascular events. In addition to their primary role, CPOUs should focus on primary prevention and reduction of long-term risk.