Perfusate Composition and Duration of Ex-Vivo Normothermic Perfusion in Kidney Transplantation: A Systematic Review.

Ex-vivo normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions prior to transplantation. The optimal perfusate composition and duration, however, remain undefined. A systematic literature search (Embase; Medline; Scopus; and BIOSIS Previews) was conducted. We identified 1,811 unique articles dating from January 1956 to July 2021, from which 24 studies were deemed eligible for qualitative analysis. The perfusate commonly used in clinical practice consisted of leukocyte-depleted, packed red blood cells suspended in Ringer's lactate solution with Mannitol, dexamethasone, heparin, sodium bicarbonate and a specific nutrient solution supplemented with insulin, glucose, multivitamins and vasodilators. There is increasing support in preclinical studies for non-blood cell-based perfusates, including Steen solution, synthetic haem-based oxygen carriers and acellular perfusates with supraphysiological carbogen mixtures that support adequate oxygenation whilst also enabling gradual rewarming. Extended durations of perfusion (up to 24 h) were also feasible in animal models. Direct comparison between studies was not possible due to study heterogeneity. Current evidence demonstrates safety with the aforementioned widely used protocol, however, extracellular base solutions with adequate oxygenation, supplemented with nutrient and metabolic substrates, show promise by providing a suitable environment for prolonged preservation and resuscitation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231381, identifier PROSPERO 2021 CRD42021231381.

Viability assessment and utilization of declined donor kidneys with rhabdomyolysis using ex vivo normothermic perfusion without preimplantation biopsy.

The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m2 ), at 2 months posttransplant.

Transplantation of kidneys after normothermic perfusion: A single center experience.

BACKGROUND: In order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.1,2 NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP. METHODS: Data was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). RESULTS: Six-hundred and thirty-two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One-year graft loss rate was 3.4% for NRP and 6.0% for standard DCD. CONCLUSION: This data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.

Direct venous pressure assessment pre-renal transplantation to optimise graft venous drainage.

BACKGROUND: Renal transplantation is the modality of choice in the treatment of end-stage kidney disease. Surgically challenging aspects of renal transplantation may include creation of vascular anastomoses where there is complex vascular anatomy. We present a paediatric case of living-related donor (LRD) renal transplantation in whom direct intravenous pressure measurement guided the management of the vascular anastomoses in the context of inferior vena cava (IVC) obstruction. CASE-DIAGNOSIS/TREATMENT: During venography for transplant assessment, 150 mL of 0.9% sodium chloride was infused for over 20 s into well-developed collateral paravertebral veins to simulate the anticipated high-volume venous return from an implanted kidney. Direct venous pressure measurements were 20 mmHg in the right paravertebral vein and 19 mmHg in the left paravertebral vein. We were reassured by this result that the collateralised venous system could sustain the high venous drainage and maintain the arteriovenous (AV) gradient required for adequate graft perfusion. Intra-operative measurement at the time of transplantation, following release of venous clamps, of 22 mmHg supported the validity of this approach. CONCLUSIONS: In children with complex venous anatomy pre-transplant, direct intravenous pressure measurement may provide a useful adjunct in deciding which vessel is most suitable for transplant anastomosis.

Stoma-Related Complications Following Ostomy Surgery in 3 Acute Care Hospitals: A Cohort Study.

PURPOSE: The aim of this study was to evaluate both surgical and patient-centered stomal complications after stoma formation, with emphasis on underreported symptoms and complaints. DESIGN: Prospective, single-group study. SUBJECTS AND SETTING: Patients undergoing emergency and elective ostomy surgery between January 1, 1999, and June 1, 2016, in 3 acute care hospitals were followed up by stoma care nurse specialists in NHS Lanarkshire, Scotland. METHODS: Data were collected on surgery type (emergency or elective), stoma type (ileostomy or colostomy), stoma-related complications including surgical complications (stenosis, retractions, hernia, and prolapse) and so-called "patient-centered" complications (skin changes, odor, leakage, soiling, and nighttime emptying) at 5 time points: 10 days, 3 months, 6 months, 1 year, and 2 years postoperatively. For this study, we report comparisons at 10 days and 2 years, using frequencies reported as percentages. RESULTS: Data from 3509 consecutive stoma surgeries were analyzed. Complication rates were similar in both emergency and elective cases. The nighttime symptoms of leakage and soiling were significantly greater in the ileostomy group and worsened over the 2-year period. The parastomal hernia rate was 34.5% at 2 years, a finding more common in the colostomy group (46.4% vs 20.1%, P < .001). However, the rate of clinically significant hernia was similar when comparing the colostomy group with the ileostomy group (3.6% vs 2.2%, P = .38). Emergency stoma surgeries (40.2%) were preoperatively sited compared with 95.9% of elective cases. CONCLUSIONS: Our prospective multicenter study demonstrated that stoma-related complications are similar irrespective of whether the stoma was formed via an elective surgery or emergency surgery. Nighttime symptoms of leakage, soiling, and emptying were high post-stoma formation, particularly in the ileostomy group, and worsened over the 2-year period. Findings from our study highlight the presence and persistence of complications. We believe our work highlights the importance of having frequent discussions with patients about making decisions about approaches to reduce complications to enhance patient outcomes.

Patient consent in the post-Montgomery era: A national multi-speciality prospective study.

BACKGROUND: The Montgomery ruling has had a wide-ranging impact on the consent process and has been the subject of new guidelines by bodies, including the Royal College of Surgeons (RCSEng). This is the first study to examine the current standard of consent for surgical procedures at a national level. METHOD: A national collaborative research model was used, with prospective data collection performed across hospitals in Scotland. Variables associated with the consent process were audited across three surgical specialities (general surgery, urology and orthopaedics) and measured against standards set by RCSEng, the Scottish Public Services Ombudsman and medical defence organisations. RESULTS: A total of 289 cases were identified from 12 hospitals. The majority of patients were reviewed by a consultant surgeon in clinic (79.9%) or on the day of surgery (55.4%). The clinic consent rate was 27.0%, while a copy of the documented discussion was only provided to 4.2% of patients. On the day of surgery, the benefits, risks and alternatives to the planned procedure were discussed in less than half of cases. This rate was similar across different clinician grades, while marked variation was seen across hospitals. CONCLUSION: In this prospective multi-centre study we have demonstrated wide variation in the consent processes in many surgical specialities across Scotland. Following the Montgomery ruling, we have demonstrated the current consent process in elective surgery is likely to be substandard, and may require additional steps to be taken by clinicians to ensure patients are fully informed to make decisions regarding their treatment.

The impact of renal artery stenting on therapeutic aims.

Renal artery stenosis manifests as poorly-controlled hypertension, impaired renal function or pulmonary oedema, therefore the success of treatment is dependent on indication. This study aims to determine the outcomes of patients undergoing renal artery stenting (RASt) based on therapeutic aim compared to criteria used in the largest randomised trial. Retrospective case-note review of patients undergoing RASt between 2008-2021 (n = 74). The cohort was stratified by indication for intervention (renal dysfunction, hypertension, pulmonary oedema) and criteria employed in the CORAL trial, with outcomes and adverse consequences reported. Intervention for hypertension achieved significant reduction in systolic blood pressure and antihypertensive agents at 1 year (median 43 mmHg, 1 drug), without detrimental impact on renal function. Intervention for renal dysfunction reduced serum creatinine by a median 124 µmol/L, sustained after 6 months. Intervention for pulmonary oedema was universally successful with significant reduction in SBP and serum creatinine sustained at 1 year. Patients who would have been excluded from the CORAL trial achieved greater reduction in serum creatinine than patients meeting the inclusion criteria, with equivalent blood pressure reduction. There were 2 procedure-related mortalities and 5 procedural complications requiring further intervention. 5 patients had reduction in renal function following intervention and 7 failed to achieve the intended therapeutic benefit. Renal artery stenting is effective in treating the indication for which it has been performed. Previous trials may have underestimated the clinical benefits by analysis of a heterogenous population undergoing a procedure rather than considering the indication, and excluding patients who would maximally benefit.

Research priorities in emergency general surgery (EGS): a modified Delphi approach.

BACKGROUND: Emergency general surgery (EGS) patients account for more than one-third of admissions to hospitals in the National Health Service (NHS) in England. The associated mortality of these patients has been quoted as approximately eight times higher than that of elective surgical admissions. This study used a modified Delphi approach to identify research priorities in EGS. The aim was to establish a research agenda using a formal consensus-based approach in an effort to identify questions relevant to EGS that could ultimately guide research to improve outcomes for this cohort. METHODS: Three rounds were conducted using an electronic questionnaire and involved health care professionals, research personnel, patients and their relatives. In the first round, stakeholders were invited to submit clinical research questions that they felt were priorities for future research. In rounds two and three, participants were asked to score individual questions in order of priority using a 5-point Likert scale. Between rounds, an expert panel analysed results before forwarding questions to subsequent rounds. RESULTS: Ninety-two EGS research questions were proposed in Phase 1. Following the first round of prioritisation, forty-seven questions progressed to the final phase. A final list of seventeen research questions were identified from the final round of prioritisation, categorised as condition-specific questions of high interest within general EGS, emergency colorectal surgery, non-technical and health services research. A broad range of research questions were identified including questions on peri-operative strategies, EGS outcomes in older patients, as well as non-technical and technical influences on EGS outcomes. CONCLUSIONS: Our study provides a consensus delivered framework that should determine the research agenda for future EGS projects. It may also assist setting priorities for research funding and multi-centre collaborative strategies within the academic clinical interest of EGS.

Living donor kidney transplant following nephrectomy for renal artery stenosis with arterial reconstruction and viability assessment using ex vivo normothermic perfusion.

Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.

The New UK National Kidney Allocation Scheme With Maximized "R4-D4" Kidney Transplants: Better Patient-to-Graft Longevity Matching May Be at the Cost of More Resources.

OBJECTIVES: A new kidney matching scheme for allocation of deceased donor kidneys for transplantation was introduced in the United Kingdom in September 2019. Donors and recipients are stratified into quartiles derived from demographic and retrieval indices associated with risk of adverse outcome. We present data on 2 years of transplants, with the aim of understanding the potential impacts ofthe scheme on patient/transplant outcomes, hospitalization, and resource utilization. MATERIALS AND METHODS: All deceased donortransplants from 2015 and 2016 were reclassified using the risk quartiles (D1-D4 for donor and R1-R4 for recipient, where 4 is highestrisk). Inpatientlength of stay, kidney function defined by estimated glomerular rate at 1 year, and patient survival data were collected. RESULTS: Of the 195 deceased donor transplants analyzed, 144 recipients (73.4%) were in the highest risk R4 category, including 55 with R4-D4 combination (28.1%). Recipients in the R4 category had longer index admissions (mean of 12.4 vs 8.1 days for R1-R3; P = .002) and higher subsequent admission rates 90 days posttransplant(185.7 vs 122.7/1000 patient days for R1-R3; P < .001). Kidney transplant function at 1 year was lower for grafts categorized as D4 (mean estimated glomerular filtration rate of 35.7 vs 54.8 mL/min/1.73 m2 for D1-D3; P < .001). However, survival for R4 recipients with D4 kidneys was not significantly differentfrom R4 recipients with D1 to D3 kidneys (4-year patient survival rate with R4-D4 combination was 90.9%). CONCLUSIONS: The principles ofthe allocation scheme in matching graft and patient survival were already largely being observed (matching higher risk deceased donor kidneys to higher risk recipients). However, an increase in D4 proportions in the R4 group may be associated with longer hospitalization posttransplant. Consideration should be given to mitigation strategies to address this. Despite poorer graft function, patient survival appears satisfactory.

Algorithm optimization for multitined radiofrequency ablation: comparative study in ex vivo and in vivo bovine liver.

PURPOSE: To prospectively optimize multistep algorithms for largest available multitined radiofrequency (RF) electrode system in ex vivo and in vivo tissues, to determine best energy parameters to achieve large predictable target sizes of coagulation, and to compare these algorithms with manufacturer's recommended algorithms. MATERIALS AND METHODS: Institutional animal care and use committee approval was obtained for the in vivo portion of this study. Ablation (n = 473) was performed in ex vivo bovine liver; final tine extension was 5-7 cm. Variables in stepped-deployment RF algorithm were interrogated and included initial current ramping to 105 degrees C (1 degrees C/0.5-5.0 sec), the number of sequential tine extensions (2-7 cm), and duration of application (4-12 minutes) for final two to three tine extensions. Optimal parameters to achieve 5-7 cm of coagulation were compared with recommended algorithms. Optimal settings for 5- and 6-cm final tine extensions were confirmed in in vivo perfused bovine liver (n = 14). Multivariate analysis of variance and/or paired t tests were used. RESULTS: Mean RF ablation zones of 5.1 cm +/- 0.2 (standard deviation), 6.3 cm +/- 0.4, and 7 cm +/- 0.3 were achieved with 5-, 6-, and 7-cm final tine extensions in a mean of 19.5 min +/- 0.5, 27.9 min +/- 6, and 37.1 min +/- 2.3, respectively, at optimal settings. With these algorithms, size of ablation at 6- and 7-cm tine extension significantly increased from mean of 5.4 cm +/- 0.4 and 6.1 cm +/- 0.6 (manufacturer's algorithms) (P <.05, both comparisons); two recommended tine extensions were eliminated. In vivo confirmation produced mean diameter in specified time: 5.5 cm +/- 0.4 in 18.5 min +/- 0.5 (5-cm extensions) and 5.7 cm +/- 0.2 in 21.2 min +/- 0.6 (6-cm extensions). CONCLUSION: Large zones of coagulation of 5-7 cm can be created with optimized RF algorithms that help reduce number of tine extensions compared with manufacturer's recommendations. Such algorithms are likely to facilitate the utility of these devices for RF ablation of focal tumors in clinical practice.

Superior predictive ability for death of a basic metabolic profile risk score.

BACKGROUND: The basic metabolic profile (BMP) is a common blood test containing information about standard blood electrolytes and metabolites. Although individual variables are checked for cardiovascular health and risk, combining them into a total BMP-derived score, as to maximize BMP predictive ability, has not been previously attempted. METHODS: Patients (N = 279,337) that received a BMP and had long-term follow-up for death were studied. Risk models were created in a training group (60% of study population, n = 167,635), validated in a test group (40% of study population, n = 111,702), and confirmed in the NHANES III (Third National Health and Nutrition Examination Survey) participants (N = 17,752). The BMP models were developed for 30-day, 1-year, and 5-year death using logistic regression with adjustment for age and sex. The BMP parameters were categorized as low, normal, or high based on the standard range of normal. Glucose was categorized as normal, intermediate, and high. Creatinine >or=2 mg/dL was further categorized as very high. RESULTS: Average age was 53.2 +/- 20.1 years, and 44.3% were male. The areas under the curve for the training and test groups for 30-day, 1-year, and 5-year death were 0.887 and 0.882, 0.850 and 0.848, and 0.858 and 0.847, respectively. The predictive ability of these risk scores was further confirmed in the NHANES III population and independent of the Framingham Risk Score. CONCLUSION: In large, prospectively followed populations, a highly significant predictive ability for death was found for a BMP risk model. We propose a total BMP score as an optimization of this routine baseline test to provide an important new addition to risk prediction.

Surgical revascularization is associated with improved long-term outcomes compared with percutaneous stenting in most subgroups of patients with multivessel coronary artery disease: results from the Intermountain Heart Registry.

BACKGROUND: Coronary artery bypass surgery (CABG) and percutaneous coronary intervention with stenting (PCI-S) are both safe and effective approaches for revascularization in patients with multivessel coronary artery disease. However, conflicting information exists when comparing the efficacy of the two methods. In this study, we examined the outcomes of major adverse cardiovascular events and death for subgroups of typical "real-world" patients undergoing coronary revascularization in the modern era. METHODS AND RESULTS: Patients were included if they were revascularized by CABG or PCI-S, had > or = 5 years of follow-up, and had > or = 2-vessel disease. Patients were followed for an average of 7.0+/-3.2 years for incidence of death and major adverse cardiovascular events (death, myocardial infarction, or repeat revascularization). Multivariate regression models were used to correct for standard cardiac risk factors including age, sex, hyperlipidemia, diabetes mellitus, family history of coronary artery disease, smoking, hypertension, heart failure, and renal failure. Subgroup analyses were also performed, stratified by age, sex, diabetes, ejection fraction, and history of PCI-S, CABG, or myocardial infarction. A total of 6369 patients (CABG 4581; PCI-S 1788) were included. Age averaged 66+/-10.9 years, 76% were male, and 26% were diabetic. Multivariate risk favored CABG over PCI-S for both death (hazard ratio 0.85; P=0.001) and major adverse cardiovascular events (hazard ratio 0.51; P<0.0001). A similar advantage with CABG was also found in most substrata, including diabetes. CONCLUSIONS: In this large observational study of patients undergoing revascularization for multivessel coronary artery disease, a long-term benefit was found, in relationship to both death and major adverse cardiovascular events, for CABG over PCI-S regardless of diabetic status or other stratifications.

Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen study).

Diabetes mellitus is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia. Besides acting on traditional lipids, statins and fibrates may also exert beneficial effects on various pro- and antiatherogenic lipid subparticles. This analysis was undertaken to evaluate combination therapy on lipid subparticles in the Diabetes and Combined Lipid Therapy Regimen (DIACOR) study. Patients with type 2 diabetes mellitus and no histories of coronary heart disease were evaluated (n = 498). Eligible patients underwent a 6- to 8-week washout period of all lipid-lowering medications and were enrolled if they demonstrated mixed dyslipidemia (having >or=2 of the following 3 lipid parameters: low-density lipoprotein [LDL] cholesterol >or=100 mg/dl, triglycerides >or=200 mg/dl, and high-density lipoprotein cholesterol <40 mg/dl). Patients were randomized to simvastatin 20 mg, fenofibrate 160 mg, or combined simvastatin 20 mg and fenofibrate 160 mg. Lipid subparticles were assessed 12 weeks after randomization by the Vertical Auto Profile II method. A total of 300 patients (mean age 61.6 +/- 11.5 years, 55% men) were randomized. Combination therapy was superior in lowering LDL cholesterol pattern B (-33.9 mg/dl) and dense very low-density lipoprotein cholesterol (-10.0 mg/dl) and increasing high-density lipoprotein3 (+2.3 mg/dl) and exerted the greatest change in altering the LDL cholesterol size profile. A potential effect on lipoprotein(a) (-0.5 mg/dl) was also found. For those with triglycerides >170 mg/dl, combination therapy was superior in lowering dense very low density lipoprotein cholesterol (-10.7 mg/dl) and LDL cholesterol pattern B (-35.8 mg/dl), the lipids that tend to be formed in the presence of elevated triglycerides. In conclusion, in this trial of mixed dyslipidemic patients with diabetes, combination therapy was more effective in changing a variety of other cardiovascular risk markers.

Usefulness of routine periodic fasting to lower risk of coronary artery disease in patients undergoing coronary angiography.

Coronary artery disease (CAD) is common and multifactorial. Members of the Church of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower cardiac mortality than other Utahns and the US population. Although the LDS proscription of smoking likely contributes to lower cardiac risk, it is unknown whether other shared behaviors also contribute. This study evaluated potential CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated for the association of religious preference with CAD diagnosis (> or = 70% coronary stenosis using angiography) or no CAD (normal coronaries, <10% stenosis). Consequently, another set of patients (n(2) = 448) were surveyed (2004 to 2006) for the association of behavioral factors with CAD, with routine fasting (i.e., abstinence from food and drink) as the primary variable. Secondary survey measures included proscription of alcohol, tea, and coffee; social support; and religious worship patterns. In population 1 (initial), 61% of LDS and 66% of all others had CAD (adjusted [including for smoking] odds ratio [OR] 0.81, p = 0.009). In population 2 (survey), fasting was associated with lower risk of CAD (64% vs 76% CAD; OR 0.55, 95% confidence interval 0.35 to 0.87, p = 0.010), and this remained after adjustment for traditional risk factors (OR 0.46, 95% confidence interval 0.27 to 0.81, p = 0.007). Fasting was also associated with lower diabetes prevalence (p = 0.048). In regression models entering other secondary behavioral measures, fasting remained significant with a similar effect size. In conclusion, not only proscription of tobacco, but also routine periodic fasting was associated with lower risk of CAD.

Soluble CD40 ligand as a predictor of coronary artery disease and long-term clinical outcomes in stable patients undergoing coronary angiography.

BACKGROUND: In patients with acute coronary syndrome (ACS), elevated levels of soluble CD40 ligand (sCD40L) are associated with increased risk of cardiovascular events. We evaluated sCD40L levels and future cardiovascular events in patients not experiencing ACS. METHODS: Serum sCD40L levels were measured in 909 patients undergoing angiography. A three-way matching scheme (age, gender and catheterization time period) identified 303 patients with coronary artery disease (CAD) who experienced a cardiac event within 1 year (CAD/event), 303 patients with CAD free of events (CAD/no event) and 303 patients without CAD and free of events (no CAD). RESULTS: Average age was 64 +/- 11 years; 74% were males. Median (+/- SE) sCD40L levels were higher for no CAD patients (335 +/- 60 pg/ml) compared to CAD (248 +/- 65 pg/ml, p = 0.01) and to CAD/event (233 +/- 63 pg/ml, p < 0.001). There was no significant difference in median sCD40L levels between CAD/no event and CAD/event patients. Higher sCD40L quartiles were associated with a significant decrease in the risk of CAD/event versus no CAD (quartile 4 versus quartile 1: odds ratio = 0.59, p = 0.03). There was a nonsignificant trend towards a decreased risk of CAD as compared to no CAD, and for CAD/event versus CAD. CONCLUSIONS: In non-ACS patients, higher sCD40L levels were associated with a decreased risk of CAD. This novel interaction of sCD40L raises interesting questions for CAD pathogenesis.

Comparison of effects of high (80 mg) versus low (20 mg) dose of simvastatin on C-reactive protein and lipoproteins in patients with angiographic evidence of coronary arterial narrowing.

Although previous studies have demonstrated that various "statins" decrease levels of high-sensitivity C-reactive protein (hs-CRP), the dose-response relation for lowering hs-CRP by the clinically important drug simvastatin compared with lipid lowering is unclear. A 16-week, randomized, double-blind study was performed in patients with stable coronary artery disease and high hs-CRP levels (>3 mg/L). Subjects were randomized to placebo, 20 mg of simvastatin, or 80 mg of simvastatin for 12 weeks. Those currently on a statin first underwent a 4-week washout. Of the 107 total patients randomized, 96 completed the trial, and 89 were able to be evaluated for efficacy. Changes in hs-CRP differed across simvastatin and placebo groups (change score +1.6 vs -0.6 mg/L, p = 0.004), but no dose response was observed when comparing 80 with 20 mg/day (-0.6 vs -0.5 mg/L, respectively). A strong dose response was observed for changes in total (p <0.01) and low-density lipoprotein (p <0.001) cholesterol. hs-CRP changes did not correlate with low-density lipoprotein changes. In conclusion, this randomized trial in patients with chronic stable coronary artery disease showed a strong dose response for simvastatin for total and low-density lipoprotein cholesterol lowering but not for hs-CRP.

A Multifaceted Quality Improvement Programme to Improve Acute Kidney Injury Care and Outcomes in a Large Teaching Hospital.

Acute kidney injury (AKI) is now widely recognised as a serious health care issue, occurring in up to 25% of hospital in-patients, often with worsening of outcomes. There have been several reports of substandard care in AKI. This quality improvement (QI) programme aimed to improve AKI care and outcomes in a large teaching hospital. Areas of documented poor AKI care were identified and specific improvement activities implemented through sequential Plan-Do-Study-Act (PDSA) cycles. An electronic alert system (e-alert) for AKI was developed, a Priority Care Checklist (PCC) was tested with the aid of specialist nurses whilst targeted education activities were carried out and data on care processes and outcomes monitored. The e-alert had a sensitivity of 99% for the detection of new cases of AKI. Key aspects of the PCC saw significant improvements in their attainment: Detection of AKI within 24 hours from 53% to 100%, fluid assessment from 42% to 90%, drug review 48% to 95% and adherence to nine key aspects of care from 40% to 90%. There was a significant reduction in variability of delivered AKI care. AKI incidence reduced from 9% of all hospitalisations at baseline to 6.5% (28% reduction), AKI related length of stay reduced from 22.1 days to 17 days (23% reduction) and time to recovery (AKI days) 15.5 to 9.8 days (36% reduction). AKI related deaths also showed a trend towards reduction, from an average of 38 deaths to 34 (10.5%). The number of cases of hospital acquired AKI were reduced by 28% from 120 to 86 per month. This study demonstrates significant improvements related to a QI programme combining e-alerts, a checklist implemented by a nurse and education in improving key processes of care. This resulted in sustained improvement in key patient outcomes.

Lipoprotein-associated phospholipase A2 independently predicts the angiographic diagnosis of coronary artery disease and coronary death.

BACKGROUND: Whereas C-reactive protein (CRP) is a nonspecific marker of coronary artery disease (CAD) and cardiovascular (CV) events, Lp-PLA2 may be a nonvariable inflammatory biomarker. We evaluated the independent association of lipoprotein-associated phospholipase A2 (Lp-PLA2) to angiographic CAD and CV events adjusting for standard factors, lipids, and CRP. METHODS: Lipoprotein-associated phospholipase A2 (PLAC test, diaDexus, Inc, San Francisco, CA) and CRP were measured from samples donated by consecutive consenting patients (N = 1493) enrolled in the registry of the Intermountain Heart Collaborative Study. All patients underwent coronary angiography (1996-1998) for CAD determination and were followed for 6.7 +/- 0.5 years (range 5.7-7.9 years) for CV events (death [including all-cause, CAD, and non-CAD CV death], myocardial infarction, and cerebrovascular accident). RESULTS: Lipoprotein-associated phospholipase A2 weakly correlated with lipids (low-density lipoprotein: r = 0.22, P < .001; high-density lipoprotein: r = -0.13, P < .001), but not CRP (r = 0.03, P = .26). Increasing quartile (Q) of Lp-PLA2 predicted greater the presence of CAD (vs Q1) for Q2 (adjusted odds ratio [OR] 1.15, 95% CI 0.78-1.71, P = .48), for Q3 (OR 1.53, 95% CI 1.02-2.31, P = .042), and for Q4 (OR 2.44, 95% CI 1.58-3.79, P < .001), although CRP was also predictive (vs Q1, Q2: OR 1.47, P = .057; Q3: OR 1.93, P = .002; Q4: OR 3.43, P < .001). In Cox regression, Lp-PLA2 predicted CAD death (vs Q1; Q2: adjusted hazard ratio [HR] 1.27, 95% CI 0.58-2.78, P = .55; Q3: HR 2.18, 95% CI 1.04-4.57, P = .04; Q4: HR 1.73, 95% CI 0.84-3.61, P = .14). CONCLUSION: Lipoprotein-associated phospholipase A2 was confirmed to predict the presence of CAD, even among patients undergoing coronary angiography. Uniquely, Lp-PLA2 predicted the risk of CAD death, but not all-cause death, myocardial infarction, or cerebrovascular accident.