Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery

Aim: To test whether short‐term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients. Methods: We conducted a double‐blind, randomized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI. Patients were randomized to atorvastatin (40 mg once daily for 4 days starting preoperatively) or identical placebo capsule. Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy. Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification (RIFLE R, I or F), change in urinary neutrophil gelatinase‐associated lipocalin (NGAL) concentration, requirement for renal replacement therapy, length of stay in intensive care, length of stay in hospital and hospital mortality. Results: Study groups were well matched. For each patient maximal increase in creatinine during the 5 days after surgery was assessed; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group (P = 0.62). RIFLE R or greater occurred in 26% of patients with atorvastatin and 32% with placebo (P = 0.65). Postoperatively urine NGAL changes were similar (median NGAL : creatinine ratio at intensive care unit admission: atorvastatin group 1503 ng/mg, placebo group 1101 ng/mg; P = 0.22). Treatment was well tolerated and adverse events were similar between groups. Conclusion: Short‐term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL. (ClinicalTrials.gov NCT00910221).     

Propeller DICAP flap for a large defect on the back—Case report and review of the literature

Reconstruction of large soft tissue defects of the back is a challenging problem. Large defects of the back were reconstructed with multiple random pattern or local pedicled muscle (and skin graft) or musculocutaneous flaps. The clinical use of perforator flaps has demonstrated that harvesting of flaps on a single perforator is possible for reconstruction of large defects. We present a 71‐year‐old male with a lesion on his left mid back that measured 10 × 10 × 4 cm³. Biopsy of the lesion was consistent with dermatofibrosarcoma protruberans. Wide local excision of the lesion with 4 cm margin was performed. The soft tissue defect, ～20 cm in diameter, was reconstructed with a large propeller dorsal intercostal artery perforator (DICAP) flap. The DICAP flap measured 40 × 15 cm² based on a single perforator—lateral branch of dorsal rami of the seventh posterior intercostal artery on the right side. The perforator flap was elevated at the subfascial level and transposed 180° into the defect. The donor site on the right side of the back was closed directly. This case illustrates the size of the propeller DICAP flap that could be safely harvested on a single perforator from the dorsal rami of the posterior intercostal artery. To our knowledge this is the largest reported pedicled perforator flap harvested on a single perforator on the posterior trunk. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.     

Surgical management of unruptured aneurysms: prognostic indicators

BACKGROUND: The treatment of unruptured aneurysms (UA) remains controversial. Therefore, it has become necessary to define various prognostic indicators in the surgical treatment of unruptured aneurysms not associated with previously ruptured aneurysms. METHODS: During a 6-year period, 78 unruptured aneurysms were managed. The results of management were retrospectively reviewed to define the prognostic indicators. RESULTS: There were 104 patients with unruptured aneurysms who underwent surgical treatment. Seventy-five patients without previous subarachnoid hemorrhage (SAH) were selected for data analysis. Eighty-seven percent of the aneurysms were on the anterior circulation. The most common location was the middle cerebral artery (MCA) followed by the posterior communicating artery (PCom), ophthalmic artery, and anterior communicating artery (ACom). Six percent were found on the basilar artery. The mean size of aneurysms was 12.5 mm (range = 3-30 mm, SD = 7.4). At surgery, rupture of the aneurysm was encountered in eight cases with temporary control of the parent vessel being required in 31 procedures. In four cases, intraoperative angiography warranted clip reapplication. The Glasgow Outcome Scale (GOS) was used as an outcome measure. Surgical treatment resulted in good outcome (GOS 1) in 87% and 10.7% had fair outcome; 2.3% were in GOS 3 (severe disability) at 6 month follow-up. There was no mortality. Logistic regression identified significant relationships between GOS and intraoperative rupture (p < 0.0002), rupture and size (p < 0.003), and size and age (p < 0.01). CONCLUSIONS: Large size aneurysms were associated with intraoperative rupture, which had a strong correlation with poor outcome. Increased age showed a linear relationship with the size of the aneurysm. Overall results of treatment for UA are gratifying. There was no mortality. Early diagnosis and surgical extirpation of UA may reduce both intraoperative difficulties as well as poor outcome probability.     

Scar formation following excisional and burn injuries in a red Duroc pig model

Scar research is challenging because rodents do not naturally form excessive scars, and burn depth, size, and location cannot be controlled in human longitudinal studies. The female, red Duroc pig model has been shown to form robust scars with biological and anatomical similarities to human hypertrophic scars. To more closely mimic the mode of injury, recreate the complex chemical milieu of the burn wound environment and enhance scar development, an animal model of excessive burn‐induced scarring was developed and compared with the more commonly used model, which involves excisional wounds created via dermatome. Standardized, full‐thickness thermal wounds were created on the dorsum of female, red Duroc pigs. Wounds for the dermatome model were created using two different total dermatome settings: ～1.5 mm and ≥ 1.9 mm. Results from analysis over 150 days showed that burn wounds healed at much slower rate and contracted more significantly than dermatome wounds of both settings. The burn scars were hairless, had mixed pigmentation, and displayed fourfold and twofold greater excess erythema values, respectively, compared with ～1.5 mm and ≥ 1.9 mm deep dermatome injuries. Burn scars were less elastic, less pliable, and weaker than scars resulting from excisional injuries. Decorin and versican gene expression levels were elevated in the burn group at day 150 compared with both dermatome groups. In addition, transforming growth factor‐beta 1 was significantly up‐regulated in the burn group vs. the ～1.5 mm deep dermatome group at all time points, and expression remained significantly elevated vs. both dermatome groups at day 150. Compared with scars from dermatome wounds, the burn scar model described here demonstrates greater similarity to human hypertrophic scar. Thus, this burn scar model may provide an improved platform for studying the pathophysiology of burn‐related hypertrophic scarring, investigating current anti‐scar therapies, and development of new strategies with greater clinical benefit.     

Risk factors for postoperative sepsis in laparoscopic gastric bypass

Introduction

Postoperative sepsis is a rare but serious complication following elective surgery. The purpose of this study was to identify the rate of postoperative sepsis following elective laparoscopic gastric bypass (LGBP) and to identify patients’ modifiable, preoperative risk factors.

Methods

The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2013 for factors associated with the development of postoperative sepsis following elective LGBP. Patients who developed sepsis were compared to those who did not. Results were analyzed using the Chi-square test for categorical variables and Wilcoxon two-sample test for continuous variables. A multivariate logistic regression analysis was utilized to calculate adjusted odds ratios for factors contributing to sepsis.

Results

During the study period, 66,838 patients underwent LGBP. Of those, 546 patients developed postoperative sepsis (0.82 %). The development of sepsis was associated with increased operative time (161 ± 77.8 vs. 135.10 ± 56.5 min; p < 0.0001) and a greater number of preoperative comorbidities, including diabetes (39.6 vs. 30.6 %; p < 0.0001), hypertension requiring medication (65.2 vs. 54 %; p < 0.0001), current tobacco use (16.7 vs. 11.5 %; p = 0.0002), and increased pack-year history of smoking (8.6 ± 18.3 vs. 5.6 ± 14.2; p = 0.0006), and the Charlson Comorbidity Index (0.51 ± 0.74 vs. 0.35 ± 0.57, p < 0.0001). Sepsis resulted in an increased length of stay (10.1 ± 14.4 vs. 2.4 ± 4.8 days; p < 0.0001) and a 30 times greater chance of 30-day mortality (4.03 vs. 0.11 %, p < 0.0001). Multivariate logistic regression analysis showed that current smokers had a 63 % greater chance of developing sepsis compared to non-smokers, controlling for age, race, gender, BMI, and CCI score (OR 1.63, 95 % CI 1.23–2.14; p = 0.0006).

Conclusions

Laparoscopic gastric bypass is uncommonly associated with postoperative sepsis. When it occurs, it portends a 30 times increased risk of death. A patient history of diabetes, hypertension, and increasing pack-years of smoking portend an increased risk of sepsis. Current smoking status, a preoperative modifiable risk factor, is independently associated with the chance of postoperative sepsis. Preoperative patient optimization and risk reduction should be a priority for elective surgery, and patients should be encouraged to stop smoking prior to gastric bypass.

     

Biomarkers for the early detection of acute kidney injury

Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), represents a persistent problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, akin to troponins in acute myocardial disease, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies such as functional genomics and proteomics to human and animal models of AKI has uncovered several novel genes and gene products that are emerging as biomarkers. The most promising of these are chronicled in this article. These include a plasma panel [neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C] and a urine panel [NGAL, interleukin 18 (IL-18), and kidney injury molecule 1 (KIM)-1]. As they represent sequentially expressed biomarkers, it is likely that the AKI panels will be useful for timing the initial insult and assessing the duration of AKI. Based on the differential expression of the biomarkers, it is also likely that the AKI panels will distinguish between the various types and etiologies of AKI. It will be important in future studies to validate the sensitivity and specificity of these biomarker panels in clinical samples from large cohorts and from multiple clinical situations.     

Reduction of hepatic and adipose tissue glucocorticoid receptor expression with antisense oligonucleotides improves hyperglycemia and hyperlipidemia in diabetic rodents without causing systemic glucocorticoid antagonism

Glucocorticoids (GCs) increase hepatic gluconeogenesis and play an important role in the regulation of hepatic glucose output. Whereas systemic GC inhibition can alleviate hyperglycemia in rodents and humans, it results in adrenal insufficiency and stimulation of the hypothalamic-pituitary-adrenal axis. In the present study, we used optimized antisense oligonucleotides (ASOs) to cause selective reduction of the glucocorticoid receptor (GCCR) in liver and white adipose tissue (WAT) and evaluated the resultant changes in glucose and lipid metabolism in several rodent models of diabetes. Treatment of ob/ob mice with GCCR ASOs for 4 weeks resulted in approximately 75 and approximately 40% reduction in GCCR mRNA expression in liver and WAT, respectively. This was accompanied by approximately 65% decrease in fed and approximately 30% decrease in fasted glucose levels, a 60% decrease in plasma insulin concentration, and approximately 20 and 35% decrease in plasma resistin and tumor necrosis factor-alpha levels, respectively. Furthermore, GCCR ASO reduced hepatic glucose production and inhibited hepatic gluconeogenesis in liver slices from basal and dexamethasone-treated animals. In db/db mice, a similar reduction in GCCR expression caused approximately 40% decrease in fed and fasted glucose levels and approximately 50% reduction in plasma triglycerides. In ZDF and high-fat diet-fed streptozotocin-treated (HFD-STZ) rats, GCCR ASO treatment caused approximately 60% reduction in GCCR expression in the liver and WAT, which was accompanied by a 40-70% decrease in fasted glucose levels and a robust reduction in plasma triglyceride, cholesterol, and free fatty acids. No change in circulating corticosterone levels was seen in any model after GCCR ASO treatment. To further demonstrate that GCCR ASO does not cause systemic GC antagonism, normal Sprague-Dawley rats were challenged with dexamethasone after treating with GCCR ASO. Dexamethasone increased the expression of GC-responsive genes such as PEPCK in the liver and decreased circulating lymphocytes. GCCR ASO treatment completely inhibited the increase in dexamethasone-induced PEPCK expression in the liver without causing any change in the dexamethasone-induced lymphopenia. These studies demonstrate that tissue-selective GCCR antagonism with ASOs may be a viable therapeutic strategy for the treatment of the metabolic syndrome.     

Anatomic Bladder Neck Preservation During Robotic-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes

Background

Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted despite a daunting learning curve with bladder neck dissection as a challenging step for newcomers.

Objective

To describe an anatomic, reproducible technique of bladder neck preservation (BNP) and associated perioperative and long-term outcomes.

Design, settings, and participants

From September 2005 to May 2009, data from 619 consecutive RALP were prospectively collected and compared on the basis of bladder neck dissection technique with 348 BNP and 271 standard technique (ST).

Surgical procedure

RALP with BNP.

Measurements

Tumor characteristics, perioperative complications, and post-operative urinary control were evaluated at 4, 12 and 24 months using (1) the Expanded Prostate Cancer Index (EPIC) urinary function scale scored from 0–100; and (2) continence defined as zero pads per day.

Results and limitations

Mean age for BNP versus ST was 57.1 ± 6.6 yr versus 58.9 ± 6.7 yr (p = 0.033), while complication rates did not vary significantly by technique. Estimated blood loss was 183.7 ± 95.8 ml versus 224.6 ± 108 ml (p = 0.938) in men who underwent BNP versus ST. The overall positive margin rate was 12.8%, which did not differ at the prostate base for BNP versus ST (1.4% vs. 2.2%, p = 0.547). Mean urinary function scores for BNP versus ST at 4, 12, and 24 mo were 64.6 versus 57.2 (p = 0.037), 80.6 versus 79.0 (p = 0.495), and 94.1 versus 86.8 (p < 0.001). Similarly, BNP versus ST continence rates at 4, 12, and 24 mo were 65.6% versus 26.5% (p < 0.001), 86.4% versus 81.4% (p = 0.303), and 100% versus 96.1% (p = 0.308).

Conclusions

BNP versus ST is associated with quicker recovery of urinary function and similar cancer control.