Harendra Arora

μ-Opioid receptor gene A118G polymorphism predicts survival in patients with breast cancer.

Background: Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the &mgr;-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival. Methods: A total of 2,039 women ages 23–74 yr (38% African-American, 62% European-American, 55% postmenopausal) diagnosed with breast cancer between 1993–2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival. Results: After Bonferroni correction for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (P < 0.001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared with A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; P = 0.006). Conclusions: These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted.

Simulator training enhances resident performance in transesophageal echocardiography.

Background:Standardized training via simulation as an educational adjunct may lead to a more rapid and complete skill achievement. The authors hypothesized that simulation training will also enhance performance in transesophageal echocardiography image acquisition among anesthesia residents. Methods:A total of 42 clinical anesthesia residents were randomized to one of two groups: a control group, which received traditional didactic training, and a simulator group, whose training used a transesophageal echocardiography–mannequin simulator. Each participating resident was directed to obtain 10 commonly used standard views on an anesthetized patient under attending supervision. Each of the 10 selected echocardiographic views were evaluated on a grading scale of 0 to 10, according to predetermined criteria. The effect of the intervention was assessed by using a linear mixed model implemented in SAS 9.3 (SAS Institute Inc., Cary, NC). Results:Residents in the simulation group obtained significantly higher-quality images with a mean total image quality score of 83 (95% CI, 74 to 92) versus the control group score of 67 (95% CI, 58 to 76); P = 0.016. On average, 71% (95% CI, 58 to 85) of images acquired by each resident in the simulator group were acceptable for clinical use compared with 48% (95% CI, 35 to 62) in the control; P = 0.021. Additionally, the mean difference in score between training groups was the greatest for the clinical anesthesia-1 residents (difference 24; P = 0.031; n = 7 per group) and for those with no previous transesophageal echocardiography experience (difference 26; P = 0.005; simulator n = 13; control n = 11). Conclusion:Simulation-based transesophageal echocardiography education enhances image acquisition skills in anesthesiology residents.

Combined versus sequential injection of mepivacaine and ropivacaine for supraclavicular nerve blocks.

Background: An ideal local anesthetic with rapid onset and prolonged duration has yet to be developed. Clinicians use mixtures of local anesthetics in an attempt to combine their advantages. We tested the hypothesis that sequential supraclavicular injection of 1.5% mepivacaine followed 90 secs later by 0.5% ropivacaine speeds onset of sensory block and prolongs duration of analgesia compared with simultaneous injection of the same 2 local anesthetics. Methods: We enrolled 103 patients undergoing surgery suitable for supraclavicular anesthesia. The primary outcome was time to 4-nerve sensory block onset in each of the 4 major nerve distributions: median, ulnar, radial, and musculocutaneous. Secondary outcomes included time to onset of first sensory block, time to complete motor block, duration of analgesia, pain scores at rest and with movement, and total opioid consumption. Outcomes were compared using the Kaplan-Meier analysis with the log-rank test or the analysis of variance, as appropriate. Results: Times to 4-nerve sensory block onset were not different between sequential and combined anesthetic administration. The time to complete motor block onset was faster in the combined group as compared with the sequential. There were not significant differences between the 2 randomized groups in other secondary outcomes, such as the time to onset of first sensory block, the duration of analgesia, the pain scores at rest or with movement, or the total opioid consumption. Conclusions: Sequential injection of 1.5% mepivacaine followed 90 secs later by 0.5% ropivacaine provides no advantage compared with simultaneous injection of the same doses.

Long‐term survival after 67 hours of anhepatic state due to primary liver allograft nonfunction

Primary liver allograft nonfunction immediately after transplantation poses a life‐threatening situation for the recipient. Emergency retransplantation may not be immediately possible due to organ unavailability. Total hepatectomy with temporary portacaval shunt has been described as a bridge to retransplantation when the presence of the graft appears to be harming the recipient. Case reports of retransplantation after total hepatectomy with anhepatic times greater than 48 hours routinely describe poor outcomes. We present a case with excellent patient outcome after 95 hours of clinical anhepatic state, including 67 hours of anatomical anhepatic time, because of primary liver allograft nonfunction. This case report documents the longest anhepatic time with subsequent successful transplant to date. Liver Transpl 16:1428–1433, 2010.

Influenza-binding antibodies immobilise influenza viruses in fresh human airway mucus

Airway mucus is thought to serve as a dynamic filter that can trap respiratory viruses in the dense mucin network [1], and quickly eliminate them along with airway mucus from the respiratory tract. Nevertheless, viruses must penetrate airway mucus to infect the airway epithelium, and we and others have found that various viruses can readily penetrate physiological mucus gels [2–4]. We were particularly interested in whether airway mucus can serve as a barrier against influenza viruses, due to the prevalence and health burden of seasonal outbreaks. It has been suggested that airway mucus protects against influenza by presenting sialylated “decoys” on mucins that bind to influenza haemagglutinin and trap the virions in mucus. Alternatively, we have shown that antibodies in cervicovaginal mucus can trap viruses via multiple low-affinity Fc–mucin bonds between antibodies on the virus surface and mucins, akin to a Velcro patch [4]. To gain insight into how airway mucus might serve as a barrier against influenza, we characterised the mobility of influenza virions and virus-like particles (VLPs) in human airway mucus using real-time high-resolution multiple particle tracking. Common influenza viruses are immobilised in fresh human airway mucus, probably by influenza-binding antibodies http://ow.ly/yxu0305bqh6

Paravertebral Block for Thoracic Surgery

Local anesthetic injected into a wedge-shaped space lateral to the spinal nerves as they emerge from the intervertebral foramina produces somatosensory and sympathetic nerve blockade effective for anesthesia and for managing pain of unilateral origin from the chest and abdomen. Paravertebral blockade (PVB) is versatile and may be applied unilaterally or bilaterally. Unlike thoracic epidural, the PVB technique may be used to avoid contralateral sympathectomy, thereby minimizing hypotension and leading to better preservation of blood pressure. There are no reports on systemic toxicity associated with bilateral PVB despite the need for relatively large doses of local anesthetics. This review includes an important historic background and captures the resurgence of PVB-an almost lost technique. Thoracic PVB provides post-thoracotomy pain relief comparable with thoracic epidural analgesia (TEA) with lower side effects supported by moderate-quality evidence. The feasibility and potential of bilateral thoracic PVB for bilateral thoracic surgery appear practical. However, there is existing controversy in the assumption that thoracic PVB is a satisfactory, safer alternative when anticoagulation status is a contraindication to thoracic epidural placement. During the last 2 decades of systematic reviews and meta-analyses, both TEA and PVB have been deemed appropriate in the management of thoracic surgery. A multimodal approach to analgesia includes regional techniques for thoracic surgery that may reduce the likelihood of the development of postoperative complications and chronic pain. PURPOSE OF THIS REVIEW The authors evaluated current opinion, clinical practice, new multimodal adjuvants, regional anesthesia, and innovation and technology related PVB in the thoracic surgery patient population. The review focuses on history, techniques, application, ease of placement, and relative safety of this regional technique. For this review, studies and reference lists were retrieved from the Cochrane library, Embase, and Medline from January 1995 through January 2017. SUMMARY Existing evidence demonstrates noninferiority of thoracic PVB compared with TEA for postoperative analgesia, with fewer side effects for unilateral and bilateral thoracic surgery, including video-assisted thoracoscopy. The determining factors in selecting the regional technique of choice include the following: (1) tolerance of side effects associated with TEA, (2) consensus on best practice or technique, and (3) operator experience. There is no consensus on the optimal approach for thoracic PVB technique or any standardization when comparing the landmark, ultrasound-guided, or stimulation-based PVB approaches. Moreover, the efficacy of TEA compared with PVB in preventing post-thoracotomy chronic pain syndrome has not been investigated thoroughly and requires future clinical trials.

Pro: Patients at Risk for Spinal Cord Ischemia After Thoracic Endovascular Aortic Repairs Should Receive Prophylactic Cerebrospinal Fluid Drainage

horacic endovascular aortic repair (TEVAR) has become aneurysms were included and the extent of aortic coverage or Testablished as a less invasive option for the management of descending thoracic aortic diseases compared with conventional open surgical repair. TEVAR has reduced morbidity and mortality compared with open surgical repair, but still it is associated with a significant risk of spinal cord ischemia (SCI), which can lead to permanent paraplegia. The 2 major recognized medical interventions to prevent and treat spinal cord ischemia in patients undergoing TEVAR are arterial pressure augmentation and lumbar cerebrospinal fluid (CSF) drainage. Despite limited evidence from randomized controlled trials, the published clinical experience supports the effectiveness of CSF drainage as an adjunct for the treatment of patients with SCI and in prevention of permanent paraplegia as a consequence of TEVAR. Although there is little controversy regarding the use of lumbar CSF drainage for the treatment of SCI, considerable controversy exists as to whether preoperative insertion of a lumbar CSF drain is warranted as a prophylactic measure in patients undergoing TEVAR. Based on the existing clinical experience published in the medical literature, an argument can be made to support the routine use of prophylactic CSF drainage among patients undergoing TEVAR who are deemed preoperatively to be at high risk for SCI. The reported incidence of SCI after TEVAR ranges between 0% and 10.3%, with the average incidence being between 3% and 5%. Published clinical series suggested that the risk of SCI associated with TEVAR was less than that associated with open surgical repair; however, there was significant anatomic heterogeneity in these series. Indeed, most TEVAR procedures were performed for aortic pathology limited to the descending thoracic aorta. When patients with thoracoabdominal aortic

Acquired "Gerbode-like" defect in aortic valve endocarditis: an imposter for tricuspid regurgitation?

e v e t fi t a m w e m e i v 4 A59-YEAR-OLD woman with a bioprosthetic aortic valve was referred to the authors’ heart and vascular institute for rosthetic valve endocarditis with blood cultures positive for ethicillin-sensitive Staphylococcus aureus. The transesophaeal echocardiogram (TEE) showed mobile densities on the ortic and ventricular surfaces of the Carpentier-Edwards aortic alve leaflets. The patient was scheduled for an urgent valve eplacement with an aortic valve homograft. After an un-

PRO: Transesophageal Echocardiography Should Be Routinely Used for All Liver Transplant Surgeries

From the Department of Anesthesiology, University of North Carolina School of Medicine, UNC Hospitals, Chapel Hill, NC. Address reprint requests to Harendra Arora, MD, Department of Anesthesiology, N2198, University of North Carolina Hospitals, Campus Box 7010, Chapel Hill, NC. E-mail: harora@aims.unc.edu

Pro: ACE Inhibitors Should Be Continued Perioperatively and Prior to Cardiovascular Operations

ECISIONS INVOLVING the initiation or discontinuation of any medical intervention should be undertaken only after careful consideration of all available evidence. The risks and benefits must be evaluated for each individual patient and circumstance, especially in situations where the evidence is not as clear as in the question about continuation of perioperative angiotensin-converting enzyme (ACE) inhibitors. Major medical societies such as the American College of Cardiology and American Heart Association (ACC/AHA) and European societies recommend continuation of ACE inhibitors in the perioperative period. 1,2 Based on currently available evidence, the authors agree with their recommendation and argue in support of the continuation of ACE inhibitors prior to cardiovascular operations. ACE inhibitors were first introduced to the general public in the early 1980s. Initially, dosing of the pilot drug captopril proved to be problematic and multiple studies showed profound hypotension when the drug was initiated. 3 As dosing adjustments were made and newer agents like enalapril were introduced, the real benefit of ACE inhibitors came to light. The CONSENSUS trial published in 1987 was a doubleblinded study in which 253 patients with severe congestive heart failure (New York Heart Association [NYHA] functional Class IV) were randomly assigned to conventional treatment plus placebo or conventional treatment plus enalapril. 4 Mortality after six months was 26% in the enalapril group and 44% in the placebo group, representing a 40% reduction in mortality. At 1 year, mortality was reduced 31% in the enalapril group as compared to the placebo group, and these patients were shown to have a reduction in left ventricular size and an improvement in their NYHA classification. Although the CONSENSUS trial demonstrates the value of ACE inhibitors in patients with severe heart failure, further studies also have proven their benefit in patients with less severe disease. In 1992, the SAVE trial randomized 2,231 patients from multiple centers who had suffered a myocardial infarction with ejection fractions of 40% or less and without heart failure symptoms to receive treatment with either placebo or captopril within 3 to 16 days after their myocardial infarction. 5 All-cause mortality was reduced by 19% in the captopril group. Furthermore, they found a 37% risk reduction from severe heart failure, a 22% risk reduction in heart failure requiring hospitalization, and a 25% risk reduction in recurrent myocardial infarction. Since then, it has been well established that ACE inhibitors reduce sudden cardiac death in patients with heart failure and prevent remodeling and dilation of the left ventricle that can occur after a myocardial infarc