Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia

PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.     

Clinical endpoints for drug development in prostate cancer

PURPOSE OF REVIEW: Overall survival remains the benchmark in phase III settings of novel agents in castration-resistant metastatic prostate cancer. This review highlights many of the current potential early measures of response and clinical benefit that are worthy of future study and validation in this disease. RECENT FINDINGS: The clinical evaluation of novel agents in advanced prostate cancer remains challenging for several reasons. Men with metastatic prostate cancer often have bone-only disease in which formal radiologic response and progression criteria may not apply. Declines in serum prostate-specific antigen levels may be modest surrogates of response to cytotoxic agents such as docetaxel, but have not been validated for agents with novel mechanisms of action, such as antiangiogenic, immunologic, or cytostatic drugs. Novel radiologic imaging techniques such as PET scans are not yet validated for use in monitoring or staging advanced prostate cancer. Measures of delay, control, and palliation of metastatic disease such as pain response, time to progression and progression-free survival, while appealing endpoints that may highlight the clinical benefit of novel agents, have been difficult to define rigorously and have not yet demonstrated adequate surrogacy for overall survival. SUMMARY: The measures of response highlighted in this review, if validated, may improve the current evaluation of novel agents in phase II settings and the potential accelerated approval of these agents.     

Plantar pressure and radiographic changes after distal calcaneal lengthening in children and adolescents

Eleven feet (nine patients) with symptomatic flatfoot deformities of various etiologies that had failed nonoperative treatment underwent distal calcaneal lengthenings. Pre- and postoperative plantar pressure measurements and radiographic parameters were compared and a postoperative clinical evaluation was performed using the AOFAS ankle and hindfoot scoring system. Follow-up ranged from 4 to 20 months (mean, 11.1 months). Plantar pressure parameters including contact area, mean, and peak pressures indicated significant lateral shifts in the weight-bearing surface of the foot. The most significant radiographic changes were an improvement in the talonavicular coverage angle (mean, 17.3 degrees) on the anteroposterior view and an improvement in the talo-first metatarsal angle (16.2 degrees) on the lateral view. The average postoperative American Orthopedic Foot and Ankle Society score was 90 with seven excellent, three good, and one poor results.     

Duplex scan surveillance after carotid angioplasty and stenting: a rational definition of stent stenosis

OBJECTIVE: A duplex ultrasound (DUS) surveillance algorithm used after carotid endarterectomy (CEA) was applied to patients after carotid stenting and angioplasty (CAS) to determine the incidence of high-grade stent stenosis, its relationship to clinical symptoms, and the outcome of reintervention. METHODS: In 111 patients who underwent 114 CAS procedures for symptomatic (n = 62) or asymptomatic (n = 52) atherosclerotic or recurrent stenosis after CEA involving the internal carotid artery (ICA), DUS surveillance was performed 300 cm/s, diastolic velocity >125 cm/s, internal carotid artery stent/proximal common carotid artery ratio >4) involving the stented arterial segment prompted diagnostic angiography and repair when >75% diameter-reduction stenosis was confirmed. Criteria for >50% CAS stenosis was a PSV >150 cm/s with a PSV stent ratio >2. RESULTS: All 114 carotid stents were patent on initial DUS imaging, including 90 (79%) with PSV <150 cm/s (94 +/- 24 cm/s), 23 (20%) with PSV >150 cm/s (183 +/- 34 cm/s), and one with high-grade, residual stenosis (PSV = 355). During subsequent surveillance, 81 CAS sites (71%) exhibited no change in stenosis severity, nine sites demonstrated stenosis regression to <50% diameter reduction, and five sites developed velocity spectra of a high-grade stenosis. Angiography confirmed >75% diameter reduction in all six CASs with DUS-detected high-grade stenosis, all patients were asymptomatic, and treatment consisted of endovascular (n = 5) or surgical (n = 1) repair. During the mean 33-month follow-up period, three patients experienced ipsilateral, reversible neurologic events at 30, 45, and 120 days after CAS; none was associated with severe stent stenosis. No stent occlusions occurred, and no patient with >50% CAS stenosis on initial or subsequent testing developed a permanent ipsilateral permanent neurologic deficit or stroke-related death. CONCLUSION: DUS surveillance after CAS identified a 5% procedural failure rate due to the development of high-grade in-stent stenosis. Both progression and regression of stent stenosis severity was observed on serial testing, but 70% of CAS sites demonstrated velocity spectra consistent with <50% diameter reduction. The surveillance algorithm used, including reintervention for asymptomatic high-grade CAS stenosis, was associated with stent patency and the absence of disabling stroke.     

Surgical treatment of paravalvular abscess: long-term results.

OBJECTIVE: To examine the outcomes of surgery for active infective endocarditis with paravalvular abscess. METHODS: Paravalvular abscess was defined as infective necrosis of the valve annulus that required patch reconstruction before implanting a new valve. Of 383 patients with active infective endocarditis who underwent surgical treatment, 135 (35%) had paravalvular abscess. Patients' mean age was 51+/-16 years and 68% were men. The infected valve was native in 69 patients and prosthetic in 66. The abscess involved the aortic annulus in 73 patients, the mitral annulus in 27, the aortic and mitral annuluses in 33, and the aortic and tricuspid and/or pulmonary annuluses in 2. Surgery consisted of radical resection of the abscess, reconstruction of the annulus with patches and valve replacement. Mean follow-up was 6.2+/-5.2 years and complete. RESULTS: There were 21 (15.5%) operative deaths. Preoperative shock and abscess in the aortic and mitral annuluses were independent predictors of operative death. There were 34 (25%) late deaths. Survival at 15 years was 43+/-6% for all patients, 50+/-8% for native valve endocarditis and 35+/-9% for prosthetic (p=0.41). Age by increments of 5 years and recurrent endocarditis were independent predictors of late death. There were 16 episodes of recurrent endocarditis in 15 patients, and the freedom from recurrent endocarditis was 82+/-4% at 15 years. Fifteen reoperations were performed in 14 patients. Freedom from reoperation was 72+/-9% at 15 years. CONCLUSIONS: Surgery for active endocarditis with paravalvular abscess was associated with high operative mortality, particularly in patients in shock and abscess of both mitral and aortic annuluses. Long-term survival was adversely affected by age and recurrent bouts of endocarditis.     

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study

BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). RESULTS: The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.     

Leiomyosarcoma of the inguinal canal

We describe a rare case of a leiomyosarcoma in the inguinal canal in a patient presenting clinically with an inguinal hernia. The clinical details, histological findings and surgical management are reviewed.     

Beyond survival: how well do transplanted livers work? A preliminary comparison of standard‐risk,high‐risk,and living donor recipients

To help decrease mortality on the liver transplant waitlist, transplant centers are using living donors (LD) and high‐risk donors (HRD) in addition to standard‐risk donors (SRD). HRD is defined as having a donor risk index score higher than 1.6, which suggests a great risk of graft failure. Recent studies have examined survival rates between HRD and SRD recipients; however, little is known about outcomes other than survival, specifically psychosocial outcomes. The purpose of this preliminary, prospective study was to compare post‐transplant psychosocial and recovery outcomes between SRD and LD and HRD liver recipients. These outcomes include cognitive functioning, psychological distress, quality of life, and self‐reported and objective measures of recovery. Eighty‐four patients provided baseline and six‐month post‐transplant data. There were generally no statistically significant differences at baseline or the six‐month follow‐up, suggesting that patients receiving HRD livers have similar outcomes to those who receive SRD livers. However, some effect sizes suggest potential advantages for LD recipients compared to SRD recipients. Transplant centers may be more willing to encourage patients to accept HRD or LD livers knowing that they may have comparable outcomes to SRD recipients, which also has implications for the transplant waitlist.