Multislice computed tomography angiography in pediatric liver transplantation

BACKGROUND: Preoperative delineation of any vascular anomalies offers planning for possible alteration of surgical procedures, especially in pediatric recipients undergoing living-related liver transplantation. PURPOSE: We assess the efficacy of three-dimensional (3D) multislice computed tomography (CT) angiography in the hope of replacing conventional angiography as the pretransplant evaluation of the hepatic vascular system for potential recipients of liver transplantation. METHODS: 3D CT angiography was performed in 38 children with biliary atresia. Conventional angiography was also performed in the first 15 patients. Twelve patients underwent living-related liver transplantation. The findings on 3D CT angiography were compared with conventional angiography and operative findings. RESULTS: 3D CT angiography was successfully performed in 37 pediatric patients. All findings of 3D CT angiography on hepatic artery, portal vein, and inferior vena cava paralleled those of catheter angiography and operative findings. Four patients were unsuitable to receive living grafts because of pathologic insults of the hepatic artery (one patient) and the portal vein (three patients). Three patients were advised to undergo a venous graft for portal anastomoses. Eight patients demonstrated portosystemic shunts that may require closure. CONCLUSION: 3D CT angiography proves to be a better tool in the demonstration of the vascular system and identification of pathologic insults in pediatric patients. It is superior to conventional angiography because it is less invasive, more convenient, and more efficient in providing thorough preoperative information that would have a major impact on patient selection and surgical planning.     

Bilateral infraorbital nerve blocks decrease postoperative pain but do not reduce time to discharge following outpatient nasal surgery

Purpose

While infraorbital nerve blocks have demonstrated analgesic benefits for pediatric nasal and facial plastic surgery, no studies to date have explored the effect of this regional anesthetic technique on adult postoperative recovery. We designed this study to test the hypothesis that infraorbital nerve blocks combined with a standardized general anesthetic decrease the duration of recovery following outpatient nasal surgery.

Methods

At a tertiary care university hospital, healthy adult subjects scheduled for outpatient nasal surgery were randomly assigned to receive bilateral infraorbital injections with either 0.5% bupivacaine (Group IOB) or normal saline (Group NS) using an intraoral technique immediately following induction of general anesthesia. All subjects underwent a standardized general anesthetic regimen and were transported to the recovery room following tracheal extubation. The primary outcome was the duration of recovery (minutes) from recovery room admission until actual discharge to home. Secondary outcomes included average and worst pain scores, nausea and vomiting, and supplemental opioid requirements.

Results

Forty patients were enrolled. A statistically significant difference in mean [SD] recovery room duration was not observed between Groups IOB and NS (131 [61] min vs 133 [58] min, respectively; P = 0.77). Subjects in Group IOB did experience a reduction in average pain on a 0–100 mm scale (mean [95% confidence interval]) compared to Group NS (?11 [?21 to 0], P = 0.047), but no other comparison of secondary outcomes was statistically significant.

Conclusions

When added to a standardized general anesthetic, bilateral IOB do not decrease actual time to discharge following outpatient nasal surgery despite a beneficial effect on postoperative pain.     

Medium-Term Anatomic and Functional Results of Laparoscopic Sacrocolpopexy Beyond the Learning Curve

Background

Limited prospective data on the anatomic and functional outcome after laparoscopic sacrocolpopexy (LSC) are available in the literature.

Objective

To describe the medium-term anatomic and functional outcome of LSC.

Design, setting, and participants

Prospective consecutive series of 132 women with vaginal vault prolapse undergoing LSC between 2001 and 2006, which was after our learning curve. Patients with urodynamically proven stress incontinence (SI) underwent a concomitant tension-free vaginal tape (TVT) procedure.

Intervention

Patients underwent LSC with a polypropylene implant.

Measurements

Principal outcome measures were anatomic cure (stage 1 or lower) assessed by the Pelvic Organ Prolapse Quantification (POPQ) system and subjective cure and impact on quality of life measured by a standardised interview and, since its introduction in 2004, by a prolapse-specific quality-of-life questionnaire (P-QOL).

Results and limitations

At a mean follow-up of 12.5 mo, the anatomic cure rate for the apex was 98%. Anatomic failures elsewhere were mainly at the posterior compartment (18%). Subjective prolapse cure rate was 91.7%, and no patients required reoperation for recurrent prolapse. Symptoms of preoperative SI, urge incontinence, or constipation were cured in 43%, 46%, and 42% of patients, respectively. The rate of de novo SI was 7.3%. De novo constipation developed in 5% and de novo dyspareunia developed in 19%. Patients’ quality of life improved significantly. Erosions occurred in 4.5%, all within 1 yr. A limitation of the study is that the quality-of-life assessment score became available halfway through the study, limiting the number of preoperative observations (n = 36).

Conclusions

We demonstrated that LSC results in good anatomic outcome and subjective cure of prolapse symptoms at medium term. The posterior compartment was most vulnerable for recurrence.     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).