Thymectomy may not be associated with clinical improvement in MuSK myasthenia gravis

Introduction: A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti–muscle-specific kinase (MuSK)-MG. Methods: The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK-MG. Results: Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12–1.53, P = 0.19). Discussion: Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK-MG patients. Muscle Nerve 59:404–410, 2019     

The effect of body mass index on surgical outcomes and survival following pelvic exenteration

Objective

We sought to evaluate whether preoperative body mass index (BMI) impacts surgical outcomes, complication rates, and/or recurrence rates in women undergoing pelvic exenteration.

Methods

All women who underwent pelvic exenteration for gynecologic indications at our institution from 1993 through 2010 were included. Women were stratified into 3 groups based on BMI. Baseline characteristics, surgical outcomes, early (< 60 days) and late (≥ 60 days) postoperative complications, and recurrence/survival outcomes were collected. Multivariate logistic regression analyses were performed. Kaplan-Meier survival curves were compared using log-rank test.

Results

161 patients were included (59 normal weight, 44 overweight, 58 obese). Median follow-up times were 22, 29, and 25 months. Most patients underwent total pelvic exenteration (68%); 64.6% had a vaginal reconstruction. On multivariate analysis, both overweight and obese patients had a higher risk of early superficial wound separation compared to normal weight patients — OR 10.74 (3.33-34.62, p < 0.001) and OR 4.35 (1.40-13.52, p = 0.011), respectively. Length of surgery was significantly longer for overweight (9.6 h, OR 1.26, 1.02-1.55, p = 0.032) and obese (10.1 h, OR 1.24, 1.04-1.47, p = 0.014) patients than for normal weight patients (8.7 h). Late postoperative complications for patients in the normal weight, overweight, and obese groups were 47.5%, 45.5%, and 43.1% (p = 0.144). There were no differences in time to recurrence (p = 0.752) or overall survival (p = 0.103) between groups.

Conclusion

Although operative times were longer and risk for superficial wound separation was significantly higher, pelvic exenteration appears to be feasible and safe in overweight and obese women with overall complication rates and survival outcomes comparable to normal weight women.     

The importance of acid digestion of urine prior to spontaneous deposition of 210Po

Historically, radiochemical analysis of 210Po in urine has used spontaneous deposition of the nuclide directly from raw urine onto a suitable metal disc. Consequently, the urinary excretion fraction for Po in some current metabolic and dosimetric models is based on studies which inherently assume that metabolized (i.e., filtered out of the blood by the kidneys) 210Po is plated with the same efficiency as tracer 210Po which has been added to urine samples. Urine samples collected after intravenous administration of 210Po citrate to two species of nonhuman primates were divided and simultaneously analyzed via two methods: the historical procedure of plating 210Po from raw urine for one sample and a method which includes the addition of 208Po tracer and sample digestion with concentrated HNO3 prior to 210Po deposition for the other sample. A more significant amount of 210Po was consistently recovered when the urine was wet ashed then when it was not wet ashed. A temporal relationship was found to describe the change in the ratio of the deposition recoveries for the two methods. Possible mechanisms for this phenomenon and its dosimetric implications are discussed.     

Complex III staining in blue native polyacrylamide gels

For more than a decade now blue native polyacrylamide gel electrophoresis (BN-PAGE) has been used for the study of the oxidative phosphorylation (OXPHOS) complexes. Catalytic activities of complexes I, II, IV and V can be assessed, after separation by gel electroforesis, by incubation of the BN-PAGE gel in specific staining solutions. However, until now, a reliable staining method for testing ubiquinol cytochrome c oxidoreductase (complex III) activity by BN-PAGE gel techniques was not available. In addition, spectrophotometric methods currently in use for detection of complex III deficiency in patients are not very sensitive. Here, we describe a newly developed diagnostic method for visualization of complex III activity by direct in-gel evaluation of ubiquinol cytochrome oxidoreductase activity. We validated the method by reporting the results in six patients with previously characterised complex III defects.