Faculty Bibliography

INTRODUCTION AND HYPOTHESIS: We investigated the efficiency and efficacy of vaginal mesh attachment using interrupted, non-barbed, delayed absorbable sutures in comparison with a running, barbed, delayed absorbable suture during laparoscopic sacrocolpopexy (LSC) and robotic sacrocolpopexy (RSC). METHODS: Women undergoing LSC or RSC were recruited. Participants were randomized to at least six 0 PDS non-barbed interrupted sutures or at least six passes of a 1 PDS barbed suture (Quill) on each anterior and posterior polypropylene mesh leaflet. The primary outcome was the time to attach the mesh to the vagina. The LSC and RSC groups were block randomized by suture type. Secondary outcomes included: (1) intraoperative surgeon assessment of satisfaction as measured using a 10-cm visual analog scale (VAS), (2) postoperative POP-Q evaluation for anatomic failure, and (3) overall appearance of vaginal walls measured using a VAS. RESULTS: Of the 64 included subjects who were randomized, 32 had mesh attachment with the barbed suture (16 LSC, 16 RSC) and 32 had attachment with non-barbed sutures (16 LSC, 16 RSC). Among all the subjects (LSC and RSC), the non-barbed suture group had significantly longer mesh attachment times than the barbed suture group (42 vs. 29 min, p < 0.001). The non-barbed suture group had significantly better scores for intraoperative ease of suture placement, surgeon satisfaction with mesh appearance, and global satisfaction. At 12 months, there were no significant differences in anatomic failure between the suture groups or overall appearance of the vaginal walls (p > 0.05). CONCLUSIONS: The barbed suture technique was 11 - 16 min faster for attaching mesh to the vagina than the non-barbed suture technique. Anatomic outcomes at 12 months were comparable between the suture groups. It is reasonable to use a running, barbed suture in minimally invasive sacrocolpopexy.

AIMS: This study examined the association between the need for a repeat voiding trial after midurethral sling (MUS) surgery and 1-year success rates. METHODS: We conducted this secondary analysis of the participants in the Urinary Incontinence Treatment Network trial of midurethral sling (TOMUS) study which compared retropubic versus transobturator MUS. A standard voiding trial was attempted on all subjects. The "repeat voiding trial" group included subjects discharged with catheterization. All others were considered "self voiding." Success rates between the groups at 1-year were compared, followed by multivariate analyses controlling for previously reported clinical predictors of success. RESULTS: Most women (76%) were self-voiding, while 24% required a repeat voiding trial. The objective success rate at 1-year was 85.8% in the repeat voiding trial group and 75.3% in the self-voiding group (P = 0.01). Subjective success rate at 1-year was 61.0% in the repeat voiding trial group and 55.1% in the self-voiding group (P = 0.23). Women in the repeat voiding trial group continued to demonstrate greater objective success than the self-voiding group in multivariate analysis that controlled for previous incontinence surgery, pad weight, urethral mobility, urge score, and type of MUS (P = 0.04, OR 1.82, 95% CI 1.03-3.22). CONCLUSIONS: Women who require a repeat voiding trial following MUS surgery have greater objective success at 1-year postoperatively when compared to those who are self-voiding at the time of discharge. These results may help reassure women who require catheterization after MUS surgery that their outcome is not compromised by this immediate transient post-operative result.

Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (+/- SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 +/- 1.27 mug/mL (baseline, n = 28), 5.59 +/- 2.24 mug/mL (1,200 mg/day, week 4, n = 26), 6.38 +/- 3.25 mug/mL (2,400 mg/day, week 8, n = 25), 7.49 +/- 4.09 mug/mL (3,600 mg/day, week 12, n = 23), and 6.78 +/- 3.36 mug/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.

We conducted case-control and prospective longitudinal studies to examine risk factors and predictors of disease progression for ALS. Ninety-five subjects with ALS and 106 healthy control subjects were enrolled. All subjects completed a risk factor questionnaire at enrollment. The ALS subjects were prospectively followed for one year to define factors that influence the rate of disease progression, measured by rate of change in percent predicted forced vital capacity (%FVC) and the ALS functional rating scale (ALSFRS) score. The association of each potential risk factor with ALS was determined using univariate logistic regression. A random slope model was used to determine the association of each risk factor with disease progression. The demographic characteristics of ALS subjects and controls at enrollment did not differ. Significant risk factors for ALS included reported exposure to lead (p = 0.02) and pesticides (p = 0.03). Disease progression was faster in the ALS subjects having bulbar onset and a shorter time period between onset of symptoms and diagnosis. Pertinent variables not associated with either causation or progression of ALS included physical activity, cigarette smoking and a history of physical trauma or other clinical disorders.

An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.

BACKGROUND: Retroviral involvement in the etiology of sporadic ALS has been suspected for several years since the recognition that both murine and human retroviruses can cause motor neuron disease-like syndromes. In a pilot study, an increased prevalence of a retroviral marker (reverse transcriptase [RT] activity) was demonstrated in the serum of British patients with ALS. The current investigation was designed to confirm and extend these findings in a geographically distinct patient cohort under blinded testing conditions. METHODS: A highly sensitive product-enhanced RT assay was employed to test coded sera obtained from 30 American patients with sporadic ALS and from 14 of their blood relatives, 16 of their spouses, and 28 nonrelated, nonspousal control subjects. RESULTS: Serum RT activity was detected in a higher proportion of ALS patients (47%) than in non-blood-related controls (18%; p = 0.008). The prevalence of RT activity in the serum of spousal controls (13%) was similar to that in other non-blood-related controls. Unexpectedly, the prevalence of serum RT activity in blood relatives of ALS patients (43%) approached that in the ALS patients themselves. CONCLUSIONS: These results confirm that patients with ALS have a significantly higher prevalence of serum reverse transcriptase (RT) activity than that seen in unrelated control subjects. The finding of a similarly increased prevalence in blood relatives of ALS patients raises the possibility that the observed RT activity might be due to an inherited endogenous retrovirus.