Device-Related Reoperations 8 Years Following Sacral Neuromodulation Implantation in Older Women.

INTRODUCTION AND HYPOTHESIS: The objective was to describe long-term device-related reoperations at 8 years following sacral neuromodulation (SNM) in women older than 65 years for the indications of overactive bladder (OAB), fecal incontinence (FI), and/or idiopathic urinary retention (UR). METHODS: The 2010-2019 Medicare 100% Outpatient Limited Dataset was used to identify women aged 65 years and older who underwent SNM to treat OAB, FI, and/or UR. The primary study outcome was any device-related reoperation within 8 years following initial implantable pulse generator (IPG) implantation defined as: IPG revision or removal; IPG replacement; or neuro-electrode revision or removal. Kaplan-Meier survival analysis was also performed to evaluate time to adverse event. RESULTS: The cohort included 32,454 women with a mean age of 74 years. The most common indication for SNM was OAB (71%) followed by UI and FI (13%) and FI only (8%). Staged SNM procedures were performed more frequently (60%) than percutaneous nerve evaluation/full implants. The overall rate of device-related reoperations was 24% over 8 years: 12% of patients underwent removal or revision of the neuro-electrode, 11% underwent removal or revision of the IPG, and 13% underwent replacement of the IPG. The mean follow-up was 3.9 ± 2.4 years. The cumulative incidence of any device-related reoperations was 9.4% at 1 year, 20% at 3 years, and 43% at 8 years. CONCLUSIONS: In the 8 years following SNM implantation, the rate of device-related reoperation among female Medicare beneficiaries was 43%, and staged implants were associated with a 17% lower likelihood of undergoing any device-related reoperations.

Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort.

PURPOSE: To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants. METHODS: After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21 years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter. Data analyses employed ANOVAs and non-linear regressions. RESULTS: Analyses of age group differences revealed that participants 12-21 years old had a larger initial pupil diameter and pupil diameter after light stimulus, with males aged 12-18 years demonstrating a larger pupil diameter than all younger participants (ps < 0.05). Participants 12-18 years old had a slower maximum constriction velocity than participants 6-11 years old, with no sex differences (ps < 0.05). Furthermore, males aged 12-18 years old had a smaller percent constriction than males 6-11 years old (ps < 0.05). Regressions revealed that percent constriction and dilation velocity seemed to mature linearly, initial pupil diameter and ending pupil diameter matured quadratically, and the constriction velocity terms matured cubically. CONCLUSIONS: Results revealed maturation of the pupillary light response by age and sex in healthy pediatric participants. Given the value of the pupillary light response as a biomarker, the results provide normative benchmarks for comparison in health and disease, including opiate-exposed and concussion patients.

Objective Changes in Pelvic Floor Muscle Strength and Length in Women With High-Tone Pelvic Floor Dysfunction After Pelvic Floor Physical Therapy (RELAX Trial).

IMPORTANCE: Although pelvic floor physical therapy (PFPT) is effective in treating high-tone pelvic floor dysfunction (HTPFD), data on the mechanism of improvement are limited. OBJECTIVES: This study aimed to compare squeeze intravaginal closure force after 6 weeks of PFPT in women affected by HTPFD and, secondarily, to describe changes in levator dimensions and short-term effects of PFPT on bladder, bowel, and pain symptoms. METHODS: We conducted a prospective cohort study of patients undergoing 6 sessions of PFPT for the diagnosis of HTPFD. At baseline, we measured intravaginal closure force using an instrumented speculum, levator hiatal dimension using a 3-dimensional endovaginal ultrasonography, and symptom severity using 3 validated questionnaires. Intravaginal closure force and symptoms were reevaluated after the second, fourth, and sixth PFPT sessions, and levator hiatus was reevaluated at the sixth session. RESULTS: Twenty-six women were enrolled and 22 completed 6 sessions and are included in the analysis. Contrary to our hypothesis, mean ± SD vaginal closure force (N) did not demonstrate a significant change (3.27 ± 2.34 vs 3.67 ± 2.02 N, P = 0.18). However, mean levator hiatal area (cm2) increased between visit 1 (13.71 ± 1.77 cm2) and visit 6 (14.43 ± 2.17 cm2, P = 0.05), as did the transverse diameter (3.83 ± 0.03 vs 3.95 ± 0.03 cm, P = 0.04). Survey responses demonstrated significant improvements across all measures of genitourinary symptoms, pain, lower gastrointestinal symptoms and quality-of-life measures after 6 sessions of PFPT. CONCLUSION: Although the levator hiatal area increased after 6 sessions of PFPT (suggesting muscle lengthening), we were unable to demonstrate that this changed the force generated by pelvic floor muscles as measured by a speculum.

Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation.

Muscle dysfunction often occurs in patients with chronic obstructive pulmonary diseases (COPD) and affects ventilatory and non-ventilatory skeletal muscles. We have previously reported that hypercapnia (elevated CO2 levels) causes muscle atrophy through the activation of the AMPKα2-FoxO3a-MuRF1 pathway. In the present study, we investigated the effect of normoxic hypercapnia on skeletal muscle regeneration. We found that mouse C2C12 myoblasts exposed to elevated CO2 levels had decreased fusion index compared to myoblasts exposed to normal CO2. Metabolic analyses of C2C12 myoblasts exposed to high CO2 showed increased oxidative phosphorylation due to increased fatty acid oxidation. We utilized the cardiotoxin-induced muscle injury model in mice exposed to normoxia and 10% CO2 for 21 days and observed that muscle regeneration was delayed. High CO2-delayed differentiation in both mouse C2C12 myoblasts and skeletal muscle after injury and was restored to control levels when cells or mice were treated with a carnitine palmitoyltransfearse-1 (CPT1) inhibitor. Taken together, our data suggest that hypercapnia leads to changes in the metabolic activity of skeletal muscle cells, which results in impaired muscle regeneration and recovery after injury.