Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

BACKGROUND AND PURPOSE: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. MATERIALS AND METHODS: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. RESULTS: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. CONCLUSIONS: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Surgical management of pelvic organ prolapse.

Despite pelvic organ prolapse being a universal problem experienced in nearly 50% of parous women, the surgical management of vaginal prolapse remains an enigma to many, with wide variation in the rates and types of intervention performed. As part of the 6th International Consultation on Incontinence (ICI) our committee, charged with producing an evidence-based report on the surgical management of prolapse, produced a pathway for the surgical management of prolapse. The 2017 ICI surgical management of prolapse evidence-based pathway will be presented and summarized. Weaknesses of the data and pathway will be discussed and avenues for future research proposed.

Urinary symptoms and impact on quality of life in women after treatment for endometrial cancer.

The primary objective of our study is to describe urinary symptoms in women treated for endometrial cancer. We performed a cross-sectional survey of women who had undergone surgical treatment for endometrial cancer. Three validated questionnaires were utilized: the Sandvik Severity Index, the Urinary Distress Inventory-6 (UDI-6), and Incontinence Impact Questionaire-7 (IIQ-7). Our study included 70 women treated for endometrial cancer; 35.7% (25/70) of women reported adjuvant radiation therapy after surgical staging. Urinary incontinence was reported in over 80% of women. Mean UDI-6 and IIQ-7 scores for women treated with adjuvant radiation therapy were higher compared to women with no adjuvant radiation therapy [47(+/-26.8) vs. 35.6(+/-21.7; p = 0.05)] and [24.4(+/-28.5) vs. 8.1(+/-16.4; p = 0.004)], respectively. Treatment with adjuvant radiation therapy was associated with more severe incontinence symptoms and impact on quality of life.

Management of stress urinary incontinence.

Stress urinary incontinence (SUI) is a common disorder that does not require treatment unless bothersome to the patient. The evaluation includes a thorough history and physical in order to evaluate for other bladder and pelvic floor disorders. Multichannel urodynamics are not necessary for the diagnosis of SUI, but may be helpful when choosing among appropriate treatment options and for patient counseling. Behavioral and physical therapies are appropriate first-line treatments and should be discussed with all patients, even those desiring surgical treatment. Conservative treatments include the use of pessaries to improve urethral support. Multiple surgical options exist. While mid-urethral slings are commonly used today, there is a still a role for traditional pubovaginal slings and the Burch retropubic urethropexy.

Impact of menopause on collagen subtypes in the arcus tendineous fasciae pelvis.

OBJECTIVE: The arcus tendineous fasciae pelvis (ATFP) provides support to the anterior vagina. The objective of this study was to determine the impact of menopause on the structural components of the ATFP. STUDY DESIGN: Biopsy specimens of the ATFP were obtained from 10 premenopausal, 5 postmenopausal, and 12 postmenopausal women on hormone therapy. Scanning confocal microscopy of fluorescent micrographs was used to define the amount of collagen subtypes, smooth muscle, and elastin. Collagen fiber orientation was determined by scanning electron microscopy. RESULTS: The ATFP is comprised primarily of parallel bundles of type III collagen fibers (84%), an intermediate amount of elastin (13%), and very little smooth muscle. The ratio of collagen I/(III+V) was decreased in postmenopausal not on hormones relative to premenopausal women (P=.04) due to a 75% decrease in collagen I (P=.046). The decrease in collagen I and change in collagen ratios was not present in women on hormone therapy. Comparison of the amounts of elastin and smooth muscle showed no difference in the ATFP of premenopausal and postmenopausal women. CONCLUSION: Menopause in the absence of hormone therapy is associated with a decrease in quantity of collagen I in the ATFP resulting in a decrease in the ratio of collagen I/(III+V). This may compromise the tensile strength and an increase susceptibility to anterior vaginal wall prolapse.

A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression.

Even though all of the energy contained with the UV wavelengths of solar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress immune responses to Ag introduced at distant nonirradiated sites. In addition, data from a number of laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinoctyes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets. Although IL-10 can influence Th1 cell activation by altering Ag presentation and suppressing IFN-gamma secretion, the major signal for the development of a Th2 response is IL-4. Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV-irradiated mice with anti-IL-4 blocked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prostaglandins released by irradiated keratinocytes induce serum IL-4 since treating UV-irradiated mice with a cyclooxygenase-2 inhibitor blocked its production. Moreover, we found that treating UV-irradiated mice with anti-IL-4 suppressed serum IL-10 levels. In addition, injecting normal mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV exposure activates a cytokine cascade (PGE2 --> IL-4 --> IL-10) that ultimately results in systemic immune suppression.

Assisted hatching in mouse embryos using a noncontact Ho:YSGG laser system.

PURPOSE: A noncontact holmium:yttrium scandium gallium garnet (Ho:YSGG) laser system has been designed and tested for the micromanipulation of mammalian embryos. The purpose of this preliminary investigation was to determine the effectiveness of this laser for assisted hatching and evaluate its impact on embryo viability. The Ho:YSGG system, utilizing 250-microsecond pulses at a wavelength of 2.1 microns and 4 Hz, was used to remove a portion of the zona pellucida (ZP) of two- to four-cell FVB mouse embryos. RESULTS: In the first experiment there was no difference in blastocyst production or hatching rates following laser or conventional assisted hatching (LAH or AH, respectively) in contrast to control embryos cultured in a 5% CO2 humidified air incubator at 37 degrees C. In the second experiment a blastocyst antihatching culture model was employed and LAH-treated embryos were cultured in a serum-free HTF medium (HTF-o). Blastocyst formation was not influenced by LAH treatment and hatching was increased (P < 0.01) from 4 to 60% compared to HTF-o control group. CONCLUSIONS: These preliminary data demonstrate the utility and nontoxic properties of the Ho:YSGG laser system for quick and precise ZP drilling.