Patient Receptivity to Integration of Telehealth in Pelvic Floor Physical Therapy Regimens.

IMPORTANCE: Limited research has focused on patient perceptions and barriers to integration of virtual care in the pelvic health arena. OBJECTIVES: The purpose of this study was to determine the willingness of patients to consider telehealth as a means to seek pelvic floor physical therapy (PFPT) care and the promoters and deterrents for deployment in this treatment modality. METHODS: This is a cross-sectional study of patients (≥18 years of age) at a multidisciplinary pelvic health service in an academic medical center in Northwest Ohio. The data collection occurred over 6 months in the latter half of 2021 using a novel 21-question survey based on focus group perceived patient requests, needs, and concerns that were aligned and cross-referenced with published literature. RESULTS: The survey was completed by 210 patients, with up to 40% (n = 83) being new PFPT patients. Of those interested in telehealth being a component of their PFPT therapeutic regimen (n = 142 [68%]), interest was driven by convenience (78%). Privacy (n = 52 [76%]) was the main barrier impeding interest in this modality. Up to 80% (n = 169) preferred to establish care through in-person visits before initiating PFPT regimens remotely, with 44% (n = 93) suggesting that incorporation of telehealth would positively affect their adherence with care regimens. CONCLUSION: Offering patients in-person visits or hybrid alternatives may be optimal for improving adherence to therapeutic regimens especially when considering access to care.

The role of nonpharmacologic therapies in management of chronic pelvic pain: what to do when surgery fails.

PURPOSE OF REVIEW: To provide an update on nonsurgical and nonpharmacologic strategies for the management of chronic pelvic pain (CPP). RECENT FINDINGS: Effective treatment of patients with CPP requires a multifaceted approach, with thoughtful consideration of surgical, pharmacologic, and nonpharmacologic strategies. Evidence for physical therapy and trigger point injections for treatment of myofascial components of CPP is increasing. Neuromodulation techniques, such as percutaneous tibial nerve stimulation and transcutaneous electrical stimulation, have limited but favorable preliminary data in patients with CPP. Behavioral strategies, such as exercise, cognitive behavioral therapy, and mindfulness, have demonstrated significant improvements in pain, function and quality of life in patients with a variety of chronic pain conditions and are promising avenues for future research in CPP. SUMMARY: Nonpharmacologic therapies are important adjuncts to surgical and pharmacologic treatment for CPP and should be considered integral to a comprehensive treatment approach.

Effects of intrauterine contraception on the vaginal microbiota.

OBJECTIVES: There have been conflicting reports of altered vaginal microbiota and infection susceptibility associated with contraception use. The objectives of this study were to determine if intrauterine contraception altered the vaginal microbiota and to compare the effects of a copper intrauterine device (Cu-IUD) and a levonorgestrel intrauterine system (LNG-IUS) on the vaginal microbiota. STUDY DESIGN: DNA was isolated from the vaginal swab samples of 76 women using Cu-IUD (n=36) or LNG-IUS (n=40) collected prior to insertion of intrauterine contraception (baseline) and at 6 months. A third swab from approximately 12 months following insertion was available for 69 (Cu-IUD, n=33; LNG-IUS, n=36) of these women. The V4 region of the bacterial 16S rRNA-encoding gene was amplified from the vaginal swab DNA and sequenced. The 16S rRNA gene sequences were processed and analyzed using the software package mothur to compare the structure and dynamics of the vaginal bacterial communities. RESULTS: The vaginal microbiota from individuals in this study clustered into 3 major vaginal bacterial community types: one dominated by Lactobacillus iners, one dominated by Lactobacillus crispatus and one community type that was not dominated by a single Lactobacillus species. Changes in the vaginal bacterial community composition were not associated with the use of Cu-IUD or LNG-IUS. Additionally, we did not observe a clear difference in vaginal microbiota stability with Cu-IUD versus LNG-IUS use. CONCLUSIONS: Although the vaginal microbiota can be highly dynamic, alterations in the community associated with the use of intrauterine contraception (Cu-IUD or LNG-IUS) were not detected over 12 months. IMPLICATIONS: We found no evidence that intrauterine contraception (Cu-IUD or LNG-IUS) altered the vaginal microbiota composition. Therefore, the use of intrauterine contraception is unlikely to shift the composition of the vaginal microbiota such that infection susceptibility is altered.

Laparoscopic Removal of a Retroperitoneal Hysteroscopic Microinsert Using Fluoroscopy.

Perforation during placement of hysteroscopic microinserts for permanent sterilization occurs in approximately .9% to 2.6% of women undergoing the procedure. Most of the time perforation results in intraperitoneal placement of the hysteroscopic microinsert requiring laparoscopy or laparotomy for removal of the device. Herein we present a case of hysteroscopic microinsert perforation with subsequent retroperitoneal identification of the device. This is the first such case to our knowledge of retroperitoneal identification and retrieval of a perforated device that required real-time fluoroscopy during laparoscopy.

Resveratrol inhibits ovarian tumor growth in an in vivo mouse model.

BACKGROUND: Resveratrol inhibits the growth of ovarian carcinoma cells in vitro through the inhibition of glucose metabolism and the induction of both autophagy and apoptosis. In the current study, we investigated the metabolic and therapeutic effects of resveratrol in vivo. METHODS: A fluorescent xenograft mouse model of ovarian cancer was used. Mice were treated with cisplatin, resveratrol, or vehicle alone. Tumor burden was assessed using whole-body imaging. The effect of resveratrol on glucose uptake in vivo was determined using micro-positron emission tomography scanning. To determine whether resveratrol could inhibit tumor regrowth, tumor-bearing mice were treated with cisplatin followed by either daily resveratrol or vehicle. Autophagic response in resected tumors taken from mice treated with resveratrol was examined by transmission electron microscopy. Glycolysis and mitochondrial respiration in ovarian tumor cells after treatment with resveratrol was assessed. RESULTS: Mice treated with resveratrol and cisplatin were found to have a significantly reduced tumor burden compared with control animals (P<.001). Resveratrol-treated mice demonstrated a marked decrease in tumor uptake of glucose compared with controls. After treatment with cisplatin, "maintenance" resveratrol resulted in the suppression of tumor regrowth compared with mice receiving vehicle alone (P<.01). Tumors resected from mice treated with resveratrol exhibited autophagosomes consistent with the induction of autophagy. Treatment with resveratrol inhibited glycolytic response in ovarian tumor cells with high baseline glycolytic rates. CONCLUSIONS: Treatment with resveratrol inhibits glucose uptake and has a significant antineoplastic effect in a preclinical mouse model of ovarian cancer. Resveratrol treatment suppresses tumor regrowth after therapy with cisplatin, suggesting that this agent has the potential to prolong disease-free survival. Cancer 2016;122:722-729. © 2015 American Cancer Society.

Glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells.

OBJECTIVES: Upregulation of glycolysis has been demonstrated in multiple tumor types. Glucose deprivation results in diminished intracellular ATP; this is counteracted by AMPK activation during energy deficiency to restore ATP levels. We sought to determine whether glucose deprivation could induce cytotoxicity in ovarian cancer cells through activation of AMPK, and whether AMPK activators could mimic glucose deprivation induced cytotoxicity. METHODS: Sensitivity to 2DG induced cytotoxicity and glucose deprivation was determined in a panel of ovarian cancer cells. Cellular growth rate, rate of glucose uptake, and response to glucose deprivation were determined. Expression of Glut-1, HIF1-α, AMPK and Akt was determined by immunoblotting. RESULTS: Incubation of ovarian cancer cells with glucose-free media, 2-DG and AMPK activators resulted in cell death. The glycolytic phenotype of ovarian cancer cells was present in both normoxic and hypoxic conditions, and did not correlate with HIF1-α expression levels. Sensitivity to glucose deprivation was independent of growth rate, rate of glucose uptake, and appeared to be dependent upon constitutive activation of Akt. Glucose deprivation resulted in activation of AMPK and inhibition of Akt phosphorylation. Treatment with AMPK activators resulted in AMPK activation, Akt inhibition, and induced cell death in ovarian cancer cells. CONCLUSIONS: Ovarian cancer cells are glycolytic as compared to normal, untransformed cells, and are sensitive to glucose deprivation. Because ovarian cancer cells are dependent upon glucose for growth and survival, treatment with AMPK activators that mimic glucose deprivation may result in broad clinical benefits to ovarian cancer patients.

Inhibition of glycolysis enhances cisplatin-induced apoptosis in ovarian cancer cells.

OBJECTIVE: Up-regulation of glycolysis has been demonstrated in multiple tumor types and is believed to originate as an adaptive response to the selective pressure of the tumor microenvironment. We hypothesized that ovarian cancer cells are dependent on the glycolytic pathway for adenosine triphosphate generation and that this phenotype could be exploited for therapeutic intervention. STUDY DESIGN: Expression of glucose transporter 1 (Glut1), phosphorylated protein kinase B (pPKB/pAkt), and phosphorylated mammalian target of rapamycin (pmTOR) was assessed in ovarian carcinoma tumors and cell lines. Cells were incubated with 2-deoxyglucose and rapamycin; growth inhibition, viability, and mechanism of cell death were determined. RESULTS: Ovarian carcinoma cells overexpress Glut1, pAkt, and pmTOR compared with benign ovarian epithelial cells. 2-deoxyglucose and rapamycin markedly enhance apoptotic and nonapoptotic cell death in ovarian cancer cells. CONCLUSION: The glycolytic phenotype of ovarian cancer cells can be targeted for therapeutic intervention. Combined treatment modalities that target multiple cellular pathways hold promise for the treatment of chemoresistant ovarian cancer cells.

Expression of metabolically targeted biomarkers in endometrial carcinoma.

OBJECTIVES: The differential metabolic phenotype observed between malignant and non-transformed cells may constitute a biochemical basis for therapeutic intervention. Increased glucose uptake is one of the major metabolic changes found in malignant tumors, a process that is mediated by glucose transporters such as Glut1. Cellular growth can be regulated by mTOR in response to the nutrient milieu. In this study, we sought to determine if endometrial carcinoma cells express Glut1 and mTOR, and if inhibition of these factors is cytotoxic to endometrial carcinoma cells in vitro. METHODS: Expression of Glut1, pAkt, and pmTOR was assessed in tissue microarrays constructed from 42 type I and 34 type II endometrial tumors by immunohistochemistry, and in a panel of endometrial carcinoma cell lines. Representative endometrial carcinoma cells with wild type or mutant endogenous PTEN were treated with the glucose analog 2-deoxyglucose (2-DG) and rapamycin, an mTOR inhibitor or cisplatin. Inhibition of cell growth and mechanism of cell death was determined. RESULTS: Glut1, pAkt, and pmTOR were expressed strongly in both types I and II endometrial carcinoma. 2-DG and rapamycin induced apoptotic cell death in type I endometrial carcinoma cells, and profound growth inhibition and cytostasis in type II endometrial carcinoma cells. CONCLUSIONS: Glut1, pAkt, and pmTOR are overexpressed in endometrial carcinomas. Distinct alterations in the phosphatidylinositol 3'-kinase (PI3K) pathway upstream of mTOR, such as pAkt, may identify endometrial carcinoma patients who may benefit from adjuvant treatment with mTOR inhibitors and/or glucose analogs.

Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells.

BACKGROUND: Ginger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-kappaB. NF-kappaB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro. METHODS: The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-kappaB and and production of VEGF and IL-8 was determined in the presence or absence of ginger. RESULTS: Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8. CONCLUSION: Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.

Resveratrol inhibits glucose metabolism in human ovarian cancer cells.

OBJECTIVES: Resveratrol is a phytoalexin found in grapes that inhibits the in vitro growth of multiple tumor cell types. We showed previously that resveratrol induces autophagic cell death in ovarian cancer cells. Because autophagy is typically an adaptive response to nutrient starvation, we hypothesized that autophagy would also be triggered when ovarian cancer cells are nutrient deprived and that resveratrol could in fact be acting by inducing a starvation-like signaling response. METHODS: Ovarian cancer cells were incubated with normal media, media containing resveratrol, glucose free media, or media lacking amino acids. Growth inhibition was determined using the sulforhodamine assay. Cells were evaluated for autophagocytosis by analyzing cleavage of LC3. Glucose uptake, lactate production, and activation of glycolytic regulators pAkt and pmTOR were analyzed following resveratrol treatment. RESULTS: We show here that epithelial ovarian cancer cells are highly sensitive to glucose-deprivation-induced cell death and like resveratrol, glucose deprivation induces caspase-independent cell death with hallmarks of autophagy. Consistent with the hypothesis that resveratrol treatment results in biochemical conditions that mirror a nutrient deprived state, we found that resveratrol dramatically reduces glucose uptake and lactate production. Moreover, resveratrol reduces the levels of phosphorylated Akt and mTOR, two signals that increase glucose uptake and the rate limiting steps in glycolysis. CONCLUSIONS: Our findings are consistent with the hypothesis that resveratrol-induced changes in glucose utilization comprise the mechanism that underlies resveratrol-induced autophagocytosis in ovarian cancer. Inhibition of glycolysis in ovarian cancer with resveratrol or other compounds may be effective therapy for ovarian cancer.

Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer cells.

OBJECTIVE: Curcumin, the active component of turmeric (Curcuma longa), exhibits growth inhibitory activity against prostate, colon, and breast cancer; however, the effect of curcumin on ovarian cancer cells is not known. We hypothesized that curcumin could induce cell death in ovarian cancer cells, and enhance apoptosis induced by tumor necrosis factor-related apoptosis inducing Apo2 ligand/TRAIL. METHODS: Chemoresistant ovarian cancer cell lines SKOV3 and ES-2 were used. The cytotoxic effect of curcumin, Apo2L/TRAIL, and curcumin+Apo2L/TRAIL in combination was determined by sulforhodamine assay. Apoptotic fraction was determined by staining cells with propidium iodide followed by analysis of the sub-G0 DNA content of cells by flow cytometry. Caspase activation was determined by immunoblotting. RESULTS: Curcumin alone had a cytotoxic effect in cisplatin-resistant cells at 25 microM. Curcumin at low doses (5-15 microM) or Apo2L/TRAIL alone was not significantly cytotoxic to the cell lines tested. Preincubating cells with curcumin at low doses prior to treating with Apo2L/TRAIL resulted in markedly enhanced cell death. The combined treatment of curcumin and Apo2L/TRAIL resulted in activation of both the extrinsic, receptor-mediated apoptotic pathway (cleavage of caspase-8) and the intrinsic, mitochondria-mediated apoptotic pathway (cleavage of caspase-9). CONCLUSIONS: Combined curcumin and Apo2L/TRAIL treatment results in enhanced induction of apoptotic cell death. Because curcumin and Apo2L/TRAIL together can activate both the extrinsic and intrinsic pathways of apoptosis, they may circumvent chemoresistance to conventional chemotherapeutic agents.