A scoping review of existing research between 1990 and 2023: Measuring virtual communities of practice across disciplines.

Virtual communities of practice (VCoPs) can decrease social, structural, and professional isolation, provide opportunities for knowledge-sharing abilities, and may improve participants' self-reported sense of connectedness to one another and their profession. However, more research is needed to examine measurement of VCoPs effectiveness on participants. In this scoping review our research question was: What is the state of the science for VCoPs and how are these communities measured in current research specific to education and health/health education? Guided by Arksey and O'Malley's five stages for conducting a rigorous scoping review, we identified gaps in the evidence regarding the overall state of the science on measurement of VCoPs inclusive of quantitative and mixed-methods literature describing validated VCoP measurement in both English or Spanish from January 1990 to July 2023, and within the health, education, or health education disciplines. Initial searches yielded 2350 articles. Authors independently screened papers and extracted data. The results of this scoping review (N = 13 articles) highlight the measurement of VCoPs specific to education, healthcare, health education research. We found that measures had been tested in VCoPs within health, education, health education, and professional education information technologies disciplines, with the Community of Inquiry framework being the most common theoretical foundation. The findings provide an understanding of measurement tools and impacts and outcomes of VCoP participation and we make recommendations for future VCoP measurement tool development.

Analysis of Differentially Expressed MicroRNAs and Circulating Tumor Cells as Predictive Biomarkers of Platinum Chemoresistance in Primary Ovarian Carcinomas: A Prospective Study.

LESSON LEARNED: Circulating tumor cells, microRNA markers, or other biomarkers merit examination as part of correlative scientific analyses in prospective clinical trials. BACKGROUND: Platinum chemotherapy resistance occurs in approximately 25% of patients with ovarian carcinoma; however, no biomarkers of ovarian carcinoma chemoresistance have been validated. We performed a prospective trial designed to identify tumor-based predictive biomarkers of platinum resistance. METHODS: Tumor specimens were collected from 29 women with newly diagnosed histopathologically proven primary ovarian carcinoma. Of these, 23 women had specimens accessible for assessment and outcome data available regarding chemosensitive versus chemoresistance status via review of the medical record. Tumor slices were stained with antibodies against two microRNAs (miRNAs 29b and 199a) differentially expressed in chemoresistant ovarian cancer cell lines. Additionally, blood samples obtained at the time of diagnosis were analyzed for the presence of circulating tumor cells (CTCs). RESULTS: The average age of the patients was 64 years, and 82.6% had high-grade epithelial carcinomas. The baseline median CA-125 was 464 (range 32-2,782). No statistically significant differences were observed in miR29b or 199a expression in platinum-resistant/refractory versus platinum-sensitive tumors. Furthermore, the presence of CTCs was not found to be statistically significantly predictive of eventual platinum resistance. CONCLUSION: Our analysis showed no differences in miR29b and 199a expression, and differences in baseline CTCs in women with newly diagnosed ovarian tumors were not statistically significant.

Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer.

Intercellular communication plays a critical role in the ever-evolving landscape of invasive cancers. Recent studies have elucidated the potential role of tunneling nanotubes (TNTs) in this function. TNTs are long, filamentous, actin-based cell protrusions that mediate direct cell-to-cell communication between malignant cells. In this study, we investigated the formation of TNTs in response to variable concentrations of the chemotherapeutic drug doxorubicin, which is used extensively in the treatment of cancer patients. Doxorubicin stimulated an increased formation of TNTs in pancreatic cancer cells, and this occurred in a dose-dependent fashion. Furthermore, TNTs facilitated the intercellular redistribution of this drug between connected cells in both pancreatic and ovarian cancer systems in vitro. To provide supportive evidence for the relevance of TNTs in pancreatic cancer in vivo, we performed multiphoton fluorescence microscopy and imaged TNTs in tumor specimens resected from three human patients with pancreatic adenocarcinoma, and one with neuroendocrine carcinoma. In sum, TNT formation was upregulated in aggressive forms of pancreatic carcinoma, was further stimulated after chemotherapy exposure, and acted as a novel method for drug efflux. These findings implicate TNTs as a potential novel mechanism of drug resistance in chemorefractory forms of cancer.

Enhanced Recovery Program and Length of Stay After Laparotomy on a Gynecologic Oncology Service: A Randomized Controlled Trial.

OBJECTIVE: To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service. METHODS: We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications. RESULTS: A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge. CONCLUSION: When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.

The impact of perioperative ß blocker use on patient outcomes after primary cytoreductive surgery in high-grade epithelial ovarian carcinoma.

OBJECTIVE: To quantify the impact of perioperative ß blocker use on survival after primary cytoreductive surgery for epithelial ovarian cancer. METHODS: We conducted a multi-center retrospective study of all women who underwent primary cytoreductive surgery for ovarian cancer (2000-2010). One institution had routinely used perioperative ß blockers for patients "at risk" for coronary events. The other institution did not routinely use perioperative ß blockers. Demographic, operative, and follow up data were collected. Cox proportional hazards models were used to assess the effect of ß blockers on progression-free interval (PFI) as well as overall survival (OS). RESULTS: Out of 185 eligible patients, 70 received ß blockers and 115 underwent cytoreductive surgery without perioperative ß blockers. Both groups were similar in demographics. A history of hypertension was present more often in the ß blocker group compared to the group that did not receive ß blockers (22% and 6%, p=0.002). PFI in ß blocker group was greater at 18.2 vs. 15.8months (p=0.66). The OS in the ß blocker group was significantly higher at 44.2 vs. 39.3months (p=0.01). In multivariate analysis, perioperative ß blocker use was associated with significant improvement in OS (HR 0.68 (0.46-0.99); p=0.046). CONCLUSION: Our study showed an association between perioperative ß blocker use and longer overall survival in patients undergoing primary ovarian cancer cytoreductive surgery. A prospective randomized clinical trial in this population would further validate these results.

Tunneling nanotube formation is stimulated by hypoxia in ovarian cancer cells.

In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200).We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy. Additionally, TNT formation was detected in co-cultures including between platinum-resistant SKOV3 cells, between SKOV3 cells and platinum-chemosensitive A2780 cells, and between SKOV3 cells cultured with benign ovarian epithelial (IOSE) cells; these findings indicate that TNTs are novel conduits for malignant cell interactions and tumor cell interactions with other cells in the microenvironment. When chemoresistant C200 and parent chemosensitive A2780 cells were co-cultured, chemoresistant cells displayed a higher likelihood of TNT formation to each other than to chemosensitive malignant or benign epithelial cells. Hypoxia-induced TNT formation represents a potential mechanism for intercellular communication in ovarian cancer and other forms of invasive refractory cancers.

A multi-institutional study of outcomes in stage I-III uterine carcinosarcoma.

OBJECTIVE: To evaluate the use of adjuvant therapy after primary surgery for stage I-III uterine carcinosarcoma (CS). METHODS: A multi-institutional retrospective study of women with stage I-III CS was conducted. Analyses were stratified by stage (I/II and III). Patients were categorized according to adjuvant therapy: observation (OBS), radiation (RT), chemotherapy (CT) or multimodal therapy (CT+RT). Overall survival (OS) and progression-free survival (PFS) were analyzed using log-rank tests and Cox proportional hazards models. RESULTS: 303 patients were identified across four institutions: 195 with stage I/II and 108 with stage III disease. In stage I/II disease, 75 (39.9%) received OBS, 33 (17.6%) CT, 37 (19.7%) RT, and 43 (22.9%) CT+RT. OBS was associated with a fourfold increased risk of death compared to CT (adjusted hazard ratio (aHR)=4.48, p=0.003). Patients receiving CT+RT had significantly improved PFS compared to those receiving CT alone (aHR=0.43, p=0.04), but no difference in OS. In the stage III cohort, 16 (15.0%) received OBS, 34 (31.8%) CT, 20 (18.7%) RT, and 37 (34.6%) CT+RT. OBS was associated with worse OS and PFS compared to CT (OS: aHR=2.46, p=0.04; PFS: aHR=2.39, p=0.03, respectively). A potential improvement in PFS was seen for those treated with CT+RT compared to CT alone, however it was not statistically significant (aHR=0.53, p=0.09). CONCLUSIONS: Observation after surgery was associated with poor outcomes in uterine CS compared to CT and RT alone. Multimodality therapy for women with stage I/II disease was associated with improved PFS compared to chemotherapy alone. Novel treatment options are needed to improve outcomes in this aggressive disease.

Tumor-stromal cross talk: direct cell-to-cell transfer of oncogenic microRNAs via tunneling nanotubes.

Tunneling nanotubes (TnTs) represent a novel mechanism by which intercellular components such as proteins, Golgi vesicles, and mitochondria can be transferred from cell to cell in the complex tumor microenvironment. Here, we report data showing that microRNAs (miRNAs) are transferred through TnTs in osteosarcoma (OS) and ovarian cancer as in vitro model systems. miRNA array analysis demonstrated significant upregulation of miR-19a in OS tumors resected from human patients, and differential expression of miR-199a in ovarian cancer cell lines resistant or sensitive to platinum chemotherapy. K7M2 murine OS cells were transfected with miR-19a and cultured with nontransfected K7M2 cells in low-serum, hyperglycemic medium for up to 72 hours to induce TnT formation. miRNA transfer via TnTs was detected by time-lapse microscopic imaging. miR-19a was also transported via TnTs connecting transfected K7M2 cells and nontransfected stromal MC3T3 murine osteoblast cells. Similar findings were observed in studies of TnT-mediated transport of miR-199a among SKOV3 ovarian cancer cells and nonmalignant immortalized ovarian epithelial cells. To quantify TnT-mediated transport of miRNAs, we used modified Boyden chambers to separate miR-19a-transfected K7M2 cells (top chamber) and DiI-labeled MC3T3 cells (bottom chamber) compared with open culture of these cells. Fluorescence-activated cell sorting analysis of cells collected after 48 hours of culture indicated that miR-19a-positive MC3T3 cells were 3-fold higher in open culture; this finding suggests that miR-19a transfer occurred via TnTs, exclusive of other forms of cell-cell communication. These studies demonstrate that TnTs mediate direct transfer of genetic material between tumor and stromal cells.

The effect of anesthesia choice on post-operative outcomes in women undergoing exploratory laparotomy for a suspected gynecologic malignancy.

OBJECTIVE: To determine how anesthesia choice in women undergoing laparotomy for gynecologic malignancy affects pain control and narcotic use. METHODS: This is a retrospective study of women who underwent laparotomy for suspected gynecologic malignancy from May 2012 to January 2013. Patients were categorized into one of three groups: 1) patient controlled analgesia (PCA); 2) PCA+transversus abdominis plane block (TAP); and 3) patient-controlled epidural analgesia (PCEA). Mean narcotic use and patient reported pain scores were compared. RESULTS: The analysis includes 112 women (44 PCA, 30 TAP, 38 PCEA). Intraoperative factors were not different between groups with the exception of a significant difference in the rate of intra-operative complications (p=0.020), with lower rates in the PCEA group. The groups differed in intravenous narcotic use in each of the first three postoperative days (day 0: p=0.014; day 1: p<0.0001; day 2: p=0.048), with patients in the TAP group using the least on day 0 and those in the PCEA group using less on postoperative days 1 and 2. In addition, the PCEA group reported lower pain scores on postoperative days 1 and 2 (day 1: p=0.046; day 2: p=0.008). CONCLUSIONS: The use of patient controlled epidural anesthesia after laparotomy for gynecologic malignancy is associated with decreased IV and PO narcotic use and improved pain control without increasing complications or length of hospital stay. Further investigation with prospective randomized trials is warranted to elucidate the optimal post-operative pain management technique.

Cervical cytology and multiple type HPV infection: a study of 8182 women ages 31-65.

OBJECTIVE: The aim of this study is to determine the rates of single and multiple type human papillomavirus (HPV) infection in women in the United States ages 31-65 with known cervical cytology results. METHODS: Type-specific HPV analyses were conducted using the first samples of women who had HPV typing performed by Access Genetics as part of cervical cancer screening between July 2007 and May 2011. Women 31-65years at testing with associated abnormal cytology results were included. The odds of abnormal cytology (compared to normal results) for multiple vs. single HPV infections were calculated for each cytology sub-type and odds ratios (OR) and 95% confidence intervals (CI) are reported. RESULTS: The analysis included 8182 women. The majority (67.7%) had ASCUS cervical cytology. A total of 329 (4.0%) were positive for 2 or more HPV types. For all cervical cytology subtypes considered (ASCUS, ASCUS-H, LSIL or HSIL), women with multiple type infections were more likely to have abnormal cytology (compared to normal cytology) with the highest OR associated with HSIL (OR 1.81 (1.26-2.60)). When analyzing HPV type 16 alone, women with multiple type infections were more likely to have abnormal cytology, with the highest OR associated with HSIL cytology (OR 2.98 (1.57-5.64)). Few women had HPV type 18 infections and no results reached statistical significance. Results based on phylogenic family organization focusing on the alpha 9 phylogenic family showed similar results as HPV type 16. CONCLUSIONS: Women ages 31-65 with multiple type HPV infections were more likely to have abnormal cytology than those with single HPV type infections.

Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells.

Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24-48 h; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3-1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells.

A prospective, randomized trial of integrative medicine for women with ovarian cancer.

OBJECTIVES: Despite increased use of integrative medicine in cancer therapy, little data exist on its efficacy. This prospective, randomized, pilot trial sought to evaluate the feasibility of combined modality integrative medicine (CM-IM) in women with ovarian cancer (OvCA) and evaluate its effects on quality of life (QoL), chemotherapy toxicity and immunologic profiles. METHODS: Women with newly diagnosed OvCA requiring chemotherapy were offered enrollment. Those randomized to the experimental arm received hypnosis, therapeutic massage and healing touch with each cycle of chemotherapy. The control arm received chemotherapy without CM-IM. All patients completed QoL questionnaires prior to cycles 1, 3 and 6, and 6-months after chemotherapy. Immunologic profiles were measured. Statistical analysis was based on intent-to-treat. Student's t-test and Fischer's exact-test were used to determine differences. RESULTS: Forty-three women enrolled. All women randomized to CM-IM were successfully treated. There were no statistical differences between the groups in age, stage, grade, histologic cell type, CA125 levels, or surgical cytoreductive status. There was no difference in overall QoL measurements. Re-hospitalization rates, treatment delays, anti-emetic use, and infection rates were similar. Immunologic profiles revealed no difference between arms for WBC or salivary IgA levels. Women receiving CM-IM had consistently higher levels of CD4, CD8 and NK cells, although this did not reach statistical significance. CONCLUSIONS: Prospective clinical evaluation of integrative medicine for women with gynecologic malignancy is feasible. This first, pilot study of CM-IM in gynecologic oncology demonstrated no improvement in QoL or chemotherapy toxicity. Integrative medicine-associated improvements in immunologic profiles warrant further investigation.

Gonadal dysgenesis and gynecologic cancer.

BACKGROUND: Gonadal dysgenesis encompasses a variety of sexual differentiation disorders. Within this population of patients, there is an increased risk of gonadal tumor formation. CASES: In this case series of three patients, two with Swyer's syndrome (complete gonadal dysgenesis) and one with mosaic Turner's syndrome, three separate histologic subtypes of tumors were identified: dysgerminoma, seminoma, and gonadoblastoma. The patients with dysgerminoma and seminoma had regular menses and were without recurrent disease. We recommend that the patient with gonadoblastoma start on hormone therapy. CONCLUSION: Once the diagnosis of gonadal dysgenesis is made, prophylactic gonadectomy should be performed owing to the probability of malignant transformation. These patients illustrate the potential different presentations with gonadal dysgenesis and the importance of complete evaluation of patients with primary amenorrhea.

Old fashion clinical judgment in the era of protocols: is mandatory chest X-ray necessary in injured patients?

BACKGROUND: The ATLS Course advocates that injured patients have a chest x-ray (CXR) to identify potential injuries. The purpose of this study was to correlate clinical indications and clinician judgment with CXR results to ascertain if a selective policy would be beneficial. METHODS: Patients treated at a Level I trauma center over 12 months were prospectively evaluated. Before obtaining a CXR, signs, symptoms, and history suggestive of thoracic injury were identified. Additionally, a trauma surgeon (TS) recorded whether in their judgment a CXR was clinically indicated. These findings were compared with final CXR diagnoses. The sensitivity of individual clinical indicators, combinations of clinical indicators, and TS judgment for CXR abnormalities were calculated with a 95% confidence interval. RESULTS: During the twelve-month study period, data were acquired on 772 patients (age 0-102 years). Seventy percent were male and 86.0% were injured by blunt force. Only 29% (N = 222) of the patients manifested one or more of the clinical indicators (signs and symptoms). The negative predictive value for the TS judgment was 98.2% which was superior to the clinical indicators. Reliance on the opinion of the TS to determine the need for a CXR would have eliminated 49.9% of CXRs and avoided hospital and radiologist reading charges totaling $100,078.22. CONCLUSION: Mandatory CXR for all trauma patients has a low yield for abnormal findings. A selective policy relying on surgical judgment guided by clinical indicators is safe and efficacious while reducing cost and conserving resources.