Academic Research Hospital Research Articles

Compassionate drug uses in Italy. Analysis at single-center level.

Using a database from two pharmaceutical companies that managed several compassionate use programs in the last few years in Italy, we have previously analyzed the data by the number of patients and centers in each region and province, showing that the use of compassionate drugs is largely diffused in the country, in a manner directly related to the size of population of each region. In the present study we used the same database to expand the analysis to single-center level, aiming to test the hypothesis whether, despite a good diffusion of compassionate drug uses in each region, the majority of them concentrates within a relatively low number of centers. Data from different programs were grouped per center, and the centers were ordered per the number of compassionate uses dispensed, and per region. Two cutoff levels, at 75% and 90%, were drawn to look at the number of centers accounting for such percentages of compassionate uses in each region. Out of 343 centers throughout Italy, 93 and 156 centers (i.e., 27.11% and 45.48% of the total) account for about 75% and 90% of all compassionate drugs dispensed in Italy. In 6 regions out of 20 (Valle d'Aosta, Liguria, Umbria, Lazio, Molise and Campania) the centers accounting for 75% of all compassionate drugs dispensed are located in a single town. Forty and 20 out of the 93 centers dispensing 75% of all compassionate drugs are academic hospitals and research hospitals (Istituti di Ricovero e Cura a Carattere Scientifico, IRCCS), respectively. In this study we have demonstrated that, in spite of widespread diffusion of compassionate drug uses in all Italian regions, their management is restricted to a relatively low number of dispensing centers in each region.

Predictive Performance of Triglyceride-Glucose Index on Asymptomatic Multiple Organ Damage in Patients with Newly Diagnosed Hypertension.

Background: Insulin resistance (IR) contributes to the development of hypertension and mediated organ damage (HMOD) through various mechanisms. Objectives: The objective of the study was to assess the diagnostic performance of the triglyceride-glucose (TyG) index, a surrogate marker of IR, in predicting the presence and severity of HMOD in newly diagnosed untreated hypertensive patients from an academic training and research hospital. Methods: The study included 438 patients with newly diagnosed, untreated hypertension. The control group comprised normotensive individuals matched on a 1:1 ratio based on age, gender, body mass index, and smoking using the nearest neighbor method. The presence of HMOD was defined by renal damage (microalbuminuria > 30 mg/day or proteinuria > 150 mg/day), vascular damage (carotid intima-media thickness > 0.9 mm or presence of plaque), or cardiac damage (left ventricular mass index > 95 g/m2 in women and > 115 g/m2 in men). The severity of HMOD was considered as single-, two-, or triple-organ damage. Results: TyG index values were higher in the hypertensive group than the normotensive group. An increased TyG index was independently associated with HMOD (OR: 1.33, p < 0.001). The TyG index exhibited gradually increasing threshold values for distinguishing patients with single-organ HMOD (> 8.8 with 77.8% sensitivity and 74.3% specificity), two-organ HMOD (> 9.1 with 77.6% sensitivity and 71.4% specificity), and triple-organ HMOD (> 9.4 with 71.5% sensitivity and 87.7% specificity). Conclusions: In newly diagnosed hypertensive patients, the TyG index exhibits significant diagnostic performance in predicting multiple-organ damage beyond the presence of HMOD. Since the detection of multiple-organ HMOD requires a multidisciplinary approach, the TyG index can serve as a simple and inexpensive screening tool. (REV INVEST CLIN. 2023;75(5):221-32).

A roadmap to engaging patients in research: The experience of a large academic research hospital in Canada

A roadmap to engaging patients in research: The experience of a large academic research hospital in Canada

Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study

TP53-mutated acute myeloid leukaemia is associated with poor outcomes. Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. We aimed to evaluate the combination of eprenetapopt and venetoclax with or without azacitidine in patients with TP53-mutated acute myeloid leukaemia. This phase 1, multicentre, open-label, dose-finding and cohort expansion study was done at eight academic research hospitals in the USA. Inclusion criteria were age of at least 18 years; at least one pathogenic TP53 mutation; treatment-naive acute myeloid leukaemia according to the 2016 WHO classification; an ECOG performance status of 0-2; and a life expectancy of at least 12 weeks. In dose-finding cohort 1 patients received previous therapy with hypomethylating agents for myelodysplastic syndromes. In dose-finding cohort 2, previous use of hypomethylating agents was not permitted. Treatment cycles were 28 days. Patients in cohort 1 received intravenous eprenetapopt 4·5 g/day on days 1-4 and oral venetoclax 400 mg/day on days 1-28; those in cohort 2 also received subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7. The expansion part of the study proceeded with patients enrolled as in cohort 2. Primary endpoints were safety in all cohorts (assessed in patients receiving at least one dose of assigned treatment) and complete response in the expansion cohort (assessed in patients who completed at least one treatment cycle and had at least one post-treatment clinical response assessment). The trial is registered with ClinicalTrials.gov, NCT04214860, and is complete. Between Jan 3, 2020, and July 22, 2021, 49 patients were enrolled across all cohorts. Six patients were initially enrolled into each of dose-finding cohorts 1 and 2; after no dose-limiting toxicities were observed, cohort 2 was expanded to enrol an additional 37 patients. The median age was 67 years (IQR 59-73). 24 (49%) of 49 patients were female and 25 (51%) male, and 40 (82%) were White. At data cutoff (Oct 1, 2021), the median length of follow-up was 9·5 months (IQR 6·1-11·5). No dose-limiting toxicities were recorded and the recommended phase 2 dose for eprenetapopt combinations was 4·5 g/day on days 1-4. Across all patients, adverse events of grade 3 or worse occurring in at least 20% of patients were febrile neutropenia (23 [47%] of 49 patients), thrombocytopenia (18 [37%] patients), leukopenia (12 [25%] patients), and anaemia (11 [22%] patients). Treatment-related serious adverse events occurred in 13 (27%) of 49 patients and there was one (2%) treatment-related death (sepsis). 25 (64%, 95% CI 47-79) of 39 patients had an overall response with eprenetapopt and venetoclax with azacytidine; 15 (38%, 23-55) had a complete response. Eprenetapopt and venetoclax with azacitidine had an acceptable safety profile and encouraging activity, supporting further frontline evaluation of this combination in the treatment of TP53-mutated acute myeloid leukaemia. Aprea Therapeutics.

Urinary trehalase activitiy in contrast-associated acute kidney injury.

Contrast-associated acute kidney injury (CA-AKI) is the third most common cause of hospital-acquired AKI. Sensitive biomarkers can detect kidney injury early on because kidney damage begins immediately after the administration of a contrast medium. Due to its proximal tubule specificity, urinary trehalase can be a useful and early marker for detecting tubular damage. This study aimed to reveal the power of urinary trehalase activity in diagnosing CA-AKI. This is a prospective, observational, and diagnostic validity study. The study was performed in an academic research hospital's emergency department. Patients aged 18 years and over who underwent contrast-enhanced computed tomography in the emergency department were included in the study. Urinary trehalase activities were measured before and 12, 24, and 48 hours after the administration of a contrast medium. The primary outcome was the occurrence of CA-AKI, while the secondary outcomes were risk factors for CA-AKI, duration of hospital stay after contrast use, and the mortality rate in the hospital. A statistically significant difference between the CA-AKI group and the non-AKI group was found in the activities measured 12 hours after the administration of the contrast medium. Notably, the mean age of the patient group with CA-AKI was considerably higher than that of the non-AKI group. The risk of mortality was found to be remarkably more elevated in patients with CA-AKI. Further, there was a positive correlation between trehalase activity and HbA1c. In addition, a crucial correlation was found between trehalase activity and poor glycemic control. Urinary trehalase activity can be useful as a marker of acute kidney injuries due to proximal tubule damage. In the diagnosis of CA-AKI, especially the activity of trehalase in the 12th hour might be useful.

MP67-12 UROLOGY-DIRECTED INTERNATIONAL COLLABORATIONS THROUGH US-BASED ACADEMIC RESEARCH CENTERS

You have accessJournal of UrologyGlobal Health/Humanitarian (MP67)1 Sep 2021MP67-12 UROLOGY-DIRECTED INTERNATIONAL COLLABORATIONS THROUGH US-BASED ACADEMIC RESEARCH CENTERS Adrian Fernandez, Michelle Bui, Ian Metzler, and David Bayne Adrian FernandezAdrian Fernandez More articles by this author , Michelle BuiMichelle Bui More articles by this author , Ian MetzlerIan Metzler More articles by this author , and David BayneDavid Bayne More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002028.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: International surgical collaboration presents an opportunity to address the need for specialized urologic care and teaching in low-middle income countries (LMICs) and provides invaluable opportunities for education. Longitudinal relationships between academic research centers (ARCs) and hospitals in LMICs provide an opportunity for sustainable and bilateral collaboration and education, but are often the exception. The current project seeks to identify urology-directed collaborations, organized through academic research centers (ARCs) between the United States (US) and LMICs. METHODS: The webpages of each ACGME-accredited Urology residency training program were reviewed for information regarding international outreach programs. Pubmed, Google, and Google Scholar were also searched using combinations of the terms, “global”, “international”, “partnership”, “volunteer”, and “Urology” to identify international service and education work through Urologic ARCs. We specifically sought to include programs that demonstrated active collaborations between urology training programs in the US and training urology programs or specific hospitals in LMICs for more than two consecutive years. RESULTS: One hundred and forty ACGME-accredited Urology residency training programs were included and 14/140 (10%) programs listed opportunities for international work. A total of 8/140 (6%) programs listed independent, longitudinal relationships with specific hospitals in LMICs. India and Kenya were the countries with the most affiliations with US ARCs in Urology. CONCLUSIONS: Collaborations between US ARCs in Urology and hospitals in LMICs allow for institutionally sustainable educational, clinical, and research work. At the moment, approximately 6% of ACGME accredited Urology residency programs demonstrate formal collaborations with training institutions/hospitals in LMICs as part of their online presence, suggesting an opportunity for greater global impact from formalized Urology ARCs. Source of Funding: UCSF Center for Health Equity in Surgery and Anesthesia © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e514-e514 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adrian Fernandez More articles by this author Michelle Bui More articles by this author Ian Metzler More articles by this author David Bayne More articles by this author Expand All Advertisement Loading ...

Potential release of toxic metal elements from Essure® device in symptomatic patients: First results of the French Ablimco cohort

ObjectiveMany patients with Essure® devices request the removal of these implants due to persistent adverse effects. The pathophysiology remains unknown, but a corrosion of the implants in the in-vivo environment leading to metal ion release may be suspected. The implants consist of polyester fibers, nickel-titanium alloy and other metals including chromium. The purpose of this study is to deliver the first results on the concentrations of nickel and chromium (two potential toxic metal elements) in peritoneal fluid and in the fallopian tube tissue during laparoscopic removal of Essure®. Study designIn this prospective observational study conducted in a French academic research hospital (University hospital of Lyon), nickel and chromium concentrations were determined in the fallopian tube tissue and peritoneal liquid from symptomatic patients with Essure® by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis in a PerkinElmer NexION 350. ResultsSignificant metal element concentrations were showed in the peritoneal fluid. There was also a differential concentration in the fallopian tube tissue with higher concentration close to the implant then lower at a distance from this implant. There was a correlation between the concentrations of the two metals. ConclusionThe presence of nickel and chromium in the fallopian tube tissue and the peritoneal fluid raises the question of a possible relationship between the symptoms attributed to Essure® implants and the dissemination of potential toxic metals due to galvanic corrosion of the devices.

Food Industry Donations to Academic Programs: A Cross-Sectional Examination of the Extent of Publicly Available Data.

No studies have documented the prevalence of the food industry’s funding of academic programs, which is problematic because such funding can create conflicts of interest in research and clinical practice. We aimed to quantify the publicly available information on the food industry’s donations to academic programs by documenting the amount of donations given over time, categorizing the types of academic programs that receive food industry donations, cataloguing the source of the donation information, and identifying any stated reasons for donations. Researchers cataloged online data from publicly available sources (e.g., official press releases, news articles, tax documents) on the food industry’s donations to academic programs from 2000 to 2016. Companies included 26 food and beverage corporations from the 2016 Fortune 500 list in the United States. Researchers recorded the: (1) monetary value of the donations; (2) years the donations were distributed; (3) the name and type of recipient; (4) source of donation information; and (5) reasons for donations. Adjusting for inflation, we identified $366 million in food industry donations (N = 3274) to academic programs. Universities received 45.2% (n = 1480) of donations but accounted for 67.9% of total dollars given in the sample. Community colleges, schools (i.e., preschool, elementary, middle, and high schools), and academic nonprofits, institutes, foundations, and research hospitals collectively received 54.8% of the donations, but made up less than one-third of the monetary value of donations. Half of the donations (49.0%) did not include a stated reason for the donation. In our sample, donations grew from $3 million in 2000 to $24 million in 2016. Food companies in our sample donated millions of dollars to universities and other academic programs but disclosed little information on the purpose of the donations. Achieving transparency in donation practices may only be possible if federal policies begin to require disclosures or if companies voluntarily disclose information.

Antiretroviral Prescribing Practices Among Pregnant Women Living With HIV in the United States, 2008-2017

Since 1994, the US Department of Health and Human Services has published treatment guidelines for pregnant women living with HIV. Understanding how well prescribing patterns correspond with treatment guidelines could inform health policy and influence future clinical practice. To compare antiretroviral prescribing practices over time among pregnant women living with HIV with Department of Health and Human Services treatment guidelines and identify factors associated with receiving recommended regimens. A prospective cohort study of 1582 pregnant women living with HIV were enrolled in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART (antiretroviral therapy) Toxicities study between January 1, 2008, and June 30, 2017. The study was conducted at 18 academic research hospitals in the United States. Antiretroviral medications (ARVs) prescribed during pregnancy. Proportion of regimens prescribed to pregnant women living with HIV qualifying as preferred or alternative according to Department of Health and Human Services guidelines, stratified by timing of initiation. Of 1867 pregnancies (among 1582 pregnant women living with HIV with a mean [SD] age of 28.6 [6.1] years at conception), 1264 (67.7%) occurred among women self-identified as black, 480 (25.7%) self-identified as white, and 123 (6.6%) self-identified as other or unreported race/ethnicity. Antiretroviral medications were initiated prior to conception for 790 women (42.3%), resumed during pregnancy for 625 women (33.5%), and initiated during pregnancy for 452 women (24.2%). Only 925 pregnancies (49.5%) were associated with prescribed ARVs designated as preferred or alternative, while 492 (26.4%) involved ARVs with insufficient evidence for use during pregnancy and 136 (7.3%) involved ARVs that were not recommended during pregnancy. A higher proportion of treatment-naive pregnant women initiating ARVs were prescribed preferred or alternative ARVs compared with those resuming ARVs or those treated with ARVs before conception (316 of 452 [69.9%] vs 325 of 625 [52.0%] vs 284 of 790 [35.9%]; P < .001). A total of 91 of 452 women (20.1%) initiating ARVs during pregnancy were prescribed ARVs with insufficient evidence for use during pregnancy or not recommended during pregnancy. Among women resuming ARVs, those with a viral load greater than 1000 copies/mL early in pregnancy had higher odds of being prescribed guideline-recommended ARVs (adjusted odds ratio, 2.03 [95% CI, 1.33-3.10]) compared with those with a viral load of 400 copies/mL or less. This study suggests that US ARV prescribing practices for pregnant women living with HIV do not align well with national guidelines. This finding is particularly concerning when treatment is initiated during pregnancy. Further research is needed to understand disparities between prescribing practices and evidence-based guideline recommendations.

A Survey of Turkish Nurses' Knowledge of Incontinence-Associated Dermatitis.

The purpose of this study was to determine the knowledge of incontinence-associated dermatitis (IAD) among nurses working in intensive care units. Descriptive study. The study was conducted in 6 intensive care units of a 550-bed academic research hospital in Turkey. Licensed practical and registered nurses with a minimum of a Bachelor of Science in Nursing degree employed full-time on these units were invited to participate. The survey consisted of statements that examined the demographic characteristics (14 questions) and knowledge levels (59 statements) of the nurses. For each statement, nurses were required to mark only one of the following options: "correct," "incorrect," or "no knowledge." Data were collected from July to September 2016. The Shapiro-Wilk test, Mann-Whitney U test, Kruskal-Wallis H test, post hoc multiple comparison test, and Spearman's correlation coefficient were used to analyze the data. Of the 126 RNs who participated in the study, 46.83% (n = 59) had an undergraduate degree in nursing. The majority (29.37%) practiced in gastroenterology surgery and urology intensive care units. The mean knowledge score was 33.05 ± 10.16 (min = 0, max = 59). The most correctly answered statement (94.44%; n = 119) was "The pH of the skin plays a role in skin barrier function." The statement with the most incorrect or "no knowledge" answers (96.03%; n = 120) was "The natural moisturizing factor found in the structure of corneocytes helps the skin to maintain its oil levels." Based on correctly answered statements, we found knowledge levels of the prevention and treatment of IAD were higher among nurses with a master of science degree in nursing (40.67 ± 4.32) and lower among licensed practical nursing (29.12 ± 10.08) (P < .05). In this study, knowledge of the nurses on identification, prevention, and treatment of IAD was low. Comprehensive basic nursing education and in-service training programs on IAD are recommended.

Quality of life after laparoscopic removal of Essure® sterilization devices.

Objective(s)To assess changes in quality of life after laparoscopic removal of Essure® sterilization devices (Bayer AG, Leverkusen, Germany).Study DesignIn this prospective observational study in an academic research hospital, 80 women with new or worsening symptoms since placement of Essure® sterilization devices undergoing subsequent surgical removal were included. Laparoscopic removal of Essure® devices and salpingectomy with or without cornual excision were performed. Concomitant uterine procedures could be associated where indicated for gynaecological complaints. Comparison using the T student test for coupled series was done in this before-and-after study.ResultsHealth related quality of life (HRQL) was the primary outcome measured by the Short Form 12 (SF-12) questionnaire and a global 10 cm visual analogue scale (VAS). Secondary outcomes included assessment of pain, using continuous (VAS) and ordinal scales (Modified McGill Pain Questionnaire), menstrual bleeding (pictorial blood loss assessment chart (PBAC) score) and surgical feasibility and safety. There was a significant improvement in quality of life in both mental and physical health aspects of the SF-12 (34.02 (+/−1.19) vs. 49.61 (+/−1.42, P < .0001) and 36.55 (+/−0.99) vs. 43.32 (+/−1.18, P < .0001 respectively) as well as global VAS assessment (+2.91 (SD +/−0.27)) at the end of the first post-operative month. These improvements were maintained at three and six months. Mean pain decreased at one month following surgery compared to baseline (VAS 3.6 (+/−0.36) to 1.4 (+/−0.25), P < .0001 and McGill pain score 18.70 (+/−1.88) to 4.73 (+/−0.90), P < .0001). Improvements of a similar magnitude were observed when analysis was restricted to the 47 women without concomitant uterine surgery. No significant changes in bleeding were seen following of Essure® device removal. Planned procedures were all successfully completed.ConclusionLaparoscopic removal of Essure® devices in symptomatic women is technically successful and associated with short and medium-term improvement in quality of life as well as reduction in pelvic pain.

A Prospective Study of Early Pregnancy Essential Metal(loid)s and Glucose Levels Late in the Second Trimester.

Studies suggest many essential trace metal(loid)s are involved in glucose metabolism, but the associations among pregnant women are unclear. To assess associations between early pregnancy plasma zinc, selenium, copper, and molybdenum levels and blood glucose levels later in the second trimester. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies‒Singleton Cohort is a prospective cohort study conducted between July 2009 and January 2013. Twelve academic research hospitals in the United States. A total of 1857 multiracial, nonobese, healthy women. Blood glucose levels from 1-hour 50-g gestational load test (GLT) at 24 to 28 weeks of gestation. Higher concentrations of first-trimester copper were associated with higher glucose levels from the GLT (i.e., every 50% increase in copper concentration was related to 4.9 mg/dL higher glucose level; 95% CI: 2.2, 7.5 mg/dL) adjusted for maternal sociodemographic characteristics and reproductive history. In contrast, every 50% increase in molybdenum concentration was associated with 1.2 mg/dL lower mean glucose level (95% CI: -2.3, -0.1 mg/dL). The magnitude of these associations was greater at the upper tails of glucose level distribution based on quantile regressions of the 10th, 50th, and 90th percentiles. Higher copper and lower molybdenum concentrations could increase the risk of glucose dysregulation during pregnancy, with women at higher risk of gestational diabetes mellitus potentially affected to a greater extent. Further work is needed to understand the mechanisms involved with early pregnancy essential metal(loid)s to inform clinical diagnosis and prevention of glucose intolerance during pregnancy.

Hybrid Music Perception Outcomes: Implications for Melody and Timbre Recognition in Cochlear Implant Recipients.

To examine whether or not electric-acoustic music perception outcomes, observed in a recent Hybrid L24 clinical trial, were related to the availability of low-frequency acoustic cues not present in the electric domain. Prospective, repeated-measures, within-subject design. Academic research hospital. Nine normally hearing individuals. Simulated electric-acoustic hearing in normally hearing individuals. Acutely measured melody and timbre recognition scores from the University of Washington Clinical Assessment of Music Perception (CAMP) test. Melody recognition scores were consistently better for listening conditions that included low-frequency acoustic information. Mean scores for both acoustic (73.5%, S.D. = 15.5%) and electric-acoustic (67.9%, S.D. = 21.2%) conditions were significantly better (p < 0.001) than electric alone (39.2%, S.D. = 18.1%). This was not the case for timbre recognition for which scores were more variable across simulated listening modes with no significant differences found in mean scores across electric (36.1%, S.D. = 17.7%), acoustic (38.0%, S.D. = 20.4%), and electric-acoustic (40.7%, S.D. = 19.7%) conditions (p > 0.05). Recipients of hybrid cochlear implants demonstrate music perception abilities superior to those observed in traditional cochlear implant recipients. Results from the present study support the notion that electric-acoustic stimulation confers advantages related to the availability of low-frequency acoustic hearing, most particularly for melody recognition. However, timbre recognition remains more limited for both hybrid and traditional cochlear implant users. Opportunities remain for new coding strategies to improve timbre perception.

Are Hospital Efficiency and Quality of Care Affordable without External Revenue?

This qualitative study explored strategies academic research hospital administrators in Ontario, Canada, apply to generate nongovernment revenue to remain sustainable. The participants in the study consisted of senior-level academic research hospital executives with extensive experience in the subject area from major academic research hospitals, ranking the hospitals from highest to lowest in revenue generation. From this study, five themes emerged: working within the fiscal reality, the impact of the political environment, the focus on the mission, nongovernment revenue generation, and opportunities for the Ontario academic research hospitals. Findings from this study may contribute to discussions on implementing change by encouraging hospital executives to adopt a more coordinated and consistent approach to generating nongovernment revenue to support the mission of their hospitals.

Assessment of Synthetic Glue for Mesh Attachment in Laparoscopic Sacrocolpopexy: A Prospective Multicenter Pilot Study

Study ObjectiveTo assess the anatomic efficacy and safety of synthetic glue to fix prosthetic material in laparoscopic sacrocolpopexy. DesignA 1-year follow-up in a prospective multicenter pilot study between November 2013 and November 2014 (Canadian Task Force Classification II-2). SettingAn academic urogynecology research hospital. PatientsSeventy consecutive patients with Pelvic Organ Prolapse Quantification stage ≥3 anterior and/or medial prolapse underwent laparoscopic sacrocolpopexy. InterventionsAll women underwent laparoscopic sacrocolpopexy with the same standardized technique using a synthetic surgical glue to fix anterior and posterior meshes. Measurements and Main ResultsPatients were followed up at 1 month and 1 year, with anatomic and functional assessment (Pelvic Floor Distress Inventory-20, Pelvic Floor Impact Questionnaire-7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12). Anatomic success was defined as 1-year Pelvic Organ Prolapse Quantification stage ≤1. Sixty-six patients were included; the mean age was 56.7 ± 1.2 years. The mean operative time was 145 ± 5 minutes. The mean glue fixation time was less than 2 minutes for both anterior and posterior meshes. The 1-year anatomic success rate was 87.5% in the anterior compartment (Ba at −2.3 cm, p < .0001) and 95.3% in the medial compartment (point C at −6.1 cm, p < .0001). There were no intra- or postoperative complications and no cases of mesh exposure; 5 cases of mesh shrinkage (7.8%) were observed at 1 year. The postoperative urinary stress incontinence rate was 29.7% at 1 year. Eight patients (12.1%) underwent revision surgery with transobturator tape. All quality of life scores showed significant improvement (p < .0001) at 1 year. ConclusionSynthetic glue attachment of prosthetic material in laparoscopic sacrocolpopexy proved straightforward, safe, time-saving, and effective at 1 year. Prospective randomized studies will be needed to confirm the long-term benefit.

Neurocognitive and Patient-Reported Outcomes in Adult Survivors of Childhood Osteosarcoma.

This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma. To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma. Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors. Outcome data were collected from June 2008 to August 2014. Data analysis was completed in April 2015. Survivors of osteosarcoma recruited from the St Jude Lifetime Cohort Study were compared with community controls. Neurocognitive function, neurobehavioral symptoms, emotional distress, and quality of life. Outcomes were examined in relation to pharmacokinetic indices of methotrexate exposure and current chronic health conditions, which were assessed through medical examination and coded according to Common Terminology Criteria for Adverse Events, Version 4.03. Eighty survivors of osteosarcoma (mean [SD] age, 38.9 [7.6] years; time since diagnosis, 24.7 [6.6] years; 42% female) were compared with 39 community controls (age, 39.0 [11.7] years; 56% female). Survivors demonstrated lower mean scores in reading skills (-0.21 [95% CI, -0.32 to -0.10] vs 0.05 [95% CI, -0.13 to 0.23]; P = .01), attention (-0.78 [95% CI, -1.32 to -0.24] vs 0.24 [95% CI, -0.07 to 0.55]; P = .002), memory (-0.24 [95% CI, -0.48 to 0] vs 0.27 [95% CI, -0.08 to 0.62]; P = .01), and processing speed (-0.15 [95% CI, -0.35 to 0.05] vs 0.74 [95% CI, 0.44 to 1.03]; P < .001). Results of pharmacokinetic analysis showed that high-dose methotrexate maximum plasma concentration (estimate = 0; P = .48), median clearance (estimate = -0.11; P = .76), and median/cumulative exposure (estimate = 0; P = .45) were not associated with neurocognitive outcomes. Any grade 3 or 4 Common Terminology Criteria for Adverse Events cardiac, pulmonary, or endocrine condition was associated with poorer memory (t = 2.93; P = .006) and slower processing speed (t = 3.03; P = .002). Survivor-reported poor general health was associated with decreased sustained attention (estimate = 0.24; P = .05) and processing speed (estimate = 0.34; P = .005). Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. Prospective longitudinal studies are needed to identify onset and progression of impairment to inform optimal interventions.

A small grant funding program to promote innovation at an academic research hospital.

Innovation is important for the improvement of health care. A small grant innovation funding program was implemented by the Hospital for Sick Children(SickKids) for the Perioperative Services group, awarding relatively small funds (approximately $10 000) in order to stimulate innovation. Of 48 applications,26 (54.2%) different innovation projects were funded for a total allocation of $227 870. This program demonstrated the ability of small grants to stimulate many applications with novel ideas, a wide range of innovations and reasonable academic productivity.

Up-regulation of Bcl-2 by CD147 Through ERK Activation Results in Abnormal Cell Survival in Human Endometriosis

Human endometriosis (EMS) is characterized by insufficient apoptosis. Our previous studies have shown elevated CD147 expression in human endometriotic tissues and its involvement in endometrial cell apoptosis. However, the exact underlying mechanism remains elusive. The objective was to examine the correlation of the highly expressed CD147 with anti-apoptotic factor Bcl-2 in human endometriotic tissues and to determine the CD147-regulated apoptotic pathway in human endometrial epithelial cell line (HES). This was a laboratory study using human tissue analysis and HES cell culture. The setting was an academic research center and hospital. Patients were 30 women with ovarian EMS and 12 women without EMS. mRNA levels of CD147 and Bcl-2 were evaluated in endometriotic tissues by quantitative real-time PCR. HES cells were transfected with pcDNA3.0-CD147 overexpressing plasmid or immune-depleted by CD147 antibody. Main outcome measures were reverse transcription, quantitative real-time PCR, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and Western blotting. In human endometriotic tissues, Bcl-2 was up-regulated and positively correlated with CD147 expression, accompanied by activated ERK signaling. In HES cells, overexpression of CD147 increased viable cells and up-regulated Bcl-2 expression by activation of ERK signaling. Interference with CD147 function suppressed ERK signaling and decreased Bcl-2 expression, followed by accumulation of apoptotic factors, including cleaved caspase-9, cleaved caspase-3, and cleaved poly ADP-ribose polymerase. The presently found strong correlations between Bcl-2 and CD147, ERK, and CD147 in human endometriotic lesions and the demonstrated reduced cell apoptosis through CD147-ERK-Bcl-2 intrinsic apoptosis signaling axis suggest that this CD147-regulated signaling may contribute to the enhanced cell survival in the progression of human EMS.

In silico analysis of RET variants in medullary thyroid cancer: from the computer to the bedside.

The American Thyroid Association (ATA) medullary thyroid cancer (MTC) guidelines group RET variants, in the setting of familial medullary thyroid cancer and multiple endocrine neoplasia type 2, into 4 classes of severity based on epidemiological data. The aim of this study was to determine if genotype correlates with phenotype in RET missense mutations. In silico mutational tolerance prediction. Academic research hospital. We analyzed all RET variants currently listed in the ATA guidelines for the management of MTC using 2 computer-based (in silico) mutation tolerance prediction approaches: PolyPhen-2 HumVar and PolyPhen-2 HumDiv. Our analysis also included 27 different RET single-nucleotide polymorphisms resulting in missense variants. There was a statistically significant difference in the overall HumDiv score between ATA groups A and B (P = .025) and a statistically significant different HumVar score between benign polymorphisms and ATA group A (P = .023). Overall, RET variants associated with a less aggressive clinical phenotype generally had a lower Hum Div/Var score. Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C). In silico genetic analyses, with proper validation, may predict the phenotypic severity of RET variants, providing clinicians with a tool to aid clinical decision making in cases in which the RET variant is currently unknown or little epidemiological data are available.

Tubo-ovarian dysplasia in relationship with ovulation induction in rats

To assess tubo-ovarian dysplasia via morphologic and immunohistochemical study of rats exposed to ovulation stimulation protocols. Animal experimental study. Academic research hospital. 72 female Wistar rats divided into three groups. Stimulation protocols using follicle-stimulating hormone (FSH) or clomiphene citrate for 3, 6, or 12 cycles, after which the animals were killed. Ovarian and tubal dysplasia score and immunohistochemical assessment using p53 and Ki67. The ovarian dysplasia score was statistically significantly higher after 12 stimulation cycles in the groups receiving FSH (group B) or clomiphene citrate (group C) compared with control (group A). The tubal dysplasia score was statistically significantly increased after only three stimulation cycles in groups B and C. The Ki67 proliferation marker was statistically significantly expressed in the ovaries from group C, and in the fallopian tubes from groups B and C. P53 was constantly low in all three groups. Ovulation stimulation may induce tubal and ovarian histopathologic and immunohistochemical abnormalities with a dose effect. The role of the fallopian tubes and their interaction with the ovaries require further study.