Birinapant selectively enhances immunotoxin-mediated killing of cancer cells conditional on the IAP protein levels within target cells.

Immunotoxins (ITs) target cancer cells via antibody binding to surface antigens followed by internalization and toxin-mediated inhibition of protein synthesis. The fate of cells responding to IT treatment depends on the amount and stability of specific pro-apoptotic and pro-survival proteins. When treated with a pseudomonas exotoxin-based immunotoxin (HB21PE40), the triple-negative breast cancer (TNBC) cell line MDA-MB-468 displayed a notable resistance to toxin-mediated killing compared to the epidermoid carcinoma cell line, A431, despite succumbing to the same level of protein synthesis inhibition. In a combination screen of ~1912 clinically relevant and mechanistically annotated compounds, we identified several agents that greatly enhanced IT-mediated killing of MDA-MB-468 cells while exhibiting only a modest enhancement for A431 cells. Of interest, two Smac mimetics, birinapant and SM164, exhibited this kind of differential enhancement. To investigate the basis for this, we probed cells for the presence of inhibitor of apoptosis (IAP) proteins and monitored their stability after the addition of immunotoxin. We found that high levels of IAPs inhibited immunotoxin-mediated cell death. Further, TNFα levels were not relevant for the combination's efficacy. In tumor xenograft studies, combinations of immunotoxin and birinapant caused complete regressions in MDA-MB-468tumor-bearing mice but not in mice with A431 tumors. We propose that IAPs constitute a barrier to immunotoxin efficacy which can be overcome with combination treatments that include Smac mimetics.

Animal models for partial heart transplantation.

BACKGROUND: Partial heart transplantation delivers growing heart valve implants by transplanting the part of the heart containing the necessary heart valve only. In contrast to heart transplantation, partial heart transplantation spares the native ventricles. This has important implications for partial heart transplant biology, including the allowable ischemia time, optimal graft preservation, primary graft dysfunction, immune rejection, and optimal immunosuppression. AIMS: Exploration of partial heart transplant biology will depend on suitable animal models. Here we review our experience with partial heart transplantation in rodents, piglets, and non-human primates. MATERIALS & METHODS: This review is based on our experience with partial heart transplantation using over 100 rodents, over 50 piglets and one baboon. RESULTS: Suitable animal models for partial heart transplantation include rodent heterotopic partial heart transplantation, piglet orthotopic partial heart transplantation, and non-human primate partial heart xenotransplantation. DISCUSSION: Rodent models are relatively cheap and offer extensive availability of research tools. However, rodent open-heart surgery is technically not feasible. This limits rodents to heterotopic partial heart transplant models. Piglets are comparable in size to children. This allows for open-heart surgery using clinical grade equipment for orthoptic partial heart transplantation. Piglets also grow rapidly, which is useful for studying partial heart transplant growth. Finally, nonhuman primates are immunologically most closely related to humans. Therefore, nonhuman primates are most suitable for studying partial heart transplant immunobiology and xenotransplantation. CONCLUSIONS: Animal research is a privilege that is contingent on utilitarian ethics and the 3R principles of replacement, reduction and refinement. This privilege allows the research community to seek fundamental knowledge about partial heart transplantation, and to apply this knowledge to enhance the health of children who require partial heart transplants.

The impact of heart valve and partial heart transplant models on the development of banking methods for tissues and organs: A concise review.

Cryopreserved human heart valves fill a crucial role in the treatment for congenital cardiac anomalies, since the use of alternative mechanical and xenogeneic tissue valves have historically been limited in babies. Heart valve models have been used since 1998 to better understand the impact of cryopreservation variables on the heart valve tissue components with the ultimate goals of improving cryopreserved tissue outcomes and potentially extrapolating results with tissues to organs. Cryopreservation traditionally relies on conventional freezing, employing cryoprotective agents, and slow cooling to sub-zero centigrade temperatures; but it is plagued by the formation of ice crystals and cell damage upon thawing. Researchers have identified ice-free vitrification procedures and developed a new rapid warming method termed nanowarming. Nanowarming is an emerging method that utilizes targeted application of energy at the nanoscale level to rapidly rewarm vitrified tissues, such as heart valves, uniformly for transplantation. Vitrification and nanowarming methods hold great promise for surgery, enabling the storage and transplantation of tissues for various applications, including tissue repair and replacement. These innovations have the potential to revolutionize complex tissue and organ transplantation, including partial heart transplantation. Banking these grafts addresses organ scarcity by extending preservation duration while preserving biological activity with maintenance of structural fidelity. While ice-free vitrification and nanowarming show remarkable potential, they are still in early development. Further interdisciplinary research must be dedicated to exploring the remaining challenges that include scalability, optimizing cryoprotectant solutions, and ensuring long-term viability upon rewarming in vitro and in vivo.

Examining online international health professions education: a mixed methods review of barriers, facilitators, and early outcomes☠.

BACKGROUND: Access to quality healthcare education across the world is disproportionate. This study explores the potential for Cardiovascular Perfusion education to be delivered online to reach international students. METHODS: Exploratory mixed methods were used to identify the barriers, facilitators, and early outcomes of online international health professions education. RESULTS: Qualitative analysis yielded four primary and nine subthemes. Multiple interventions were implemented in the planning of a novel online international Extracorporeal Science (ECS) program based on these themes. Quantitative data from the first semester of the new ECS program was collected along with data from the traditional entry-level program and historic data from previous entry-level cohorts. No significant correlations or differences were found between students. Student satisfaction surveys were determined to be equivalent for each group. Mixed data analysis revealed exceptional student satisfaction in areas where qualitative feedback was incorporated into the program design. CONCLUSIONS: Online international education may be a viable option in the health professions. Barriers and facilitators to this mode of education were identified and utilized in designing one such program. Early outcomes from the novel ECS program reveal that student performance and satisfaction are equivalent to those of a traditional in-person training program.

Advances in remote and cloud-based simulation through web conferencing platforms.

INTRODUCTION: Simulation-based learning has become an essential element in entry-level perfusion education. While the use of simulation has been demonstrated to improve patient outcomes, few institutions possess the budgetary resources to build and maintain a high-fidelity simulation environment. This project aims to identify novel uses of web conferencing platforms to support in-person, remote, and virtual simulation exercises. METHODS: The Zoom Virtual Meeting platform (Zoom Video Communications, Inc.) was incorporated into the perfusion simulation curriculum at the Medical University of South Carolina CVP Program. Among the observed benefits of incorporating meeting platform software included high-definition audio/visual outputs and recording capabilities, 3-D remote simulation, remote simulation proctoring, and classroom-based learning. Additional Zoom features included remote controlled screen access and sharing, annotations, and break-out rooms and activities. CONCLUSION: The combination of high-fidelity simulation with virtual and remote features may enhance the learning experience in healthcare education. Future developments in technology and software, simulation education, and instructions through virtual/remote learning may provide a pathway for the future of cardiovascular perfusion education.

An investigation of the use of app technology to support clinical management of patients with chronic myeloid leukaemia (CML).

INTRODUCTION: The availability of healthcare apps to support patient self-management of various medical conditions, including cancer, has increased considerably in the past decade. However, there are limited published data on the role of apps in the management of chronic myeloid leukaemia (CML). The primary aim of this study was to investigate the current and future role of apps as a means of supporting patients with CML. METHODS: A 31-item questionnaire was developed and distributed to patients via three on-line CML support groups. RESULTS: Responses were received from 286 patients. There was an approximate 2:1 female: male split and the majority (54%, n = 155) resided in the United Kingdom. 91% (n = 260) of respondents were currently receiving drug treatment for their CML. 23.4% (n = 67) of respondents were aware that apps were available to support their CML management and 11.5% (n = 33) had experience of using such an app. 94.1% (n = 238) of those who had not used a patient support app in the past stated that they would consider using an app in the future to help manage their disease. App awareness was significantly higher amongst male patients (30.3% vs. 19.9%). Likelihood of being a current or previous app user was higher amongst younger patients (16.3% for <55 years old vs. 5.6% for ≥55 years old) whilst younger patients and those with a more recent diagnosis of CML were both more likely to be interested in using an app in the future. When asked about potential app functionality, a drug interaction checker was the feature of greatest interest to respondents. CONCLUSIONS: We have identified both a lack of awareness of and a low uptake of patient support apps amongst CML patients. Importantly, we have demonstrated a clear interest in CML-specific apps amongst this population. Based on the functionality that study participants were most interested in, we will work with health care professionals, app developers and patients to develop a new app to deliver holistic support to CML patients.

Adult Clinical Perfusion Practice Survey: 2020 results.

Background: Cardiovascular perfusion is a dynamic healthcare profession where new practices are frequently introduced. Despite the emergence of evidence-based clinical practice guidelines, little is known about their dissemination at the institutional level. Clinical practice surveys have been used to identify current trends in perfusion practice in the areas of equipment, techniques, and staffing. This survey aims to describe clinical perfusion practices across adult cardiac surgical programs located in a large, single, geographical region of the United States. Methods: Following Institutional Review Board (IRB) approval, an 81-question survey was distributed to 167 adult perfusion programs across the Zone IV region of the American Society of Extracorporeal Technology (AmSECT), a non-profit professional society representing the extracorporeal technology community. Surveys were distributed to chief perfusionists through the Research Electronic Data Capture (REDCap) web-based survey response system. Results: Responses were received from 58 of 167 centers across (34.7% response rate). Centrifugal pumps were used at 81% (n = 47) of centers and 96.6% (n = 56) use an open venous system or hard-shell venous reservoir. Del Nido was the most frequently used cardioplegia strategy with 62.1% (n = 36) of centers reporting its use. The use of electronic medical records was reported in 43% (n = 25) of centers, while 84.5% (n = 49) reported using Cardiopulmonary Bypass (CPB) protocols (>75% of all CPB activities). Extracorporeal Membrane Oxygenation (ECMO) support was reported in 93.1% (n = 54) of programs, with 59.2% of programs (n = 34) employing a perfusionist as ECMO Coordinator. The n + 1 staffing model was reported by 50% (n = 29), with 24% supporting the n + 1 staffing for after-hours and on-call procedures. Conclusion: Clinical practice surveys can be effective tools to inform clinicians about contemporary perfusion practice and identify deviations from professional standards and guidelines. Subsequent surveys may describe trends over time, assess standardization of practice, measure adherence to evidence-based guidelines, and foster improved patient care and outcomes.

A quality improvement initiative to increase adult ECMO decision-making abilities in a perfusion education program: The use of 3D ECMO simulation.

INTRODUCTION: Adult and pediatric ECMO procedures have been increasingly established as conventional life-saving modalities in critical care services across the world. Since 2017, a multidisciplinary team of program advisors for our perfusion education program have aimed to increase cardiovascular perfusion (CVP) student ECMO exposure and improve clinical decision-making. In this QI intervention, the use of 3D computer-based simulation was assessed in establishing a standardized process to improve the diagnosis and treatment of adult ECMO complications among first year CVP students. METHODS: The Califia 3D Patient Simulator was incorporated into the curriculum for first year CVP students (n = 26) along with traditional lecture for the adult ECMO complication laboratory session. Pre-class knowledge assessments using de-identified polling software were compared to post-class assessments following the first assigned learning activity. Assessments from students that received simulation before lecture (SIM, n = 15) were compared to students receiving lecture before simulation (LEC, n = 11). User experience questionnaires (UEQ) consisting of 26 questions for six scales of simulation instruction were administered to measure the comprehensive impression of the student experience. RESULTS: Overall median [IQR] pre- and -post knowledge assessment scores were 74% [11] and 84% [11], respectively (p = 0.01). There were no significant differences in pre-class assessment scores between the SIM and LEC groups (74.0% and 74.0%, respectively, p = 0.959). The LEC group achieved higher median post-assessment scores than the SIM group (84% vs 79%, p = 0.032). Among the 26 UEQ survey scales, 23 were positively evaluated (>0.8), and three were a neutral evaluation (-0.8 to 0.8). Cronbach Alpha-Coefficients of >0.78 were measured for attractiveness, perspicuity, efficacy, and stimulation. The coefficient for dependability was 0.37. 25 (96.2%) students indicated that 3D simulation was beneficial to improving ECMO clinical decision-making. CONCLUSIONS: In this QI intervention, the implementation of computer-based 3D simulation following lecture was perceived by learners to help improve the diagnosis and treatment of ECMO-related complications.

Impact of hidradenitis suppurativa-specific wound dressing system on patient quality of life and dressing-related pain: pilot study.

OBJECTIVE: It is theorised that adhesive-free wound care developed specifically for patients with hidradenitis suppurativa (HS) can improve their quality of life (QoL). Our study aimed to investigate the impact of a novel wound care device on Dermatology Life Quality Index (DLQI) scores, and other factors related to experienced pain, time spent changing dressings, comfort, ease of use and body image. METHOD: A 21-day, single-arm, unblinded, pilot trial was conducted to assess ease of use and the impact of effective wound care on various aspects of wound management in patients with HS. Participants were provided two trial garments and trial dressings as required, to use over a 21-day period in the home setting. A seven-item questionnaire and the DLQI questionnaire was completed on days 0, 7, 14 and 21. RESULTS: All 15 participants were female, aged >18 years old and with a diagnosis of HS. Mean DLQI score at baseline (day 0) was 19.3, which was reduced to 4.53 on day 21, a significant improvement in 100% of participants (p<0.001). High levels of dressing-related pain, assessed using an 11-point Visual Analogue Scale, reduced from 5.53 at baseline to 0.8 on day 21. Other significant improvements in terms of patient comfort, time spent on changing dressings, body confidence and the dressing's ability to retain exudate were also noted. CONCLUSION: The results illustrated the improvement made to study participants' day-to-day activities and QoL when effective HS-specific wound care products were provided. Wound care is an essential component in the treatment journey of patients.

The Effect of Aerobic Exercise on Concussion Recovery: A Pilot Clinical Trial.

OBJECTIVE: The purpose of this study was to pilot safety and tolerability of a 1-week aerobic exercise program during the post-acute phase of concussion (14-25 days post-injury) by examining adherence, symptom response, and key functional outcomes (e.g., cognition, mood, sleep, postural stability, and neurocognitive performance) in young adults. METHOD: A randomized, non-blinded pilot clinical trial was performed to compare the effects of aerobic versus non-aerobic exercise (placebo) in concussion patients. The study enrolled three groups: 1) patients with concussion/mild traumatic brain injury (mTBI) randomized to an aerobic exercise intervention performed daily for 1-week, 2) patients with concussion/mTBI randomized to a non-aerobic (stretching and calisthenics) exercise program performed daily for 1-week, and 3) non-injured, no intervention reference group. RESULTS: Mixed-model analysis of variance results indicated a significant decrease in symptom severity scores from pre- to post-intervention (mean difference = -7.44, 95% CI [-12.37, -2.20]) for both concussion groups. However, the pre- to post-change was not different between groups. Secondary outcomes all showed improvements by post-intervention, but no differences in trajectory between the groups. By three months post-injury, all outcomes in the concussion groups were within ranges of the non-injured reference group. CONCLUSIONS: Results from this study indicate that the feasibility and tolerability of administering aerobic exercise via stationary cycling in the post-acute time frame following post-concussion (14-25 days) period are tentatively favorable. Aerobic exercise does not appear to negatively impact recovery trajectories of neurobehavioral outcomes; however, tolerability may be poorer for patients with high symptom burden.

Seizures, Meds, and Vtach: A Journey to a Brugada Diagnosis.

ABSTRACT: Sudden cardiac arrest of cardiac etiology is rare in children and adolescents and most often occurs with exertion. Conversely, syncope is a common pediatric emergency department complaint but rarely is associated with a serious underlying cardiac disorder. This report describes a case of the channelopathy Brugada syndrome (BrS) as a cause of sudden cardiac arrest in a febrile preadolescent child taking medications known to affect cardiac conduction. The patient received cardiopulmonary resuscitation and was successfully defibrillated. Initial electrocardiogram (ECG) demonstrated findings consistent with BrS. Confirmatory electrophysiologic testing was performed, and an implantable cardiac defibrillator was placed. Pediatric emergency specialists must recognize both the importance of ECG in the workup of syncope and be familiar with the specific ECG findings suggestive of BrS. Ventricular arrhythmias that occur at rest should raise the suspicion of this genetic cardiac channelopathy, regardless of age.

Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up.

Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase 1 testing in relapsed/refractory hairy cell leukemia (HCL; n = 28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 doses in 4-week cycles. These patients plus 12 previously reported at this upper dose level received 143 cycles without dose-limiting toxicity. The combined 33-patient cohort achieved 64% CR and 88% overall response rates, with median CR duration of 42.4 months. Of 32 50-µg/kg patients evaluable for MRD by bone marrow aspirate flow cytometry (most stringent assessment), median CR duration was 13.5 (4.9-42.4) months in 9 MRD-positive CRs vs 42.1 (24.0-69.2) months in 11 MRD-negative CRs (P < .001). Among MRD-negative CRs, 10 patients had ongoing CR, 9 without MRD, at end of study. To our knowledge, moxetumomab pasudotox is the only nonchemotherapy regimen that can eliminate MRD in a significant percentage of HCL patients, to enhance CR duration. Repeated dosing, despite early neutralizing antibodies, increased active drug levels without detectable toxicity from immunogenicity. The activity and safety profiles of moxetumomab pasudotox support ongoing phase 3 testing in HCL. This trial was registered at www.clinicaltrials.gov as #NCT00586924.

Reducing the Impact of Perfusion Medical Waste on the Environment.

The U.S. healthcare system generates more than five billion pounds of waste each year. Waste disposal has become a serious environmental problem facing healthcare institutions. The operating room is the second largest source of hospital waste, and no current standards exist regarding perfusion waste reuse or recycling. A typical perfusion circuit produces approximately 15 pounds of plastic that ends up incinerated once used. Contaminated perfusion circuits consisting primarily of polyvinyl chloride (PVC) and polycarbonate are difficult to sterilize, reuse, or recycle. A literature review of Internet-based and peer-reviewed publications was conducted to identify all resources that describe sterilizing, dechlorinating, reusing, and recycling of medical-grade disposable products. There are several chemical methods available to re-harvest PVC after it has been properly decontaminated and melted down. Dichlorination by near-critical methanol shows promise in the recovery of additives such as plasticizers, stabilizers, and lubricants. The reinjection of PVC may have ecological and economic advantages. Dechlorinated PVC also creates a less toxic by-product when incinerated. Although this process is not recycling, it lessens the impact of poisonous chlorine gas release into the atmosphere. Sterilizing, dechlorinating, and recycling the perfusion circuit may be a promising avenue for reducing the ecological impact of perfusion waste. Although an economically sensitive mode of reusing, reducing, and recycling a circuit does not currently exist, this presentation will explore the perfusion waste dilemma and present potential solutions in hopes of promoting future reuse and recycling opportunities.

Evaluating Changes in del Nido Cardioplegia Practices in Adult Cardiac Surgery.

There has been a rapid adoption of the use of del Nido cardioplegia (DC) among adults undergoing cardiac surgery. We leveraged a multicenter database to evaluate differences over time in the choice and impact of cardioplegia type (DC vs. blood) among patients undergoing cardiac surgery. We evaluated 26,373 patients undergoing non-emergent coronary artery bypass and/or valve surgery between 2014-2015 (early period) and 2017-2018 (late period) at 31 centers. DC was compared with blood-based cardioplegia (BC: 1:1, 2:1, 4:1, 8:1, and variable ratio). We evaluated whether treatment choice differed across prespecified patient characteristics, procedure type, and perfusion practices by time period. We evaluated increased DC use with clinical outcomes (major morbidity and mortality, prolonged intubation, and renal failure), after adjusting for baseline characteristics, procedure type, center, and year. DC use increased from 19.6% in 2014-2015 to 41.5% in 2017-2018, p < .001. Increased DC use occurred among coronary artery bypass grafting (CABG), valve, and CABG + valve procedures, all p < .001. Differences in median procedural duration increased over time (DC vs. BC): 1) bypass duration was 11.0 minutes shorter with DC in the early period and 27.0 minutes shorter in the late period, and 2) cross-clamp duration was 7.0 minutes shorter with DC in the early period and 17.0 minutes shorter in the late period, all p < .001. There were no statistical differences in adjusted odds of major morbidity and mortality (odds ratio [OR]adj: 1.01), prolonged intubation (ORadj: .99), or renal failure (ORadj: .80) by DC use (p > .05). In this large multicenter experience, DC use increased over time and was associated with reduced bypass and ischemic time absent any significant differences in adjusted outcomes.

Development of the Adult ECMO Specialist Certification Examination.

The American Society of Extracorporeal Technology Board of Directors, consistent with the American Society of Extracorporeal Technology's safe patient care improvement mission, charged the International Board of Blood Management to write a knowledge and skill certification examination for healthcare personnel employed as adult extracorporeal membrane oxygenation (ECMO) specialists. Nineteen nationally recognized ECMO subject-matter experts were selected to complete the examination development. A job analysis was performed, yielding a job description and examination plan focused on 16 job categories. Multiple-choice test items were created and validated. Qualified ECMO specialists were identified to complete a pilot examination and both pre- and post-examination surveys. The examination item difficulty and candidate performance were ranked and matched using Rasch methodology. Candidates' examination scores were compared with their profession, training, and experience as ECMO specialists. The 120-item pilot examination form ranked 76 ECMO specialist candidates consistent with their licensure, ECMO training, and clinical experience. Forty-three registered nurses, 28 registered respiratory therapists, four certified clinical perfusionists, and one physician assistant completed the pilot examination process. Rasch statistics revealed examination reliability coefficients of .83 for candidates and .88 for test items. Candidates ranked the appropriateness for examination items consistent with the item content, difficulty, and their personal examination score. The pilot examination pass rate was 80%. The completed examination product scheduled for enrollment in March 2020 includes 100 verified test items with an expected pass rate of 84% at a cut score of 67%. The online certification examination based on a verified job analysis provides an extramural assessment that ranks minimally prepared ECMO specialists' knowledge, skills, and abilities (KSA) consistent with safe ECMO patient care and circuit management. It is anticipated that ECMO facilities and ECMO service providers will incorporate the certification examination as part of their process improvement, safety, and quality assurance plans.

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

BACKGROUND: Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation. METHODS: We utilized prospective cohort studies of critically ill sepsis (n = 120) and trauma (n = 180) patients and measured plasma RIPK3 at presentation and 48 h. Patients were followed for 6 days for ARDS by the Berlin definition. We used multivariable logistic regression to determine the association of plasma RIPK3 with ARDS in each cohort, adjusting for confounders. In mice, we determined whether plasma and lung tissue RIPK3 levels rise concomitantly 4 h after injection with lipopolysaccharide and ZVAD-FMK, an apoptosis inhibitor. RESULTS: The change in plasma RIPK3 from presentation to 48 h (ΔRIPK3) was associated with ARDS in sepsis (OR 1.30, 95% CI 1.03-1.63, per ½ standard deviation) and trauma (OR 1.79, 95% CI 1.33-2.40). This association was not evident for presentation RIPK3 levels. Secondary analyses showed similar findings for the association of ΔRIPK3 with acute kidney injury and 30-day mortality. Mice injected with lipopolysaccharide and ZVAD-FMK had significantly higher plasma (p < 0.001) and lung (p = 0.005) RIPK3 than control mice. CONCLUSIONS: The change in plasma RIPK3 from presentation to 48 h in both sepsis and trauma patients is independently associated with ARDS, and plasma RIPK3 may reflect RIPK3 activity in lung tissue.

Use of Online or Paper Surveys by Australian Women: Longitudinal Study of Users, Devices, and Cohort Retention.

BACKGROUND: There is increasing use of online surveys to improve data quality and timeliness and reduce costs. While there have been numerous cross-sectional studies comparing responses to online or paper surveys, there is little research from a longitudinal perspective. OBJECTIVE: In the context of the well-established Australian Longitudinal Study on Women's Health, we examined the patterns of responses to online or paper surveys across the first two waves of the study in which both modes were offered. We compared the following: differences between women born between 1946 and 1951 and between 1973 and 1978; types of device used for online completion; sociodemographic, behavioral, and health characteristics of women who responded online or using mailed paper surveys; and associations between mode of completion in the first survey and participation and mode of completion in the second survey. METHODS: Participants in this study, who had responded to regular mailed surveys since 1996, were offered a choice of completing surveys using paper questionnaires or Web-based electronic questionnaires starting in 2012. Two groups of women were involved: an older cohort born between 1946 and 1951 aged in their 60s and a younger cohort born between 1973 and 1978 aged in their 30s when the online surveys were first introduced. We compared women who responded online on both occasions, women who responded online at the first survey and used the paper version of the second survey, women who changed from paper to online, and those who used paper for both surveys. RESULTS: Of the 9663 women in their 60s who responded to one or both surveys, more than 50% preferred paper surveys (5290/9663, 54.74%, on the first survey and 5373/8621, 62.32%, on the second survey). If they chose the online version, most used computers. In contrast, of the 8628 women in their 30s, 56.04% (4835/8628) chose the online version at the first survey. While most favored computers to phones or tablets, many did try these alternatives on the subsequent survey. Many women who completed the survey online the first time preferred the paper version on the subsequent survey. In fact, for women in their 60s, the number who went from online to paper (1151/3851, 29.89%) exceeded the number who went from paper to online (734/5290, 13.88%). The online option was more likely to be chosen by better educated and healthier women. In both cohorts, women who completed paper surveys were more likely than online completers to become nonrespondents on the next survey. Due to the large sample size, almost all differences were statistically significant, with P<.001. CONCLUSIONS: Despite the cost-saving advantages of online compared to paper surveys, paper surveys are likely to appeal to a different population of potential respondents with different sociodemographic, behavioral, and health characteristics and greater likelihood of attrition from the study. Not offering a paper version is therefore likely to induce bias in the distribution of responses unless weighting for respondent characteristics (relative to the target population) is employed. Therefore, if mixed mode (paper or online) options are feasible, they are highly likely to produce more representative results than if only the less costly online option is offered.

Evaluation of the Effect of Low-Dose Aspirin on Biochemical and Biophysical Biomarkers for Placental Disease in Low-Risk Pregnancy: Secondary Analysis of a Multicenter RCT.

OBJECTIVE: To assess the effect of aspirin use in low-risk pregnancy on: (1) pregnancy-associated plasma protein-A (PAPP-A) and placental-like growth factor (PLGF); (2) urinary albumin-to-creatinine ratio (ACR) and blood pressure; (3) fetal growth parameters; and (4) placental histopathology. STUDY DESIGN: This secondary analysis from the T rial of low-dose aspirin with an E arly S creening T est for preeclampsia and growth restriction randomized controlled trial was based on low-risk nulliparous women randomized at 11 weeks to (1) aspirin 75 mg; (2) no aspirin; and (3) aspirin based on the preeclampsia Fetal Medicine Foundation screening test. At baseline, women underwent assessment of blood pressure, PAPP-A, PLGF, and ACR, repeated 9 to 10 weeks postaspirin, in addition to fetal growth assessment. Gross and histopathological placental analyses were performed in line with Amsterdam criteria. RESULTS: A total of 445 subjects were included (aspirin n = 163 [36.6%]; no aspirin n = 282 [63.4%]). Although the fetal-to-placental weight ratio was significantly greater in the aspirin group (7.5 [±1.3] vs. 7.3 [±1.4], p = 0.045), as was change in ultrasound assessed estimated fetal weight from second to third trimesters (1,624.5 g [±235.1] vs. 1,606.2 [±189.4], p = 0.042), this was invalidated by the lack of a difference in birth weight. Aspirin did not significantly impact on change in serum or urine preeclampsia biomarkers, maternal blood pressure, or placental histopathology. CONCLUSION: Aspirin use in low-risk pregnancy does not appear to impact on preeclampsia biomarkers, fetal growth, or placental pathology.

Net Prime Volume Is Associated with Increased Odds of Blood Transfusion.

Hemodilutional anemia has been cited as a contributing factor to red blood cell (RBC) transfusions in cardiac surgery patients. Accordingly, efforts have been made to minimize hemodilution by reducing cardiopulmonary bypass (CPB) prime volume. We sought to assess the impact of these efforts on intraoperative RBC transfusions. We evaluated 21,360 patients undergoing coronary artery bypass with or without aortic valve surgery between July 2011 through December 2016 at any of 42 centers participating in the Perfusion Measures and Outcomes registry. The primary exposure was net CPB prime volume (total prime volume minus retrograde autologous prime volume) indexed to body surface area (mL/m2), which was further divided into quartiles (Q1: <262 mL/m2, Q2: 262-377 mL/m2, Q3: 377-516 mL/m2, and Q4: >516 mL/m2). The primary outcome was intraoperative RBC transfusion. We modeled the effect of index net prime volume on transfusion, adjusting for patient (age, gender, race, diabetes, vascular disease, previous myocardial infarction, ejection fraction, creatinine, preoperative hematocrit (HCT), total albumin, status, aspirin, and antiplatelet agents), procedural (procedure types) characteristics, surgical year, and hospital. The median net prime volume was 378 mL/m2 (25th percentile: 262 mL/m2, 75th percentile: 516 mL/m2). Relative to patients in Q1, patients in Q4 were more likely to be older, female, nondiabetic, have higher ejection fraction, have more ultrafiltration volume removed, and undergo more elective and aortic valve procedures (all p < .05). Patients in Q4 relative to Q1 were exposed to lower nadir HCTs on bypass, p < .05. The net prime volume was associated with an increased risk of transfusion (8.9% in Q1 vs. 22.6% in Q4, p < .001). After adjustment, patients in Q4 (relative to Q1) had a 2.9-fold increased odds (ORadj = 2.9, 95% CI [2.4, 3.4]) of intraoperative RBC transfusion. In this large, multicenter experience, patients exposed to larger net prime volumes were associated with greater adjusted odds of receiving intraoperative transfusions. Our findings reinforce the importance of efforts to reduce the net CPB prime volume. Based on these findings and other supporting evidence, the net prime volume should be adopted as a national quality measure.

Temporal lobe epilepsy affects spatial organization of entorhinal cortex connectivity.

Evidence for structural connectivity patterns within the medial temporal lobe derives primarily from postmortem histological studies. In humans and nonhuman primates, the parahippocampal gyrus (PHg) is subdivided into parahippocampal (PHc) and perirhinal (PRc) cortices, which receive input from distinct cortical networks. Likewise, their efferent projections to the entorhinal cortex (ERc) are distinct. The PHc projects primarily to the medial ERc (M-ERc). The PRc projects primarily to the lateral portion of the ERc (L-ERc). Both M-ERc and L-ERc, via the perforant pathway, project to the dentate gyrus and hippocampal (HC) subfields. Until recently, these neural circuits could not be visualized in vivo. Diffusion tensor imaging algorithms have been developed to segment gray matter structures based on probabilistic connectivity patterns. However, these algorithms have not yet been applied to investigate connectivity in the temporal lobe or changes in connectivity architecture related to disease processes. In this study, this segmentation procedure was used to classify ERc gray matter based on PRc, ERc, and HC connectivity patterns in 7 patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis (mean age, 14.86 ±â€¯3.34 years) and 7 healthy controls (mean age, 23.86 ±â€¯2.97 years). Within samples paired t-tests allowed for comparison of ERc connectivity between epileptogenic and contralateral hemispheres. In healthy controls, there were no significant within-group differences in surface area, volume, or cluster number of ERc connectivity-defined regions (CDR). Likewise, in line with histology results, ERc CDR in the control group were well-organized, uniform, and segregated via PRc/PHc afferent and HC efferent connections. Conversely, in TLE, there were significantly more PRc and HC CDR clusters in the epileptogenic than the contralateral hemisphere. The surface area of the PRc CDR was greater, and that of the HC CDRs was smaller, in the epileptogenic hemisphere as well. Further, there was no clear delineation between M-ERc and L-ERc connectivity with PRc, PHc or HC in TLE. These results suggest a breakdown of the spatial organization of PHg-ERc-HC connectivity in TLE. Whether this breakdown is the cause or result of epileptic activity remains an exciting research question.