Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

BACKGROUND: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes. METHODS: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases. An interrupted time-series analysis, adjusting for patient- and procedure-related characteristics and secular trends over time, was used to assess the associations between education-based interventions and the frequency of TOF monitoring, postoperative pulmonary complications (PPCs), 90-day mortality, and sugammadex dosage. For each outcome and intervention phase, we tested whether the intervention at that phase was associated with an immediate change in the outcome or its trend (weekly rate of change) over time. In a sensitivity analysis, the association between education-based interventions and postoperative outcomes was adjusted for TOF monitoring. RESULTS: Of 19,422 cases, 11,636 (59.9%) had documented TOF monitoring. Monitoring frequency increased from 44.2% in the first week of preintervention stage to 83.4% in the final week of the postintervention phase. During the preintervention phase, the odds of TOF monitoring trended upward by 0.5% per week (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.007). Phase 1 saw an immediate 54% increase (OR, 1.54; 95% CI, 1.33-1.79) in the odds, and the trend OR increased by 3% (OR, 1.03; 95% CI, 1.01-1.05) to 1.035, or 3.5% per week (joint Wald test, P < .001). Phase 2 was associated with a further immediate 29% increase (OR, 1.29; 95% CI, 1.02-1.64) but no significant association with trend (OR, 0.96; 95% CI, 0.93-1.01) of TOF monitoring (joint test, P = .04). Phase 3 and postintervention phase were not significantly associated with the frequency of TOF monitoring (joint test, P = .16 and P = .61). The study phases were not significantly associated with PPCs or sugammadex administration. The trend OR for 90-day mortality was larger by 24% (OR, 1.24; 95% CI, 1.06-1.45; joint test, P = .03) in phase 2 versus phase 1, from a weekly decrease of 8% to a weekly increase of 14%. However, this trend reversed again at the transition from phase 3 to the postintervention phase (OR, 0.82; 95% CI, 0.68-0.99; joint test, P = .05), from a 14% weekly increase to a 6.2% weekly decrease in the odds of 90-day mortality. In sensitivity analyses, adjusting for TOF monitoring, we found similar associations between study initiatives and postoperative outcomes. TOF monitoring was associated with lower odds of PPCs (OR, 0.69; 95% CI, 0.55-0.86) and 90-day mortality (OR, 0.79; 95% CI, 0.63-0.98), but not sugammadex dosing (mean difference, -0.02; 95% CI, -0.04 to 0.01). CONCLUSIONS: Our education-based interventions were associated with both TOF utilization and 90-day mortality but were not associated with either the odds of PPCs or sugammadex dosing. TOF monitoring was associated with reduced odds of PPCs and 90-day mortality.

Machine Learning Predicts Cerebral Vasospasm in Subarachnoid Hemorrhage Patients.

Background: Cerebral vasospasm (CV) is a feared complication occurring in 20-40% of patients following subarachnoid hemorrhage (SAH) and is known to contribute to delayed cerebral ischemia. It is standard practice to admit SAH patients to intensive care for an extended period of vigilant, resource-intensive, clinical monitoring. We used machine learning to predict CV requiring verapamil (CVRV) in the largest and only multi-center study to date. Methods: SAH patients admitted to UCLA from 2013-2022 and a validation cohort from VUMC from 2018-2023 were included. For each patient, 172 unique intensive care unit (ICU) variables were extracted through the primary endpoint, namely first verapamil administration or ICU downgrade. At each institution, a light gradient boosting machine (LightGBM) was trained using five- fold cross validation to predict the primary endpoint at various timepoints during hospital admission. Receiver-operator curves (ROC) and precision-recall (PR) curves were generated. Results: A total of 1,750 patients were included from UCLA, 125 receiving verapamil. LightGBM achieved an area under the ROC (AUC) of 0.88 an average of over one week in advance, and successfully ruled out 8% of non-verapamil patients with zero false negatives. Minimum leukocyte count, maximum platelet count, and maximum intracranial pressure were the variables with highest predictive accuracy. Our models predicted "no CVRV" vs "CVRV within three days" vs "CVRV after three days" with AUCs=0.88, 0.83, and 0.88, respectively. For external validation at VUMC, 1,654 patients were included, 75 receiving verapamil. Predictive models at VUMC performed very similarly to those at UCLA, averaging 0.01 AUC points lower. Conclusions: We present an accurate (AUC=0.88) and early (>1 week prior) predictor of CVRV using machine learning over two large cohorts of subarachnoid hemorrhage patients at separate institutions. This represents a significant step towards optimized clinical management and improved resource allocation in the intensive care setting of subarachnoid hemorrhage patients.

IL-17 and IFN-γ-producing respiratory tissue resident memory CD4†T cells persist for decades in adults immunized as children with whole cell pertussis vaccines.

The objective was to determine if antigen-specific tissue resident memory T (TRM) cells persist in respiratory tissues of adults immunized as children with whole cell pertussis (wP) or acellular pertussis (aP) vaccines. Mononuclear cells from tonsil or nasal tissue cells were cultured with Bordetella pertussis antigens and TRM cells quantified by flow cytometry. Adults immunized with wP vaccines as children had significantly more IL-17A and IFN-y-producing TRM cells that respond to B. pertussis antigens in respiratory tissues when compared with aP-primed donors. Our findings demonstrate that wP vaccines induce CD4 TRM cells that can persist in respiratory tissues for decades.

PeRiOperative Glucose PRAgMatic (PROGRAM) trial protocol and statistical analysis plan for comparing automated intraoperative reminders to standardise insulin administration in surgical patients at high risk of hyperglycaemia.

INTRODUCTION: Studies finding perioperative hyperglycaemia is associated with adverse patient outcomes in surgical procedures spurred the development of blood glucose guidelines at many institutions. In this trial, we will assess the implementation of a clinical decision support tool that is integrated into the intraoperative portion of our electronic health record and provides real-time best practice recommendations for intraoperative insulin dosing in surgical patients at high risk for hyperglycaemia. METHODS AND DESIGN: We will assess this intervention using a sequential and repeated cross-over design at the institutional level with periods of time for wash-out, control and study intervention. The unit of analysis will be the surgical case. The primary outcome will be the frequency of hyperglycaemia (>180 mg/dL (10 mmol/L)) at first postoperative anaesthesia care unit measurement. There are several prespecified secondary analyses focused on perioperative glycaemic control. DISCUSSION: This protocol and statistical analysis plan describes the methodology, primary and secondary analyses. The PeRiOperative Glucose PRAgMatic (PROGRAM) trial was approved by the Vanderbilt University Institutional Review Board (IRB), Vanderbilt University Medical Center, Nashville, Tennessee, USA (IRB, 220991). The study results will be disseminated via publication in a peer-reviewed journal and presented at national scientific conferences. The results of PROGRAM trial will inform best practice for perioperative standardised insulin administration in surgical patients at high risk of hyperglycaemia. TRIAL REGISTRATION NUMBER: NCT05426096.

Anatomic, histologic, and mechanical features of the right atrium: implications for leadless atrial pacemaker implantation.

BACKGROUND: Leadless pacemakers (LPs) may mitigate the risk of lead failure and pocket infection related to conventional transvenous pacemakers. Atrial LPs are currently being investigated. However, the optimal and safest implant site is not known. OBJECTIVES: We aimed to evaluate the right atrial (RA) anatomy and the adjacent structures using complementary analytic models [gross anatomy, cardiac magnetic resonance imaging (MRI), and computer simulation], to identify the optimal safest location to implant an atrial LP human. METHODS AND RESULTS: Wall thickness and anatomic relationships of the RA were studied in 45 formalin-preserved human hearts. In vivo RA anatomy was assessed in 100 cardiac MRI scans. Finally, 3D collision modelling was undertaken assessing for mechanical device interaction. Three potential locations for an atrial LP were identified; the right atrial appendage (RAA) base, apex, and RA lateral wall. The RAA base had a wall thickness of 2.7 ± 1.6 mm, with a low incidence of collision in virtual implants. The anteromedial recess of the RAA apex had a wall thickness of only 1.3 ± 0.4 mm and minimal interaction in the collision modelling. The RA lateral wall thickness was 2.6 ± 0.9 mm but is in close proximity to the phrenic nerve and sinoatrial artery. CONCLUSIONS: Based on anatomical review and 3D modelling, the best compromise for an atrial LP implantation may be the RAA base (low incidence of collision, relatively thick myocardial tissue, and without proximity to relevant epicardial structures); the anteromedial recess of the RAA apex and lateral wall are alternate sites. The mid-RAA, RA/superior vena cava junction, and septum appear to be sub-optimal fixation locations.

Nasal vaccines for pertussis.

Whooping cough, caused by Bordetella pertussis, is still a major cause of morbidity and mortality worldwide. Current acellular pertussis (aP) vaccines induce potent circulating IgG and prevent severe disease in children/adults and in infants born to vaccinated mothers. However, they do not prevent nasal infection, allowing asymptomatic transmission of B. pertussis. Studies in animal models have demonstrated that, unlike natural infection, immunization with aP vaccines fails to induce secretory immunoglobulin A (IgA) or interleukin-17 (IL-17)-secreting tissue-resident memory CD4 T (TRM) cells, required for sustained sterilizing immunity in the nasal mucosa. Live-attenuated vaccines or aP vaccines formulated with novel adjuvants that induce respiratory IgA and TRM cells, especially when delivered by the nasal route, are in development and have considerable promise as next-generation vaccines against pertussis.

Improving Compliance With Institutional Performance on Train of Four Monitoring.

Background: We performed a multistep quality improvement project related to neuromuscular blockade and monitoring to evaluate the effectiveness of a comprehensive quality improvement program based upon the Multi-institutional Perioperative Outcomes Group (MPOG) Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) metrics targeted specifically at improving train of four (TOF) monitoring rates. Methods: We adapted the plan-do-study-act (PDSA) framework and implemented 2 PDSA cycles between January 2021 and December 2021. PDSA Cycle 1 (Phase I) and PDSA Cycle 2 (Phase II) included a multipart program consisting of (1) a departmental survey assessing attitudes toward intended results, outcomes, and barriers for TOF monitoring, (2) personalized MPOG ASPIRE quality performance reports displaying provider performance, (3) a dashboard access to help providers complete a case-by-case review, and (4) a web-based app spaced education module concerning TOF monitoring and residual neuromuscular blockade. Our primary outcome was to identify the facilitators and barriers to implementation of our intervention aimed at increasing TOF monitoring. Results: In Phase I, 25 anesthesia providers participated in the preintervention and postintervention needs assessment survey and received personalized quality metric reports. In Phase II, 222 providers participated in the preintervention needs assessment survey and 201 participated in the postintervention survey. Thematic analysis of Phase I survey data aimed at identifying the facilitators and barriers to implementation of a program aimed at increasing TOF monitoring revealed the following: intended results were centered on quality of patient care, barriers to implementation largely encompassed issues with technology/equipment and the increased burden placed on providers, and important outcomes were focused on patient outcomes and improving provider knowledge. Results of Phase II survey data was similar to that of Phase I. Notably in Phase II a few additional barriers to implementation were mentioned including a fear of loss of individualization due to standardization of patient care plan, differences between the attending overseeing the case and the in-room provider who is making decisions/completing documentation, and the frequency of intraoperative handovers. Compared to preintervention, postintervention compliance with TOF monitoring increased from 42% to 70% (28% absolute difference across N = 10 169 cases; P < .001). Conclusions: Implementation of a structured quality improvement program using a novel educational intervention showed improvements in process metrics regarding neuromuscular monitoring, while giving us a better understanding of how best to implement improvements in this metric at this magnitude.

Double outlet ventricles: review of anatomic and imaging characteristics.

Hearts with double outlet ventricles and concordant atrioventricular connections account for about 1%-3% of all cases of congenital heart disease. We review hearts with two ventricles and concordant atrioventricular connections with double outlet right ventricle (DORV), double outlet left ventricle (DOLV) and double outlet both ventricles (DOBV) from the morphological and clinical imaging perspectives. These hearts are a heterogeneous group of congenital cardiac malformations with a wide range of pathophysiologies that require an individualised surgical approach based on a precise understanding of the complex cardiovascular anatomy. Owing to their differing temporal, spatial and contrast resolutions, we propose that multimodality imaging provides optimal characterisation of various intracardiac morphological features of double outlet hearts. This approach aids clinical diagnosis for optimising treatment options across these malformations.

Association of Time to Surgery After COVID-19 Infection With Risk of Postoperative Cardiovascular Morbidity.

Importance: The time interval between COVID-19 infection and surgery is a potentially modifiable but understudied risk factor for postoperative complications. Objective: To examine the association between time to surgery after COVID-19 diagnosis and the risk of a composite of major postoperative cardiovascular morbidity events within 30 days of surgery. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted among 3997 adult patients (aged ≥18 years) with a previous diagnosis of COVID-19, as documented by a positive polymerase chain reaction test result, who were undergoing surgery from January 1, 2020, to December 6, 2021. Data were obtained through Structured Query Language access of an existing perioperative data warehouse. Statistical analysis was performed March 29, 2022. Exposure: The time interval between COVID-19 diagnosis and surgery. Main Outcomes and Measures: The primary outcome was the composite occurrence of major cardiovascular comorbidity, defined as deep vein thrombosis, pulmonary embolism, cerebrovascular accident, myocardial injury, acute kidney injury, and death within 30 days after surgery, using multivariable logistic regression. Results: A total of 3997 patients (2223 [55.6%]; median age, 51.3 years [IQR, 35.1-64.4 years]; 667 [16.7%] African American or Black; 2990 [74.8%] White; and 340 [8.5%] other race) were included in the study. The median time from COVID-19 diagnosis to surgery was 98 days (IQR, 30-225 days). Major postoperative adverse cardiovascular events were identified in 485 patients (12.1%). Increased time from COVID-19 diagnosis to surgery was associated with a decreased rate of the composite outcome (adjusted odds ratio, 0.99 [per 10 days]; 95% CI, 0.98-1.00; P = .006). This trend persisted for the 1552 patients who had received at least 1 dose of COVID-19 vaccine (adjusted odds ratio, 0.98 [per 10 days]; 95% CI, 0.97-1.00; P = .04). Conclusions and Relevance: This study suggests that increased time from COVID-19 diagnosis to surgery was associated with a decreased odds of experiencing major postoperative cardiovascular morbidity. This information should be used to better inform risk-benefit discussions concerning optimal surgical timing and perioperative outcomes for patients with a history of COVID-19 infection.

Validation of an Intensive Care Unit Data Mart for Research and Quality Improvement.

Data derived from the electronic health record (EHR) is frequently extracted using undefined approaches that may affect the accuracy of collected variables. Further, efforts to assess data accuracy often suffer from limited collaboration between clinicians and data analysts who perform the extraction. In this manuscript, we describe the methodology behind creation of a structured, rigorously derived intensive care unit (ICU) data mart based on data automatically and routinely derived from the EHR. This ICU data mart includes high-quality data elements commonly used for quality improvement and research purposes. These data elements were identified by physicians working closely with data analysts to iteratively develop and refine algorithmic definitions for complex outcomes and risk factors. We contend that this methodology can be reproduced and applied across other institution or to other clinical domains to create high quality data marts, inclusive of complex outcomes data.

Development of a cardiovascular magnetic resonance-compatible large animal isolated heart model for direct comparison of beating and arrested hearts.

Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT-CMR). Here, we develop a CMR-compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D-printed chamber and perfusion circuit re-established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT-CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT-CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT-CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT-CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic-like state. A contiguous stack of 313 5-µm histological sections at and a 100-µm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT-CMR data were obtained. A CMR-compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.

Predicting Survival in Repaired Tetralogy of Fallot: A Lesion-Specific and Personalized Approach.

OBJECTIVES: This study sought to identify patients with repaired tetralogy of Fallot (rTOF) at high risk of death and malignant ventricular arrhythmia (VA). BACKGROUND: To date there is no robust risk stratification scheme to predict outcomes in adults with rTOF. METHODS: Consecutive patients were prospectively recruited for late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) to define right and left ventricular (RV, LV) fibrosis in addition to proven risk markers. RESULTS: The primary endpoint was all-cause mortality. Of the 550 patients (median age 32 years, 56% male), 27 died (mean follow-up 6.4 ± 5.8; total 3,512 years). Mortality was independently predicted by RVLGE extent, presence of LVLGE, RV ejection fraction ≤47%, LV ejection fraction ≤55%, B-type natriuretic peptide ≥127 ng/L, peak exercise oxygen uptake (V02) ≤17 mL/kg/min, prior sustained atrial arrhythmia, and age ≥50 years. The weighted scores for each of the preceding independent predictors differentiated a high-risk subgroup of patients with a 4.4%, annual risk of mortality (area under the curve [AUC]: 0.87; P < 0.001). The secondary endpoint (VA), a composite of life-threatening sustained ventricular tachycardia/resuscitated ventricular fibrillation/sudden cardiac death occurred in 29. Weighted scores that included several predictors of mortality and RV outflow tract akinetic length ≥55 mm and RV systolic pressure ≥47 mm Hg identified high-risk patients with a 3.7% annual risk of VA (AUC: 0.79; P < 0.001) RVLGE was heavily weighted in both risk scores caused by its strong relative prognostic value. CONCLUSIONS: We present a score integrating multiple appropriately weighted risk factors to identify the subgroup of patients with rTOF who are at high annual risk of death who may benefit from targeted therapy.

Feasibility of non-invasive cardiac output monitoring at birth using electrical bioreactance in term infants.

BACKGROUND: Non-invasive cardiac output monitoring (NICOM) provides continuous estimation of cardiac output. This has potential for use in the delivery suite in the management of acutely depressed term infants. This study aims to measure cardiac output in term infants at delivery and in the first hours of life. METHODS: Parents of term infants due to be born by elective caesarean section or vaginal delivery at Cork University Maternity Hospital, Ireland were approached in the antenatal period to participate. Cardiac output was measured using a CHEETAH NICOM device, which uses electrical bioreactance technology, at birth and at 2 hours of life. RESULTS: Forty-nine newborns were included. The median gestational age was 39 (IQR: 39-40) weeks and the median birth weight was 3.50 (IQR: 3.14-3.91) kg. Cardiac output measurements were obtained at a median of 8 (IQR: 5-12) min of life. The mean (SD) cardiac output was 101 (24) mL/kg/min in the delivery room and 89 (22) mL/kg/min at 2 hours of life. There was a statistically significant decrease in cardiac output from birth to 2 hours of life (difference in mean (95% CI): 13.5 (9.2 to 17.9) mL/kg/min, p<0.001, n=47). There were no adverse effects associated with NICOM. DISCUSSION: This technique is feasible and safe in the delivery room. Mean cardiac output measures using NICOM are lower than those found in studies which used echocardiography to determine cardiac output at birth.

Three-Dimensional Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Predicts Inducibility of Ventricular Tachycardia in Adults With Repaired Tetralogy of Fallot.

BACKGROUND: Adults with repaired tetralogy of Fallot die prematurely from ventricular tachycardia (VT) and sudden cardiac death. Inducible VT predicts mortality. Ventricular scar, the key substrate for VT, can be noninvasively defined with late gadolinium enhancement (LGE) cardiovascular magnetic resonance but whether this relates to inducible VT is unknown. METHODS: Sixty-nine consecutive repaired tetralogy of Fallot patients (43 male, mean 40±15 years) clinically scheduled for invasive programmed VT-stimulation were prospectively recruited for prior 3-dimensional LGE cardiovascular magnetic resonance. Ventricular LGE was segmented and merged with reconstructed cardiac chambers and LGE volume measured. RESULTS: VT was induced in 22 (31%) patients. Univariable predictors of inducible VT included increased RV LGE (odds ratio [OR], 1.15; P=0.001 per cm3), increased nonapical vent LV LGE (OR, 1.09; P=0.008 per cm3), older age (OR, 1.6; P=0.01 per decile), QRS duration ≥180 ms (OR, 3.5; P=0.02), history of nonsustained VT (OR, 3.5; P=0.02), and previous clinical sustained VT (OR, 12.8; P=0.003); only prior sustained VT (OR, 8.02; P=0.02) remained independent in bivariable analyses after controlling for RV LGE volume (OR, 1.14; P=0.003). An RV LGE volume of 25 cm3 had 72% sensitivity and 81% specificity for predicting inducible VT (area under the curve, 0.81; P<0.001). At the extreme cutoffs for ruling-out and ruling-in inducible VT, RV LGE >10 cm3 was 100% sensitive and >36 cm3 was 100% specific for predicting inducible VT. CONCLUSIONS: Three-dimensional LGE cardiovascular magnetic resonance-defined scar burden is independently associated with inducible VT and may help refine patient selection for programmed VT-stimulation when applied to an at least intermediate clinical risk cohort.

The morphologically right and left ventricles cannot be distinguished by their coronary arterial pattern.

OBJECTIVES: The morphologically right and left ventricles are distinguished from each other based on their internal anatomical features, because their external (epicardial) surfaces do not appear to have any distinguishing mark for such ventricular identification. Nevertheless, ventricular identification based on epicardial characteristics, if these were possible, would be interesting to surgeons, because this would enable them to identify each ventricle rapidly upon opening the chest. This made us curious as to whether or not the two ventricles may be distinguished based on their epicardial coronary arterial patterns, because this is the most obvious epicardial ventricular feature. METHODS: This idea led us to formulate the following 2 hypotheses: (i) The morphologically left ventricle is always the one that receives the higher number of the marginal arteries as compared to the morphologically right ventricle. (ii) Only the morphologically left ventricle receives the diagonal arteries from the anterior and posterior interventricular arteries. These hypotheses were tested in this anatomical observational study by examination of 98 normal and 398 congenitally malformed formaldehyde-preserved hearts encompassing most malformations, including rare ones and hearts in which 1 ventricle is hypoplastic. RESULTS: These examinations show that both hypotheses are false. CONCLUSIONS: The two ventricles cannot be distinguished from each other based on the number of marginal arteries that they receive or which one receives diagonal arteries; both ventricles may receive diagonal arteries from either or both interventricular arteries.

Parental opinion of consent in neonatal research.

BACKGROUND: Neonatal research, particularly neonatal emergency research is a challenging area, notably in relation to obtaining valid prospective informed consent. The aim of this study is to determine parental perceptions of the consent process involved in performing research in newborn care, to explore methods used to obtain consent and their acceptability to parents. METHODS: A parental questionnaire was developed that examined attitudes towards research and hypothetical research studies, in which the acceptability of various methods of consent was examined (informed, waived, deferred). These research scenarios were of varying time sensitivity and perceived risk level. The study setting was an Irish maternity hospital. RESULTS: There were 600 responses to the questionnaire. In 93% of cases, parents felt that their involvement in the consent process was essential. In emergency situations, 52% felt full prospective informed consent was necessary; however, almost 28% of parents would feel pressure to consent. Most (75%) parents would prefer to be approached to discuss neonatal research studies antenatally, irrespective of study type and 40% of parents felt that neonates involved in research studies received overall better care. Acceptability of deferred consent was greater than waived, and was highest for the more emergency-based scenarios presented. DISCUSSION: Parents feel that they should play a central role in research involving their children. There were differences in the acceptability of various consent methods with strongest agreement for informed consent and lowest agreement for waived consent. Parents were more willing to accede to deferred consent in the cardiopulmonary resuscitation scenario study. These findings provide useful insights to consent strategies in future newborn research studies.

Anatomy of the atrial septum and interatrial communications.

Deficiencies in the septum separating the two atrial chambers are among the most common of congenital heart malformations. This article reviews the developmental aspects of the partitioning of the primitive atrium into right and left atrial chambers, the anatomical components of the atrial septum, and deficiencies that produce the various types of interatrial communications. Knowledge of the components of the true atrial septum in the developed heart clarifies the morphology of various types of interatrial communications. The oval fossa defect (also termed secundum ASD) is located within the true septum. The patent foramen ovale (PFO) is a tunnel-like passageway between the free edge of the overlapping ovale fossa valve and its muscular rim. Other defects such as superior and inferior sinus venosus defects, coronary sinus defects, and ostium primum defects lie outside the area of the true septum.

Personalized computational modeling of left atrial geometry and transmural myofiber architecture.

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by complete absence of coordinated atrial contraction and is associated with an increased morbidity and mortality. Personalized computational modeling provides a novel framework for integrating and interpreting the role of atrial electrophysiology (EP) including the underlying anatomy and microstructure in the development and sustenance of AF. Coronary computed tomography angiography data were segmented using a statistics-based approach and the smoothed voxel representations were discretized into high-resolution tetrahedral finite element (FE) meshes. To estimate the complex left atrial myofiber architecture, individual fiber fields were generated according to morphological data on the endo- and epicardial surfaces based on local solutions of Laplace's equation and transmurally interpolated to tetrahedral elements. The influence of variable transmural microstructures was quantified through EP simulations on 3 patients using 5 different fiber interpolation functions. Personalized geometrical models included the heterogeneous thickness distribution of the left atrial myocardium and subsequent discretization led to high-fidelity tetrahedral FE meshes. The novel algorithm for automated incorporation of the left atrial fiber architecture provided a realistic estimate of the atrial microstructure and was able to qualitatively capture all important fiber bundles. Consistent maximum local activation times were predicted in EP simulations using individual transmural fiber interpolation functions for each patient suggesting a negligible effect of the transmural myofiber architecture on EP. The established modeling pipeline provides a robust framework for the rapid development of personalized model cohorts accounting for detailed anatomy and microstructure and facilitates simulations of atrial EP.

Evaluation of Discordance in Primary Tumor and Lymph Node Response After Neoadjuvant Therapy in Breast Cancer.

BACKGROUND: Neoadjuvant therapy (NAT) offers a unique opportunity to assess tumor response to systemic agents. However, a discrepancy may exist between the response of the primary tumor and involved nodes. We report on the frequency of response discordance after NAT in breast cancer. PATIENTS AND METHODS: All consecutive node-positive patients receiving NAT in our department from 2009 to 2014 were identified. Patient demographics, and radiologic and pathologic features were tabulated. Tumor response was estimated by magnetic resonance imaging of the breast. Lymph node (LN) response was estimated from pathologic treatment response measurements. Statistical analysis was performed. RESULTS: A total of 108 node-positive patients treated with NAT were eligible for inclusion. Median age was 51.73 years (range, 20-87 years). All patients underwent axillary clearance, and 62% underwent mastectomy. A 40% mean reduction in tumor size was observed. Statistically, a positive correlation between tumor and LN response after NAT was observed (Spearman correlation coefficient, r = 0.46, P < .001). Complete pathologic response was observed in 17 patients (15.7%). However, 21 patients experienced complete LN response, with only 81% of these patients (n = 17) experiencing a complete response in tumor also. A complete response was observed in tumor in 20 patients, and this predicted complete nodal response in 85% of cases (n = 17). Fifteen percent of primary tumors with complete pathologic response had persistently positive LNs. CONCLUSION: A significant discordance exists between the primary tumor and LN response, representing a concern for the lack of response of occult regional or systemic metastases due to potential biologic heterogeneity.