Search

Objective The Norwood neoaortic arch biomechanical properties are abnormal due to reduced vessel wall compliance and abnormal geometry. Others have previously described neoaortic geometric distortion by the degree of diameter reduction (tapering) and associated this with mismatched ventricular-neoaortic coupling, abnormal flow hemodynamic parameters, and worse patient outcome. Our purposes were to investigate the influence of neoaortic tapering (ie, diameter reduction) on flow-mediated viscous energy loss (EL') in post-Norwood palliated hypoplastic left heart syndrome patients, and correlate flow-geometry with single ventricle power generation. Methods Twenty-six palliated hypoplastic left heart syndrome patients underwent comprehensive cardiac evaluation with 4-dimensional-flow magnetic resonance imaging. Patients were grouped into high- (group H, n = 13) and low- (group L, n = 13) degree neoaortic tapering using the median cutoff value of neoaortic diameter variance. EL' was calculated along standardized segments using 4-dimensional-flow magnetic resonance imaging. Flow-mediated power loss as a percentage of total power generated by the single ventricle was determined. Results Group H had a higher prevalence of abnormal recirculating flow in the neoaorta and elevated neoaortic EL' in the ascending aorta (1.0 vs 0.6 mW; P = .004). Group H EL' was increased across the entire thoracic aorta (2.6 vs 1.3 mW; P = .002) and accounted for 0.7% of generated ventricular power versus 0.3% in group L (P = .024). EL' directly correlated with the degree of ascending aortic dilation (R = 0.49; P = .012). Conclusions Patients with high degree neoaortic tapering have more perturbed flow through the neoaorta and increased EL'. Flow-mediated energy loss due to abnormal flow represents irreversibly wasted power generated by the single right ventricle. In patients with high-degree neoaortic tapering, EL' was more than 2-fold greater than low-degree tapering patients. These data suggest that oversizing the Norwood neoaortic reconstruction should be avoided and that patients with distorted neoaortic geometry may warrant increased surveillance for single-ventricle deterioration.

Background Norwood palliation for hypoplastic left heart syndrome typically results in retrograde perfusion of the native aortic root. This may predispose to native aortic root thrombosis (NART). Methods Patients who underwent stage 1 Norwood palliation at Children’s Hospital Colorado between 2003 and 2019 were retrospectively reviewed for NART. Additional patients were identified by a systematic literature review. Patient factors, operative details, presentation, diagnostic methods, treatments, and outcomes were analyzed. Results Three patients with NART were identified among 241 patients who had undergone stage 1 Norwood palliation at Children’s Hospital Colorado (mean follow-up, 48 months). A fourth patient identified at Children’s Hospital Colorado had undergone stage 1 palliation elsewhere. The systematic literature review identified 12 additional patients. Among the 16 patients, patients presented with new arrhythmias (38% [n = 6]), evidence of ischemia (31% [n = 5]), incidentally (19% [n = 3]), inability to wean from postoperative support (6% [n = 1]), and cardiac arrest (6% [n = 1). The diagnosis was made by transthoracic echocardiography (TTE) in 50% (n = 8), transesophageal echocardiography in 19% (n = 3), cardiac catheterization in 25% (n = 4), and cardiac computed tomography in 6% (n = 1). Importantly, 44% (n = 7) of patients were missed by TTE and subsequently diagnosed by other methods. Treatment strategies were surgical thrombectomy in 38% (n = 6), anticoagulation alone in 38% (n = 6), direct catheter thrombolysis in 19% (n = 3), and systemic thrombolysis in 6% (n = 1). The rate of mortality or transplant listing was 44% (n = 7). Conclusions NART is an underappreciated complication of Norwood palliation with high mortality. There should be a high index of suspicion for NART in patients after Norwood palliation with an unexplained complicated clinical course. Importantly, NART is frequently missed by TTE.

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images. QSIPrep is a software platform for processing of most diffusion MRI datasets and ensures that adequate workflows are used.

Cor Pulmonale or right ventricular (RV) dysfunction due to pulmonary disease is an expected complication of COPD resulting primarily from increased afterload mediated by chronic alveolar hypoxemia and resulting hypoxic pulmonary vasoconstriction. Early detection of elevated RV afterload has been previously demonstrated by visualization of abnormal flow patterns in the proximal pulmonary arteries. Prior analysis of helicity in the pulmonary arteries in pulmonary hypertension patients has demonstrated a strong association between helicity and increased RV afterload. However, these flow hemodynamics have yet to be fully explored in patients with COPD. We hypothesized that patients with COPD will have abnormal pulmonary flow as evaluated by 4D-Flow MRI and associated with RV function and pulmonary arterial stiffness. Patients with COPD (n = 15) (65 years ± 6) and controls (n = 10) (58 years ± 9) underwent 4D-Flow MRI to calculate helicity. The helicity was calculated in the main pulmonary artery (MPA) and along the RV outflow tract (RVOT)-MPA axis. Main pulmonary arterial stiffness was measured using the relative area change (RAC). We found COPD patients had decreased helicity relative to healthy controls in the MPA (19.4 ± 7.8vs 32.8 ± 15.9, P = 0.007) and reduced helicity along the RVOT-MPA axis (33.2 ± 9.0 vs 43.5 ± 8.3, P = 0.010). Our investigation indicates a strong association between helicity along the MPA-RV outflow tract axis and RV function and suggests that 4D-Flow MRI might be a sensitive tool in evaluating RV-pulmonary arterial coupling in COPD.

Degenerative cervical myelopathy (DCM) results from compression of the cervical spine cord as a result of age related changes in the cervical spine, and affects up to 2% of adults, leading to progressive disability. Surgical decompression is the mainstay of treatment, but there remains significant variation in surgical approaches used. This survey was conducted in order to define current practice amongst spine surgeons worldwide, as a possible prelude to further studies comparing surgical approaches.An electronic survey was developed and piloted by the investigators using SurveyMonkey. Collected data was categorical and is presented using summary statistics. Where applicable, statistical comparisons were made using a Chi-Squared test. The level of significance for all statistical analyses was defined as p 0.05. All analysis, including graphs was performed using R (R Studio).127 surgeons, from 30 countries completed the survey; principally UK (66, 52%) and North America (15, 12%). Respondents were predominantly Neurosurgeons by training (108, 85%) of whom 84 (75%) reported Spinal Surgery as the principal part of their practice. The majority indicated they selected their surgical procedure for multi-level DCM on a case by case basis (62, 49%). Overall, a posterior approach was more popular for multi-level DCM (74, 58%). Region, speciality or annual multi-level case load did not influence this significantly. However, there was a trend for North American surgeons to be more likely to favour a posterior approach.A posterior approach was favoured and more commonly used to treat multi-level DCM, in an international cohort of surgeons. Posterior techniques including laminectomy, laminectomy and fusion or laminoplasty appeared to be equally popular.

Despite significant morbidity among infants with single ventricle heart disease (SVHD), clinical monitoring is limited by poor understanding of the underlying pathobiology. Proteomics can identify novel biomarkers and important pathways in complex disease. No prior study has evaluated whether the proteome of SVHD infants differs from healthy controls, how it shifts after stage 2 palliation, or whether differences can predict post-operative outcomes. We present a prospective cohort study of cardiovascular proteomic phenotyping in infants with SVHD undergoing stage 2 palliation. Twenty-nine pre-stage-2 SVHD infants and 25 healthy controls were enrolled. Outcomes included postoperative hypoxemia and endotracheal intubation time. Serum samples were drawn pre-operatively (systemic and pulmonary vein) and at 24 hours postoperation. Targeted cardiovascular proteomic analysis included 184 proteins. Partial least squares discriminant analysis distinguished cases from controls (Accuracy = 0.98, R2 = 0.93, Q2 = 0.81) with decreased inflammatory mediators and increased modulators of vascular tone. Partial least squares discriminant analysis also distinguished cases pre-operation vs. post-operation (Accuracy=0.98, R2=0.99, Q2 = 0.92) with postoperative increase in both inflammatory and vascular tone mediators. Pre-operation pulmonary vein tissue inhibitor of metalloproteinase-1 (1.8x-fold, p=1.6 × 10−4) and nidogen-1 (1.5x-fold, p=1.7 × 10−4) were higher in subjects with longer endotracheal intubation time. Postoperation matrix metalloproteinase 7 levels were higher in subjects with greater postoperative hypoxemia (1.5x-fold, P= 1.97 × 10−5). Proteomic analysis identifies significant changes among SVHD infants pre- and post-stage 2, and healthy controls. Tissue inhibitor of metalloproteinase-1, nidogen-1, and matrix metalloproteinase 7 levels are higher in SVHD cases with greater morbidity suggesting an important role for regulation of extracellular matrix production. Proteomic profiling may identify high-risk SVHD infants.

Gastric enterochromaffin-like cell (ECL) tumours can occur in patients with multiple endocrine neoplasia type 1 (MEN1), especially in those affected by Zollinger Ellison syndrome (ZES). Since the prevalence of ECL lesions is not well defined yet, the present study evaluated the presence and extent of ECL lesions in MEN1 patients with and without ZES.Multiple endocrine neoplasia type 1 patients being part of a regular screening program (2014-2018) underwent gastroduodenoscopies with biopsies of the stomach and determination of serum gastrin and chromogranin A levels. Haematoxylin- and immunostaining with chromogranin A, gastrin and VMAT I and II (vesicular monoamine transporter I and II) of the biopsies were performed.Thirty-eight MEN1 patients, of whom 16 (42%) were diagnosed and treated earlier for ZES, were analysed. In ten of 16 (62.5%) ZES patients, a locally scattered, mixed image of diffuse, linear and micronodular mild hyperplasia was present. In addition, two of these patients (13%) showed small (max 1.5 mm in size) intramucosal ECL tumours. Neither ECL changes, nor tumours were found in MEN1 patients without ZES (n = 22). In MEN1/ZES patients, the median serum gastrin level was significantly elevated compared to MEN1 patients without ZES (206 pg/ml vs. 30.5 pg/ml, p .001). A subgroup analysis of the serum gastrin and chromogranin A levels of MEN1/ZES patients with or without ECL hyperplasia did not show significant differences (gastrin level: p = .302, chromogranin A: p = .464).Enterochromaffin-like cell hyperplasia and gastric carcinoids occur only in MEN1 patients with ZES, but less frequently than reported.

The GE81112 complex has garnered much interest due to its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification of its key pharmacophores. A key feature of our medicinal chemistry effort is the incorporation of additional biocatalytic hydroxylations in modular analogue synthesis to rapidly enable exploration of relevant chemical space.

Background Anaesthetic induction occurs at higher plasma drug concentrations than emergence in animal studies. Some studies find evidence for such anaesthetic hysteresis in humans, whereas others do not. Traditional thinking attributes hysteresis to drug equilibration between plasma and the effect site. Indeed, a key difference between human studies showing anaesthetic hysteresis and those that do not is in how effect-site equilibration was modelled. However, the effect-site is a theoretical compartment in which drug concentration cannot be measured experimentally. Thus, it is not clear whether drug equilibration models with experimentally intractable compartments are sufficiently constrained to unequivocally establish evidence for the presence or absence of anaesthetic hysteresis. Methods We constructed several models. One lacked hysteresis beyond effect-site equilibration. In another, neuronal dynamics contributed to hysteresis. We attempted to distinguish between these two systems using drug equilibration models. Results Our modelling studies showed that one can always construct an effect-site equilibration model such that hysteresis collapses. So long as the concentration in the effect-site cannot be measured directly, the correct effect-site equilibration model and the one that erroneously collapses hysteresis are experimentally indistinguishable. We also found that hysteresis can naturally arise even in a simple network of neurones independently of drug equilibration. Conclusions Effect-site equilibration models can readily collapse hysteresis. However, this does not imply that hysteresis is solely attributable to the kinetics of drug equilibration.

Background Elevated systemic afterload in patients with Fontan circulation may lead to impaired single ventricular function. Wave intensity analysis (WIA) enables evaluation of compression and expansion waves traveling through vasculature. We aimed to investigate the unfavorable wave propagation causing excessive afterload may be an important contributor to the overall single ventricle function and to the limited functional capacity in this patient population. Methods Patients with hypoplastic left heart syndrome (HLHS) (n = 25), single left ventricle (SLV) (n = 24), and normal controls (n = 10) underwent phase-contrast MRI based WIA analysis evaluated in the ascending aorta. Forward compression wave (FCW) representing dP/dt, backward compression wave (BCW) reflecting vascular stiffness, and forward decompression wave (FDW) representing LV relaxation were recorded and indexed to each other. Results FCW was lowest in HLHS patients (1098 mm5/s), and higher in the SLV group (1457 mm5/s), and controls (6457 mm5/s) (P Conclusions Patients with HLHS and SLV have unfavorable aortic WIA patterns with increased BCW/FCW ratio indicating increased systemic afterload due to retrograde compression waves. Reduced FCW and systolic MRI indices correlated with peak VO2 suggesting that abnormal systolic wave propagation may play a role in exercise intolerance for Fontan patients.

We describe a successful bridge to recovery by coronary reimplantation and Berlin Heart EXCOR left ventricular assist device in a child with left main coronary artery ostial atresia and severe ischemic cardiomyopathy.

Microscopy enables fast and effective diagnostics. However, in resource-limited regions microscopy is not accessible to everyone. Smartphone-based low-cost microscopes could be a powerful tool for diagnostic and educational purposes. In this paper, the imaging quality of a smartphone-based microscope with four different optical parameters is presented and a systematic overview of the resulting diagnostic applications is given. With the chosen configuration, aiming for a reasonable trade-off, an average resolution of 1.23 μm and a field of view of 1.12 mm2 was achieved. This enables a wide range of diagnostic applications such as the diagnosis of Malaria and other parasitic diseases.

Purpose Surgery is recommended for most patients with gastro-entero-pancreatic neuroendocrine neoplasias (GEP-NENs). Rates of complications and perioperative mortality have been reported in few mostly retrospective single-center series, but there has been no detailed analysis on risk factors for perioperative complications and mortality to date. Methods Data of patients with GEP-NENs operated between January 2015 and September 2018 were retrieved from EUROCRINE©, a European online endocrine surgical quality registry, and analyzed regarding rate and risk factors of surgical complications. Risk factors were assessed by logistic regression. Results Some 376 patients (211 female, 167 male; age median 63, range 15–89 years) were included. Most NENs were located in the small intestine (SI) (n = 132) or pancreas (n = 111), the rest in the stomach (n = 34), duodenum (n = 30), appendix (n = 30), colon, and rectum (n = 22), or with unknown primary (n = 15). Of the tumors, 320 (85.1%) were well or moderately differentiated, and 147 (39.1%) of the patients had distant metastases at the time of operation. Severe complications (Dindo-Clavien ≥ 3) occurred in 56 (14.9%) patients, and 4 (1.1%) patients died perioperatively. Severe complications were more frequent in surgery for duodenopancreatic NENs (n = 31; 22.0%) compared with SI-NENs (n = 15; 11.4%) (p = 0.014), in patients with lymph node metastases operated with curative aim of surgery (n = 24; 21.4%) versus non-metastasized tumors or palliative surgery (n = 32; 12.1%) (p = 0.020), and in functioning tumors (n = 20; 23.0%) versus non-functioning tumors (n = 30; 13.5%) (p = 0.042). Complication rates were not significantly associated with tumor stage or grade. Conclusions Severe complications are frequent in GEP-NEN surgery. Besides duodenopancreatic tumor location, curative resection of nodal metastases and functioning tumors are risk factors for complications.

The present study aimed to compare robotic-assisted versus laparoscopic distal pancreatic resection and enucleation for potentially benign pancreatic neoplasms. Patients were retrieved from a prospectively maintained database. Demographic data, tumor types, and the perioperative outcomes were retrospectively analyzed. In a 10-year period, 75 patients (female, n = 44; male, n = 31; median age, 53 years [range, 9–84 years]) were identified. The majority of patients had pancreatic neuroendocrine neoplasms (n = 39, 52%) and cystic neoplasms (n = 23, 31%) with a median tumor size of 17 (3–60) mm. Nineteen (25.3%) patients underwent enucleation (robotic, n = 11; laparoscopic, n = 8) and 56 (74.7%) patients underwent distal pancreatic resection (robotic, n = 24; laparoscopic, n = 32), of those 48 (85%) underwent spleen-preserving procedures. Eight (10.7%) procedures had to be converted to open surgery. The rate of vessel preservation in distal pancreatectomy was significantly higher in robotic-assisted procedures (62.5% vs. 12.5%, p = 0.01). Twenty-six (34.6%) patients experienced postoperative complications (Clavien–Dindo grade > 3). Twenty (26.7%) patients developed a pancreatic fistula type B. There was no mortality. After a median follow-up period of 58 months (range 2–120 months), one patient (1.3%) developed local recurrence (glucagonoma) after enucleation, which was treated with a Whipple procedure. The robotic approach is comparably safe, but increases the rate of splenic vessel preservation and reduces the risk of conversion to open surgery.

Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR ( n = 64) and healthy controls ( n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls ( P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit. NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening.

BackgroundIn the Netherlands, the obstetric and neonatal healthcare system consists of multiple healthcare organizations. Due to this system, transfers between healthcare professionals are inevitable. Transfers can interrupt the continuity of care, which is an important aspect of care quality. The aim of this study is to examine how healthcare professionals transfer their clients and to understand factors that facilitate or impede continuity of care.MethodsWe conducted 15 semi-structured interviews with community midwives (4), obstetricians/clinical midwives (4), maternity care assistants (4), and youth healthcare nurses (3) between June and September 2016. After discussing the meaning of transfers of care, we introduced a vignette on the care process of a pregnant woman and asked about the methods the professional would use to transfer a client and about factors that facilitate or impede continuity of care.ResultsObstetric and neonatal healthcare professionals mentioned 19 factors that facilitate or impede continuity of care. The facilitating factors were, e.g., usage of protocols and standard formats, transfers in person, being accessible, and multidisciplinary meetings. Impeding factors included, e.g., acute situations, experienced hierarchy, insufficient knowledge of protocols, and privacy concerns.ConclusionProfessionals mentioned a broad variety of factors facilitating and impeding continuity of care.

Aortopathy is a recognized comorbidity of Tetralogy of Fallot (TOF). Aortic flow in children with repaired TOF is abnormal despite normal aortic valve anatomy and early surgical repair that results in aortic size normalization. The purpose of this study was to investigate the flow hemodynamics inside the left ventricle (LV) of children with repaired TOF using 4D-Flow MRI derived vorticity. Vorticity is the spatial derivative of flow velocity and is sensitive to anatomic and geometric variations. Vorticity was calculated inside the LV of children with repaired TOF having normal aortic size (n = 14) and normal controls (n = 10) during systolic ejection phase. All subjects underwent comprehensive biventricular analysis including the MRI based feature-tracking based LV strain analysis and mechanical dyssynchrony. Right ventricular (RV) volumetric indices along with LV mechanical indices were correlated with LV vorticity. All TOF patients had supraphysiologic helical flow in the ascending aorta. The generated peak systolic vorticity integrated over the LV volume was elevated in TOF group compared to control (median: 1344 vs. 858 s−1, P

Background: Some gender-related differences have been reported in multiple endocrine neoplasia type 1 (MEN1), although not all reports are conclusive. This systematic review with analysis of the own MEN1 cohort evaluates gender differences and potential consequences for screening. Methods: A systematic review of the literature between 1990 and 2019 with the search terms “MEN1” or “multiple endocrine neoplasia type 1” and “gender” or “sex” was performed. In addition, the prospectively collected data of a genetically confirmed MEN1 cohort of the Philipps University Marburg were retrospectively analyzed. Results: Review of the literature identified five retrospective case series with original data of 1,057 MEN1 patients. One series suggested a higher frequency of pancreatic neuroendocrine neoplasms (NEN), especially gastrinomas, in men (61 vs. 54%) and a higher frequency of pituitary tumors in women (47 vs. 30%), but others did not. Only thymic NEN occurred predominantly in men throughout all studies. Women with MEN1 were found to have an increased risk of breast cancer. In the own series consisting of 116 MEN1 patients (male = 58, female = 58), thymic lesions were also more frequently detected in male patients (male = 5, female = 1). No gender difference was found with regard to the other manifestations. Conclusion: Regarding the typical MEN1 tumor manifestations, gender-adapted diagnostic and therapeutic approaches cannot be recommended. Female MEN1 patients should be encouraged to participate in breast cancer screening programs.

STUDY DESIGN: Systematic review. OBJECTIVES: To evaluate the impact of cannabinoids on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI), with the aim of determining suitability for clinical trials involving SCI patients. METHODS: A systematic search was performed in MEDLINE and Embase databases, following registration with PROPSERO (CRD42019149671). Studies evaluating the impact of cannabinoids (agonists or antagonists) on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI were included. Data extracted from relevant studies, included sample characteristics, injury model, neurobehavioural outcomes assessed and study results. PRISMA guidelines were followed and the SYRCLE checklist was used to assess risk of bias. RESULTS: The search returned 8714 studies, 19 of which met our inclusion criteria. Sample sizes ranged from 23 to 390 animals. WIN 55,212-2 (n = 6) and AM 630 (n = 8) were the most used cannabinoid receptor agonist and antagonist respectively. Acute SCI models included traumatic injury (n = 16), ischaemia/reperfusion injury (n = 2), spinal cord cryoinjury (n = 1) and spinal cord ischaemia (n = 1). Assessment tools used assessed locomotor function, pain and anxiety. Cannabinoid receptor agonists resulted in statistically significant improvement in locomotor function in 9 out of 10 studies and pain outcomes in 6 out of 6 studies. CONCLUSION: Modulation of the endo-cannabinoid system has demonstrated significant improvement in both pain and locomotor function in pre-clinical SCI models; however, the risk of bias is unclear in all studies. These results may help to contextualise future translational clinical trials investigating whether cannabinoids can improve pain and locomotor function in SCI patients., NIHR Clinical Doctoral Research Fellowship.

Objectives Pancreatic neuroendocrine neoplasias (pNENs) frequently occur in multiple endocrine neoplasia type 1 (MEN1). Their distribution referring to embryology, that is, the pancreatic anlagen, has not been investigated yet. Methods In the time between 1998 and 2019, we studied the distribution of pNENs in MEN1 concerning the embryologic origin of the pancreas, that is, the dorsal versus ventral anlage using endoscopic ultrasound in 117 MEN1 patients: 56 women, 61 men; aged 40 years (standard deviation, 14 years) at first endoscopic ultrasound. Results In 105 patients, a total of 628 pNENs were detected. They were located in the pancreatic tail: 231; pancreatic body: 177; pancreatic head/uncinate process: 220. Of the latter, 22 were located in the ventral anlage, 176 in the dorsal anlage, and 22 remained undefined. In summary, just 3.5% of all detected pNENs were located in the ventral anlage, 93.0% in the dorsal anlage, and 3.5% could not be assigned. Conclusions Our study indicates that the vast majority of pNENs in MEN1 is located in the dorsal anlage, whereas the ventral anlage of the pancreas seems to be to a large extend spared from pNENs. Implications for new surgical strategies might be considered.

Study Design: Cross-sectional survey. Objectives: Degenerative cervical myelopathy (DCM) is a common syndrome of acquired spinal cord impairment caused by canal stenosis secondary to arthritic changes of the spine. International guidelines consider physiotherapy an option for mild, stable DCM; however, few studies have been conducted on nonoperative management. The objective was to determine current usage and perceptions of nonoperative physiotherapy for DCM. Methods: Persons with DCM were recruited to a web-based survey. Participants with complete responses that had not received surgery were included (n = 167). Variables included symptom duration, treatment history, current disability, and demographic characteristics. Results: Disease and demographic characteristics were equivalent between those who did and did not receive physiotherapy. In all, 19.5% of physiotherapy recipients reported subjective benefit from physiotherapy. Those perceiving benefit had significantly higher mJOA (modified Japanese Orthopaedic Association) scores, lower neck pain scores, and shorter symptom duration. In multivariate logistic regression analysis, those with mild DCM were more likely to perceive benefit than those with severe DCM, as were those with moderate DCM (to a lesser extent). Individuals whose diagnosis was delayed 1 to 2 years were less likely to perceive benefit than those that waited 0 to 6 months. Conclusions: The provision of nonoperative physiotherapy in the management of DCM is inconsistent and appears to differ from international guidelines. Few patients perceived benefit from physiotherapy; however, this was more likely in those with mild DCM and in those with shorter symptom durations. Further work is needed to establish the appropriate role of physiotherapy for this population.

Importance Guidelines advocate subtotal parathyroidectomy (SPTX) or total parathyroidectomy with autotransplantation (TPTX) with bilateral cervical thymectomy for primary hyperparathyroidism (pHPT) associated with multiple endocrine neoplasia type 1 (MEN1). However, both procedures are associated with a significant risk of permanent hypoparathyroidism. Objective The aim of the current study was to compare long-term results of either single gland excision (SGE, 1-2 glands), SPTX and TPTX for the treatment of MEN1-associated pHPT. Design and setting Data of genetically confirmed MEN1 patients who underwent surgery for pHPT between 1987 and 2017 were retrieved from a prospective database and were retrospectively analysed. Results Eighty-nine MEN1 patients underwent either TPTX (n = 38, 42.7%), SPTX (n = 23, 25.8%) or SGE (n = 28, 31.5%). The rate of disease persistence after initial surgery was 2.6%, 0% and 14.2% in the TPTX, SPTX and SGE groups, respectively. After median follow-up of 112 (range 7-411) months, the rate of recurrent pHPT was significantly higher in the SGE group (n = 19, 21.3%) compared with the TPTX (n = 4, 4.4%, P = .001) and the SPTX (n = 9, 10.1%, P = .03) groups. Analysis of the recurrence-free time among the surgical groups revealed a significant difference (P = .036). The median time to recurrence was significantly shorter after SGE (101, range 3-301 months) than after SPTX (139, range 28-278 months, P = .018) and TPTX (204, range 75-396 months, P = .049). Twelve (32%) patients who underwent TPTX developed permanent hypoparathyroidism compared with only 4 (17%, P = .06) in the SPTX and 0 in the SGE group (P = .001). Conclusion Given the high rate of postoperative permanent hypoparathyroidism after TPTX and SPTX, SGE is a valid option for the treatment of MEN1-associated pHPT.

Prophylactic central neck dissection in patients with papillary thyroid carcinoma is controversial. Sentinel node biopsy might be an adjunct to optimize surgical treatment for these patients. Earlier studies reported inconsistent detection rates and diagnostic value of this technique, and the role of sentinel lymph node biopsy in thyroid cancer needs to be established. During a single-center prospective interventional study between 2010 and 2017, sentinel lymph node biopsy using 99mTc-nanocolloidal albumin tracer was performed on patients undergoing thyroid surgery for suspected thyroid cancer by fine needle aspiration cytology. All eligible patients without clinical lymph node involvement were invited to participate. Central neck dissection was performed on all patients after the detection of sentinel lymph nodes. Ninety-six patients participated in the study. The detection rates of the sentinel node were 67% and 45% by scintigraphy and intraoperative gamma probe, respectively. The detection rate was not associated with Bethesda score, malignancy, or presence of lymph node metastases. Sensitivity, negative predictive value, and accuracy were 80%, 97%, and 98%, respectively, for the sentinel node to represent the status of lymph node metastasis in the central neck compartment. The false negative rate was 20%. Sentinel lymph node biopsy had a low detection rate and only moderate sensitivity in patients with suspected thyroid carcinoma and is not a useful adjunct to surgery in the context of current treatment concepts.

OBJECTIVES Aortopathy in tetralogy of Fallot (TOF) is characterized by increased aortic stiffness, dilation and reduced left ventricular (LV) function. Repair in infancy normalizes aortic dimensions in early childhood. Our prior work demonstrated that early TOF repair does not normalize aortic compliance and that abnormal ascending aortic flow patterns are prevalent. The objectives of this study were to: (i) determine whether proximal aortic flow-mediated viscous energy loss (EL′) is elevated in patients with early TOF repair compared with healthy controls, and (ii) determine whether the degree of EL′ is associated with LV function. METHODS Forty-one patients post TOF repair with normalized aortic size and 15 healthy controls underwent 4-dimenisonal-flow magnetic resonance imaging flow analysis and EL′ assessment. Correlations between EL′, aortic size, and LV function were assessed. RESULTS The TOF group had increased peak systolic thoracic aorta EL′ (3.8 vs 1.5 mW, P = 0.004) and increased averaged EL′ throughout the cardiac cycle (1.2 vs 0.5 mW, P = 0.003). Peak and mean systolic EL′ in the ascending aorta was increased 2-fold in the TOF group compared with control (peak: 2.0 vs 0.9 mW, P = 0.007). Peak EL′ measured along the entire thoracic aortic length correlated with LV ejection fraction (R = −0.45, P = 0.009), indexed LV end-systolic volume (R = −0.40, P = 0.010), and right ventricular end-systolic volume (R = −0.37, P = 0.034). CONCLUSIONS Patients with repaired TOF exhibit abnormal aortic flow associated with increased EL′ in the thoracic aorta. The magnitude of EL′ is associated with LV function and volumes. Increased aortic EL′ in TOF is likely due to inherently abnormal LV outflow geometry and or right ventricular interaction. Reduced aortic flow efficiency in TOF increases cardiac work and may be an important factor in long-term cardiac performance.

Background Bovine jugular vein (BJV) conduits are commonly used for pulmonary valve replacement in pediatric patients. They are available in supported (sBJV) and unsupported (uBJV) versions. The purpose of this study was to compare outcomes of sBJV and uBJV conduits. Methods In this single-center retrospective review of patients younger than 18 years undergoing BJV placement (2009 to 2017), blinded cardiologists reviewed postoperative 6-, 12-, 24-, 36-month, and the most recent echocardiogram before any valve-related event or death. Outcomes assessed included conduit stenosis (m/s), regurgitation (none to mild vs moderate to severe) and right ventricular function (normal vs abnormal). Cox proportional models and Kaplan-Meier analyses were performed. Results BJV conduits (N = 109) were placed (39 supported, 70 unsupported) in 101 patients. Patient characteristics and conduit size were not different between cohorts. sBJV had more stenosis at 6 and 12 months (p = 0.02 and p = 0.03), but Vmax in both groups was mild (≤2 m/s). A greater proportion of uBJV had moderate to severe regurgitation at 12 months compared with sBJV (p = 0.03). Right ventricular function did not differ at any time point. On last follow-up echocardiogram, sBJV conduits had higher gradients (p = 0.01). This was not associated with increased intervention or replacement. Freedom from replacement or intervention did not differ between valve types (median follow-up, 3.6 years). There was a 9% incidence of endocarditis at median follow-up 2.4 years. Seventy percent of cases with endocarditis were managed medically. Conclusions There were no clinically significant echocardiographic or outcome differences between sBJV and uBJV conduits. We identified a relatively high incidence of endocarditis, which is consistent with prior reports.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Recent studies of anesthetic-induced unconsciousness in healthy volunteers have focused on functional brain connectivity patterns, but the protocols rarely parallel the depth and duration of surgical anesthesia. Furthermore, it is unknown whether there is a single functional connectivity pattern that correlates with general anesthesia for the duration of prolonged anesthetic exposure. Methods The authors analyzed electroencephalographic data in 30 healthy participants who underwent induction of anesthesia with propofol followed by 3 h of isoflurane anesthesia at age-adjusted 1.3 minimum alveolar concentration. Functional connectivity was assessed by frequency-resolved weighted phase lag index between frontal and parietal channels and between prefrontal and frontal channels, which were classified into a discrete set of states through k-means cluster analysis. Temporal dynamics were evaluated by the occurrence rate and dwell time distribution for each state as well as the transition probabilities between states. Results Burst suppression was present, with mean suppression ratio reducing from 44.8 ± 32.3% to 14.0 ± 20.2% (mean ± SD) during isoflurane anesthesia (P < 0.001). Aside from burst suppression, eight connectivity states were classified by optimizing the reproducibility of clustering solutions, with each characterized by distinct properties. The temporal progression of dominant states revealed a successive shifting trajectory from the state associated with alpha frontal-parietal connectivity to those associated with delta and alpha prefrontal-frontal connectivity during induction, which was reversed during emergence. Cortical connectivity was dynamic during maintenance period, and it was more probable to remain in the same state (82.0 ± 8.3%) than to switch to a different state (P < 0.001). However, transitions to other states were structured, i.e., occurred more frequently than expected by chance. Conclusions Anesthesia-induced alterations of functional connectivity are dynamic despite the stable and prolonged administration of isoflurane, in the absence of any noxious stimuli. Changes in connectivity over time will likely yield more information as a marker or mechanism of surgical anesthesia than any single pattern.

Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults ( n = 10) and children ( n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult ( n = 10) and pediatric ( n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSSmax) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (EL) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSSmax was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSSmax was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average EL was increased in adult patients with PAH when compared with the same age group along both MPA-RPA ( P = 0.020) and MPA-LPA ( P = 0.025) tracts. There were no differences in EL indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.

We report a case of a 23-year-old male with failing Fontan circulation who was taken to the catheterization lab to better evaluate the Fontan circulation and hemodynamics. Catheterization revealed arteriovenous malformations exclusively present in the right lung leading to the consideration of placing stents to direct the inferior vena cava flow through the Fontan circuit to the right pulmonary artery (RPA), thus increasing the RPA concentration of the hepatic factor. However, comprehensive 4D-Flow MRI analyses indicated sufficient distribution of the hepatic flow between branch pulmonary arteries, and consequently no further invasive intervention to redirect hepatic flow was performed.

Visual Abstract, Highlights • Mitochondrial function is impaired in explanted failing pediatric and adult human hearts. • Elamipretide is a novel mitochondria-targeted drug that is targeted to cardiolipin on the inner mitochondrial membrane and improves coupling of the electron transport chain. • Treatment of explanted human hearts with elamipretide improves human cardiac mitochondrial function. • The study provides novel methods to evaluate the influence of compounds on mitochondria in the human heart and provides proof of principle for the use of elamipretide to improve mitochondrial energetics in failing myocardium due to multiple etiologies and irrespective of age., Summary Negative alterations of mitochondria are known to occur in heart failure (HF). This study investigated the novel mitochondrial-targeted therapeutic agent elamipretide on mitochondrial and supercomplex function in failing human hearts ex vivo. Freshly explanted failing and nonfailing ventricular tissue from children and adults was treated with elamipretide. Mitochondrial oxygen flux, complex (C) I and CIV activities, and in-gel activity of supercomplex assembly were measured. Mitochondrial function was impaired in the failing human heart, and mitochondrial oxygen flux, CI and CIV activities, and supercomplex-associated CIV activity significantly improved in response to elamipretide treatment. Elamipretide significantly improved failing human mitochondrial function.

The question of how general anesthetics suppress consciousness has persisted since the mid-19th century, but it is only relatively recently that the field has turned its focus to a systematic understanding of emergence. Once assumed to be a purely passive process, spontaneously occurring as residual levels of anesthetics dwindle below a critical value, emergence from general anesthesia has been reconsidered as an active and controllable process. Emergence is driven by mechanisms that can be distinct from entry to the anesthetized state. In this narrative review, we focus on the burgeoning scientific understanding of anesthetic emergence, summarizing current knowledge of the neurotransmitter, neuromodulators, and neuronal groups that prime the brain as it prepares for its journey back from oblivion. We also review evidence for possible strategies that may actively bias the brain back toward the wakeful state.

Elastic properties of the thoracic aorta are responsible for buffering systemic afterload, and may be particularly important in patients with Fontan circulation, in whom heart failure is a major source of attrition. The purpose of this study was to characterize regional stiffness in the ascending and descending aorta in patients with hypoplastic left heart syndrome and single left ventricle morphology after Fontan operation by cardiac magnetic resonance imaging, and to assess whether changes in aortic stiffness are associated with the ventricular function.Phase-contrast-derived pulse-wave velocity (PWV) and relative-area change (RAC) were measured in the ascending and descending aorta of patients with hypoplastic left heart syndrome (n = 9), patients with single left ventricle circulation (n = 18), and normal controls (n = 8) by magnetic resonance imaging. Stiffness metrics were then correlated with the ventricular volumetric and functional indices.Patients with hypoplastic left heart syndrome had elevated ascending aortic PWV along with reduced RAC when compared with controls (both P values .001). Patients with a single left ventricle presented no change in PWV but had reduced RAC in comparison to controls (P .01). There were no differences in PWV and RAC between all considered groups in the descending aorta. PWV and RAC measured in the ascending aorta correlated with end-systolic and end-diastolic volume indices, ventricular ejection fraction, and ventricular-vascular coupling ratio.Aortic stiffness is most elevated in patients with hypoplastic left heart syndrome, yet patients with single left ventricle morphology show signs of abnormal stiffness as well in the form of reduced aortic strain. Stiffness indices measured in the ascending aorta were associated with overall ventricular function and measures of aortoventricular coupling in both patient populations.

Long-acting synthetic somatostatin analogues (SSA) are an essential part of the treatment of neuroendocrine neoplasms. We evaluated the chemopreventive effects of a long-acting somatostatin analogue on the development of pancreatic neuroendocrine neoplasms (pNENs) in a genetically engineered MEN1 knockout mouse model. Heterozygote MEN1 knockout mice were injected every 28 days subcutaneously with the somatostatin analogue lanreotide (Somatuline Autogel©; Ipsen Pharma) or a placebo starting at day 35 after birth. Mice were euthanized after 6, 9, 12, 15 and 18 months, and the size and number of pNENs were measured due histological analysis and compared to the placebo group. The median tumor size of pNENs was statistically significantly smaller after 9 (control group vs. SSA group; 706.476 µm2 vs. 195.271 µm2; p = 0.0012), 12 (placebo group vs. SSA group 822.022 vs. 255.482; p ≤ 0.001), 15 (placebo group vs. SSA group 1192.568 vs. 273.533; p ≤ 0.001) and after 18 months (placebo group vs. SSA group 1328.299 vs. 864.587; p ≤ 0.001) in the SSA group. Comparing the amount of tumors in both groups, a significant reduction was achieved in treated Men1(+/−) mice (41%, p = 0.002). Immunostaining showed, however, no significant difference in the expression of the apoptosis marker caspase-3, but a significant difference in Ki67 index as a marker for tumor cell proliferation (p ≤ 0.005). Long-acting somatostatin analogues may be an effective chemopreventive approach to delay the progression of MEN1-associated pNENs. After our preclinical results, we would recommend to evaluate the effects of long-acting SSA in a prospective clinical trial.

Objective The reversed Potts shunt is an increasingly applied mode of surgical palliation of severe pulmonary hypertension (PH). However, the long-term flow hemodynamic effect of the Potts shunt physiology and desirable long-term hemodynamic end-points are not defined. The purpose of this descriptive study was to analyze a series of pediatric patients who underwent surgical Potts shunt as a part of end-stage PH palliation using 4D-Flow MRI to 1) quantitate the flow through the anastomosis, 2) correlate the shunting pattern with phases of cardiac cycle and PH comorbidities, and 3) describe chronologic changes in shunting pattern. Methods This was a two-center study evaluating four patients seen by the Pulmonary Hypertension Clinic at Children’s Hospital Colorado who were evaluated and selected to undergo surgical reverse Potts shunt at Washington University School of Medicine and were serially followed using comprehensive imaging including cardiac MRI and 4D-Flow MRI. Results Post procedure each child underwent two 4D-Flow MRI evaluations. Pulmonary pressure offload was evident in all patients as demonstrated by positive systolic right-to-left flow across the Potts shunt. All patients experienced some degree of the flow reversal which occurs primarily in diastole. Interventricular dyssynchrony further contributed to flow reversal across the Potts shunt. Lastly, systemic and pulmonary blood mixing in the descending aorta results in secondary helical flow persisting throughout the diastole. Conclusions 4D-Flow MRI demonstrates that children who have undergone a Potts shunt for severe PH can experience shunt flow reversal. Cumulatively this left-to-right pulmonary shunt adds to RV volume overload. We speculate that a valved conduit may decrease the left to right shunting and improve overall cardiac output.

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, just prior to the recovery of consciousness, frontal-parietal dynamics returned to baseline. Consistent with our hypothesis, cognitive reconstitution after anesthesia evolved over time. Contrary to our hypothesis, executive function returned first. Early engagement of prefrontal cortex in recovery of consciousness and cognition is consistent with global neuronal workspace theory., eLife digest Anesthesia is a state of reversable, controlled unconsciousness. It has enabled countless medical procedures. But it also serves as a tool for scientists to study how the brain regains consciousness after disruptions such as sleep, coma or medical procedures requiring general anesthesia. It is still unclear how exactly the brain regains consciousness, and less so, why some patients do not recover normally after general anesthesia or fail to recover from brain injury. To find out more, Mashour et al. studied the patterns of reemerging consciousness and cognitive function in 30 healthy adults who underwent general anesthesia for three hours. While the volunteers were under anesthesia, their brain activity was measured with an EEG; and their sleep-wake activity was measured before and after the experiment. Each participant took part in a series of cognitive tests designed to measure the reaction speed, memory and other functions before receiving anesthesia, right after the return of consciousness, and then every 30 minutes thereafter. Thirty healthy volunteers who did not have anesthesia also completed the scans and tests as a comparison group. The experiments showed that certain normal EEG patterns resumed just before a person wakes up from anesthesia. The return of thinking abilities was an extended, multistep process, but volunteers recovered their cognitive abilities to nearly the same level as the volunteers within three hours of being deeply anesthetized. Mashour et al. also unexpectedly found that abstract problem-solving resumes early in the process, while other functions such as reaction time and attention took longer to recover. This makes sense from an evolutionary perspective. Sleep leaves individuals vulnerable. Quick evaluation and decision-making skills would be key to respond to a threat upon waking. The experiments confirm that the front of the brain, which handles thinking and decision-making, was especially active around the time of recovery. This suggests that therapies targeting this part of the brain may help people who experience loss of consciousness after a brain injury or have difficulties waking up after anesthesia. Moreover, disorders of cognition, such as delirium, in the days following surgery may be caused by factors other than the lingering effects of anesthetic drugs on the brain.

Background Pulmonary arterial hypertension (PAH) manifests with progressive right ventricular (RV) dysfunction, which eventually impairs the left ventricular function. We hypothesized that 4‐dimensional–flow magnetic resonance imaging can detect flow hemodynamic changes associated with efficient intracardiac flow during noninvasive inhaled nitric oxide (iNO) challenge in children with PAH. Methods and Results Children with PAH (n=10) underwent 2 same‐day separate iNO challenge tests using: (1) 4‐dimensional–flow magnetic resonance imaging and (2) standard catheterization hemodynamics. Intracardiac flow was evaluated using the particle tracking 4‐flow component analysis technique evaluating the direct flow , retained inflow , delayed ejection flow , and residual volume . Respective flow hemodynamic changes were compared with the corresponding catheterization iNO challenge results. The RV analysis revealed decreased direct flow in patients with PAH when compared with controls ( P P P =0.004) and increased proportion of the residual volume ( P =0.014). There was an increase in the RV direct flow during iNO delivery ( P =0.009), with parallel decrease in the residual volume ( P =0.008). Conclusions Children with PAH have abnormal biventricular flow associated with impaired diastolic filling. The flow efficiency is significantly improved in the RV on iNO administration with no change in the left ventricle. The changes in the RV flow have occurred despite the minimal change in catheterization hemodynamics, suggesting that flow hemodynamic evaluation might provide more quantitative insights into vasoreactivity testing in PAH.

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were recorded before, during, and after anesthetic-induced unconsciousness, at the following time points: Baseline; light sedation with propofol (Light Sedation); deep unconsciousness following three hours of surgical levels of anesthesia with isoflurane (Unconscious); five minutes prior to the recovery of consciousness (Pre-ROC); and three hours following the recovery of consciousness (Recovery). Support vector machine classification was applied to the source-localized EEG in the alpha (8–13 Hz) frequency band in order to investigate the ability of AEC and wPLI (separately and together) to discriminate i) the four states from Baseline; ii) Unconscious (“deep” unconsciousness) vs. Pre-ROC (“light” unconsciousness); and iii) responsiveness (Baseline, Light Sedation, Recovery) vs. unresponsiveness (Unconscious, Pre-ROC). AEC and wPLI yielded different patterns of global connectivity across states of consciousness, with AEC showing the strongest network connectivity during the Unconscious epoch, and wPLI showing the strongest connectivity during full consciousness (i.e., Baseline and Recovery). Both measures also demonstrated differential predictive contributions across participants and used different brain regions for classification. AEC showed higher classification accuracy overall, particularly for distinguishing anesthetic-induced unconsciousness from Baseline (83.7 ± 0.8%). AEC also showed stronger classification accuracy than wPLI when distinguishing Unconscious from Pre-ROC (i.e., “deep” from “light” unconsciousness) (AEC: 66.3 ± 1.2%; wPLI: 56.2 ± 1.3%), and when distinguishing between responsiveness and unresponsiveness (AEC: 76.0 ± 1.3%; wPLI: 63.6 ± 1.8%). Classification accuracy was not improved compared to AEC when both AEC and wPLI were combined. This analysis of source-localized EEG data demonstrates that envelope- and phase-based FC provide different information about states of consciousness but that, on a group level, AEC is better able to detect relative alterations in brain FC across levels of anesthetic-induced unconsciousness compared to wPLI.

Apert syndrome is a form of acrocephalosyndactyly involving craniosynostosis, syndactyly, and less commonly tracheal cartilaginous sleeve (TCS), a potential cause of tracheal stenosis. Slide tracheoplasty is performed in children with tracheal stenosis. No reports exist for its application in stenosis related to TCS. We present a case in which slide tracheoplasty was utilized for expansion of long segment tracheal stenosis due to TCS in a newborn with Apert syndrome. Using this technique, a safe and durable airway was achieved without tracheostomy.

Objective This study used cardiac magnetic resonance imaging to evaluate flow characteristics and ventricular hemodynamics for children with single right (hypoplastic left heart syndrome) and single left (hypoplastic right heart syndrome) systemic ventricle anatomy after Fontan palliation compared with normal biventricular controls. Methods Twenty children with single ventricle anatomy (hypoplastic left heart syndrome, n = 10; hypoplastic right heart syndrome, n = 10) underwent standardized 4-dimensional flow cardiac magnetic resonance and were compared with age-matched controls (n = 10). End-diastolic volume was partitioned into 4 defined components of variable kinetic energy (direct flow, retained inflow, delayed ejection, and residual volume) and compared between groups. Further, volumetric and functional parameters as defined by cardiac magnetic resonance were evaluated. Results Children with hypoplastic left heart syndrome had significantly increased indexed end-diastolic and end-systolic volumes compared with both hypoplastic right heart syndrome and control groups. Flow component analysis demonstrated diastolic inefficiency in both hypoplastic left heart syndrome and hypoplastic right heart syndrome groups compared with controls as defined by decreased direct flow and increased residual volumes. Decreased direct flow correlated with decreased ejection fraction and increased end-diastolic and end-systolic volume indices. Increased residual volume correlated with decreased ejection fraction and increased end-systolic volume index. Conclusions Fontan-palliated patients with single ventricle physiology (hypoplastic left heart syndrome and hypoplastic right heart syndrome) demonstrate altered and inefficient flow patterns in the systemic ventricle as defined by 4-dimensional flow cardiac magnetic resonance compared with normal biventricular controls. Decreased direct flow and increased residual volume indicate that diastolic ventricular dysfunction is prevalent after Fontan palliation. This study provides a foundation for future predictive modeling and cardiac magnetic resonance flow diagnostic studies in this high-risk patient population.

Having a concentrated stock or other ownership position is common for corporate executives, offering many potential rewards but also substantial risks. The “right” stock can be a significant wealth creator, but concentrating in a single position can become a wealth destroyer. There are many disciplines and techniques that should be considered to address the risks of concentration, though each has its advantages and disadvantages. A gradual diversification strategy often works best, though factors such as taxes, risk tolerance, time horizon, and legal restrictions must be considered. Various tax-reduction strategies are available to manage the tax costs of any sales. There are also several hedging strategies that should be considered, along with the potential use of exchange funds or charitable vehicles.

In broad terms, insurance is a form of risk management. While there are myriad types of insurable risks, the authors focus on those personal risks that most commonly can disrupt or devastate individual and, by extension, family financial planning. Those risks are associated with health, life, property, and personal liability for negligent acts or omissions. The authors discuss key concepts and definitions related to insurance and then explore how best to analyze and utilize the following forms of insurance: health insurance, including through COBRA; disability insurance; life insurance, including term insurance and permanent insurance; long-term-care insurance; and property and casualty insurance, including personal excess liability and umbrella insurance.

People like David and Abby often overlook estate planning because they tend to believe in one of two myths: (1) estate planning is all about taxes, and therefore, it’s only for the ultra-wealthy or (2) estate planning is all about what happens to your stuff after you die, so it’s only important for older or sick people. The main objectives of estate planning are welfare planning, income continuity, orderly distribution of estate property, tax mitigation, asset protection, beneficiary security, and philanthropy. The essentials of effective estate planning include addressing the need for: powers of attorney; living wills and healthcare proxies; HIPAA authorizations; insurance; proper titling of assets and beneficiary designations; lifetime gifts; wills; and trusts. Taxes must also be considered, including the estate tax, gift tax, and generation-skipping-transfer (GST) tax. Select estate-planning strategies and a sample plan to mitigate these taxes and achieve other goals are explored.

Achieving financial independence starts with a dispassionate, objective census of all resources, assets, opportunities, risks, and liabilities. The key to this exercise is the personal definition of one’s own goals, such as housing security, education, and retirement. Asset accumulation is relegated to a utilitarian role, as a marker of progress. Key assumptions must be made regarding: future income sources; future expenses; liabilities; inflation of expenses; and growth of investments. An actionable financial plan should be memorialized in writing and should be accompanied by supporting documents, including a balance sheet, stock-plan schedules, and a cash-flow plan. Monte Carlo analysis can offer a stress test on a straight-line cash-flow plan, but persistent monitoring and review are necessary to ensure that progress toward financial independence is not derailed.

Through careful, advance planning, taxes can be minimized, and the burden of taxation can be satisfied. When done right, tax planning is a broad-based, continuous, and dynamic process. David, Abby, and other executives and entrepreneurs should follow the “Ten Commandments of Tax Planning” to optimize their after-tax results: optimize the deferral of income; maximize and accelerate deductions and credits; plan for tax withholding and estimated taxes; coordinate debt and taxes; understand and plan for the difference between ordinary income and capital gains; maximize the after-tax value of home ownership; consider taxes when making investment decisions; take advantage of tax-advantaged ways to pay for education; beware of all types of income-based taxes, including employment taxes; and maintain good tax hygiene.

Given how things worked out, David should have spent more time understanding, discussing, and even negotiating his employment agreement with Goliath. The authors use the story of David and Goliath to highlight the importance of a strong, balanced employment agreement in maximizing the rewards of being a corporate executive. They consider the many ways to address provisions that are nearly universal in all agreements, including: the scope and nature of the employment relationship; title, duties, and responsibilities; reporting structure; exclusivity; fixed and incentive compensation; equity incentives and participation; employee benefits; term, termination, and severance; assignment and changes of control; restrictive covenants; reimbursement of expenses; restrictions on liability; ownership of intellectual and other property; and applicable law and dispute resolution.

Effective charitable giving involves far more than just donating money. There are tax, legal, and personal considerations that need to be assessed. There are five key elements to charitable gifting for every donor: establishing a budget; becoming familiar with the basic income tax rules; selecting the most tax-efficient assets to give; choosing how to make the gift; and making an impact. The authors consider the tax rules surrounding philanthropy and consider techniques that include donating appreciated assets as well as using donor-advised funds, gift annuities, charitable remainder trusts, charitable lead trusts, and private foundations. The authors also consider how donors can ensure that their funds are going to organizations that will use their gifts most effectively while also creating a family legacy.