Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients.

A stage I non-small cell lung cancer (NSCLC) serum profiling platform is presented which is highly efficient and accurate. Test sensitivity (0.95) for stage I NSCLC is the highest reported so far. Test metrics are reported for discriminating stage I adenocarcinoma vs squamous cell carcinoma subtypes. Blinded analysis identified 23 out of 24 stage I NSCLC and control serum samples. Group-discriminating mass peaks were targeted for tandem mass spectrometry peptide/protein identification, and yielded a lung cancer phenotype. Bioinformatic analysis revealed a novel lymphocyte adhesion pathway involved with early-stage lung cancer.

Heme oxygenase derived carbon monoxide and iron mediated plasmatic hypercoagulability in a patient with calcific mitral valve disease.

We present a case of a patient with calcific mitral valve stenosis and plasmatic hypercoagulability. Using thrombelastography, the patient was determined to have an abnormally large velocity of plasma thrombus growth and strength with reduced vulnerability to lysis. Critically, increased carboxyhemoglobin concentration (2.4 %) was present, likely secondary to hemolysis from mitral stenosis and engagement of systemic heme oxygenase. It was determined that the patient's plasmatic hypercoagulability was in part due to carboxyhemefibrinogen formation and iron-enhancement of coagulation via two thrombelastographic methods. In conclusion, future investigation of the involvement of both carbon monoxide and iron mediated hypercoagulability in the setting of stenotic valve disease is warranted.

Construction of a reusable, high-fidelity model to enhance extracorporeal membrane oxygenation training through simulation.

Initiation of extracorporeal membrane oxygenation (ECMO) is stressful, especially for inexperienced extracorporeal life support providers. The main objective of this study was to create a novel, reusable mannequin for high-fidelity simulation of ECMO initiation. We modified a Laerdal neonatal mannequin (SimNewB; Stavanger, Norway) so that it could be used to simulate an ECMO initiation. A simulation of a neonatal patient suffering from meconium aspiration was performed in the pediatric intensive care unit, and participants included new extracorporeal life support specialists in addition to the composition of the clinical ECMO team. A total of 17 individuals participated in the neonatal ECMO initiation simulation. Questionnaire results showed that 88% of participants felt better prepared to assist in an ECMO initiation after the simulation. All participants (100%) agreed that the modified mannequin and the environment were realistic and that this simulation helps teamwork and communication in future initiations of ECMO. Simulation can be used for the prevention, identification, and reduction of anxiety-related crisis situations that novice providers may infrequently encounter during routine clinical use of mechanical circulatory support. Use of a reusable, high-fidelity mannequin may be beneficial for effective team training of complex pediatric ECMO-related procedures.

Histotaphonomic analysis of bone bioerosion reveals a regional framework of diverse deathways in the Neolithic of Southeast Italy.

The wide diversity of Neolithic funerary practices is increasingly recognised. In Southeast Italy, recent studies have drawn attention to the co-existence of multiple ways of treating the dead within single sites and across the region. In this study, we address how such diverse deathways form a regional framework of ritual practice through histotaphonomic analysis of bone bioerosion. Samples were obtained from articulated, semi-articulated and disarticulated remains from four sites in Apulia which each presented different modes of treatment and disposal of the dead. Bone thin sections were analysed by light microscopy to characterise microstructural preservation through features including bacterial bioerosion, staining, inclusions, and Wedl tunnelling. We investigate the early post-mortem histories of individuals whose remains ended up in various states of dis/articulation and diverse depositional contexts. Disarticulated remains frequently displayed arrested or extensive bacterial bioerosion, which was also found in articulated and semi-articulated skeletons. Additionally, remains deposited in similar contexts, as well as articulated and disarticulated remains deposited together in the same context, often showed different histotaphonomic characteristics, suggesting diverse early post-mortem trajectories. As a result, we argue that Neolithic deathways in southeastern Italy incorporated a high level of diversity in the early post-mortem treatment of the body. A framework for funerary practices emerges, whereby disarticulated remains probably originated from bodies which had been buried previously and subjected to varying extents of shelter, exposure to invertebrates, and duration of burial. However, we acknowledge the ongoing research into the origins of bacterial bioerosion and the problem of equifinality, which leaves open the possibility for further scenarios of early post-mortem treatment.

Straightened sternal wire causes iatrogenic pectus carinatum after cardiac surgery.

Pectus carinatum is a protrusion deformity of the anterior chest wall that is most likely caused by a disproportionate growth of the costal cartilages compared with the remainder of the thoracic skeleton. A young boy had previously undergone corrective congenital heart operation, after which a prominent sternal protrusion was noted. During the past year, the protrusion had greatly increased in size and had become recurrently infected. Chest X-ray showed that a sternal wire, the ends of which were pointing toward the skin, had straightened. Operative intervention included removal of the offending wire, draining a chronic abscess, and shaving the protruding sternum so that it conformed to the rest of the sternum.

Retrospective study assessing outcomes in cardiac surgery after implementation of Quantra.

BACKGROUND: The Quantra QPlus System is a cartridge-based device with a unique ultrasound technology that can measure the viscoelastic properties of whole blood during coagulation. These viscoelastic properties correlate directly with hemostatic function. The primary objective of this study was to assess blood product utilization in cardiac surgery patients before and after the implementation of the Quantra QPlus System. METHODS: Yavapai Regional Medical Center implemented the Quantra QPlus System to aid in their efforts to reduce the transfusion of allogenic blood products and improve outcomes in patients undergoing cardiac surgery. A total of 64 patients were enrolled prior to the utilization of the Quantra (pre-Quantra cohort), and 64 patients were enrolled after (post-Quantra cohort). The pre-Quantra cohort had been managed via standard laboratory assays along with physician discretion for transfusion decisions. The utilization of blood products and frequency of transfusions were compared and analyzed between the two cohorts. (using the Student's t-test) RESULTS: The implementation of the Quantra resulted in a change in the pattern of blood product utilization leading to a demonstrated decrease in the amount of blood products transfused and the associated costs. The amount of FFP transfused was significantly decreased by 97% (P = 0.0004), whereas cryoprecipitate decreased by 67% (P = 0.3134), platelets decreased by 26% (P = 0.4879), and packed red blood cells decreased by 10% (P = 0.8027) however these trends did not reach statistical significance. The acquisition cost of blood products decreased by 41% for total savings of roughly $40,682. CONCLUSIONS: Use of the Quantra QPlus System has the potential to improve patient blood management and decrease costs. STUDY REGISTERED AT CLINICALTRIALS.GOV: NCT05501730.

Ancient Maltese genomes and the genetic geography of Neolithic Europe.

Archaeological consideration of maritime connectivity has ranged from a biogeographical perspective that considers the sea as a barrier to a view of seaways as ancient highways that facilitate exchange. Our results illustrate the former. We report three Late Neolithic human genomes from the Mediterranean island of Malta that are markedly enriched for runs of homozygosity, indicating inbreeding in their ancestry and an effective population size of only hundreds, a striking illustration of maritime isolation in this agricultural society. In the Late Neolithic, communities across mainland Europe experienced a resurgence of hunter-gatherer ancestry, pointing toward the persistence of different ancestral strands that subsequently admixed. This is absent in the Maltese genomes, giving a further indication of their genomic insularity. Imputation of genome-wide genotypes in our new and 258 published ancient individuals allowed shared identity-by-descent segment analysis, giving a fine-grained genetic geography of Neolithic Europe. This highlights the differentiating effects of seafaring Mediterranean expansion and also island colonization, including that of Ireland, Britain, and Orkney. These maritime effects contrast profoundly with a lack of migratory barriers in the establishment of Central European farming populations from Anatolia and the Balkans.

Congenital Cardiothoracic Surgeons and Palliative Care: A National Survey Study.

BACKGROUND: The majority of children with advanced heart disease in the inpatient setting die in an intensive care unit under 1 year of age following multiple interventions. While pediatric cardiology and palliative care provider attitudes have been described, little is known about pediatric cardiothoracic surgeon attitudes toward palliative care in children with advanced heart disease. OBJECTIVE: To describe perspectives of pediatric cardiothoracic surgeons regarding palliative care in pediatric heart disease. DESIGN: Cross-sectional web-based national survey. RESULTS: Of the 220 surgeons who were e-mailed the survey, 36 opened the survey and 5 did not meet inclusion criteria (n = 31). Median years of practice was 23.5 (range: 12-41 years), and 87.1% were male. Almost all (90%) reported that they had experience consulting palliative care. While 68% felt palliative care consultation was initiated at the appropriate time, 29% felt it occurred too late. When asked the appropriate timing for palliative care consultation in hypoplastic left heart syndrome, 45% selected "at time of prenatal diagnosis" and 30% selected "when surgical and transcatheter options have been exhausted." Common barriers to palliative care involvement included the perception of "giving up" (40%) and concern for undermining parental hope (36%). CONCLUSIONS: While a majority of pediatric cardiothoracic surgeons are familiar with palliative care, there is variation in perception of appropriate timing of consultation. Significant barriers to consultation still exist, including concern that parents will think they are "giving" up, undermining parental hope, and influence of palliative care on the medical care team's approach.

Language Barriers and Timely Analgesia for Long Bone Fractures in a Pediatric Emergency Department.

INTRODUCTION: Long bone fractures are common painful conditions often managed in the pediatric emergency department (PED). Delay to providing effective pediatric pain management is multifactorial. There is limited information regarding how the issue of language spoken impacts the provision of adequate and timely institution of analgesia. We sought to determine whether there is a difference between English-speaking and non-English speaking patients with respect to time to pain management for long bone fractures in a multi-ethnic urban PED. METHODS: We conducted a retrospective cohort study of consecutive cases over 29 months of children <18 years old who presented to the PED with a first-time long bone fracture. A correlation of multiple clinical variables with timeliness to providing analgesia as a primary outcome was determined. We performed regression analysis to eliminate confounding and to determine the magnitude of each variable's effect on the outcome. RESULTS: We analyzed a total of 753 patient cases (power 0.95). Regression analysis showed that the variable of English vs non-English language spoken was the most significant predictor of timeliness to pain management (p < 0.001). There was a significant difference in median time to triage measurement of pain score (1 minute vs 4 minutes for English vs non-English speakers [p < 0.001]); median time to initial analgesia (4 minutes vs 13 minutes for English vs non-English speakers (p < 0.001]); and median time to opioid analgesia (32 minutes vs 115 minutes for English vs non-English speakers (p < 0.001]), respectively. All measurements of time were from the creation of a patient's electronic health record. Just 30% of all patients received an opioid analgesic for treatment of long bone fractures, including only 37% with moderate triage pain scores. CONCLUSION: Delay to receiving analgesic medications in pediatric patients with long bone fractures can be augmented by language barriers. Time to providing analgesia for long bone fractures is significantly delayed in non-English speaking families, contributing to disproportionate care in the PED. Furthermore, use of opioid analgesia for fractures in children remains poor.

Clinical and Laboratory Predictors for the Development of Low Cardiac Output Syndrome in Infants Undergoing Cardiopulmonary Bypass: A Pilot Study.

Cardiac surgery employing cardiopulmonary bypass exposes infants to a high risk of morbidity and mortality. The objective of this study was to assess the utility of clinical and laboratory variables to predict the development of low cardiac output syndrome, a frequent complication following cardiac surgery in infants. We performed a prospective observational study in the pediatric cardiovascular ICU in an academic children's hospital. Thirty-one patients with congenital heart disease were included. Serum levels of nucleosomes and a panel of 20 cytokines were measured at six time points in the perioperative period. Cardiopulmonary bypass patients were characterized by increased levels of interleukin-10, -6, and -1α upon admission to the ICU compared to non-bypass cardiac patients. Patients developing low cardiac output syndrome endured longer aortic cross-clamp time and required greater inotropic support at 12 h postoperatively compared to bypass patients not developing the condition. Higher preoperative interleukin-10 levels and 24 h postoperative interleukin-8 levels were associated with low cardiac output syndrome. Receiver operating characteristic curve analysis demonstrated a moderate capability of aortic cross-clamp duration to predict low cardiac output syndrome but not IL-8. In conclusion, low cardiac output syndrome was best predicted in our patient population by the surgical metric of aortic cross-clamp duration.

Serum discrimination and phenotype assessment of coronary artery disease patents with and without type 2 diabetes prior to coronary artery bypass graft surgery.

Diabetes Mellitus (DM) accelerates coronary artery disease (CAD) and atherosclerosis, the causes of most heart attacks. The biomolecules involved in these inter-related disease processes are not well understood. This study analyzes biomolecules in the sera of patients with CAD, with and without type (T) 2DM, who are about to undergo coronary artery bypass graft (CABG) surgery. The goal is to develop methodology to help identify and monitor CAD patients with and without T2DM, in order to better understand these phenotypes and to glean relationships through analysis of serum biomolecules. Aorta, fat, muscle, and vein tissues from CAD T2DM patients display diabetic-related histologic changes (e.g., lipid accumulation, fibrosis, loss of cellularity) when compared to non-diabetic CAD patients. The patient discriminatory methodology utilized is serum biomolecule mass profiling. This mass spectrometry (MS) approach is able to distinguish the sera of a group of CAD patients from controls (p value 10-15), with the CAD group containing both T2DM and non-diabetic patients. This result indicates the T2DM phenotype does not interfere appreciably with the CAD determination versus control individuals. Sera from a group of T2DM CAD patients however are distinguishable from non-T2DM CAD patients (p value 10-8), indicating it may be possible to examine the T2DM phenotype within the CAD disease state with this MS methodology. The same serum samples used in the CAD T2DM versus non-T2DM binary group comparison were subjected to MS/MS peptide structure analysis to help identify potential biochemical and phenotypic changes associated with CAD and T2DM. Such peptide/protein identifications could lead to improved understanding of underlying mechanisms, additional biomarkers for discriminating and monitoring these disease conditions, and potential therapeutic targets. Bioinformatics/systems biology analysis of the peptide/protein changes associated with CAD and T2DM suggested cell pathways/systems affected include atherosclerosis, DM, fibrosis, lipogenesis, loss of cellularity (apoptosis), and inflammation.

Initial experience with dual antiplatelet thromboprophylaxis using clopidogrel and aspirin in patients with mechanical aortic prostheses.

BACKGROUND AND AIM OF THE STUDY: The aortic mechanical prosthesis (AMP) generates shear stress and causes erythrocyte fragmentation with ADP release that leads to platelet activation, the cause of thromboembolism. Thromboprophylaxis with the antiplatelet agents clopidogrel and aspirin (Clop-ASA) should reduce thromboembolic events in patients receiving an AMP. METHODS: Over an eight-year period at the authors' institutions, a total of 135 patients underwent aortic valve replacement (AVR), with or without concomitant thoracic aortic procedures, and received Clop-ASA as thromboprophylaxis. Platelet reactivity was measured using the Verify Now system. Thromboelastography was commenced in August 2006, and patients were followed at six-month intervals, with echocardiography and assessment of platelet reactivity. RESULTS: The total follow up was 4,776 months (equivalent to 398 patient-years (pt-yr)); the average follow up was 35.4 +/- 25 months. During follow up, 18 patients (13.3%) died, eight from coronary artery disease and three from valve-related causes. Five patients (3.7%; 1.2%/pt-yr) had bleeding complications, but none experienced valve thrombosis. Two patients (1.5%; 0.5%/pt-yr) had a transient ischemic attack (TIA); one of these occurred in a patient who discontinued Clop-ASA, and the other in a responder to Clop-ASA. Seven patients (5.2%; 1.7%/pt-yr) had strokes, one of which occurred at 48.5 months after AVR. Of the remaining six patients who had a stroke, one was a non-responder to clopidogrel and five had stopped taking Clop-ASA. The incidence of strokes before using the Accumetrics and TEG devices was 2.5% per pt-yr, but only 1.0% per pt-yr thereafter. CONCLUSION: Thromboprophylaxis in patients with AMP receiving Clop-ASA seems to be effective. Patients had a low incidence of bleeding, TIA and ischemic stroke, and no valve thrombosis. The use of assays to determine platelet reactivity helped to identify those patients who were resistant to clopidogrel, hyporesponders, and poorly compliant patients. Notably, the incidence of strokes after implementing assays to monitor platelet reactivity was reduced. Deaths were due primarily to myocardial infarction, and none of the deaths was anticoagulant-related. Patients receiving Clop-ASA should undergo routine testing of platelet reactivity, and also continue antiplatelet therapy so as to reduce the risk of ischemic stroke.

Right atrial myxoma presenting as a pulmonary embolism in a 32-year-old female.

Primary cardiac tumors are typically benign, with myxomas being most common. We present a 32-year-old female with a chief complaint of dyspnea and a constant non-radiating chest pressure along the left sternal border. She was found to have a pulmonary embolism that was ultimately caused by embolization of a right atrial myxoma with remnants of a large, highly mobile mass attached to the right inter-atrial septum prolapsing through the tricuspid valve. The patient underwent a median sternotomy, right atrial mass resection, pulmonary embolectomy, and inter-atrial septum reconstruction using the patient's pericardium. The importance of finding the etiology of initial diagnoses is stressed with long-term outcomes for patients.

Pediatric Ureteral Stent Placement to Manage Right Kidney Hemorrhage Following Coarctation Angioplasty.

This is the first case report of a catastrophic renal bleeding into the renal collecting system causing hemorrhagic shock in a child after a cardiac catheterization. In this case report, we discuss how we used nontraditional means of endourologic intervention in treating our hemodynamically unstable patient resulting in saving the patient's life and kidney.

Neonatal vocal fold motion impairment after complex aortic arch reconstruction: What should parents expect after diagnosis?

OBJECTIVES: To study the incidence, sequelae, follow up, and recovery rate of vocal fold motion impairment (VFMI) after complex aortic arch reconstruction in neonates. STUDY DESIGN: Retrospective case control study. METHODS: We retrospectively evaluated 105 neonates who underwent complex aortic arch reconstruction from 2014 to 2016. We compared patients that did have VFMI compared to a control group of patients with normal vocal fold movement. Descriptive statistics were computed for all demographic and clinical variables by treatment group. RESULTS: 36% of patients were evaluated for VFMI (n = 38) by an otolaryngologist. The incidence of VFMI was 22% (n = 23). Females were more likely to have VFMI (p = 0.02). Aspiration was more common in patients with VFMI (p = 0.006). The difference in age, weight, incidence of pneumonia, nasogastric tube, gastrostomy, total length of stay, genetic anomaly, and reintubation was not significant between the VFMI group and control group (p > 0.05). Tracheostomy was not performed in any patients with unilateral paralysis. Only 61% of patients followed up in clinic (n = 14). 64% of patients showed improvement or resolution (n = 9). Average time to improvement was 4.8 months. Average time to complete resolution was 10.5 months. CONCLUSIONS: VFMI after complex aortic arch reconstruction is relatively common. Despite increased aspiration in patients with VFMI, pneumonia did not occur at all in either group. Tracheostomy was not necessary in any patients with a unilateral paralysis. Most patients showed an improvement in the VFMI within 5 months of surgery. Our data support the need for otolaryngology follow-up after the diagnosis of VFMI.

Delaying Decannulation After Extracorporeal Membrane Oxygenation Is Safe and Advantageous.

Removal of extracorporeal membrane oxygenation (ECMO) cannulae and discontinuing systemic anticoagulation typically occurs soon after separation from ECMO. We have found, however, that delaying decannulation after terminating ECMO therapy does not predispose to adverse outcomes and may be advantageous. Between January 2014 and June 2016, 36 postcardiotomy patients at the Children's Hospital of Oklahoma required ECMO. In this cohort of 36 patients, there was a need for 42 ECMO runs. Of the 42 ECMO runs, 29 (69%) survived to decannulation. Of those ECMO runs that survived to decannulation, 18 (62%) were cannulated centrally and 11 (38%) were cannulated via the neck. For the runs where the patient survived to decannulation, the mean number of days on ECMO support was 4 ± 2 days. There was an average time interval of 21 ± 14 hours from ECMO termination to decannulation. A single patient failed being separated from ECMO support and required reinstitution of ECMO 18 hours after separation (but did not require recannulation).

Integration of Pediatric Palliative Care Into Cardiac Intensive Care: A Champion-Based Model.

Integration of pediatric palliative care (PPC) into management of children with serious illness and their families is endorsed as the standard of care. Despite this, timely referral to and integration of PPC into the traditionally cure-oriented cardiac ICU (CICU) remains variable. Despite dramatic declines in mortality in pediatric cardiac disease, key challenges confront the CICU community. Given increasing comorbidities, technological dependence, lengthy recurrent hospitalizations, and interventions risking significant morbidity, many patients in the CICU would benefit from PPC involvement across the illness trajectory. Current PPC delivery models have inherent disadvantages, insufficiently address the unique aspects of the CICU setting, place significant burden on subspecialty PPC teams, and fail to use CICU clinician skill sets. We therefore propose a novel conceptual framework for PPC-CICU integration based on literature review and expert interdisciplinary, multi-institutional consensus-building. This model uses interdisciplinary CICU-based champions who receive additional PPC training through courses and subspecialty rotations. PPC champions strengthen CICU PPC provision by (1) leading PPC-specific educational training of CICU staff; (2) liaising between CICU and PPC, improving use of support staff and encouraging earlier subspecialty PPC involvement in complex patients' management; and (3) developing and implementing quality improvement initiatives and CICU-specific PPC protocols. Our PPC-CICU integration model is designed for adaptability within institutional, cultural, financial, and logistic constraints, with potential applications in other pediatric settings, including ICUs. Although the PPC champion framework offers several unique advantages, barriers to implementation are anticipated and additional research is needed to investigate the model's feasibility, acceptability, and efficacy.

Advancing the Legislative Priorities of Cardiothoracic Surgeons: The Society of Thoracic Surgeons Political Action Committee.

In the late 1990s, several federal government health policy decisions threatened the viability of thoracic surgery as a specialty. To respond to such decisions, active participation in political processes was given extremely high priority by the Executive Committee of The Society of Thoracic Surgeons (STS). Creation of the STS Political Action Committee (STS-PAC) in 1997 was a part of the platform of participation. The purpose of the STS-PAC is to enhance the Society's voice and stature in health care policymaking. Although the STS-PAC receives voluntary contributions from STS members, on average, only 10% of STS members contribute to the STS-PAC. For the 2015-2016 election cycle, there were 542 contributors to the STS-PAC totaling $273,000. An annual contribution of $100 from every STS member would put the STS-PAC into the top 10 for medical PACs (whereas currently it is ranked 22nd of 28 in the group of physician and dental association PACs). Despite the relatively small dollar amount the STS-PAC directs, its strategic disbursement of these dollars has yielded impressive results. For example, the STS-PAC was able to use its influence to effectively stop the Centers for Medicare and Medicaid Services from implementing a potentially calamitous rule that would effectively end traditional global surgical payments. Other advocacy successes include providing guidance to the Centers for Medicare and Medicaid Services in developing the national coverage determination for transcatheter aortic valve replacement and structuring its complex reimbursement schedule, and ensuring that a provision was included in the bill that would give the STS National Database access to claims data. The STS-PAC is a principal component of the STS' advocacy armamentarium. Despite the many successes of the STS-PAC, with even modest contributions by more STS members, the STS-PAC could become a leading medical PAC, and would give the STS an even stronger presence and voice in Washington, DC. Clearly, contributing to the STS-PAC provides STS members the opportunity to have a voice and an impact on health policy and the care of their patients.

The Role of Pediatric Palliative Care in Complex Congenital Heart Disease: Three Illustrative Cases.

BACKGROUND: Although the role of pediatric palliative care (PPC) is well described in oncology, neonatal, and pediatric intensive care patients, the involvement of PPC in patients with congenital heart disease (CHD) is not well explored. CHD is a leading cause of neonatal morbidity and can cause ongoing morbidity throughout the course of a child's life. PPC, with its focus on quality of life and longitudinal care through the course of an illness, could be of benefit to this population. OBJECTIVE: This case description reviews the role of PPC teams in the care of patients with complex CHD. DESIGN: Case study and analysis of three pediatric patients with complex CHD who also received PPC services. CONCLUSIONS: Involvement of PPC teams in patients with complex CHD can be beneficial for both families and caregivers. PPC teams can aid with advance care planning, goal setting, medical decision making, and bereavement support. Further research is needed to better quantify the benefits of PPC teams' involvement in this population.