Cerebral blood flow dynamics during cardiac surgery in infants.

BACKGROUND: In this pilot study, we investigated continuous cerebral blood flow velocity measurements to explore cerebrovascular hemodynamics in infants with congenital heart disease undergoing cardiac surgery. METHODS: A non-invasive transfontanellar cerebral Doppler monitor (NeoDoppler) was used to monitor 15 infants (aged eight days to nine months) during cardiac surgery with cardiopulmonary bypass. Numerical and visual analyses were conducted to assess trends and events in Doppler measurements together with standard monitoring equipment. The mean flow index, calculated as the moving Pearson correlation between mean arterial pressure and time averaged velocity, was utilized to evaluate dynamic autoregulation. Two levels of impaired autoregulation were defined (Mean flow index >0.3/0.45), and percentage of time above these limits were calculated. RESULTS: High quality recordings were achieved during 90.6% of the monitoring period. There was a significant reduction in time averaged velocity in all periods of cardiopulmonary bypass. All patients showed a high percentage of time with impaired dynamic autoregulation, with Mean flow index >0.3 and 0.45: 73.71% ± 9.06% and 65.16% ± 11.27% respectively. Additionally, the system promptly detected hemodynamic events. CONCLUSION: Continuous transfontanellar cerebral Doppler monitoring could become an additional tool in enhancing cerebral monitoring in infants during cardiac surgery. IMPACT: This pilot study demonstrates the feasibility of continuous transfontanellar Doppler monitoring of cerebral blood flow velocities during cardiac surgery in infants. It also demonstrates a high proportion of time with impaired cerebral autoregulation during cardiac surgery based on the Mean flow index. Continuous transfontanellar Doppler could become a useful tool to improve cerebral monitoring and provide new pathophysiological insight.

Rise in Neonatal Abstinence Syndrome Rate Is Associated with Increase in Buprenorphine Prescription Numbers.

OBJECTIVES: Southern Appalachia is a region of the United States that is disproportionately affected by the opioid epidemic and by increasing rates of neonatal abstinence syndrome (NAS). NAS rates increased approximately 400% between 1999 and 2012. Buprenorphine prescriptions written to treat opioid use disorder also increased dramatically. The present study was undertaken to ascertain any relationship between the number of buprenorphine prescriptions compared with NAS rates in southern Appalachia. METHODS: A total of 250 southern Appalachian counties across seven states, including all of West Virginia and portions of Virginia, Kentucky, Maryland, North Carolina, Ohio, and Tennessee were identified. A retrospective cohort analysis of these counties was conducted for the years 2005-2018. All of the data were obtained from publicly accessible sources or direct communication with government offices. Measures from each county in southern Appalachia included annual NAS rates, buprenorphine prescription rates, drug-induced death rates, and opioid prescribing rates. Associations among these variables were examined using a generalized linear regression. RESULTS: Significant linear associations exist between the rising rate of NAS diagnoses and the rising rate of buprenorphine prescriptions (r = 0.977, R2 = 95.53%, P < 0.001) and between the rising rate of buprenorphine prescriptions and the increase in drug-induced deaths (r = 0.712, R2 = 50.82%, P = 0.031). CONCLUSIONS: This is the first report that documents an association between rising NAS rates and increasing buprenorphine prescribing. Between the years 2010 and 2018, the NAS rate in southern Appalachia rose by 335%, and the number of buprenorphine prescriptions rose by 413%. Discussions regarding the current policies for buprenorphine management during pregnancy are warranted. We suggest a reevaluation of buprenorphine prescribing recommendations during pregnancy and further research on establishing the lowest effective buprenorphine dose for each pregnant patient.

A review of the advances in composites/nanocomposites for triboelectric nanogenerators.

Material development is essential when studying triboelectric nanogenerators (TENGs). This importance is because the performance of TENGs is highly dependent on the properties of the utilized triboelectric materials. To obtain more specific properties, composites have been developed that combine the features of their components. According to Google Scholar, 55% of published papers related to triboelectric nanogenerators have utilized or mentioned composites. This number is 34.5% if one searches with the keyword nanocomposites instead of composites. The importance of composites is because they can exhibit new dielectric properties, better mechanical strength, enhanced charge affinities, etc. Therefore, the development of new composites has great importance in TENG studies. In this paper, we review the production of nanocomposites, the types of nanocomposites, and their application in TENG studies. This review gives an overview of how nanocomposites boost the performance of TENGs and provides guidance for future studies.

Changes in For-Profit Medication-Assisted Therapy Clinics in an Appalachian City.

OBJECTIVES: This study is a follow-up to previous research regarding buprenorphine medication-assisted therapy (MAT) in Johnson City, Tennessee. For-profit MAT clinics were surveyed to determine changes in tapering practice patterns and insurance coverage during the last 3 years. METHODS: Johnson City for-profit MAT clinics; also called office based opioid treatment centers, were surveyed by telephone. Clinic representatives were asked questions regarding patient costs for therapy, insurance coverage, counseling offered onsite, and opportunities for tapering while pregnant. RESULTS: All of the MAT clinics representatives indicated that tapering in pregnancy could be considered even though tapering in pregnancy is contrary to current national guidelines. Forty-three percent of the clinics now accept insurance as compared with 0% in the 2016 study. The average weekly cost per visit remained consistent. CONCLUSIONS: The concept of tapering buprenorphine during pregnancy appears to have become a standard of care for this community, as representatives state it is offered at all of the clinics that were contacted. Representatives from three clinics stated the clinics require tapering, even though national organizations such as the American College of Obstetricians and Gynecologists and the American Society of Addiction Medicine do not recommend this approach. Although patients who have government or other insurance are now able to obtain buprenorphine with no expense at numerous clinics, the high cost for uninsured patients continues to create an environment conducive to buprenorphine diversion.

Prevention of Neonatal Abstinence Syndrome in an Outpatient Prenatal Buprenorphine Tapering Program.

OBJECTIVES: Many addicted pregnant patients receiving buprenorphine medication-assisted therapy (MAT) wish to discontinue this medication while pregnant. This study was undertaken to determine whether outpatient detoxification from buprenorphine during pregnancy is safe and effective when confirmed with postdetoxification urine drug screens (UDSs). METHODS: This case series reports the maternal and neonatal outcomes for 21 patients who ended MAT with buprenorphine while pregnant. A retrospective chart review of both maternal and newborn electronic medical records was performed to obtain results. Newborn neonatal abstinence syndrome (NAS) diagnosis, need for morphine, maternal safety and fetal/newborn complications were assessed. Maternal sobriety was documented with UDSs at the time of admission for delivery. Umbilical cord blood also was assessed for substances of abuse. An additional 182 pregnant women who lowered their buprenorphine doses but did not decide to end MAT were assessed via routine quality assurance methods. RESULTS: None of the women who stopped buprenorphine during their pregnancy as confirmed by UDSs and umbilical cord sampling delivered neonates who had NAS. Eleven patients ended MAT with medical assistance and 10 ended MAT without medical assistance. No overdoses were reported for the 182 additional pregnant patients who indicated an intention to taper buprenorphine dosage while pregnant but who did not decide to end MAT; the neonatal benefits were obtained without any identified maternal harm. CONCLUSIONS: The neonates of pregnant women enrolled in an outpatient buprenorphine MAT tapering program who are able to completely stop taking buprenorphine (as documented by negative urinary drug screen) are very unlikely to have NAS. Further research will be important.

High Prevalence of Buprenorphine in Prenatal Drug Screens in an Appalachian City.

OBJECTIVES: To define the magnitude of buprenorphine presence in the urine drug screens of pregnant women and to assess the presence of illicit buprenorphine use versus the presence of prescribed buprenorphine use. METHODS: Initial prenatal drug screen results for all pregnant patients in our practice for a 1-year period were analyzed and tabulated. RESULTS: Buprenorphine was found in the urine drug screens of 16% of pregnant patients. The presence of buprenorphine was by far the highest for any substance associated with neonatal abstinence syndrome (NAS). We estimate that the exposure to buprenorphine of approximately one-third of individuals in our population is associated with illicit buprenorphine use. CONCLUSIONS: The high rate of NAS in our region is primarily associated with both illicit and prescribed buprenorphine rather than other substances. Buprenorphine usage at the time that prenatal care is initiated, rather than opiate use at the onset of prenatal care, is the underlying factor that must be addressed if our region is to successfully combat our high rates of NAS.

Maker Buoy Variants for Water Level Monitoring and Tracking Drifting Objects in Remote Areas of Greenland.

Meltwater runoff from the Greenland Ice Sheet changes water levels in glacial lakes and can lead to glacial lake outburst flooding (GLOF) events that threaten lives and property. Icebergs produced at Greenland's marine terminating glaciers drift into Baffin Bay and the North Atlantic, where they can threaten shipping and offshore installations. Thus, monitoring glacial lake water levels and the drift of icebergs can enhance safety and aid in the scientific studies of glacial hydrology and iceberg-ocean interactions. The Maker Buoy was originally designed as a low-cost and open source sensor to monitor surface ocean currents. The open source framework, low-cost components, rugged construction and affordable satellite data transmission capabilities make it easy to customize for environmental monitoring in remote areas and under harsh conditions. Here, we present two such Maker Buoy variants that were developed to monitor water level in an ice-infested glacial lake in southern Greenland and to track drifting icebergs and moorings in the Vaigat Strait (Northwest Greenland). We describe the construction of each design variant, methods to access data in the field without an internet connection, and deployments in Greenland in summer 2019. The successful deployments of each Maker Buoy variant suggest that they may also be useful in operational iceberg management strategies and in GLOF monitoring programs.

Provision of Buprenorphine to Pregnant Women by For-Profit Clinics in an Appalachian City.

OBJECTIVES: This study was undertaken to confirm that patient reports on buprenorphine medication-assisted therapy in for-profit buprenorphine clinics in our community were personally costly. We contacted all 17 for-profit clinics in our community and confirmed the patient reports that a significant financial payment of ≤$100 was required for each visit. We also found that tapering of buprenorphine dosage in pregnancy was offered by several of the clinics. METHODS: A telephone survey was conducted with the 17 for-profit buprenorphine clinics located in the Johnson City, Tennessee area. The clinic representative who answered the telephone was asked questions regarding patient costs for therapy and availability of tapering programs for pregnant women. RESULTS: Patient reports that the for-profit clinics are costly were confirmed. None of the clinics accepted insurance reimbursement of any type. The most common weekly costs were $100 per visit. A majority of clinics offered biweekly or monthly visits at significantly increased rates. Clinic representatives stated that a majority of clinics would consider buprenorphine tapering programs for pregnant women. CONCLUSIONS: The high cost of for-profit clinics is a barrier for patient access to medication-assisted therapy with buprenorphine. Tapering of buprenorphine dosage in pregnant women has penetrated buprenorphine management practice in our community. Further research is needed to determine whether elimination of cost barrier would have a positive effect on the rates of neonatal abstinence syndrome.

Care of the adult patient with Down syndrome.

Individuals with Down syndrome have an increased risk for many conditions, including cardiovascular disease, cancer, infections, and osteoporosis, and endocrine, neurological, orthopedic, auditory, and ophthalmic disorders. They also are at increased risk for abuse and human rights violations and receive fewer screenings and interventions than the population without Down syndrome. In this literature review, the most common health conditions associated with Down syndrome are examined, along with the topics of sexual abuse, menstrual hygiene, contraception, and human rights. Clinical guidelines for this population are summarized in an effort to assist practicing physicians in improving their provision of health care to the adult patient with Down syndrome.

Acoustic contrast, planarity and robustness of sound zone methods using a circular loudspeaker array.

Since the mid 1990s, acoustics research has been undertaken relating to the sound zone problem-using loudspeakers to deliver a region of high sound pressure while simultaneously creating an area where the sound is suppressed-in order to facilitate independent listening within the same acoustic enclosure. The published solutions to the sound zone problem are derived from areas such as wave field synthesis and beamforming. However, the properties of such methods differ and performance tends to be compared against similar approaches. In this study, the suitability of energy focusing, energy cancelation, and synthesis approaches for sound zone reproduction is investigated. Anechoic simulations based on two zones surrounded by a circular array show each of the methods to have a characteristic performance, quantified in terms of acoustic contrast, array control effort and target sound field planarity. Regularization is shown to have a significant effect on the array effort and achieved acoustic contrast, particularly when mismatched conditions are considered between calculation of the source weights and their application to the system.

Instant Detection of Cerebral Blood Flow Changes in Infants with Congenital Heart Disease during Transcatheter Interventions.

Background: Transcatheter interventions are increasingly used in children with congenital heart disease. However, these interventions can affect cardiac output and cerebral circulation. In this pilot study, we aimed to investigate the use of NeoDoppler, a continuous transfontanellar cerebral Doppler monitoring system, to evaluate the impact of transcatheter interventions on cerebral circulation. Methods: Nineteen participants under one year of age (mean age 3.5 months) undergoing transcatheter cardiac interventions were prospectively included. Transfontanellar cerebral Doppler monitoring with the NeoDoppler system was initiated after intubation and continued until the end of the procedure. Results: Instant detection of changes in cerebral blood flow were observed across a spectrum of transcatheter interventions. Balloon aortic valvuloplasty demonstrated temporary cessation of cerebral blood flow during balloon inflation. Increase in cerebral diastolic blood flow velocity and decreased pulsatility were observed during patent ductus arteriosus occlusion. Changes in cerebral blood flow patterns were detected in two patients who encountered complications during their transcatheter interventions. There was no significant change in Doppler parameters before and after the interventions for the entire patient group. High quality recordings were achieved in 87.3% of the monitoring period. Conclusions: Continuous transfontanellar cerebral Doppler is feasible in monitoring cerebral hemodynamic trends and shows instantaneous changes associated with interventions and complications. It could become a useful monitoring tool during transcatheter interventions in infants.

Femoral nailing associated with bone marrow emboli in pigs induced a specific increase in blood IL-6 and broad inflammatory responses in the heart and lungs.

Introduction: Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear. We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses. Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow. Methods: Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs in vitro. Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1ß, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays. Results: After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004). No plasma differences in the rest of the inflammatory markers were noted across groups. However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1ß and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1ß compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). In vitro, incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03). Discussion: A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. In vitro experiments may imply bone marrow to be the primary IL-6 source.

Femoral Nailing in a Porcine Model Causes Bone Marrow Emboli in the Lungs and Systemic Emboli in the Heart and Brain.

Background: Shaft fractures of the femur are commonly treated with intramedullary nailing, which can release bone marrow emboli into the bloodstream. Emboli can travel to the lungs, impairing gas exchange and causing inflammation. Occasionally, emboli traverse from the pulmonary to the systemic circulation, hindering perfusion and resulting in injuries such as heart and brain infarctions, known as fat embolism syndrome. We studied the extent of systemic bone marrow embolization in a pig model. Methods: Twelve anesthetized pigs underwent bilateral intramedullary nailing of the femur, while 3 animals served as sham controls. Monitoring included transesophageal echocardiography (TEE), pulse oximetry, electrocardiography, arterial blood pressure measurement, and blood gas and troponin-I analysis. After surgery, animals were monitored for 240 minutes before euthanasia. Post mortem, the heart, lungs, and brain were biopsied. Results: Bone marrow emboli were found in the heart and lungs of all 12 of the pigs that underwent intramedullary nailing and in the brains of 11 of them. No emboli were found in the sham group. The pigs subjected to intramedullary nailing exhibited significant hypoxia (PaO2/FiO2 ratio, 410 mm Hg [95% confidence interval (CI), 310 to 510) compared with the sham group (594 mm Hg [95% CI, 528 to 660]). The nailing group exhibited ST-segment alterations consistent with myocardial ischemia and a significant increase in the troponin-I level compared with the sham group (1,580 ng/L [95% CI, 0 to 3,456] versus 241 ng/L [95% CI, 0 to 625] at the 240-minute time point; p = 0.005). TEE detected emboli in the right ventricular outflow tract, but not systemically, in the nailing group. Conclusions: Bilateral intramedullary nailing caused bone marrow emboli in the lungs and systemic emboli in the heart and brain in this pig model. The observed clinical manifestations were consistent with coronary and pulmonary emboli. TEE detected pulmonary but not systemic embolization. Clinical Relevance: Femoral intramedullary nailing in humans is likely to result in embolization as described in our pig model. Focused monitoring is necessary for detection of fat embolism syndrome. Absence of visual emboli in the left ventricle on TEE does not exclude the occurrence of systemic bone marrow emboli.

Use of medical simulation to teach bioterrorism preparedness: the anthrax example.

The 2001 anthrax bioterrorism attacks demonstrated vulnerability for future similar attacks. This article describes mechanisms that can be used to prepare the medical community and healthcare facilities for the diagnosis and management of a subsequent bioterrorism attack should such an event occur and the fundamentals of medical simulation and its use in teaching learners about the diagnosis of management of anthrax exposure.

Associations of age, BMI, and renal function to cortisol after dexamethasone suppression in patients with adrenal incidentalomas.

Introduction: The specificity of cortisol after 1 mg dexamethasone (cortisolDST) ≥50 nmol/L as a criterion for mild autonomous cortisol secretion (MACS) is approximately 85% in patients with adrenal incidentalomas (AI). The aim was to study the associations of cortisolDST to age, BMI, and renal function. Methods: We studied 1,129 patients with AI examined from 2005 to 2015 at Skåne University Hospital and Helsingborg Hospital. The covariates studied were gender, age, BMI, estimated glomerular filtration rate (eGFR), treatment with inhalation steroids, size of the AI, and size of the smallest AI in patients with bilateral AI (set to 0 in unilateral AI). We used machine learning models to uncover potential nonlinear associations. They were trained to fit the data and examined using feature importance analysis and partial dependence plots. Partial dependence plots show the marginal effect on cortisolDST of a covariate averaging over other covariates. Results: CortisolDST was strongly associated with the size of the AI and weakly associated with age, BMI, and eGFR according to the feature importance analysis. The partial dependence plots indicated relatively linear relationships for cortisolDST to age (positively) and eGFR (negatively). The association between cortisolDST and BMI was nonlinear. At BMI below 30 kg/m2, cortisolDST was negatively associated with BMI, but it was unchanged at higher BMI levels. Using linear regression, we found that cortisolDST increased by 11% (95% CI, 7%-14%) for each 10-year increase in age. In patients with a BMI below 30 kg/m2, cortisolDST increased by 23% (95% CI, 16%-31%) for each 5 kg/m2 decrease in BMI. We found no association at BMI levels above 30 kg/m2. CortisolDST increased by 9% (95% CI, 6%-11%) for each 10 ml/min/1.73m2 decrease in eGFR. Conclusions: CortisolDST is positively associated with age, negatively with BMI if below 30 kg/m2, and negatively with eGFR. These associations should be considered before diagnosing MACS.

Detection of Cerebral High-Intensity Transient Signals by NeoDoppler during Cardiac Catheterization and Cardiac Surgery in Infants.

There is a risk of gaseous and solid micro-embolus formation during transcatheter cardiac interventions and surgery in children with congenital heart disease (CHD). Our aim was to study the burden of high-intensity transient signals (HITS) during these procedures in infants. We used a novel color M-mode Doppler (CMD) technique by NeoDoppler, a non-invasive ultrasound system based on plane wave transmissions for transfontanellar continuous monitoring of cerebral blood flow in infants. The system displays CMD with 24 sample volumes and a Doppler spectrogram. Infants with CHD undergoing transcatheter interventions (n = 15) and surgery (n = 13) were included. HITS were manually detected based on an "embolic signature" in the CMD with corresponding intensity increase in the Doppler spectrogram. Embolus-to-blood ratio (EBR) defined HITS size. A total of 1169 HITS with a median EBR of 9.74 dB (interquartile range [IQR]: 5.10-15.80 dB) were detected. The median number of HITS in the surgery group was 45 (IQR: 11-150), while in the transcatheter group the median number was 12 (IQR: 7-24). During cardiac surgery, the highest number of HITS per hour was seen from initiation of cardiopulmonary bypass to aortic X-clamp. In this study we detected frequent HITS and determined the feasibility of using NeoDoppler monitoring for HITS detection.

Low frequency cerebral arterial and venous flow oscillations in healthy neonates measured by NeoDoppler.

Background: A cerebroprotective effect of low frequency oscillations (LFO) in cerebral blood flow (CBF) has been suggested in adults, but its significance in neonates is not known. This observational study evaluates normal arterial and venous cerebral blood flow in healthy neonates using NeoDoppler, a novel Doppler ultrasound system which can measure cerebral hemodynamics continuously. Method: Ultrasound Doppler data was collected for 2 h on the first and second day of life in 36 healthy term born neonates. LFO (0.04-0.15 Hz) were extracted from the velocity curve by a bandpass filter. An angle independent LFO index was calculated as the coefficient of variation of the filtered curve. Separate analyses were done for arterial and venous signals, and results were related to postnatal age and behavioral state (asleep or awake). Results: The paper describes normal physiologic variations of arterial and venous cerebral hemodynamics. Mean (SD) arterial and venous LFO indices (%) were 6.52 (2.55) and 3.91 (2.54) on day one, and 5.60 (1.86) and 3.32 (2.03) on day two. After adjusting for possible confounding factors, the arterial LFO index was estimated to decrease by 0.92 percent points per postnatal day (p < 0.001). The venous LFO index did not change significantly with postnatal age (p = 0.539). Arterial and venous LFO were not notably influenced by behavioral state. Conclusion: The results indicate that arterial LFO decrease during the first 2 days of life in healthy neonates. This decrease most likely represents normal physiological changes related to the transitional period. A similar decrease for venous LFO was not found.

The systems medicine of neonatal abstinence syndrome.

This review will focus on a systems medicine approach to neonatal abstinence syndrome (NAS). Systems medicine utilizes information gained from the application of "omics" technology and bioinformatics (1). The omic approaches we will emphasize include genomics, epigenomics, proteomics, and metabolomics. The goals of systems medicine are to provide clinically relevant and objective insights into disease diagnosis, prognosis, and stratification as well as pharmacological strategies and evidence-based individualized clinical guidance. Despite the increasing incidence of NAS and its societal and economic costs, there has been only a very modest emphasis on utilizing a systems medicine approach, and this has been primarily in the areas of genomics and epigenomics. As detailed below, proteomics and metabolomics hold great promise in advancing our knowledge of NAS and its treatment. Metabolomics, in particular, can provide a quantitative assessment of the exposome, which is a comprehensive picture of both internal and external environmental factors affecting health.

Cellulose-Based Fully Green Triboelectric Nanogenerators with Output Power Density of 300 W m-2.

Triboelectric nanogenerators (TENGs) have attracted increasing attention because of their excellent energy conversion efficiency, the diverse choice of materials, and their broad applications in energy harvesting devices and self-powered sensors. New materials have been explored, including green materials, but their performances have not yet reached the level of that for fluoropolymers. Here, a high-performance, fully green TENG (FG-TENG) using cellulose-based tribolayers is reported. It is shown that the FG-TENG has an output power density of above 300 W m-2 , which is a new record for green-material-based TENGs. The high performance of the FG-TENG is due to the high positive charge density of the regenerated cellulose. The FG-TENG is stable after more than 30 000 cycles of operations in humidity of 30%-84%. This work demonstrates that high-performance TENGs can be made using natural green materials for a broad range of applications.