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1. Vision-based detection and quantification of maternal sleeping position in the third trimester of pregnancy in the home setting-Building the dataset and model.

Author

Allan J Kember, Rahavi Selvarajan, Emma Park, Henry Huang, Hafsa Zia, Farhan Rahman, Sina Akbarian, Babak Taati, Sebastian R Hobson, and Elham Dolatabadi

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

In 2021, the National Guideline Alliance for the Royal College of Obstetricians and Gynaecologists reviewed the body of evidence, including two meta-analyses, implicating supine sleeping position as a risk factor for growth restriction and stillbirth. While they concluded that pregnant people should be advised to avoid going to sleep on their back after 28 weeks' gestation, their main critique of the evidence was that, to date, all studies were retrospective and sleeping position was not objectively measured. As such, the Alliance noted that it would not be possible to prospectively study the associations between sleeping position and adverse pregnancy outcomes. Our aim was to demonstrate the feasibility of building a vision-based model for automated and accurate detection and quantification of sleeping position throughout the third trimester-a model with the eventual goal to be developed further and used by researchers as a tool to enable them to either confirm or disprove the aforementioned associations. We completed a Canada-wide, cross-sectional study in 24 participants in the third trimester. Infrared videos of eleven simulated sleeping positions unique to pregnancy and a sitting position both with and without bed sheets covering the body were prospectively collected. We extracted 152,618 images from 48 videos, semi-randomly down-sampled and annotated 5,970 of them, and fed them into a deep learning algorithm, which trained and validated six models via six-fold cross-validation. The performance of the models was evaluated using an unseen testing set. The models detected the twelve positions, with and without bed sheets covering the body, achieving an average precision of 0.72 and 0.83, respectively, and an average recall ("sensitivity") of 0.67 and 0.76, respectively. For the supine class with and without bed sheets covering the body, the models achieved an average precision of 0.61 and 0.75, respectively, and an average recall of 0.74 and 0.81, respectively.

Published
2023
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2. The Era of Rhythm Control: A Review of the Epidemiology and Clinical Impact of Anti-Arrhythmic Medications in Atrial Fibrillation

Author

Cicely Anne Dye, Jamario Skeete, Asad Khan, Michael Dunleavy, Michael Dietrich, Annabelle Santos Volgman, Parikshit Sharma, and Henry Huang

Subjects
atrial fibrillation, anti-arrhythmics, rhythm control, rate control, arrhythmias, Therapeutics. Pharmacology, RM1-950, Other systems of medicine, RZ201-999, Public aspects of medicine, RA1-1270
Abstract

Atrial fibrillation has been described as a global epidemic with a three-fold increase in prevalence in the last 50 years. As the prevalence of atrial fibrillation continues to grow, multiple landmark trials have been designed to determine the best method to treat atrial fibrillation. Initial trials have stated that rate control was not inferior to rhythm control, however, as the efficacy of rhythm control of atrial fibrillation has improved, a benefit in rhythm control has been shown. Because of this trend towards increased rhythm control, more patients have been placed on anti-arrhythmic medications. This paper will review the epidemiology and clinical impact of the utilization of anti-arrhythmic medications. As we enter the era of rhythm control, increased awareness is needed regarding the monitoring and potential adverse events that can occur with these medications. Providers must balance the increased emphasis on rhythm control with the overall clinical impact on their patients due to drug-to-drug interactions and adverse effects that can occur with different co-morbidities. If the clinical momentum towards rhythm control continues, real-world data analysis will be needed to evaluate the clinical impact of the use, risk, and benefits of anti-arrhythmic medications.

Published
2023
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5. Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes.

Author

Henry Huang, Eric S Veien, Hong Zhang, David C Ayers, and Jie Song

Subjects
Medicine, Science
Abstract

Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene expressions and Smurf2 and Smurf1 proteins upon TGF-β3 or IL-1β treatment in culture. We found no differences in cortical, subchondral and trabecular bone between WT and MT in young (4 months) and old mice (16-24 months). The articular cartilage and age-related alterations between WT and MT were also similar. However, 2 months following DMM, young MT showed milder OA compared to WT (~70% vs ~30% normal or exhibiting only mild OA cartilage phenotype). The majority of the older WT and MT mice developed moderate/severe OA 2 months after DMM, but a higher subset of aged MT cartilage (27% vs. 9% WT) remained largely normal. Chondrogenic gene expression (Sox9, Col2, Acan) trended higher in MT iMACs than WT with/without TGF-β3 treatment. IL-1β treatment suppressed chondrgenic gene expression, but Sox9 expression in MT remained significantly higher than WT. Smurf2 protein in WT iMACs increased upon TGF-β3 treatment and decreased upon IL-1β treatment in a dose-dependent manner. Smurf1 protein elevated more in MT than WT upon TGF-β3 treatment, suggesting a potential, but very mild compensatory effect. Overall, our data support a role of Smurf2 in regulating OA development but suggest that inhibiting Smurf2 alone may not be sufficient to prevent or consistently mitigate post-traumatic OA across a broad age range.

Published
2016
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6. Bacterial Nucleoid-Associated Protein Uncouples Transcription Levels from Transcription Timing

Author

Igor Zwir, Won-Sik Yeo, Dongwoo Shin, Tammy Latifi, Henry Huang, and Eduardo A. Groisman

Subjects
Microbiology, QR1-502
Abstract

ABSTRACT The histone-like nucleoid-structuring (H-NS) protein binds to horizontally acquired genes in the bacterium Salmonella enterica serovar Typhimurium, silencing their expression. We now report that overcoming the silencing effects of H-NS imposes a delay in the expression of genes activated by the transcriptional regulator PhoP. We determine that PhoP-activated genes ancestral to Salmonella are expressed before those acquired horizontally. This expression timing reflects the in vivo occupancy of the corresponding promoters by the PhoP protein. These results are surprising because some of these horizontally acquired genes reached higher mRNA levels than ancestral genes expressed earlier and were transcribed from promoters harboring PhoP-binding sites with higher in vitro affinity for the PhoP protein. Our findings challenge the often-made assumption that for genes coregulated by a given transcription factor, early genes are transcribed to higher mRNA levels than those transcribed at later times. Moreover, they provide a singular example of how gene ancestry can impact expression timing. IMPORTANCE We report that gene ancestry dictates the expression behavior of genes under the direct control of the Salmonella transcriptional regulator PhoP. That is, ancestral genes are transcribed before horizontally acquired genes. This reflects both the need to overcome silencing by the H-NS protein of the latter genes and the architecture of the corresponding promoters. Unexpectedly, transcription levels do not reflect transcription timing. Our results illustrate how a bacterium can exhibit an elaborate temporal expression behavior among genes coregulated by a transcription factor even though the products encoded by the target genes do not participate in a morphological or developmental pathway.

Published
2014
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8. Defining the plasticity of transcription factor binding sites by Deconstructing DNA consensus sequences: the PhoP-binding sites among gamma/enterobacteria.

Author

Oscar Harari, Sun-Yang Park, Henry Huang, Eduardo A Groisman, and Igor Zwir

Subjects
Biology (General), QH301-705.5
Abstract

Transcriptional regulators recognize specific DNA sequences. Because these sequences are embedded in the background of genomic DNA, it is hard to identify the key cis-regulatory elements that determine disparate patterns of gene expression. The detection of the intra- and inter-species differences among these sequences is crucial for understanding the molecular basis of both differential gene expression and evolution. Here, we address this problem by investigating the target promoters controlled by the DNA-binding PhoP protein, which governs virulence and Mg(2+) homeostasis in several bacterial species. PhoP is particularly interesting; it is highly conserved in different gamma/enterobacteria, regulating not only ancestral genes but also governing the expression of dozens of horizontally acquired genes that differ from species to species. Our approach consists of decomposing the DNA binding site sequences for a given regulator into families of motifs (i.e., termed submotifs) using a machine learning method inspired by the "Divide & Conquer" strategy. By partitioning a motif into sub-patterns, computational advantages for classification were produced, resulting in the discovery of new members of a regulon, and alleviating the problem of distinguishing functional sites in chromatin immunoprecipitation and DNA microarray genome-wide analysis. Moreover, we found that certain partitions were useful in revealing biological properties of binding site sequences, including modular gains and losses of PhoP binding sites through evolutionary turnover events, as well as conservation in distant species. The high conservation of PhoP submotifs within gamma/enterobacteria, as well as the regulatory protein that recognizes them, suggests that the major cause of divergence between related species is not due to the binding sites, as was previously suggested for other regulators. Instead, the divergence may be attributed to the fast evolution of orthologous target genes and/or the promoter architectures resulting from the interaction of those binding sites with the RNA polymerase.

Published
2010
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9. Exascale applications: skin in the game.

Author

Alexander, Francis, Almgren, Ann, Bell, John, Bhattacharjee, Amitava, Chen, Jacqueline, Colella, Phil, Daniel, David, DeSlippe, Jack, Diachin, Lori, Draeger, Erik, Dubey, Anshu, Dunning, Thom, Evans, Thomas, Foster, Ian, Francois, Marianne, Germann, Tim, Gordon, Mark, Habib, Salman, Halappanavar, Mahantesh, Hamilton, Steven, Hart, William, Henry Huang, Zhenyu, Hungerford, Aimee, Kasen, Daniel, Kent, Paul RC, Kolev, Tzanio, Kothe, Douglas B, Kronfeld, Andreas, Luo, Ye, Mackenzie, Paul, McCallen, David, Messer, Bronson, Mniszewski, Sue, Oehmen, Chris, Perazzo, Amedeo, Perez, Danny, Richards, David, Rider, William J, Rieben, Rob, Roche, Kenneth, Siegel, Andrew, Sprague, Michael, Steefel, Carl, Stevens, Rick, Syamlal, Madhava, Taylor, Mark, Turner, John, Vay, Jean-Luc, Voter, Artur F, Windus, Theresa L, and Yelick, Katherine

Subjects
computational science applications, exascale, high-performance computing, machine learning, modelling and simulation, numerical algorithms, General Science & Technology
Abstract

As noted in Wikipedia, skin in the game refers to having 'incurred risk by being involved in achieving a goal', where 'skin is a synecdoche for the person involved, and game is the metaphor for actions on the field of play under discussion'. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with the skin being exascale applications and the game being delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare. This article is part of a discussion meeting issue 'Numerical algorithms for high-performance computational science'.

Published
2020

12. Universal non-polar switching in carbon-doped transition metal oxides (TMOs) and post TMOs

Author

C. A. Paz de Araujo, Jolanta Celinska, Chris R. McWilliams, Lucian Shifren, Greg Yeric, X. M. Henry Huang, Saurabh Vinayak Suryavanshi, Glen Rosendale, Valeri Afanas’ev, Eduardo C. Marino, Dushyant Madhav Narayan, and Daniel S. Dessau

Subjects
Biotechnology, TP248.13-248.65, Physics, QC1-999
Abstract

Transition metal oxides (TMOs) and post-TMOs (PTMOs), when doped with carbon, show non-volatile current–voltage characteristics, which are both universal and repeatable. We have shown spectroscopic evidence of the introduction of carbon-based impurity states inside the existing larger bandgap effectively creating a smaller bandgap, which we suggest could be a Mott–Hubbard-like correlation effects. Our findings indicate new insights for yet to be understood unipolar and nonpolar resistive switching in the TMOs and PTMOs. We have shown that device switching is not thermal-energy dependent and have developed an electronic-dominated switching model that allows for the extreme temperature operation (from 1.5 to 423 K) and state retention up to 673 K for a 1 h bake. Importantly, we have optimized the technology in an industrial process and demonstrated integrated 1-transistor/1-resistor arrays up to 1 kbit with 47 nm devices on 300 mm wafers for advanced node CMOS-compatible correlated electron random access memory. These devices are shown to operate with 2 ns write pulses and retain the memory states up to 200 °C for 24 h. The collection of attributes shown, including scalability to state-of-the-art dimensions, non-volatile operation to extreme low and high temperatures, fast write, and reduced stochasticity as compared to filamentary memories, such as resistive random-access memories, shows the potential for a highly capable two-terminal back-end-of-line non-volatile memory.

Published
2022
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14. Computational Requirements in Clean Energy and Manufacturing: Summary report of the virtual workshop held on June 28-29, 2021

Author

Matt Sieger, John Turner, Srikanth Allu, Muhsin Ameen, Santanu Chaudhuri, Jackie Chen, Yousu Chen, Flavio Dal Forno Chuahy, Charles Finney, Vyaas Gururajan, Henry Huang, Brian Kaul, Stephen Klippenstein, Hector Martin, Pinaki Pal, Slaven Peles, Alex Plotkowski, Jibonananda Sanyal, Manajit Sengupta, Sibendu Som, and Michael Sprague

Published
2023
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20. Monocytes promote acute neuroinflammation and become pathological microglia in neonatal hypoxic-ischemic brain injury

Author

Hong-Ru Chen, Ching-Wen Chen, Yi-Min Kuo, Brandon Chen, Irena S. Kuan, Henry Huang, Jolly Lee, Neil Anthony, Chia-Yi Kuan, and Yu-Yo Sun

Subjects
Inflammation, Male, Receptors, CCR2, monocyte-derived macrophages, Medicine (miscellaneous), microglia, Adoptive Transfer, chorioamnionitis, Monocytes, hypoxic ischemic encephalopathy (HIE), neuroinflammation, Mice, Inbred C57BL, Animals, Newborn, Cell Movement, Brain Injuries, Choroid Plexus, Hypoxia-Ischemia, Brain, Neuroinflammatory Diseases, CCR2, Animals, Female, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Cells, Cultured, Research Paper
Abstract

Rationale: Monocytes belong to the mononuclear phagocyte system and are immune responders to tissue injury and infection. There were also reports of monocytes transforming to microglia-like cells. Here we explore the roles of monocytes in microglia ontogeny and the pathogenesis of neonatal cerebral hypoxic-ischemic (HI) brain injury in mice. Methods: We used three genetic methods to track the development of monocytes, including CX3CR1GFP/+; CCR2RFP/+ reporter mice, adoptive transfer of GFP+ monocytes, and fate-mapping with CCR2-CreER mice, in neonatal mouse brains with or without lipopolysaccharide (LPS, 0.3 mg/kg)-sensitized Vannucci HI. We also used genetic (CCR2RFP/ RFP, CCR2 knockout) and pharmacological methods (RS102895, a CCR2 antagonist) to test the roles of monocytic influx in LPS/HI brain injury. Results: CCR2+ monocytes entered the late-embryonic brains via choroid plexus, but rapidly became CX3CR1+ amoeboid microglial cells (AMCs). The influx of CCR2+ monocytes declined after birth, but recurred after HI or LPS-sensitized HI (LPS/HI) brain injury, particularly in the hippocampus. The CCR2-CreER-based fate-mapping showed that CCR2+ monocytes became CD68+ TNFα+ macrophages within 4 d after LPS/HI, and maintained as TNFα+ MHCII+ macrophages or persisted as Tmem119+ Sall1+ P2RY12+ ramified microglia for at least five months after injury. Genetic deletion of the chemokine receptor CCR2 markedly diminished monocytic influx, the expression of pro- and anti-inflammatory cytokines, and brain damage. Post-LPS/HI application of RS102895 also reduced inflammatory responses and brain damage, leading to better cognitive functions. Conclusion: These results suggest that monocytes promote acute inflammatory responses and may become pathological microglia long after the neonatal LPS/HI insult. Further, blocking the influx of monocytes may be a potential therapy for neonatal brain injury.

Published
2022

23. Porous liquid metal-elastomer composites with high leakage resistance and antimicrobial property for skin-interfaced bioelectronics

Author

Yadong Xu, Yajuan Su, Xianchen Xu, Brian Arends, Ganggang Zhao, Daniel N. Ackerman, Henry Huang, St. Patrick Reid, Joshua L. Santarpia, Chansong Kim, Zehua Chen, Sana Mahmoud, Yun Ling, Alexander Brown, Qian Chen, Guoliang Huang, Jingwei Xie, and Zheng Yan

Subjects
Multidisciplinary
Abstract

Liquid metal–elastomer composite is a promising soft conductor for skin-interfaced bioelectronics, soft robots, and others due to its large stretchability, ultrasoftness, high electrical conductivity, and mechanical-electrical decoupling. However, it often suffers from deformation-induced leakage, which can smear skin, deteriorate device performance, and cause circuit shorting. Besides, antimicrobial property is desirable in soft conductors to minimize microbial infections. Here, we report phase separation–based synthesis of porous liquid metal–elastomer composites with high leakage resistance and antimicrobial property, together with large stretchability, tissue-like compliance, high and stable electrical conductivity over deformation, high breathability, and magnetic resonance imaging compatibility. The porous structures can minimize leakage through damping effects and lower percolation thresholds to reduce liquid metal usage. In addition, epsilon polylysine is loaded into elastic matrices during phase separation to provide antimicrobial property. The enabled skin-interfaced bioelectronics can monitor cardiac electrical and mechanical activities and offer electrical stimulations in a mechanically imperceptible and electrically stable manner even during motions.

Published
2023

24. The future of cardioneuroablation in cardiovascular medicine

Author

Tolga Aksu, Asad Khan, and Henry Huang

Subjects
Internal Medicine, General Medicine, Cardiology and Cardiovascular Medicine
Abstract

Cardioneuroablation is increasingly being utilized to improve outcomes in patients with vagally mediated bradyarrhythmias. However, there are still controversial issues in the field including patient selection, safety and efficacy, and procedural end-points.In this review, the current role of cardioneuroablation is summarized, and controversial issues related to the modality are discussed.According to small open-label cohort studies, overall freedom from syncope recurrence was higher than 90% after cardioneuroablation in patients with vasovagal syncope (VVS). Use of the electrogram-based strategy or high-frequency stimulation demonstrate similar success rate except in procedures limited to the right atrium. Based on a recently published randomized controlled trial and metanalysis, it may be possible now to make a strong recommendation for cardioneuroablation in patients40 years of age, and those with the cardioinhibitory or mixed type of VVS who continue to experience frequent and/or burdensome syncope recurrences. Considering patients with VVS are prone to significant placebo/expectation effect, sham-controlled trials may help to quantify the placebo effect. In well-selected patients with functional atrioventricular block and sinus bradycardia, may result in encouraging medium-term outcomes. However, functional bradycardia is identified in a minority of patients presenting with high-grade atrioventricular block or sinus node dysfunction.

Published
2022

25. Risk factors for the development of premature ventricular complex-induced cardiomyopathy: a systematic review and meta-analysis

Author

Jeanne du Fay de Lavallaz, Julien Mézier, Lara Mertz, Diego Mannhart, Teodor Serban, Sven Knecht, Qurrat-ul-ain Abid, Tai Tri Nguyen, Michael Kühne, Christian Sticherling, Henry Huang, Michael R. Gold, and Patrick Badertscher

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background Premature ventricular complexes (PVCs) are a potentially reversible cause of heart failure. However, the characteristics of patients most likely to develop impaired left ventricular function are unclear. Hence, the objective of this study is to systematically assess risk factors for the development of PVC-induced cardiomyopathy. Methods We performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced cardiomyopathy (PVC-CM). We investigated the reporting of PVC-CM risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis. Results A total of 26 studies (9 prospective and 17 retrospective studies) involving 16,764,641 patients were analyzed (mean age 55 years, 58% women, mean PVC burden 17%). Eleven RF were suitable for quantitative analysis (≥ 3 occurrences in multivariable model assessing a binary change in left ventricular (LV) function). Among these, age (OR 1.02 per increase in the year of age, 95% CI [1.01, 1.02]), the presence of symptoms (OR 0.18, 95% CI [0.05, 0.64]), non-sustained ventricular tachycardias (VT) (OR 3.01, 95% CI [1.39, 6.50]), LV origin (OR 2.20, 95% CI [1.14, 4.23]), epicardial origin (OR 4.72, 95% CI [1.81, 12.34]), the presence of interpolation (OR 4.93, 95% CI [1.66, 14.69]), PVC duration (OR 1.05 per ms increase in QRS-PVC duration [1.004; 1.096]), and PVC burden (OR 1.06, 95% CI [1.04, 1.08]) were all significantly associated with PVC-CM. Conclusions In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VT, LV, epicardial origin, interpolation, and PVC burden, whereas the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up of patients presenting with frequent PVCs and normal LV function.

Published
2022

31. Stereotactic body radioablation therapy as an immediate and early term antiarrhythmic palliative therapeutic choice in patients with refractory ventricular tachycardia

Author

Dursun Aras, Elif Hande Özcan Çetin, Huseyin Furkan Ozturk, Elif Ozdemir, Meryem Kara, Firdevs Aysenur Ekizler, Ozcan Ozeke, Firat Ozcan, Ahmet Korkmaz, Umit Kervan, Nesrin Turhan, Nazim Coskun, Yilmaz Tezcan, Henry Huang, Tolga Aksu, and Serkan Topaloglu

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Stereotactic body radioablation therapy (SBRT) has recently been introduced with the ability to provide ablative energy noninvasively to arrhythmogenic substrate while reducing damage to normal cardiac tissue nearby and minimizing patients' procedural risk. There is still debate regarding whether SBRT has a predominant effect in the early or late period after the procedure. We sought to assess the time course of SBRT's efficacy as well as the value of using a blanking period following a SBRT session.Methods: Eight patients (mean age 58 ±14 years) underwent eight SBRT sessions for refractory ventricular tachycardia (VT). SBRT was given using a linear accelerator device with a total dose of 25 Gy to the targeted area.Results: During a median follow-up of 8 months, all patients demonstrated VT recurrences, however, implantable cardioverter-defibrillator (ICD) therapies were significantly reduced with SBRT (8.46 to 0.83/per month, p=0.047; 18.50 to 3.29/per month, p=0.036, respectively). While analyzing the temporal SBRT outcomes, the two weeks to 3 months period demonstrated the most favorable outcomes. After 6 months, one patient was ICD therapy-free and the remaining patients demonstrated VT episodes. Conclusions: Our findings showed that the SBRT was associated with a marked reduction in the burden of VT and ICD interventions especially during first 3 months. Although SBRT doesn’t seem to succeed complete termination of VT in long-term period, our findings support the strategy that SBRT can be utilized for immediate antiarrhythmic palliation in critically ill patients with otherwise untreatable refractory VT and electrical storm.

Published
2022
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35. Postoperative pain and psychological outcomes following minimally invasive pectus excavatum repair: A report from the Society for Pediatric Anesthesia Improvement Network

Author

Joseph P. Cravero, Wallis T. Muhly, Henry Huang, Robert T. Wilder, Kristen Uhl, Allison Fernandez, and David Zurakowski

Subjects
medicine.medical_specialty, Postoperative pain, 03 medical and health sciences, 0302 clinical medicine, Pectus excavatum, 030202 anesthesiology, 030225 pediatrics, medicine, Humans, Minimally Invasive Surgical Procedures, Anesthesia, In patient, Risk factor, Child, Pain, Postoperative, Pain experience, business.industry, medicine.disease, Surgery, Distress, Anesthesiology and Pain Medicine, Funnel Chest, Pediatrics, Perinatology and Child Health, Cohort, Pediatric anesthesia, business
Abstract

Background Minimally invasive repair of pectus excavatum (MIRPE) is associated with less tissue trauma; however, it may result in increased postoperative pain. Pain experience is a known risk factor for the development of posttraumatic stress symptoms, though there are little data on its relationship with long-term psychological outcomes following major surgery in pediatric patients. Aims In this study, we examined the relationship between immediate postoperative pain and psychological outcomes at 2 weeks and three months after discharge in a cohort of pediatric patients who underwent MIRPE. We sought to determine whether immediate postoperative pain levels were associated with ongoing distress related to aspects of surgery at both time points. We were also interested in how psychological symptoms related to persistent pain concerns. Methods Data on patients undergoing MIRPE across 14 institutions were collected as part of the Society for Pediatric Anesthesia Improvement Network (SPAIN). Patients were contacted at 2 weeks and three months following discharge to track pain levels and assess psychological distress using a self-report questionnaire. Patients were grouped into cohorts based on self-report of distress related to aspects of surgery, nonsurgical distress, or absence of distress. Results Analysis revealed that a higher proportion of children reporting ongoing distress related to surgery at both 2 weeks and 3 months experienced higher immediate postoperative pain levels. A subset of patients with complete data sets for 2 weeks and 3 months (N = 76) was further examined. Among the 47 patients who endorsed surgical distress at 2 weeks, 25 (53.2%) continued to endorse surgical distress at 3 months. Additionally, report of surgical distress at 3 months was associated with longer-term postoperative pain. Conclusions Our data suggest that, in patients undergoing MIRPE, the presence of distress at 2 weeks and 3 months may be associated with higher immediate postoperative pain levels.

Published
2020
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37. Managing Pain and Discomfort in Children with Cancer

Author

Clinton Fuller, Henry Huang, and Rachel Thienprayoon

Subjects
Complementary Therapies, Oncology, Neoplasms, Humans, Pain, Pain Management, Chronic Pain, Child
Abstract

Approximately 15,600 children are diagnosed with cancer annually. Many of these children have cancer-related pain that improves with cancer treatment, but some develop intractable pain from cancer progression or sequelae from treatment modalities. The purpose of this paper is to provide a critical evaluation of the literature relevant to pain management in children with cancer. We intend to emphasize important and up-to-date findings in pharmacology, interventional pain management, and complementary and alternative medicine.Alternative medications and routes of administration, complementary and alternative medicine techniques, and interventional pain procedures offer possible routes for a multi-pronged pediatric cancer pain management plan, although high-level data is often lacking. To improve pediatric cancer pain management, a multifaceted approach embracing the biopsychosocial model of pain is recommended, incorporating evidence-based pharmacology, complementary and alternative medicine techniques, and if needed, interventional pain procedures.

Published
2022

43. Editorial: Translational advances in Alzheimer's, Parkinson's, and other dementia: Molecular mechanisms, biomarkers, diagnosis, and therapies, volume II

Author

Jiehui Jiang, Kuangyu Shi, Yiyun Henry Huang, Chih-Yu Hsu, Kenneth Scott Hettie, and Woon-Man Kung

Subjects
Aging, Aging Neuroscience, Alzheimer's disease, Parkinson's disease, dementia, neurodegenerative disorders, big data mining, imaging methods, bioinformatic applications, Cognitive Neuroscience, 610 Medicine & health, ddc
Published
2021
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44. Comparison of Electrocautery Platforms for Pulse Generator Replacement Procedures

Author

Caleb Chiang, Muhammad Ayub, Kousik Krishnan, Richard Trohman, Parikshit Sharma, Timothy Larsen, Henry Huang, Janet Haw, and Jeremiah Wasserlauf

Abstract

Introduction: Lead damage can occur during cardiovascular implantable electronic device (CIED) generator replacement procedures, resulting in additional procedures and added costs. PlasmaBlade (PL) and PhotonBlade (PH) are two commercially available insulated electrocautery devices designed to reduce this risk. Objective: This study compared complication rates of PL and PH in CIED generator replacement procedures. Methods: This retrospective study analyzed transvenous CIED generator replacements using PL or PH from 2017-2020. The primary endpoint was lead damage. Secondary endpoints included rate of pocket hematoma, superficial infection, and infections requiring device removal. Results: A total of 209 patients were included for analysis, including 86 procedures (188 leads) using PL and 123 procedures (266 leads) using PH. Lead insulation material consisted of 237 (52.2%) silicone, 66 (14.5%) polyurethane, and 151 (33.3%) copolymer leads, with no significant difference in frequency of insulation materials (p=0.91). The rate of lead damage was low for both PL and PH (0 vs. 0.4%, p=0.59). There was no significant difference in pocket hematoma (1.2% vs. 1.6%, p=0.43), superficial infection (1.2% vs. 0.8%, p=0.49), or infection requiring device removal (1.2% vs. 0%, p=0.41). The mean absolute change in lead impedance from pre- to post-procedure was similar between PL and PH (72.3 ± 126.1 ohms vs. 60.6 ± 72.3 ohms, p=0.10). Conclusions: There was a low rate of complications after CIED replacement procedures, with no significant difference between the PL and PH groups. A majority of leads with silicone insulation material may have contributed to the low rate of lead damage.

Published
2021
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45. Perioperative Outcomes and Surgical Case Volume in Pediatric Complex Cranial Vault Reconstruction

Author

Allison M. Fernandez, Srijaya K. Reddy, Heather Gordish-Dressman, Bridget L. Muldowney, José Luis Martinez, Franklin Chiao, Paul A. Stricker, Christopher Abruzzese, Jesus Apuya, Amy Beethe, Hubert Benzon, Wendy Binstock, Alyssa Brzenski, Stefan Budac, Veronica Busso, Surendrasingh Chhabada, Franklyn Cladis, Danielle Claypool, Michael Collins, Rachel Dabek, Nicholas Dalesio, Ricardo Falcon, Patrick Fernandez, John Fiadjoe, Meera Gangadharan, Katherine Gentry, Chris Glover, Susan M. Goobie, Amanda Gosman, Shannon Grap, Heike Gries, Allison Griffin, Charles Haberkern, John Hajduk, Rebecca Hall, Jennifer Hansen, Mali Hetmaniuk, Vincent Hsieh, Henry Huang, Pablo Ingelmo, Iskra Ivanova, Ranu Jain, Michelle Kars, Courtney Kowalczyk-Derderian, Jane Kugler, Kristen Labovsky, Indrani Lakheeram, Andrew Lee, Brian Masel, Eduardo Medellin, Petra Meier, Heather Mitzel Levy, Wallis T. Muhly, Jonathon Nelson, Julie Nicholson, Kim-Phuong Nguyen, Thanh Nguyen, Olutoyin Olutuye, Margaret Owens-Stubblefield, Uma Ramesh Parekh, Timothy Petersen, Vanessa Pohl, Julian Post, Kim Poteet-Schwartz, Jansie Prozesky, Russell Reid, Karene Ricketts, Daniel Rubens, Laura Ryan, Rochelle Skitt, Codruta Soneru, Rachel Spitznagel, Davinder Singh, Neil R. Singhal, Emad Sorial, Susan Staudt, Bobbie Stubbeman, Wai Sung, Tariq Syed, Peter Szmuk, Brad M. Taicher, Douglas Thompson, Lisa Tretault, Galit Ungar-Kastner, Rheana Watts, John Wieser, Karen Wong, and Lillian Zamora

Subjects
Adult, Male, medicine.medical_specialty, Hospitals, Low-Volume, Time Factors, Blood transfusion, Adolescent, medicine.medical_treatment, Blood Loss, Surgical, Craniosynostosis, law.invention, Craniosynostoses, Young Adult, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, 030202 anesthesiology, law, Pediatric surgery, medicine, Humans, Blood Transfusion, Registries, Young adult, Child, Perioperative Period, business.industry, Incidence, Incidence (epidemiology), Age Factors, Perioperative, Length of Stay, Plastic Surgery Procedures, medicine.disease, Intensive care unit, Surgery, Intensive Care Units, Treatment Outcome, Anesthesiology and Pain Medicine, Female, Observational study, business, Hospitals, High-Volume, 030217 neurology & neurosurgery
Abstract

BACKGROUND Complex cranial vault reconstruction (CCVR) performed to treat craniosynostosis can be associated with significant blood loss, transfusion, and perioperative complications. The aim of this study was to examine the effect of CCVR surgical case volume on perioperative outcomes. We hypothesized that surgical case volume is not associated with differences in perioperative outcomes. The study primary outcome was total perioperative blood donor exposures. Secondary outcomes included the total perioperative transfusion volume, major complications, and intensive care unit and hospital length of stay. METHODS The multicenter Pediatric Surgery Perioperative Registry was queried for infants and children undergoing CCVR between June 2012 and September 2016. Institutions were categorized into low, middle, or high surgical case volume groups based on tertiles of the average number of cases performed per month. Primary and secondary outcomes were analyzed with respect to these groupings. RESULTS The query yielded 1814 CCVR cases from 33 institutions. Demographics were similar among the 3 study groups. An inverse relationship between surgical case volume and total perioperative blood donor exposures was observed (P < .001). The low-volume group had higher perioperative transfusion volumes (P = .02 versus middle; P = .01 versus high). There was no significant relationship between surgical case volume and the incidence of major postoperative complications or hospital length of stay. CONCLUSIONS In this study, low surgical case volumes were associated with increased total blood donor exposures and increased perioperative transfusion volumes. Hospital length of stay was homogeneous in the 3 groups, suggesting a limited overall clinical impact of the observed transfusion outcome differences.

Published
2019
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46. The development of an opioid sparing anesthesia protocol for pediatric ambulatory tonsillectomy and adenotonsillectomy surgery—A quality improvement project

Author

Henry Huang, Shilpa Verma, Daniel King-Wai Low, Amber M Franz, John P. Dahl, Lynn D. Martin, and Lizabeth D. Martin

Subjects
Male, medicine.medical_specialty, Adolescent, Nausea, medicine.medical_treatment, Analgesic, Adenoidectomy, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, 030225 pediatrics, medicine, Humans, Pain Management, Dexmedetomidine, Child, Pain Measurement, Tonsillectomy, Pain, Postoperative, business.industry, Infant, Newborn, Infant, Perioperative, Analgesics, Non-Narcotic, Quality Improvement, Surgery, Analgesics, Opioid, Ketorolac, Anesthesiology and Pain Medicine, Child, Preschool, Anesthesia, Pediatrics, Perinatology and Child Health, Vomiting, Female, medicine.symptom, business, Postoperative nausea and vomiting, medicine.drug
Abstract

Pain management following pediatric tonsillectomy and adenotonsillectomy surgery is challenging and traditionally involves perioperative opioids. However, the recent national opioid shortage compelled anesthesiologists at Bellevue Surgery Center to identify an alternative perioperative analgesic regimen that minimizes opioids yet provides effective pain relief. We assembled an interdisciplinary quality improvement team to trial a series of analgesic protocols using the Plan-Do-Study-Act cycle. Initially, we replaced intraoperative morphine and acetaminophen (M/A protocol) with intraoperative dexmedetomidine and preoperative ibuprofen (D/I protocol). However, when results were not favorable, we rapidly transitioned to intraoperative ketorolac and dexmedetomidine (D/K protocol). The following measures were evaluated using statistical process control chart methodology and interpreted using Shewhart's theory of variation: maximum pain score in the postanesthesia care unit, postoperative morphine rescue rate, postanesthesia care unit length of stay, total anesthesia time, postoperative nausea and vomiting rescue rate, and reoperation rate within 30 days of surgery. There were 333 patients in the M/A protocol, 211 patients in the D/I protocol, and 196 patients in the D/K protocol. With the D/I protocol, there were small increases in maximum pain score and postanesthesia care unit length of stay, but no difference in morphine rescue rate or total anesthesia time compared to the M/A protocol. With the D/K protocol, postoperative pain control and postanesthesia care unit length of stay were similar compared to the M/A protocol. Both the D/I and D/K protocols had reduced nausea and vomiting rescue rates. Reoperation rates were similar between groups. In summary, we identified an intraoperative anesthesia protocol for pediatric tonsillectomy and adenotonsillectomy surgery utilizing dexmedetomidine and ketorolac that provides effective analgesia without increasing recovery times or reoperation rates.

Published
2019
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47. Perioperative Management and In-Hospital Outcomes After Minimally Invasive Repair of Pectus Excavatum

Author

Tarun Bhalla, Imelda Tjia, Seth Eisdorfer, Robert B. Bryskin, Alan Bielsky, Christopher Chinn, David Zurakowski, Sabine Kost-Byerly, Robert T. Wilder, Dawit T. Haile, Wallis T. Muhly, Dinesh K. Choudhry, Rita Agarwal, Gregory Schnepper, Giovanni Cucchiaro, Chris D. Glover, Allison Fernandez, Ralph J Beltran, Joseph P. Cravero, Henry Huang, Lynne G. Maxwell, and James J. Thomas

Subjects
Male, Research Report, Adolescent, Analgesic, Pediatrics, Perioperative Care, Pectus excavatum, medicine, Humans, Minimally Invasive Surgical Procedures, Anesthesia, Prospective Studies, Registries, Child, Prospective cohort study, Societies, Medical, business.industry, Disease Management, medicine.disease, Hospitalization, Catheter, Treatment Outcome, Anesthesiology and Pain Medicine, Opioid, Funnel Chest, Female, Observational study, Haller index, Pediatric anesthesia, business, medicine.drug
Abstract

BACKGROUND There are few comparative data on the analgesic options used to manage patients undergoing minimally invasive repair of pectus excavatum (MIRPE). The Society for Pediatric Anesthesia Improvement Network was established to investigate outcomes for procedures where there is significant management variability. For our first study, we established a multicenter observational database to characterize the analgesic strategies used to manage pediatric patients undergoing MIRPE. Outcome data from the participating centers were used to assess the association between analgesic strategy and pain outcomes. METHODS Fourteen institutions enrolled patients from June 2014 through August 2015. Network members agreed to an observational methodology where each institution managed patients based on their institutional standards and protocols. There was no requirement to standardize care. Patients were categorized based on analgesic strategy: epidural catheter (EC), paravertebral catheter (PVC), wound catheter (WC), no regional (NR) analgesia, and intrathecal morphine techniques. Primary outcomes, pain score and opioid consumption by postoperative day (POD), for each technique were compared while adjusting for confounders using multivariable modeling that included 5 covariates: age, sex, number of bars, Haller index, and use of preoperative pain medication. Pain scores were analyzed using repeated-measures analysis of variance with Bonferroni correction. Opioid consumption was analyzed using a multivariable quantile regression. RESULTS Data were collected on 348 patients and categorized based on primary analgesic strategy: EC (122), PVC (57), WC (41), NR (120), and intrathecal morphine (8). Compared to EC, daily median pain scores were higher in patients managed with PVC (POD 0), WC (POD 0, 1, 2, 3), and NR (POD 0, 1, 2), respectively (P < .001-.024 depending on group). Daily opioid requirements were higher in patients managed with PVC (POD 0, 1), WC (POD 0, 1, 2), and NR (POD 0, 1, 2) when compared to patients managed with EC (P < .001). CONCLUSIONS Our data indicate variation in pain management strategies for patients undergoing MIRPE within our network. The results indicate that most patients have mild-to-moderate pain postoperatively regardless of analgesic management. Patients managed with EC had lower pain scores and opioid consumption in the early recovery period compared to other treatment strategies.

Published
2019
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48. Shared Tobacco Cessation Curriculum Website for Health Professionals: Longitudinal Analysis of User and Utilization Data Over a Period of 15 Years

Author

Henry Huang, Nervana Elkhadragy, Jeremie Aviado, Robin L. Corelli, and Karen Suchanek Hudmon

Subjects
Medicine (General), Referral, end-user data, education, Pharmacy, 030204 cardiovascular system & hematology, shared curricula, Education, 03 medical and health sciences, health professional education, 0302 clinical medicine, R5-920, tobacco cessation, Tobacco, Behavioral and Social Science, Health care, 030212 general & internal medicine, Personal knowledge base, Curriculum, Medical education, Original Paper, Tobacco Smoke and Health, LC8-6691, business.industry, Prevention, interprofessional education, Interprofessional education, File format, Special aspects of education, Computer Science Applications, Good Health and Well Being, website, business, Psychology, Period (music)
Abstract

Background Because tobacco use is a major cause of morbidity and mortality worldwide, it is essential to prepare health care providers to assist patients with quitting smoking. Created in 1999, the “Rx for Change” tobacco cessation curriculum was designed to fill an educational gap in cessation training of health professional students. In 2004, a website was launched to host teaching materials and tools to support the efforts of educators and clinicians. Objective The objective of this study was to characterize users and utilization of a website hosting shared teaching materials over a period of 15 years. Methods Data from the Rx for Change website have been collected prospectively since its inception. In this study, end-user data were analyzed to determine user characteristics, how they heard about the website, intended use of the materials, and numbers of logins and file downloads over time. Results Total number of website registrants was 15,576, representing all 50 states in the United States and 94 countries. The most represented discipline was pharmacy (6393/15,505, 41.2%), and nearly half of users were students or residents. The most common source of referral to the website was a faculty member or colleague (33.4%, 2591/7758), and the purpose of enhancing personal knowledge and skills was the most commonly cited intended use of the curricular materials. A total of 259,835 file downloads occurred during the 15-year period, and the most commonly downloaded file type was ancillary handouts. Conclusions The Rx for Change website demonstrated sustained use, providing immediate access to tobacco cessation teaching and practice tools for educators and clinicians over the first 15 years of its existence. The website has a broad interprofessional reach, and the consistent utilization over time and large number of downloads provide evidence for the feasibility and utility of a public-access website hosting teaching materials. The shared curriculum approach averts the need for educators to create their own materials for teaching tobacco cessation to students in the health professions.

Published
2021

49. PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research

Author

Yiyun Henry Huang, Weiqi Bao, Yihui Guan, Chuantao Zuo, and Fang Xie

Subjects
0301 basic medicine, Aging, Cognitive Neuroscience, Amnesia, Neurosciences. Biological psychiatry. Neuropsychiatry, Disease, Review, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, medicine, Neuroinflammation, neuroimaging, medicine.diagnostic_test, business.industry, Prodromal Stage, Basic cognitive functions, Cognition, Alzheimer's disease, radiotracer, 030104 developmental biology, PET, clinical research, Positron emission tomography, medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery, RC321-571
Abstract

Alzheimer's Disease (AD), the leading cause of senile dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide and exerting tremendous socioeconomic burden on all societies. Although definitive diagnosis of AD is often made in the presence of clinical manifestations in late stages, it is now universally believed that AD is a continuum of disease commencing from the preclinical stage with typical neuropathological alterations appearing decades prior to its first symptom, to the prodromal stage with slight symptoms of amnesia (amnestic mild cognitive impairment, aMCI), and then to the terminal stage with extensive loss of basic cognitive functions, i.e., AD-dementia. Positron emission tomography (PET) radiotracers have been developed in a search to meet the increasing clinical need of early detection and treatment monitoring for AD, with reference to the pathophysiological targets in Alzheimer's brain. These include the pathological aggregations of misfolded proteins such as β-amyloid (Aβ) plagues and neurofibrillary tangles (NFTs), impaired neurotransmitter system, neuroinflammation, as well as deficient synaptic vesicles and glucose utilization. In this article we survey the various PET radiotracers available for AD imaging and discuss their clinical applications especially in terms of early detection and cognitive relevance.

Published
2021
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