Publications by authors named "Adam Adler"

195 Publications

Clinical Thoracic Anesthesia, 1st ed.

Anesth Analg 2021 Mar;132(3):e35

Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas,

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http://dx.doi.org/10.1213/ANE.0000000000005326DOI Listing
March 2021

Obstructive Sleep Apnea and Dementia-Common Gene Associations through Network-Based Identification of Common Driver Genes.

Genes (Basel) 2021 Apr 9;12(4). Epub 2021 Apr 9.

Department of Anesthesiology & Pediatrics, Texas Children's Hospital, Houston, TX 77030, USA.

Background: Obstructive Sleep Apnea (OSA) occurs in 7% of the adult population. The relationship between neurodegenerative diseases such as dementia and sleep disorders have long attracted clinical attention; however, no comprehensive data exists elucidating common gene expression between the two diseases. The objective of this study was to (1) demonstrate the practicability and feasibility of utilizing a systems biology approach called network-based identification of common driver genes (NICD) to identify common genomic features between two associated diseases and (2) utilize this approach to identify genes associated with both OSA and dementia.

Methods: This study utilized 2 public databases (PCNet, DisGeNET) and a permutation assay in order to identify common genes between two co-morbid but mutually exclusive diseases. These genes were then linked to their mechanistic pathways through Enrichr, producing a list of genes that were common between the two different diseases.

Results: 42 common genes were identified between OSA and dementia which were primarily linked to the G-coupled protein receptor (GPCR) and olfactory pathways. No single nucleotide polymorphisms (SNPs) were identified.

Conclusions: This study demonstrates the viability of using publicly available databases and permutation assays along with canonical pathway linkage to identify common gene drivers as potential mechanistic targets for comorbid diseases.
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http://dx.doi.org/10.3390/genes12040542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069301PMC
April 2021

Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

Nat Biotechnol 2021 Apr 15. Epub 2021 Apr 15.

Immunobiology Section, Great Ormond Street Institute of Child Health, University College London, London, England.

Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.
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http://dx.doi.org/10.1038/s41587-021-00894-8DOI Listing
April 2021

Mechanisms, diagnosis, prevention and management of perioperative opioid-induced hyperalgesia.

Pain Manag 2021 Apr 29;11(4):405-417. Epub 2021 Mar 29.

Department of Anesthesiology & Perioperative Pain Medicine, Texas Children's Hospital, Houston, TX 77030, USA.

Opioid-induced hyperalgesia (OIH) occurs when opioids paradoxically enhance the pain they are prescribed to ameliorate. To address a lack of perioperative awareness, we present an educational review of clinically relevant aspects of the disorder. Although the mechanisms of OIH are thought to primarily involve medullary descending pathways, it is likely multifactorial with several relevant therapeutic targets. We provide a suggested clinical definition and directions for clinical differentiation of OIH from other diagnoses, as this may be confusing but is germane to appropriate management. Finally, we discuss prevention including patient education and analgesic management choices. As prevention may serve as the best treatment, patient risk factors, opioid mitigation, and both pharmacologic and non-pharmacologic strategies are discussed.
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http://dx.doi.org/10.2217/pmt-2020-0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023328PMC
April 2021

There is light at the end of the tunnel, but we are still in the tunnel: universal preoperative SARS-CoV-2 testing and precautions remain vital in paediatrics.

Br J Anaesth 2021 05 27;126(5):919-920. Epub 2021 Feb 27.

Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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http://dx.doi.org/10.1016/j.bja.2021.01.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910128PMC
May 2021

The Association of Dexmedetomidine on Perioperative Opioid Consumption in Children Undergoing Adenotonsillectomy With and Without Obstructive Sleep Apnea.

Anesth Analg 2021 Jan 15. Epub 2021 Jan 15.

From the Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, Texas.

Background: Dexmedetomidine is used to reduce opioid consumption in pediatric anesthesia. However, there is conflicting evidence in pediatric adenotonsillectomy literature regarding the total perioperative opioid-sparing effects of dexmedetomidine. The aim of this study was to examine the association between dexmedetomidine and total perioperative opioid consumption in children undergoing adenotonsillectomy.

Methods: This was a retrospective cohort study of the children undergoing adenotonsillectomy surgery at Texas Children's Hospital between November 2017 and October 2018. Intraoperative dexmedetomidine was the exposure of interest. The primary outcome was total perioperative opioid consumption calculated as oral morphine equivalents (OME). Secondary outcomes of interest included opioid consumption and pain scores based on presence and absence of obstructive sleep apnea (OSA) and postanesthesia care unit (PACU) duration. We used multivariable linear regression to estimate the association of dexmedetomidine on the outcomes.

Results: A total of 941 patients met inclusion criteria, 697 (74.1%) received intraoperative dexmedetomidine. For every 0.1 µg/kg increase in intraoperative dexmedetomidine, the total perioperative OME (mg/kg) decreases by 0.021 mg/kg (95% CI, -0.027 to -0.015; P < .001). Pain scores did not significantly vary by OSA status. PACU duration increased by 1.14 minutes (95% CI, 0.30-1.99; P = .008) for each 0.1 µg/kg of intraoperative dexmedetomidine.

Conclusions: Dexmedetomidine is associated with an overall perioperative opioid-sparing effect in children undergoing adenotonsillectomy and a small but statistically significant increase in PACU duration. Additionally, children with OSA did not have reduced perioperative opioid consumption.
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http://dx.doi.org/10.1213/ANE.0000000000005410DOI Listing
January 2021

Parental Assessment of Pain Control Following Pediatric Circumcision: Do Opioids Make a Difference?

Urology 2021 Jan 5. Epub 2021 Jan 5.

Division of Pediatric Urology, Department of Surgery, Texas Children's Hospital; Baylor College of Medicine, Houston, TX.

Objective: To determine whether a postoperative prescription for opioids affects parental assessment of pain control following pediatric circumcision.

Methods: This postoperative survey assessed the parental assessment of pain control in 199 patients, ages<18 years undergoing circumcision. This study was conducted at a quaternary care children's hospital in Houston, Texas from December 2018 to January 2020. Postoperative pain regimens included acetaminophen and ibuprofen or combination hydrocodone/acetaminophen in addition to ibuprofen for postoperative analgesia based on the surgical preference. The primary study outcome was identification of the proportion of parents rating their child's analgesia following pediatric circumcision as poor or inadequate based on the postoperative analgesic regimen.

Results: Of the 502 surveys sent, the response rate was 40% (199/502) of those who received the survey email, and 64% (199/308) for those who opened the email. Between the opioid and nonopioid groups, there was no difference in, race/ethnicity (Caucasian; 28% vs 37%; P = .43) or insurance status (insured; 51% vs 45%; P = .44). The proportion of parents who rated their child's pain as poor or inadequately controlled following circumcision was relatively rare:5.5% and 1.1% in the nonopioid and opioid groups, respectively. Parents rating their child's pain as excellent with regards to pain control following circumcision were 61% and 53% in the nonopioids and opioid groups, respectively.

Conclusion: The results of this study indicate that nonopioid analgesic regimens following pediatric circumcision were not associated with decreased parental satisfaction or an increasing assessment of poor or inadequately controlled pain. Limiting opioid exposure following pediatric circumcision is feasible and does not result in worse parental satisfaction with the analgesic plan.
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http://dx.doi.org/10.1016/j.urology.2020.12.027DOI Listing
January 2021

"You can't make me!" Managing adolescent dissent to anesthesia.

Paediatr Anaesth 2021 Apr 4;31(4):397-403. Epub 2021 Feb 4.

Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX, USA.

When adolescents require health care, the need to obtain consent from the parent/legal guardian and assent from the patient can create the potential for an ethical dilemma when these two parties are not in agreement. Here, we describe a representative and common case scenario in which both parent and adolescent patient gave consent and assent, respectively, with a full understanding of the risks and benefits of the procedure and anesthetic. At the time of anesthetic induction, however, the patient expresses that she no longer wishes to have the procedure. We identify a number of considerations that inform the ethical analysis of such cases and offer recommendations about the most appropriate path forward for a practitioner faced with a difficult decision about how to respond.
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http://dx.doi.org/10.1111/pan.14119DOI Listing
April 2021

Effect of Caudal vs. Penile Block on the Incidence of Hypospadias Complications Following Primary Repairs: A Retrospective Cohort Study.

J Urol 2021 May 21;205(5):1454-1459. Epub 2020 Dec 21.

Baylor College of Medicine, Houston, Texas.

Purpose: Primary repair of hypospadias is associated with risk of complications, specifically urethrocutaneous fistula and glanular dehiscence. Caudal block may potentially increase the risk of these complications. Therefore, we studied the incidence of hypospadias complications in children who underwent correction at our institution having received either penile or caudal block.

Materials And Methods: We analyzed all primary hypospadias repair cases from December 2011 through December 2018 at Texas Children's Hospital with a minimum of 1-year followup for the presence of complications: urethrocutaneous fistula and glanular dehiscence. Surgical (surgeon, operative time, block type, local anesthetic, meatal position) and patient (age at correction, prematurity) factors were additionally analyzed.

Results: For the primary aim, 983 patients underwent primary hypospadias correction with a minimum of 1 year of postoperative followup data. There were 897 patients (91.3%) in which no complications were identified and 86 (8.7%) with either urethrocutaneous fistula (81) or glanular dehiscence (5). Of the 86 identified complications, 45/812 (5.5%) were distal, 41/171 (24%) were proximal (p <0.001) with a complication. Rate of complications was not associated with caudal block (OR 0.67, 95% CI 0.41-1.09; p=0.11). On univariable analysis, age (OR 1.12, 95% CI 1.04-1.20; p=0.04), surgical duration (OR 1.02; 95% CI 1.01-1.02; p <0.001), prematurity <32 weeks (OR 4.38, 95% CI 1.54-4.11 p <0.001) and position of meatus as proximal (OR 5.38 95% CI 3.39-8.53; p <0.001) were associated with an increased rate of complications. However, on multivariable analysis, associations of age (OR 1.13, 95% CI 1.05-1.22; p=0.001), surgery duration (OR 1.01, 95% CI 1.01-1.02; p <0.001) and meatal position (OR 3.85, 95% CI 2.32-6.39; p <0.001) were associated with increased rate of complications.

Conclusions: Our data suggest that meatal location, older age, extreme prematurity and surgical duration are associated with increased incidence of complications (urethrocutaneous fistula and glanular dehiscence) following hypospadias correction. Analgesic block was not associated with increased hypospadias complication risk.
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http://dx.doi.org/10.1097/JU.0000000000001448DOI Listing
May 2021

Intermittent Hypoxia and Effects on Early Learning/Memory: Exploring the Hippocampal Cellular Effects of Pediatric Obstructive Sleep Apnea.

Anesth Analg 2020 Nov 20. Epub 2020 Nov 20.

Department of Anesthesiology.

This review provides an update on the neurocognitive phenotype of pediatric obstructive sleep apnea (OSA). Pediatric OSA is associated with neurocognitive deficits involving memory, learning, and executive functioning. Adenotonsillectomy (AT) is presently accepted as the first-line surgical treatment for pediatric OSA, but the executive function deficits do not resolve postsurgery, and the timeline for recovery remains unknown. This finding suggests that pediatric OSA potentially causes irreversible damage to multiple areas of the brain. The focus of this review is the hippocampus, 1 of the 2 major sites of postnatal neurogenesis, where new neurons are formed and integrated into existing circuitry and the mammalian center of learning/memory functions. Here, we review the clinical phenotype of pediatric OSA, and then discuss existing studies of OSA on different cell types in the hippocampus during critical periods of development. This will set the stage for future study using preclinical models to understand the pathogenesis of persistent neurocognitive dysfunction in pediatric OSA.
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http://dx.doi.org/10.1213/ANE.0000000000005273DOI Listing
November 2020

Symptomatology and racial disparities among children undergoing universal preoperative COVID-19 screening at three US children's hospitals: Early pandemic through resurgence.

Paediatr Anaesth 2021 03 2;31(3):368-371. Epub 2020 Dec 2.

Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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http://dx.doi.org/10.1111/pan.14074DOI Listing
March 2021

Analysis of 1478 Cases of Hypospadias Repair: The Incidence of Requiring Repeated Anesthetic Exposure as Well as Exploration of the Involvement of Trainees on Case Duration.

Anesth Analg 2020 11;131(5):1551-1556

From the Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.

Background: Recently, there has been significant focus on the effects of anesthesia on the developing brain. Concern is heightened in children <3 years of age requiring lengthy and/or multiple anesthetics. Hypospadias correction is common in otherwise healthy children and may require both lengthy and repeated anesthetics. At academic centers, many of these cases are performed with the assistance of anesthesia and surgical trainees. We sought to identify both the incidence of these children undergoing additional anesthetics before age 3 as well as to understand the effect of trainees on duration of surgery and anesthesia and thus anesthetic exposure (AE), specifically focusing on those cases >3 hours.

Methods: We analyzed all cases of hypospadias repair from December 2011 through December 2018 at Texas Children's Hospital. In all, 1326 patients undergoing isolated hypospadias repair were analyzed for anesthesia time, surgical time, provider types involved, AE, caudal block, and additional AE related/unrelated to hypospadias.

Results: For the primary aim, a total of 1573 anesthetics were performed in children <3 years of age, including 1241 hypospadias repairs of which 1104 (89%) were completed with <3 hours of AE. For patients with <3 hours of AE, 86.1% had a single surgical intervention for hypospadias. Of patients <3 years of age, 17.3% required additional nonrelated surgeries. There was no difference in anesthesia time in cases performed solely by anesthesia attendings versus those performed with trainees/assistance (16.8 vs 16.8 minutes; P = .98). With regard to surgery, cases performed with surgical trainees were of longer duration than those performed solely by surgical attendings (83.5 vs 98.3 minutes; P < .001). Performance of surgery solely by attending surgeon resulted in a reduced total AE in minimal alveolar concentration (MAC) hours when compared to procedures done with trainees (1.92 vs 2.18; P < .001). Finally, comparison of patients undergoing initial correction of hypospadias with subsequent revisions revealed a longer time (117.7 vs 132.2 minutes; P < .001) and AE during the primary stage.

Conclusions: The majority of children with hypospadias were repaired within a single AE. In general, most children did not require repeated AE before age 3. While presence of nonattending surgeons was associated with an increase in AE, this might at least partially be due to differences in case complexity. Moreover, the increase is likely not clinically significant. While it is critical to maintain a training environment, attempts to minimize AE are crucial. This information facilitates parental consent, particularly with regard to anesthesia duration and the need for additional anesthetics in hypospadias and nonhypospadias surgeries.
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http://dx.doi.org/10.1213/ANE.0000000000004596DOI Listing
November 2020

Universal Screening for COVID-19 in Children Undergoing Orthopaedic Surgery: A Multicenter Report.

J Pediatr Orthop 2020 Nov/Dec;40(10):e990-e993

Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA.

Background: The COVID-19 pandemic has substantially altered the typical process around performing surgery to ensure protection of health care workers, patients, and their families. One safety precaution has been the implementation of universal preoperative screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study examines the results of universal screening on children undergoing orthopaedic surgery.

Methods: This is a retrospective cohort study evaluating the incidence and symptomatology of COVID-19 in all patients presenting for orthopaedic surgery at 3 pediatric tertiary care children's hospitals during the COVID-19 pandemic (March to June 2020). All patients underwent universal screening with a nasopharyngeal swab to detect presence of SARS-CoV-2. Bivariate and multivariate logistic regression analysis was performed to identify risk factors for positive COVID-19 screening.

Results: In total, 1198 patients underwent preoperative screening across all 3 institutions and 7 (0.58%) had detection of SARS-CoV-2. The majority of patients (1/7, 86%) were asymptomatic. Patients that tested positive were significantly more likely to be Hispanic (P=0.046) and had greater number of medical comorbidities (P=0.013), as scored on the American Society of Anesthesiologists (ASA) physical status score. A known COVID-19 positive contact was found to be a significant risk factor in the multivariate analysis (P=0.004).

Conclusions: Early results of universal preoperative screening for COVID-19 demonstrates a low incidence and high rate of asymptomatic patients. Health care professionals, especially those at higher risk for the virus, should be aware of the challenges related to screening based solely on symptoms or travel history and consider universal screening for patients undergoing elective surgery.

Level Of Evidence: Level II.
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http://dx.doi.org/10.1097/BPO.0000000000001657DOI Listing
October 2020

Pediatric obstructive sleep apnea revisited: Perioperative considerations for the pediatric Anesthesiologist.

Int J Pediatr Otorhinolaryngol 2020 Dec 3;139:110420. Epub 2020 Oct 3.

Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.

Pediatric obstructive sleep apnea presents in up to 7% of children and represents a constellation from nasal turbulence to cessation in gas exchange. There are numerous end organ sequelae including neurocognitive morbidity associated with persistent OSA. Adenotonsillectomy (AT), the first line therapy for pediatric OSA, has not been demonstrated to reduce all end organ morbidity, specifically neurological and behavioral morbidity. Furthermore, certain at-risk populations are at higher risk from neurocognitive morbidity. Precise knowledge and perioperative planning is required to ensure optimal evidence-based practices in children with OSA. This comprehensive review covers the seminal perioperative implications of OSA, including preoperative polysomnography, pharmacotherapeutics, and postoperative risk stratification.
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http://dx.doi.org/10.1016/j.ijporl.2020.110420DOI Listing
December 2020

The American Academy of Pediatrics; its structure; mission and the importance of getting involved and supporting individual subsections.

Paediatr Anaesth 2020 10;30(10):1161-1162

Department of Anesthesiology, Stanford University Medical Center, Palo Alto, CA, USA.

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http://dx.doi.org/10.1111/pan.14006DOI Listing
October 2020

Pediatric Obstructive Sleep Apnea and Neurocognition.

Anesthesiol Clin 2020 Sep 16;38(3):693-707. Epub 2020 Jul 16.

Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Baylor College of Medicine, 6621 Fannin Street, A330, Houston, TX 77030, USA.

Pediatric obstructive sleep apnea affects a large number of children and has multiple end-organ sequelae. Although many of these have been demonstrated to be reversible, the effects on some of the organ systems, including the brain, have not shown easy reversibility. Progress in this area has been hampered by lack of a preclinical model to study the disease. Therefore, perioperative and sleep physicians are tasked with making a number of difficult decisions, including optimal surgical timing to prevent disease evolution, but also to keep the perioperative morbidity in a safe range for these patients.
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http://dx.doi.org/10.1016/j.anclin.2020.05.004DOI Listing
September 2020

Perioperative Considerations for the Fontan Patient Requiring Noncardiac Surgery.

Anesthesiol Clin 2020 Sep 16;38(3):531-543. Epub 2020 Jul 16.

Department of Anesthesia, Stanford University Medical Center, 300 Pasteur Drive, Room H3580, MC 5640, Stanford, CA 94304, USA.

Children and adults with congenital heart disease undergoing noncardiac surgery are at higher risk of perioperative adverse events. Patients have significant comorbidities and syndromic associations that increase perioperative risk further. The complexity of congenital heart disease requires a thorough understanding of lesion-specific pathophysiology in order to provide safe care. Comprehensive multidisciplinary planning and the use of skilled and experienced teams achieve the best outcomes. The anesthesiologist is a perioperative physician charged with providing safe anesthesia care, instituting appropriate hemodynamic monitoring, and determining appropriate postoperative disposition on an individual basis.
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http://dx.doi.org/10.1016/j.anclin.2020.04.001DOI Listing
September 2020

Anesthetic considerations for patients with the Kasabach-Merritt phenomenon.

Paediatr Anaesth 2020 10 6;30(10):1155-1156. Epub 2020 Sep 6.

Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, Texas.

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http://dx.doi.org/10.1111/pan.13992DOI Listing
October 2020

Affinity maturation of antibodies by combinatorial codon mutagenesis versus error-prone PCR.

MAbs 2020 Jan-Dec;12(1):1803646

GigaGen, Inc ., South San Francisco, CA, USA.

In Vitro: affinity maturation of therapeutic monoclonal antibodies is commonly applied to achieve desired properties, such as improved binding kinetics and affinity. Currently there are no universally accepted protocols for generation of variegated antibody libraries or selection thereof. Here, we performed affinity maturation using a yeast-based single-chain variable fragment (scFv) expression system to compare two mutagenesis methods: random mutagenesis across the entire V(D)J region by error-prone PCR, and a novel combinatorial mutagenesis process limited to the complementarity-determining regions (CDRs). We applied both methods of mutagenesis to four human antibodies against well-known immuno-oncology target proteins. Detailed sequence analysis showed an even mutational distribution across the entire length of the scFv for the error-prone PCR method and an almost exclusive targeting of the CDRs for the combinatorial method. Though there were distinct mutagenesis profiles for each target antibody and mutagenesis method, we found that both methods improved scFv affinity with similar efficiency. When a subset of the affinity-matured antibodies was expressed as full-length immunoglobulin, the measured affinity constants were mostly comparable to those of the respective scFv, but the full-length antibodies were inferior to their scFv counterparts for one of the targets. Furthermore, we found that improved affinity for the full-length antibody did not always translate into enhanced binding to cell-surface expressed antigen or improved immune checkpoint blocking ability, suggesting that screening with full-length antibody or antigen-binding fragment formats might be advantageous and the subject of a future study.
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http://dx.doi.org/10.1080/19420862.2020.1803646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531523PMC
August 2020

Polysomnography in children with obstructive sleep apnoea and neurocognitive disorders.

Clin Otolaryngol 2020 Nov 16;45(6):885-888. Epub 2020 Sep 16.

Baylor College of Medicine, Houston, TX, USA.

Objective: The neurocognitive associations in paediatric obstructive sleep apnoea (OSA) are well known; however, whether polysomnographic features can predict these associations is unknown. Therefore, the primary objective of this study was to compare common polysomnographic parameters in children with OSA in the presence and absence of neurocognitive dysfunction.

Methods: Polysomnography data for children ages 3-6 years with mild-moderate OSA who as defined by AHI between 5 and 10 were analysed from a single sleep centre at a tertiary paediatric hospital from January 2016 to December 2018. The following parameters were identified: arousals per hour, percentage of time asleep, apnoea-hypopnoea index (AHI), oxygen desaturation nadir during sleeps, baseline oxygen saturation during sleep, time spent with SpO less than 90%, maximum transcutaneous CO2, per cent of the total sleep time spent with TcCO greater than 50 mmHg, age, body mass index (BMI), gender and type of disability in the neurocognitive dysfunction group. Neurocognitive diagnoses were recorded. Those with syndromic comorbidities were excluded. The study cohort was then compared to a cohort of 200 subjects with OSA and no neurocognitive disorders matched for age, gender and BMI. A paired column analysis by chi-squared analysis was then undertaken between the two groups.

Results: A total of 200 children were identified (126 males and 74 females) in the neurocognitive dysfunction group (OSA with neurocognitive dysfunction) and compared with 200 children in the control group (OSA without neurocognitive dysfunction) (113 males and 87 females). There were no statistical differences between groups.

Conclusion: Commonly used polysomnographic indices are not predictive of neurocognitive dysfunction in paediatric OSA.
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http://dx.doi.org/10.1111/coa.13619DOI Listing
November 2020

Incidence of COVID-19 in Pediatric Surgical Patients Among 3 US Children's Hospitals.

JAMA Surg 2020 08;155(8):775-777

The Children's Hospital of Philadelphia, Division of Orthopaedic Surgery, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1001/jamasurg.2020.2588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273313PMC
August 2020

Massively parallel interrogation and mining of natively paired human TCRαβ repertoires.

Nat Biotechnol 2020 05 16;38(5):609-619. Epub 2020 Mar 16.

GigaMune, Inc., South San Francisco, CA, USA.

T cells engineered to express antigen-specific T cell receptors (TCRs) are potent therapies for viral infections and cancer. However, efficient identification of clinical candidate TCRs is complicated by the size and complexity of T cell repertoires and the challenges of working with primary T cells. Here we present a high-throughput method to identify TCRs with high functional avidity from diverse human T cell repertoires. The approach used massively parallel microfluidics to generate libraries of natively paired, full-length TCRαβ clones, from millions of primary T cells, which were then expressed in Jurkat cells. The TCRαβ-Jurkat libraries enabled repeated screening and panning for antigen-reactive TCRs using peptide major histocompatibility complex binding and cellular activation. We captured more than 2.9 million natively paired TCRαβ clonotypes from six healthy human donors and identified rare (<0.001% frequency) viral-antigen-reactive TCRs. We also mined a tumor-infiltrating lymphocyte sample from a patient with melanoma and identified several tumor-specific TCRs, which, after expression in primary T cells, led to tumor cell killing.
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http://dx.doi.org/10.1038/s41587-020-0438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224336PMC
May 2020

Impact of the Fascia Iliaca Block on Pain, Opioid Consumption, and Ambulation for Patients With Hip Fractures: A Prospective, Randomized Study.

J Orthop Trauma 2020 Oct;34(10):533-538

Department of Orthopaedic Surgery and Rehabilitation, Texas Tech University Health Sciences Center El Paso, El Paso, TX.

Objectives: To determine the effect of the fascia iliaca block (FIB) on patients undergoing surgery for hip fractures.

Design: Prospective, randomized controlled trial.

Setting: Level I trauma center.

Patients/participants: Patients (N = 97) undergoing surgery for hip fractures were prospectively randomized to receive either a perioperative FIB (FIB group) or no block (control group) from February 2018 to April 2019.

Main Outcome Measures: Visual analog scale (VAS) score, morphine milligram equivalents, and postoperative ambulatory distance.

Results: Fifty-seven patients were randomized to the FIB group, and 40 patients were randomized to the control group. Eighteen patients crossed over from the FIB to the control group, and 12 patients crossed over from the control to the FIB group. In the intent-to-treat analysis, demographic data, mechanism of injury, radiographic fracture classification, and surgical procedure were similar between the 2 groups. The FIB group consumed fewer morphine milligram equivalents before surgery (13 vs. 17, P = 0.04), had a trend toward an improved visual analog scale score on postoperative day 2 (0 vs. 2 P = 0.06), and walked a farther distance on postoperative day 2 (25' vs. 2', P = 0.09). A greater proportion of the FIB group were discharged home (50.9% vs. 32.5%, P = 0.05). There were no differences in opioid-related, block-related, or medical complications between groups. In the as-treated and per-protocol analyses, there were no significant differences.

Conclusions: A single perioperative FIB for patients with hip fractures undergoing surgery may decrease opioid consumption and increase the likelihood that a patient is discharged home.

Level Of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001795DOI Listing
October 2020

Point-of-care ultrasound in pediatric anesthesia: perioperative considerations.

Curr Opin Anaesthesiol 2020 Jun;33(3):343-353

Arthur S. Keats Division of Pediatric Cardiovascular Anesthesiology, Department of Anesthesiology, Perioperative and Pain Medicine.

Purpose Of Review: To review the perioperative applications of point-of-care ultrasound (POCUS).

Recent Findings: The role of point-of-care ultrasonography for perioperative care is expanding with respect to perioperative application. The imaging approach can complement the physical exam and provide additional information for decision-making in pediatric perioperative medicine. This review will focus on applications in the following organ systems: airway, cardiac, pulmonary and gastric. Specifically, POCUS of the airway has been used to optimize endotracheal tube depth, aid in tube size selection and predict difficulty with laryngoscopy and intubation. Lung POCUS has been used to assess for causes hypoxemia as well as to optimize ventilatory mechanics. Cardiac POCUS has been used for assessment of hemodynamics, valvular and ventricular function. Gastric ultrasound has emerged as an evaluative mechanism of gastric content in the setting of fasting as well as to confirm placement of gastric tubes. The applications of POCUS in the perioperative setting continue to evolve as a reliable diagnostic tool that can assist in timely diagnosis, improve procedural safety and has the potential to improve patient outcomes.

Summary: The utility of perioperative POCUS has been well demonstrated, specifically for examination of the airway, stomach and cardiopulmonary system. It is advisable for the novice sonographer to perform POCUS within the guidelines set by the American Society of Echocardiography regarding basic POCUS. As with all diagnostic modalities, understanding the limitations of ultrasound and POCUS as well as continuous self-assessment is crucial.
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http://dx.doi.org/10.1097/ACO.0000000000000852DOI Listing
June 2020

Parental assessment of pain control following pediatric adenotonsillectomy: Do opioids make a difference?

Int J Pediatr Otorhinolaryngol 2020 Jul 10;134:110045. Epub 2020 Apr 10.

Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, USA; Baylor College of Medicine, USA.

Introduction: Postoperative prescribing of opioids following pediatric adenotonsillectomy can have negative consequences including unnecessary opioid exposure and potential for respiratory depression. While guidelines from The American Academy of Otolaryngology/Head & Neck Surgery recommend treatment of post adenotonsillectomy pain using acetaminophen and ibuprofen, many providers continue to prescribe opioids and may do so, in part with concern for parental dissatisfaction with post-operative analgesia. Our aim was to determine whether a post-operative prescription for opioids affects parental assessment of pain control following pediatric adenotonsillectomy.

Methods: This post-operative survey assessed the parental assessment of pain control in 324 patients, ages 1-17 years undergoing adenotonsillectomy. This study was conducted at a quaternary care children's hospital in Houston, Texas from December 1, 2018 through March 31, 2019. Post-operative pain regimens included acetaminophen and ibuprofen or combination hydrocodone/acetaminophen in addition to ibuprofen for post-operative analgesia based on the attending surgeons prescribing preferences. The primary study outcome was identification of the proportion of parents rating their child's analgesia following pediatric adenotonsillectomy as poor or inadequate based on the post-operative analgesic regimen including opioids.

Results: Of the 798 surveys sent, the response rate was 42% (324/775) of those who received the survey email, and 69% (324/470) for those who opened the email. Between the opioid and non-opioid groups, there was no difference in gender (male; 48% vs. 51.3%; p = 0.58), race/ethnicity (white; 53% vs. 46%; p = 0.35) or insurance status (insured; 62% vs. 50.9%; p = 0.06). The proportion of parents who rated their child's pain as poor or inadequately controlled following adenotonsillectomy was relatively rare: 9% and 5% in the non-opioid and opioid groups, respectively. Parents rating their child's pain as excellent with regards to pain control following adenotonsillectomy were 58% and 50% in the non-opioids and opioid groups respectively.

Conclusion: The results of this study indicate that non-opioid analgesic regimens following pediatric adenotonsillectomy were not associated with decreased parental satisfaction or an increasing assessment of poor or inadequately controlled pain. Limiting opioid exposure following pediatric adenotonsillectomy is feasible and does not result in worse parental satisfaction with the analgesic plan.
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http://dx.doi.org/10.1016/j.ijporl.2020.110045DOI Listing
July 2020

Incidence of Pelvic Ring Fractures in the U.S. Military Population.

Cureus 2020 Feb 6;12(2):e6899. Epub 2020 Feb 6.

Orthopaedic Surgery, Texas Tech University Health Science Center, El Paso, USA.

Introduction  Pelvic ring fractures occur frequently among the elderly population, but some studies demonstrate a bimodal distribution where the incidence is elevated among younger age groups as well. The mechanisms of injury also vary based on age groups. Previous studies are specific to trauma registries and centers, but epidemiological data within the U.S. military are sparse. In the U.S. military population, pelvic ring fractures can be related to high-energy trauma including motor vehicle accidents and combat warfare. The purpose of this study was to determine the incidence of pelvic ring fractures among active duty U.S. military service members between 2006 and 2015, while also describing the demographics associated with the findings. Materials and Methods All data were collected from the U.S. Defense Medical Epidemiology Database (DMED). To calculate the incidence rates, only first-time occurrences for pelvic ring fractures among military members were used. Each point was identified using International Classification of Diseases, Ninth Revision (ICD-9), clinical modification code 808 for "fractures of the pelvis." A multivariate Poisson regression analysis was used to estimate the incidence rate per 1,000 person-years and 95% confidence intervals while controlling for sex, race, age, rank, and service. Rate ratios were calculated using different referent factors based on differences in sex, race, age, rank, and service branch. This study was IRB exempt as all the data used were de-identified patient data from the DMED system. Results Over the 10-year study period, a total of 4,802 incident cases of pelvic ring fractures, and a total of 13,748,429 person-years were documented. The overall incidence rate of pelvic ring fractures was 0.35 per 1,000 person-years. The incidence of pelvic ring fractures was highest among the youngest age group (<20 years) and among the lower-ranking service members. Additionally, other demographic groups such as the White race, female sex, and Army service members showed the highest incidence rates. Conclusion Our study determined baseline epidemiological data on incidence rates of pelvic ring fractures in the U.S. military. Patient demographics may be contributing factors, and the present analysis was able to elucidate associated underlying demographics. We demonstrated that the incidence was highest among the younger age groups, and that incidence rates may be specific to age cohorts. This study also found that lower-ranking service members had the highest incidence in all service branches, suggesting a form of occupational risk. Furthermore, our findings suggest that females, White race groups, and Army enlisted service members show a significantly higher incidence rate and may be at a greater risk. Our findings are important as they broaden the understanding of the patterns of pelvic ring fractures in the U.S. military population and occupational risks associated with this population.
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http://dx.doi.org/10.7759/cureus.6899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061778PMC
February 2020

Pediatric obstructive sleep apnea: Preoperative and neurocognitive considerations for perioperative management.

Paediatr Anaesth 2020 05 25;30(5):529-536. Epub 2020 Mar 25.

Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, TX, USA.

Obstructive sleep apnea (OSA) affects up to 7.5% of the pediatric population and is associated with a variety of behavioral and neurocognitive sequelae. Prompt diagnosis and treatment is critical to halting and potentially reversing these changes. Depending on the severity of the OSA and comorbid conditions, different treatment paradigms can be pursued, each of which has its own unique risk:benefit ratio. Adenotonsillectomy is first-line recommended surgical treatment for pediatric OSA. However, it carries its own perioperative risks and the decision regarding surgical timing is therefore made in the context of procedural risk versus patient benefit. This article presents the seminal perioperative and neurocognitive risks from pediatric OSA to aid with perioperative management.
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http://dx.doi.org/10.1111/pan.13855DOI Listing
May 2020

Response to: 'Fentanyl versus remifentanil-based TIVA for pediatric scoliosis repair: does it matter?' by Kars .

Reg Anesth Pain Med 2020 Jul 28;45(7):563-564. Epub 2020 Feb 28.

Anesthesiology Perioperative and Pain Medicine, Texas Children's Hospital Pediatric Anesthesiology, Houston, Texas, USA.

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http://dx.doi.org/10.1136/rapm-2019-101125DOI Listing
July 2020

Mail-Back Envelopes for Retrieval of Opioids After Pediatric Surgery.

Pediatrics 2020 03 12;145(3). Epub 2020 Feb 12.

Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Houston, Texas; and.

Background: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery.

Methods: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well as instruction on the dangers of opioids in the home. Our primary outcome was to assess the absolute percent return rate through the use of a mail-back envelope.

Results: Between November 2017 and October 2018, we identified 355 patients, of whom 331 were included in the analysis. In total, 64 (19.3%) returned opioids. In total, >2000 mL of liquid opioids and >250 tablets or nearly 3000 mg of oral morphine equivalents were removed from the homes of the 64 participants. Of those patients returning unused medications, the median rate of return was 58% (interquartile range = 34.7%-86.1%) of the written prescription.

Conclusions: The findings suggest that providing a free mail-back return envelope is a suitable way to remove unused opioids from the home after pediatric surgery. Additional research is needed to identify barriers to return of unused medications.
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http://dx.doi.org/10.1542/peds.2019-2449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055926PMC
March 2020

GRK2 enforces androgen receptor dependence in the prostate and prostate tumors.

Oncogene 2020 03 20;39(11):2424-2436. Epub 2020 Jan 20.

Department of Immunology, School of Medicine, UConn Health, Farmington, CT, USA.

Metastatic tumors that have become resistant to androgen deprivation therapy represent the major challenge in treating prostate cancer. Although these recurrent tumors typically remain dependent on the androgen receptor (AR), non-AR-driven tumors that also emerge are particularly deadly and becoming more prevalent. Here, we present a new genetically engineered mouse model for non-AR-driven prostate cancer that centers on a negative regulator of G protein-coupled receptors that is downregulated in aggressive human prostate tumors. Thus, prostate-specific expression of a dominant-negative G protein-coupled receptor kinase 2 (GRK2-DN) transgene diminishes AR and AR target gene expression in the prostate, and confers resistance to castration-induced involution. Further, the GRK2-DN transgene dramatically accelerates oncogene-initiated prostate tumorigenesis by increasing primary tumor size, potentiating visceral organ metastasis, suppressing AR, and inducing neuroendocrine marker mRNAs. In summary, GRK2 enforces AR-dependence in the prostate, and the loss of GRK2 function in prostate tumors accelerates disease progression toward the deadliest stage.
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http://dx.doi.org/10.1038/s41388-020-1159-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072002PMC
March 2020