Norah E. Liang

All Publications

• Outcomes after metabolic and bariatric surgery in preteens versus teens using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database and center-specific data. Obesity (Silver Spring, Md.) Shah, A., Liang, N. E., Bruzoni, M., Pratt, J. S., Zitsman, J., Nadler, E. P. 2023

  Abstract

  OBJECTIVE: The American Academy of Pediatrics (AAP) recently released clinical guidelines for the treatment of childhood obesity, including surgery being appropriate for children 13years of age and older. The use of this age cut-off was due to a lack of data for children younger than 13. To address this knowledge gap, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried to compare outcomes in preteens to teens after bariatric surgery hypothesizing that there would be no difference in outcomes between the two groups.METHODS: Patients from the MSAQIP database (2016-2021) were identified and divided into groups <13years and 13-18years and were matched using propensity scores based on race, sex, and preoperative BMI. Outcomes were compared including change in BMI, complication rates, 30-day readmission or reoperation, and mortality. Additionally, the centers responsible for the bulk of the preteen patient entries queried their center-specific databases to evaluate weight loss over time.RESULTS: A total of 4755 patients were identified, 47 of whom were<13years of age. Preteens had similar sex distribution (66% vs. 75% female), were more likely to be Black (27.7% vs. 18.3%) or Hispanic (21.3% vs. 7.6%) race, and weighed less (274±58 vs. 293±85 lb, p=0.01), but they had similar BMI (46.9±7 vs. 47±13kg/m2 ) as their teen counterparts. Preteens were more likely to suffer from sleep apnea (34% vs. 19%, p<0.01) and insulin-dependent type 2 diabetes (10.6% vs. 1.8%, p<0.01). There were no complications in the preteens compared to teens (0% vs. 0.5%), and they did not undergo any unplanned readmissions (0% vs. 2.9%) or reoperations (0% vs. 0.8%) within 30days of surgery. There were also no mortalities reported in preteens (0% vs. 0.1%). The risk-adjusted decrease in BMI between preteens and teens was also comparable at 30days (4.2 [95% CI: 3.0-5.4] vs. 4.6 [95% CI: 4.4-4.7], p=0.6). Decrease in BMI in preteens was 7±3kg/m2 at 3 months and 9±4kg/m2 at 12 months after surgery, which represented a percentage BMI change of 16±7 and 20±8, respectively.CONCLUSIONS: This study demonstrates that bariatric surgery in preteens is safe and efficacious when performed at specialized centers, and that age criteria may not be required. The AAP and others are encouraged to include age cut-offs in their guidelines for children with obesity and bariatric surgery only when data are available to support their inclusion.

  View details for DOI 10.1002/oby.23908

  View details for PubMedID 37800184

• Attenuating Chronic Fibrosis: Decreasing Foreign Body Response with Acellular Dermal Matrix. Tissue engineering. Part B, Reviews Liang, N. E., Griffin, M., Berry, C. E., Parker, J. B., Downer, M. A., Wan, D. C., Longaker, M. T. 2023

  Abstract

  Surgical implants are increasingly used across multiple medical disciplines, with applications ranging from tissue reconstruction to improving compromised organ and limb function. Despite their significant potential for improving health and quality of life, biomaterial implant function is severely limited by the body's immune response to its presence: this is known as the foreign body response and is characterized by chronic inflammation and fibrotic capsule formation. This response can result in life-threatening sequelae such as implant malfunction, superimposed infection and associated vessel thrombosis, in addition to soft tissue disfigurement. Patients may require frequent medical visits, as well as repeated invasive procedures, increasing the burden on an already strained healthcare system. Currently, the foreign body response and the cells and molecular mechanisms that mediate it are poorly understood. With applications across a wide array of surgical specialties, acellular dermal matrix has emerged as a potential solution to the fibrotic reaction seen with FBR. Though the mechanisms by which acellular dermal matrix decreases chronic fibrosis remain to be clearly characterized, animal studies across diverse surgical models point to its biomimetic properties that facilitate decreased periprosthetic inflammation and improved host cell incorporation.

  View details for DOI 10.1089/ten.TEB.2023.0060

  View details for PubMedID 37212342

• The effects of mechanical force on fibroblast behavior in cutaneous injury. Frontiers in surgery Berry, C. E., Downer, M., Morgan, A. G., Griffin, M., Liang, N. E., Kameni, L., Laufey Parker, J. B., Guo, J., Longaker, M. T., Wan, D. C. 2023; 10: 1167067

  Abstract

  Wound healing results in the formation of scar tissue which can be associated with functional impairment, psychological stress, and significant socioeconomic cost which exceeds 20 billion dollars annually in the United States alone. Pathologic scarring is often associated with exaggerated action of fibroblasts and subsequent excessive accumulation of extracellular matrix proteins which results in fibrotic thickening of the dermis. In skin wounds, fibroblasts transition to myofibroblasts which contract the wound and contribute to remodeling of the extracellular matrix. Mechanical stress on wounds has long been clinically observed to result in increased pathologic scar formation, and studies over the past decade have begun to uncover the cellular mechanisms that underly this phenomenon. In this article, we will review the investigations which have identified proteins involved in mechano-sensing, such as focal adhesion kinase, as well as other important pathway components that relay the transcriptional effects of mechanical forces, such as RhoA/ROCK, the hippo pathway, YAP/TAZ, and Piezo1. Additionally, we will discuss findings in animal models which show the inhibition of these pathways to promote wound healing, reduce contracture, mitigate scar formation, and restore normal extracellular matrix architecture. Recent advances in single cell RNA sequencing and spatial transcriptomics and the resulting ability to further characterize mechanoresponsive fibroblast subpopulations and the genes that define them will be summarized. Given the importance of mechanical signaling in scar formation, several clinical treatments focused on reducing tension on the wound have been developed and are described here. Finally, we will look toward future research which may reveal novel cellular pathways and deepen our understanding of the pathogenesis of pathologic scarring. The past decade of scientific inquiry has drawn many lines connecting these cellular mechanisms that may lead to a map for the development of transitional treatments for patients on the path to scarless healing.

  View details for DOI 10.3389/fsurg.2023.1167067

  View details for PubMedID 37143767

  View details for PubMedCentralID PMC10151708

• Obstructive Jaundice Secondary to Peribiliary Cyst Within the Common Hepatic Duct AMERICAN SURGEON Gartland, R. M., Landino, S. M., Liang, N. E., Day, C. J., Berger, D. L. 2023; 89 (3): 478-480

  View details for DOI 10.1177/0003134820973359

  View details for Web of Science ID 000932257000025

  View details for PubMedID 33283523

• Multiplexed evaluation of mouse wound tissue using oligonucleotide barcoding with single-cell RNA sequencing. STAR protocols Januszyk, M., Griffin, M., Mascharak, S., Talbott, H. E., Chen, K., Henn, D., Spielman, A. F., Parker, J. B., Liang, N. E., Cotterell, A., Guardino, N., Foster, D. S., Wagh, D., Coller, J., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2022; 4 (1): 101946

  Abstract

  Despite its rapidly increased availability for the study of complex tissue, single-cell RNA sequencing remains prohibitively expensive for large studies. Here, we present a protocol using oligonucleotide barcoding for the tagging and pooling of multiple samples from healing wounds, which are among the most challenging tissue types for this application. We describe steps to generate skin wounds in mice, followed by tissue harvest and oligonucleotide barcoding. This protocol is also applicable to other species including rats, pigs, and humans. For complete details on the use and execution of this protocol, please refer to Stoeckius etal. (2018),1 Galiano etal. (2004),2 and Mascharak etal. (2022).3.

  View details for DOI 10.1016/j.xpro.2022.101946

  View details for PubMedID 36525348

• A Novel Thoracic Ultrasound Measurement After Congenital Diaphragmatic Hernia Repair Identifies Decreased Diaphragmatic Excursion Associated With Adverse Respiratory and Surgical Outcomes FRONTIERS IN PEDIATRICS Ross, J. T., Liang, N. E., Phelps, A. S., Squillaro, A., Vu, L. T. 2021; 9: 707052

  Abstract

  Background and Aim: Congenital diaphragmatic hernia (CDH) is a rare defect often associated with pulmonary hypoplasia and abnormal pulmonary vascular development. Even after successful hernia repair, pulmonary disease may persist into adulthood. Impaired diaphragmatic motility may lead to compromised respiratory function long after index repair. This study investigates whether a novel ultrasound measurement, the diaphragmatic excursion ratio, can be a simple and non-invasive method to evaluate routine diaphragmatic motion after CDH repair, and whether it correlates with adverse surgical and respiratory outcomes. Materials and Methods: A cross-sectional study was conducted in consecutive patients who presented at medium-term follow-up visit between December 2017 and December 2018 after CDH repair at single pediatric hospital. Transthoracic ultrasound was performed with craniocaudal diaphragmatic excursion measured bilaterally during routine breathing. Diaphragmatic excursion ratios (diaphragmatic excursion of repaired vs. unrepaired side) were calculated and retrospectively compared with clinical data including demographics, length of stay, respiratory adjuncts, oral feeding, and need for gastrostomy. Results: Thirty-eight patients (median age at ultrasound, 24 months, interquartile range 11-60) were evaluated. Nine patients underwent primary repair, 29 had non-primary repair (internal oblique muscle flap or mesh patch). Patients with a diaphragmatic excursion ratio below the median (0.54) had longer hospital stays (median 77 vs. 28 days, p = 0.0007) more ventilator days (median 16 vs. 9 days, p =0.004), and were more likely to have been discharged on oxygen (68 vs. 16%, p = 0.001). They were also less likely to be exclusively taking oral feeds at 1-year post-surgery (37 vs. 74%, p = 0.02) and more likely to require a gastrostomy tube in the first year of life (74 vs. 21%, p = 0.003). Conclusions: Transthoracic ultrasound after CDH repair is practical method to assess diaphragm motion, and decreased diaphragm excursion ratio is associated with worse respiratory outcomes, a longer length of stay, and dependence on gastrostomy tube feeding within 1 year. Further prospective studies may help validate this novel ultrasound measurement and offer prognostic value.

  View details for DOI 10.3389/fped.2021.707052

  View details for Web of Science ID 000687378000001

  View details for PubMedID 34422729

  View details for PubMedCentralID PMC8375432

• Development of the Minimalist Approach for Transcatheter Aortic Valve Replacement at a Veterans Affairs Medical Center JOURNAL OF INVASIVE CARDIOLOGY Lum, M. Y., Wang, S. X., Wisneski, A. D., Liang, N., Zimmet, J., Shunk, K. A., Stechert, M., London, M. J., Ge, L., Tseng, E. E. 2021; 33 (2): E108-E114

  Abstract

  While a minimalist transcatheter aortic valve replacement (TAVR) approach has shown safety and efficacy at civilian hospitals, limited data exist regarding developing this approach at Veterans Affairs (VA) medical centers (VAMCs). We implemented TAVR with minimalist approach (MA) using conscious sedation (CS) with transthoracic echocardiography (TTE) and compared safety and outcomes with general anesthesia (GA) with transesophageal echocardiography (TEE) at a university-affiliated VAMC.A total of 258 patients underwent transfemoral TAVR at a VAMC between November 2013 and October 2019. Ninety-three patients underwent GA/TEE and 165 patients underwent CS/TTE with dexmedetomidine and remifentanil. Propensity-score matching with nearest-neighbor matching was used to account for baseline differences, yielding 227 participants (81 GA, 146 CS).MA-TAVR had no effect on 30-day mortality or paravalvular leakage. No differences were found in permanent pacemaker implantation, major vascular complications, or postoperative hemodynamics. In this population, MA-TAVR did not reduce procedural time, hospital length of stay, or intensive care unit length of stay.Unlike civilian hospitals, MA with CS/TTE did not reduce overall length of stay in the veteran population; however, it was safe and effective for transfemoral TAVR without impacting clinical outcomes of mortality, major vascular complications, and paravalvular leakage.

  View details for Web of Science ID 000618245100007

  View details for PubMedID 33531442

  View details for PubMedCentralID PMC8589465

• Diagnostic Challenges in Primary Sacral Tumors and the Yield of Computed Tomography-Guided Needle Biopsy in the Modern Era WORLD NEUROSURGERY Safaee, M. M., Carrera, D. A., Chin, C. T., Mashhood, A., Eisenmenger, L., Liang, N. E., Lewis, K. M., Chou, D., Ames, C. P., Weinstein, P. R. 2020; 138: E806-E818

  Abstract

  Primary sacral tumors pose unique challenges because of their complex radiographic appearances, diverse pathologic entities, and dramatically different treatment paradigms based on tumor type. Magnetic resonance imaging and computed tomography (CT) can provide valuable information; however, sacral lesions can possess unique radiographic features and pose diagnostic dilemmas. CT-guided percutaneous needle biopsy is a critical component of the diagnostic workup. However, limited data are available on its efficacy for primary sacral tumors.The data from patients with newly diagnosed primary sacral lesions during a 12-year period at our hospital were analyzed. The preoperative magnetic resonance imaging findings, biopsy results, and pathological data for patients who required surgery were analyzed. Unique cases in which the final pathologic result was unexpected from the preoperative imaging findings have been highlighted.Of 38 patients who underwent percutaneous needle biopsy, diagnostic tissue was obtained on the first attempt for 31 (82%). Five of the remaining 7 obtained diagnostic tissue on the second attempt, yielding 95% diagnosis, with only two requiring open biopsies. In 2 patients with diagnostic tissue on CT-guided biopsy, an open biopsy was still recommended because of the clinical scenario. In both patients, the open biopsy results matched those of the CT-guided biopsy. For the 18 patients who required surgery, we found 100% correlation between the percutaneous needle biopsy findings and the final pathological diagnosis. No biopsy-induced complications or extraspinal tumor seeding occurred.CT-guided biopsy is a safe and effective technique. It represents a critical component of the diagnostic algorithm, given the diverse pathological findings of primary sacral lesions and dramatic differences in treatment.

  View details for DOI 10.1016/J.WNEU.2020.03.094

  View details for Web of Science ID 000540724700016

  View details for PubMedID 32222551

• A Rare Case of Gallbladder Small Cell Carcinoma JOURNAL OF GASTROINTESTINAL SURGERY Liang, N. E., Taylor, M. S., Ferrone, C. R. 2021; 25 (2): 561-564

  View details for DOI 10.1007/s11605-020-04620-8

  View details for Web of Science ID 000531752600001

  View details for PubMedID 32394121

  View details for PubMedCentralID 4555718

• Veterans Affairs Heart Team Experience With Transcatheter Aortic Valve Replacement and Minimally Invasive Surgical Aortic Valve Replacement JOURNAL OF INVASIVE CARDIOLOGY Liang, N. E., Wisneski, A. D., Wang, S. X., Shunk, K. A., Wozniak, C. J., Yang, J., Zimmet, J. M., Ge, L., Tseng, E. E. 2019; 31 (8): 217-222

  Abstract

  Aortic valve disease is prevalent in the veteran population. Transcatheter aortic valve replacement (TAVR) and minimally invasive surgical aortic valve replacement (MIAVR) are minimally invasive approaches predominantly performed at higher-volume cardiac centers. The study aim was to evaluate our experience with minimally invasive techniques at a Veterans Affairs Medical Center (VAMC), since outcomes from lower-volume federal facilities are relatively unknown.This study examined retrospective data from 228 consecutive patients who underwent treatment for isolated aortic valve disease with MIAVR or TAVR via intent-to-treat at a VAMC between January 2011 and July 2017. Perioperative outcomes were analyzed using Stata version 15.Operative mortality was 1.1% for MIAVR and 0.7% for TAVR (Χ² P=.79). Median length of hospital stay was 10 days (interquartile range [IQR], 7-14 days) for MIAVR and 4 days for TAVR (IQR, 3-6 days; Mann-Whitney P<.001). Postoperative new-onset atrial fibrillation occurred in 52% of MIAVR patients and 5.2% of TAVR patients (Χ² P<.001). Stroke occurred in 2.2% of MIAVR patients and 3.0% of TAVR patients (Χ² P=.71). In patients who underwent MIAVR, 5.4% required placement of a permanent pacemaker postoperatively, compared with 14% of TAVR patients (Χ² P=.04). Mild paravalvular leak (PVL) affected 2.2% of MIAVR and 28% of TAVR patients, with moderate PVL reported in 2.2% of MIAVR and 3% of TAVR patients (Χ² P<.001).The VAMC heart team offers MIAVR and TAVR to veterans with isolated aortic valve disease, and has achieved excellent outcomes despite relatively lower case volumes. Both offer excellent hemodynamic results, with low mortality in a complex population.

  View details for Web of Science ID 000494296900004

  View details for PubMedID 31088993

  View details for PubMedCentralID PMC8505266

• Clinical signs and electroencephalographic patterns of emergence from sevoflurane anaesthesia in children: An observational study EUROPEAN JOURNAL OF ANAESTHESIOLOGY Cornelissen, L., Donado, C., Lee, J. M., Liang, N. E., Mills, I., Tou, A., Bilge, A., Berde, C. B. 2018; 35 (1): 49-59

  Abstract

  Few studies have systematically described relationships between clinical-behavioural signs, electroencephalographic (EEG) patterns and age during emergence from anaesthesia in young children.To identify the relationships between end-tidal sevoflurane (ETsevoflurane) concentration, age and frontal EEG spectral properties in predicting recovery of clinical-behavioural signs during emergence from sevoflurane in children 0 to 3 years of age, with and without exposure to nitrous oxide. The hypothesis was that clinical signs occur sequentially during emergence, and that for infants aged more than 3 months, changes in alpha EEG power are correlated with clinical-behavioural signs.An observational study.A tertiary paediatric teaching hospital from December 2012 to August 2016.Ninety-five children aged 0 to 3 years who required surgery below the neck.Time-course of, and ETsevoflurane concentrations at first gross body movement, first cough, first grimace, dysconjugate eye gaze, frontal (F7/F8) alpha EEG power (8 to 12 Hz), frontal beta EEG power (13 to 30 Hz), surgery-end.Clinical signs of emergence followed an orderly sequence of events across all ages. Clinical signs occurred over a narrow ETsevoflurane, independent of age [movement: 0.4% (95% confidence interval (CI), 0.3 to 0.4), cough 0.3% (95% CI, 0.3 to 0.4), grimace 0.2% (95% CI, 0 to 0.3); P > 0.5 for age vs. ETsevoflurane]. Dysconjugate eye gaze was observed between ETsevoflurane 1 to 0%. In children more than 3 months old, frontal alpha EEG oscillations were present at ETsevoflurane 2.0% and disappeared at 0.5%. Movement occurred within 5 min of alpha oscillation disappearance in 99% of patients. Nitrous oxide had no effect on the time course or ETsevoflurane at which children showed body movement, grimace or cough.Several clinical signs occur sequentially during emergence, and are independent of exposure to nitrous oxide. Eye position is poorly correlated with other clinical signs or ETsevoflurane. EEG spectral characteristics may aid prediction of clinical-behavioural signs in children more than 3 months.

  View details for DOI 10.1097/EJA.0000000000000739

  View details for Web of Science ID 000418869400007

  View details for PubMedID 29120939

  View details for PubMedCentralID PMC5728588

• Clinical Signs and Electroencephalographic Patterns of Emergence From Sevoflurane Anesthesia in Children Cornelissen, L., Liang, N., Donado, C., Lee, J., Bilge, A., Berde, C. LIPPINCOTT WILLIAMS & WILKINS. 2017: 929

  View details for Web of Science ID 000412683000474

• Discovery of 8-Membered Ring Sulfonamides as Inhibitors of Oncogenic Mutant Isocitrate Dehydrogenase 1 ACS MEDICINAL CHEMISTRY LETTERS Law, J. M., Stark, S. C., Liu, K., Liang, N. E., Hussain, M. M., Leiendecker, M., Ito, D., Verho, O., Stern, A. M., Johnston, S. E., Zhang, Y., Dunn, G. P., Shamji, A. F., Schreiber, S. L. 2016; 7 (10): 944-949

  Abstract

  Evidence suggests that specific mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2) are critical for the initiation and maintenance of certain tumor types and that inhibiting these mutant enzymes with small molecules may be therapeutically beneficial. In order to discover mutant allele-selective IDH1 inhibitors with chemical features distinct from existing probes, we screened a collection of small molecules derived from diversity-oriented synthesis. The assay identified compounds that inhibit the IDH1-R132H mutant allele commonly found in glioma. Here, we report the discovery of a potent (IC50 = 50 nM) series of IDH1-R132H inhibitors having 8-membered ring sulfonamides as exemplified by the compound BRD2879. The inhibitors suppress (R)-2-hydroxyglutarate production in cells without apparent toxicity. Although the solubility and pharmacokinetic properties of the specific inhibitor BRD2879 prevent its use in vivo, the scaffold presents a validated starting point for the synthesis of future IDH1-R132H inhibitors having improved pharmacological properties.

  View details for DOI 10.1021/acsmedchemlett.6b00264

  View details for Web of Science ID 000385689300016

  View details for PubMedID 27774134

  View details for PubMedCentralID PMC5066158