87 results on '"Lasky, S"'
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2. Similarities and Differences Between Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis
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Van Thiel, D. H., Lasky, S., Gavaler, J. S., Whiteside, T., Schade, R. R., Galli, G., editor, and Bosisio, E., editor
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- 1985
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3. LETTERS
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LASKY, S. G., MILLER, JULIUS SUMNER, LIETZKE, M. H., PROVOST, MAURICE W., and PECKINPAUGH, C. L.
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- 1952
4. The Impact of Presurgical Nasoalveolar Molding on Midface Growth in Unilateral Cleft Lip and Palate: A Systematic Review and Meta-Analysis
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Moshal, T., Roohani, I., Jolibois, M., Lasky, S., Manasyan, A., Naidu, P., Munabi, N. C. O., Urata, M. M., Hammoudeh, J. A., and Magee, W. P.
- Abstract
Objective Nasoalveolar molding (NAM) can optimize aesthetic outcomes in patients with cleft lip and palate (CLP), particularly in those with wider clefts. However, its impact on long-term postoperative sequelae such as midface hypoplasia (MFH) remains unclear. This study analyzed cephalometric data to evaluate NAM's effect on MFH in patients with complete unilateral CLP (UCLP).Design Systematic Review and Meta Analysis.Patients Included studies reported cephalometrics of patients ≥ 7 years old with repaired UCLP who underwent presurgical NAM versus no-NAM (control). Studies of bilateral cases or unoperated clefts were excluded.Main Outcome Measures Main outcomes were cephalometric angles (sella-nasion-A point (SNA), sella-nasion-B point (SNB), and A point-nasion-B point (ANB)) of patients treated with NAM vs. no-NAM.Results Of 2063 articles, three met inclusion criteria. Cephalometrics were reported for 171 patients (89 NAM, 82 no-NAM) at an average age of 8.5 ± 0.9 years. On pooled analysis, compared to the no-NAM cohort, the NAM cohort had insignificantly smaller SNA (78.8°±1.5° vs. 76.7°±1.5°, p = 0.169), SNB (75.5°±1.0° vs. 75.5°±1.0°, p = 0.954), and ANB (3.6°±1.4° vs. 1.23°±1.2°, p = 0.089) angles. Upon meta-analysis, compared to the no-NAM cohort, the NAM cohort had significantly smaller SNA (Mean Difference (MD) −1.96 [−3.31 to −0.61], p = 0.005) and ANB angles (MD −2.22 [−3.20 to −1.24], p < 0.001).Conclusion This meta-analysis revealed that patients with UCLP who underwent presurgical NAM had significantly smaller SNA and ANB angles, possibly indicating worse MFH. Before choosing NAM, clinicians should consider CLP severity, potential sagittal growth restrictions, and feasibility, particularly in low-resource settings.
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- 2024
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5. Liver transplantation
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Van Thiel Dh, Lasky S, J. S. Gavaler, Urban E, Dindzans, Robert Leventhal, and Berman Dh
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Reoperation ,medicine.medical_specialty ,Survival ,Physiology ,medicine.medical_treatment ,Liver transplantation ,Single Center ,Liver disease ,Humans ,Medicine ,Prospective Studies ,Primary graft failure ,Fulminant hepatitis ,business.industry ,Liver Diseases ,Gastroenterology ,Cancer ,medicine.disease ,Survival Analysis ,United States ,Liver Transplantation ,Surgery ,Transplantation ,United States Department of Veterans Affairs ,Hepatic artery thrombosis ,surgical procedures, operative ,business - Abstract
The Veterans Administration entered the clinical liver transplant field in 1983 and continued its program through July 1988. During this time interval, from the 172 Veterans Administration Medical Centers in the United States, 146 contact calls were initiated to the single center authorized to do liver transplants for the Veterans Administration. One hundred one (69%) of these contact calls resulted in a patient evaluation. Of the 101 patients evaluated, 77 (76%) were accepted for liver transplantation (OLTx). Of these 77, 67 (87%) were transplanted. The reasons for denial of transplant evaluation were numerous and included metastatic cancer, active alcoholism, homosexuality, and a variety of concurrent medical problems. The reasons for denying liver transplantation after evaluation were similar and included concurrent medical problems that contraindicated transplantation (N = 14), metastatic cancer (N = 6), and liver disease of insufficient severity to justify transplantation (N = 3). The number of transplants performed annually by the Veterans Administration increased from one in 1983 to 21 in 1988. Seventeen second grafts and two third grafts were transplanted in 17 cases, resulting in a retransplant rate of 22%; 46% of the patients receiving a second graft survived. None of those receiving three grafts survived. The reasons for retransplantation included acute and/or chronic rejection (N = 6), hepatic artery thrombosis (N = 5), primary graft failure (N = 4), recurrent cancer (N = 2), fulminant hepatitis and portal venous emboli (one each). A total of 45 transplanted patients are still alive (67% of those transplanted).(ABSTRACT TRUNCATED AT 250 WORDS)
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- 1990
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6. Emotions as a lens to explore teacher identity and change: Different theoretical approaches
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Veen, K. van, Lasky, S., Veen, K. van, and Lasky, S.
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- 2005
7. Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes.
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Morgan, J W, primary, Morgan, D M, additional, Lasky, S R, additional, Ford, D, additional, Kouttab, N, additional, and Maizel, A L, additional
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- 1996
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8. Metabolism and biological activity of 1,25(OH)2D2 and its metabolites in a chronic myelogenous leukemia cell line, rwleu-4
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Clark, J.W., primary, Reddy, G.S., additional, Santos-Moore, A., additional, Wankadiya, K.F., additional, Reddy, G.P., additional, Eil, C., additional, Lasky, S., additional, Tserng, K-Y., additional, Horst, R.L., additional, and Uskokovic, M.R., additional
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- 1993
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9. Differential regulation of JunD by dihydroxycholecalciferol in human chronic myelogenous leukemia cells.
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Lasky, S R, Iwata, K, Rosmarin, A G, Caprio, D G, and Maizel, A L
- Abstract
1,25-Dihydroxyvitamin D3 inhibits the proliferation of the chronic myelogenous leukemia cell line RWLeu-4 but not the resistant variant, JMRD3. Although these cells exhibit no detectable differences in the vitamin D receptor, alterations in the interaction of nuclear extracts with the osteocalcin-1,25-dihydroxyvitamin D3-response element are noted. It is shown herein that the 1,25-dihydroxyvitamin D3 receptor binds to the osteocalcin-1,25-dihydroxyvitamin D3-response element along with activator protein-1 (AP-1) complexes and that the DNA binding activities of members of the Jun and Fos proto-oncogene families, which make up the AP-1 transcription factor, are differentially regulated by 1,25-dihydroxyvitamin D3. It is shown that JunD DNA binding activity is enhanced by 1,25-dihydroxyvitamin D3 during cell cycle arrest in the sensitive cells but is decreased in the resistant cells. These results suggest that the level of JunD DNA binding activity may be a critical factor in the regulation of proliferation.
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- 1995
10. Differential expression of alternative 5' untranslated regions in mRNAs encoding rat insulin-like growth factor I.
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Lowe, W L, Roberts, C T, Lasky, S R, and LeRoith, D
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Rat insulin-like growth factor I (IGF-I) cDNAs contain three alternative 5' untranslated sequences (termed class A, B, and C), which are associated with an identical coding region for the mature IGF-I peptide. A solution hybridization/RNase protection assay was used to simultaneously quantitate the relative abundance of IGF-I transcripts with the different 5' untranslated regions. In all the tissues studied, transcripts with the class C 5' untranslated region were most abundant. In contrast, both class A and B transcripts were tissue specific. Class A transcripts were present in moderate abundance in liver; in low abundance in kidney, lung, testes, and stomach; and were undetectable in muscle, heart, and brain; whereas class B transcripts were detected only in liver. These three classes of 5' untranslated region were also regulated independently by growth hormone. In liver, heart, kidney, and lung, growth hormone increased the abundance of class C transcripts 2- to 3-fold. In liver, growth hormone increased the abundance of the class A and B transcripts 6- to 7-fold. In lung and kidney, on the other hand, the abundance of class A transcripts was not affected by growth hormone. Thus, rat IGF-I gene transcripts contain one of three alternative 5' untranslated regions, which are expressed in a tissue-specific manner and are differentially regulated by growth hormone. Finally, cDNA probes unique to two of the three 5' untranslated regions hybridized to all three major species of IGF-I mRNA typically seen on RNA blots with a coding region probe.
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- 1987
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11. Mechanism of interferon action. Characterization of sites of phosphorylation in the interferon-induced phosphoprotein P1 from mouse fibroblasts: evidence for two forms of P1.
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Lasky, S R, Jacobs, B L, and Samuel, C E
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- 1982
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12. Mechanism of interferon action. Purification and substrate specificities of the double-stranded RNA-dependent protein kinase from untreated and interferon-treated mouse fibroblasts.
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Berry, M J, Knutson, G S, Lasky, S R, Munemitsu, S M, and Samuel, C E
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The double-stranded RNA (dsRNA)-dependent protein kinase which catalyzes the phosphorylation of ribosome-associated protein P1 and the alpha subunit of eukaryotic protein synthesis initiation factor 2 (eIF-2) was purified and characterized from mouse fibroblast L929 cells treated with either natural or recombinant interferon and from untreated cells. The dsRNA-dependent P1/eIF-2 alpha kinase was purified at least 1,500-fold from interferon-treated cells; the kinase activity that catalyzed the phosphorylation of eIF-2 alpha copurified with protein P1. The yield of P1/eIF-2 alpha protein kinase activity obtained following purification from cells treated with interferon was about 5-10 times greater than the yield from an equivalent number of untreated cells. The purified protein kinase remained dsRNA dependent. When P1 kinase was activated by dsRNA, a major phosphopeptide designated Xds was phosphorylated; Xds was not phosphorylated from P1 which had not been activated by dsRNA. The apparent native molecular weight of the purified mouse L929 dsRNA-dependent kinase as determined by sedimentation analysis was about 62,000, comparable to the molecular weight of 67,000 determined for denatured L929 phosphoprotein P1 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified protein kinase was highly selective for the alpha subunit of protein synthesis initiation factor eIF-2 and endogenous protein P1. Kinase activity was dependent upon Mg2+, and the Km for ATP was determined to be 5 X 10(-6) M. Histones (H1, H2A-B, H3, and H4) and protein synthesis initiation factors other than eIF-2 (eIF-3, eIF-4A, eIF-4B, and eIF-5) were not substrates or were very poor substrates for the purified dsRNA-dependent protein kinase. N-Ethylmaleimide, ethylenediaminetetraacetic acid, AMP, pyrophosphate, spermine, spermidine, and high concentrations of potassium inhibited both P1 and eIF-2 alpha phosphorylation by the purified kinase, whereas ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and phenanthroline did not significantly affect the phosphorylation of either protein P1 or eIF-2 alpha.
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- 1985
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13. Pathology of hepatic transplantation: A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen
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Demetris, A. J., Lasky, S., Van Thiel, D. H., Starzl, T. E., and Dekker, A.
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Adult ,Graft Rejection ,Male ,Cholestasis ,Adolescent ,Hepatitis, Viral, Human ,Cholangitis ,Liver Cirrhosis, Biliary ,Cyclosporins ,Arteries ,Middle Aged ,Liver Transplantation ,Necrosis ,Liver ,Recurrence ,Humans ,Prednisone ,Drug Therapy, Combination ,Female ,Research Article - Abstract
The pathologic specimens (n = 118) and hospital course pertinent to each of 62 adult liver allograft recipients were reviewed. Biopsies and retransplanted organs were obtained at the discretion of the surgical team on the basis of the postoperative clinical course (less than 1 day to greater than 12 years after transplantation), and final interpretation of the pathologic material was based on a correlation of all available data. Most of the specimens (n = 85) were obtained within the first 2 months, and diagnoses in this time period included rejection, biliary obstruction/cholangitis, vascular injury, herpesvirus and cytomegalovirus hepatitis, graft necrosis, and functional cholestasis. Thereafter, rejection and recurrent or primary viral hepatitis were the major causes of graft dysfunction. Histologically, hepatic rejection is manifested by a cellular mediated injury of hepatocytes and bile ductules and a spectrum of vascular lesions in medium-sized hilar arteries. Morphologic changes of biliary duct obstruction and viral liver disease were at times difficult to differentiate from rejection. Two pretransplant disorders, type B viral hepatitis and the Budd-Chiari syndrome, recurred in grafted organs. Although interpretation of pathologic material may be difficult at times, it frequently is helpful in planning an approach to management of liver allograft recipients.
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- 1985
14. Induction of DR\IA antigens in human liver allografts: An immunocytochemical and clinicopathologic analysis of twenty failed grafts
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Demetris, AJ, Lasky, S, Van Thiel, DH, Starzl, TE, Whiteside, T, Demetris, AJ, Lasky, S, Van Thiel, DH, Starzl, TE, and Whiteside, T
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Twenty failed human liver allograft specimens obtained at the time of retransplantation procedures were studied using a panel of monoclonal antibodies (T11, T4, T8, NK, B1, OKM1, OKM5, Ia, DR). A clinicopathologic analysis was used to distinguish between graft failures secondary to rejection (n=10) and those due, at least in part, to other causes (n=10). T lymphocytes constituted the major infiltrating cellular population in the liver in rejection cases, but significant numbers of B cells and monocytes/macrophages were present also. Following transplantation, but not before, the bile duct epithelium, as well as portal and central vein and hepatic artery endothelium expressed DR/Ia antigens. These structures are preferential targets of the rejection reaction. The selective destruction of bile ducts in livers undergoing rejection was manifested in these patients by striking elevations of serum gamma glutamyl transpeptidase (GGTP) activity, a marker of biliary epithelial damage. The induced expression of DR/Ia antigens on structures targeted for immune destruction may be an important event in the pathogenesis of liver allograft rejection. © 1985 by The Williams and Wilkins Co.
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- 1985
15. Pathology of hepatic transplantation. A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen
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Demetris, AJ, Lasky, S, van Thiel, DH, Starzl, TE, Dekker, A, Demetris, AJ, Lasky, S, van Thiel, DH, Starzl, TE, and Dekker, A
- Abstract
The pathologic specimens (n = 118) and hospital course pertinent to each of 62 adult liver allograft recipients were reviewed. Biopsies and retransplanted organs were obtained at the discretion of the surgical team on the basis of the postoperative clinical course (< 1 day to > 12 years after transplantation), and final interpretation of the pathologic material was based on a correlation of all available data. Most of the specimens (n = 85) were obtained within the first 2 months, and diagnoses in this time period included rejection, biliary obstruction/cholangitis, vascular injury, herpesvirus and cytomegalovirus hepatitis, graft necrosis, and functional cholestasis. Thereafter, rejection and recurrent or primary viral hepatitis were the major causes of graft dysfunction. Histologically, hepatic rejection is manifested by a cellular mediated injury of hepatocytes and bile ductules and a spectrum of vascular lesions in medium-sized hilar arteries. Morphologic changes of biliary duct obstruction and viral liver disease were at times difficult to differentiate from rejection. Two pretransplant disorders, type B viral hepatitis and the Budd-Chiari syndrome, recurred in grafted organs. Although interpretation of pathologic material may be difficult at times, it frequently is helpful in planning an approach to management of liver allograft recipients.
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- 1985
16. The ore deposits of Socorro County, New Mexico
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Lasky, S. G., primary
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- 1932
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17. The metal resources of New Mexico and their economic features
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Lasky, S. G., primary and Wootton, T. P., additional
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- 1933
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18. Mineral reserves and mineral resources
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Blondel, Fernand, primary and Lasky, S. G., additional
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- 1956
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19. Transverse fractures as coordinate structures
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Lasky, S. G., primary
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- 1930
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20. Metabolism and biological activity of 1,25(OH) 2D 2 and its metabolites in a chronic myelogenous leukemia cell line, rwleu-4
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Clark, J.W., Reddy, G.S., Santos-Moore, A., Wankadiya, K.F., Reddy, G.P., Eil, C., Lasky, S., Tserng, K-Y., Horst, R.L., and Uskokovic, M.R.
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- 1993
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21. The Emerging Role of GLP-1 Agonists in Burn Care: What Do We Know?
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Manasyan A, Cannata B, Ross E, Lasky S, Stanton EW, Malkoff N, Collier Z, Johnson MB, and Gillenwater TJ
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- Humans, Hypoglycemic Agents therapeutic use, Wound Healing drug effects, Exenatide therapeutic use, Exenatide pharmacology, Blood Glucose drug effects, Liraglutide therapeutic use, Liraglutide pharmacology, Gastrointestinal Motility drug effects, Burns drug therapy, Glucagon-Like Peptide 1 agonists
- Abstract
Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After the burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. Glucagon-like peptide-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on patients with burns is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2025
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22. A Novel Approach to Intermediate Cleft Rhinoplasty Utilizing a Pedicled Fibrofatty Flap.
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Lasky S, Moshal T, Jolibois M, Roohani I, Jimenez C, Manasyan A, Naidu P, Nagengast ES, and Magee WP 3rd
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Patients with cleft lip ± palate may experience psychosocial issues related to their secondary cleft nasal deformities. These concerns can be addressed earlier instead of being required to wait until skeletal maturity. A novel early rhinoplasty intervention utilizing a dorsal fibrofatty pedicled flap is performed by the senior author to address nasal aesthetics in patients with secondary nasal deformities. This study aimed to describe this novel intermediate rhinoplasty technique and to evaluate improvement of nasal aesthetics. A retrospective review of patients with unilateral and bilateral cleft lip who underwent open rhinoplasty by a single surgeon at less than 10 years old from 2008 to 2023 was conducted. To evaluate aesthetic improvement, preoperative and postoperative photographs of patients were graded by 2 reviewers utilizing the Asher-McDade Aesthetic Index. Paired t tests compared preoperative and postoperative Asher-McDade Aesthetic Index nasal form and nasal deviation scores. A total of 43 patients underwent early rhinoplasty utilizing this technique at an average age of 5.5 ± 1.1 years. Compared with preoperative photographs, postoperative photographs of patients demonstrated a significant improvement in nasal form ( P < 0.001) and nasal deviation ( P < 0.001). No intraoperative or postoperative complications were reported. Only 1 (2.3%) patient underwent revisional surgery. Long-term follow-up will assess the finalized revision rate. This technique is a safe and valuable tool in patients who benefit from earlier treatment of secondary cleft nasal deformities due to significant asymmetry and psychosocial concerns., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)
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- 2025
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23. The Forgotten Flap: The Pedicled Trapezius Flap's Utility in Pediatric Head and Neck Reconstruction-A Systematic Review.
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Moshal T, Lasky S, Roohani I, Jolibois MI, Manasyan A, Munabi NCO, Fahradyan A, Lee JA, and Hammoudeh JA
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- Humans, Child, Neck Injuries surgery, Head and Neck Neoplasms surgery, Plastic Surgery Procedures methods, Superficial Back Muscles transplantation, Surgical Flaps blood supply
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Background: When free tissue transfer is precluded or undesired, the pedicled trapezius flap is a viable alternative for adults requiring complex head and neck (H&N) defect reconstruction. However, the application of this flap in pediatric reconstruction is underexplored. This systematic review aimed to describe the use of the pedicled trapezius flap and investigate its efficacy in pediatric H&N reconstruction., Methods: A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles describing the trapezius flap for H&N reconstruction in pediatric patients were included. Patient demographics, surgical indications, wound characteristics, flap characteristics, complications, and functional outcomes were abstracted., Results: A systematic review identified 22 articles for inclusion. Studies mainly consisted of case reports ( n = 11) and case series ( n = 8). In total, 67 pedicled trapezius flaps were successfully performed for H&N reconstruction in 63 patients. The most common surgical indications included burn scar contractures ( n = 46, 73.0%) and chronic wounds secondary to H&N masses ( n = 9, 14.3%). Defects were most commonly located in the neck ( n = 28, 41.8%). The mean flap area and arc of rotation were 326.4 ± 241.7 cm
2 and 157.6 ± 33.2 degrees, respectively. Most flaps were myocutaneous ( n = 48, 71.6%) and based on the dorsal scapular artery ( n = 32, 47.8%). Complications occurred in 10 (14.9%) flaps. The flap's survival rate was 100% ( n = 67). No instances of functional donor site morbidity were reported. The mean follow-up was 2.2 ± 1.8 years., Conclusion: This systematic review demonstrated the reliability of the pedicled trapezius flap in pediatric H&N reconstruction, with a low complication rate, no reports of functional donor site morbidity, and a 100% flap survival rate. The flap's substantial surface area, bulk, and arc of rotation contribute to its efficacy in covering soft tissue defects ranging from the proximal neck to the vertex of the scalp. The pedicled trapezius flap is a viable option for pediatric H&N reconstruction., Competing Interests: None declared., (Thieme. All rights reserved.)- Published
- 2025
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24. Factors Influencing Fronto-Orbital Relapse in Patients With Syndromic Craniosynostosis: A 2 Decade Review.
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Moshal T, Lasky S, Roohani I, Stanton EW, Jolibois MI, Wolfe EM, Urata M, Munabi NCO, Hammoudeh JA, and Urata MM
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Fronto-orbital retrusion may occur after primary surgical correction of craniosynostosis, particularly in patients with syndromic craniosynostosis. This study investigated reoperation rates and factors contributing to FO relapse among this cohort. A retrospective review evaluated reoperation for FO relapse in patients with syndromic multisuture craniosynostosis who underwent primary fronto-orbital advancement (FOA) + calvarial vault remodeling (CVR) at our institution between 2004 and 2024. Revision surgeries included repeat FOA or monobloc advancement/distraction. FOA advancement distance was measured using postoperative computed tomography and Mimics software. ROC analysis evaluated the accuracy of FOA distance in predicting subsequent FO relapse. Conditional margins identified optimal advancement distances. Logistic regression of predictors of FO relapse adjusted for age at surgery, craniofacial syndrome, posterior vault distraction osteogenesis (PVDO), advancement distance, and postoperative helmet therapy. Fifty-two patients underwent a mean of 2.8±1.9 skeletal craniofacial procedures each. With a mean follow-up time of 9.2±6.5 years, 16 (30.8%) patients required reoperation for FO relapse. Larger advancement distances were the sole significant predictor of relapse, increasing the odds by 49.6% (OR 1.496, 95% CI: 1.085-2.063; P=0.014). Relapse rates were lower with advancements ≤17.2 mm (0.0%) than with further advancements (42.0%, P=0.002). Specifically, advancements >18.8 mm were associated with significantly higher relapse rates (P<0.05). Almost one-third of patients with multisuture syndromic craniosynostosis underwent FO region readvancement. Advancements <17.2 mm during initial FOA appeared to mitigate relapse, while advancing beyond 18.8 mm may increase the risk. Investigation of additional protective factors against FO relapse is encouraged to minimize surgical burden., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)
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- 2024
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25. Guidance for Circumflex Scapular Artery Flap Utilization in Pediatric Reconstruction.
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Lasky S, Moshal T, Roohani I, Manasyan A, Jolibois M, Wolfe EM, Munabi NCO, Fahradyan A, Daar DA, Lee JA, and Hammoudeh JA
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- Humans, Child, Adolescent, Child, Preschool, Retrospective Studies, Male, Female, Arteries surgery, Scapula transplantation, Scapula blood supply, Plastic Surgery Procedures methods, Surgical Flaps blood supply, Surgical Flaps transplantation
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Background: The circumflex scapular artery (CSA) flap system, consisting of scapular, parascapular, and chimeric flaps, is useful for pediatric reconstruction in many anatomical locations. The objectives of this case series are to offer insights into our decision-making process for selecting the CSA flap in particular pediatric reconstructive cases and to establish a framework for choosing a scapular or parascapular skin paddle. We also aim to emphasize important technical considerations of CSA flap utilization in pediatric patients., Methods: Pediatric reconstruction with CSA flaps performed at our institution between 2006-2022 was retrospectively reviewed. Patient demographics, indications, flap characteristics, complications, and operative data were abstracted. Functional donor site morbidity was assessed through postoperative physical examinations. Unpaired t test analyzed scapular versus parascapular flap size., Results: Eleven CSA flaps were successfully performed in 10 patients (6 scapular and 5 parascapular flaps). Patient ages ranged from 2 to 17 years. Scapular fasciocutaneous free flaps (n = 4) were performed in patients' ages 2-5 years for hand and forearm scar contractures. Two pedicled scapular flaps were performed for a single patient for bilateral axillary hidradenitis suppurativa. The 5 parascapular flaps were performed in patients' ages 2-14 years for calcaneus and forearm avulsion wounds and reconstruction after resection of hidradenitis suppurativa, nevus sebaceous, and Ewing sarcoma. In the sarcoma resection case, a chimeric flap with latissimus dorsi was employed. Average flap size was 101.6 ± 87.3 cm 2 (range: 18-300 cm 2 ). Parascapular flaps were significantly larger than scapular flaps (156.60 ± 105.84 cm 2 vs 55.83 ± 26.97 cm 2 , P = 0.0495). Overall, 3 complications occurred (27.3% of cases) including venous congestion (n = 2) and wound dehiscence (n = 1). There were no reported cases of compromised shoulder function at 1.9 ± 2.5-year follow-up. The successful reconstruction rate for scapular, parascapular, and chimeric flaps was 100%., Conclusions: The CSA flap treated a wide variety of indications demonstrating the flap's attributes: large vessel caliber, wide arc of rotation, reliable vascular anatomy, minimal donor site morbidity, and ability to incorporate bone and muscle. Our cases also highlight important pediatric considerations such as vascular mismatch and limited scapular bone stock. We recommend selection of the parascapular over the scapular flap with reconstruction of larger, complex defects given its ability to be harvested with a large skin paddle., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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26. REPLY: The Risk of Medication-Related Osteonecrosis of the Jaw in Children: Guidance for Antiresorptive Use in Pediatric Patients.
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Lasky S, Moshal T, Shakoori P, Roohani I, Jolibois M, Youn S, Stanton E, Urata MM, and Hammoudeh JA
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- 2024
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27. Long-term Outcomes of a Modified Straight-line Palate Repair Technique: Low Speech Correcting Surgery and Fistula Rates.
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Lasky S, Munabi NCO, Jolibois M, Roohani I, Moshal T, Collier Z, Naidu P, Nagengast ES, Wolfe EM, and Magee WP
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Background: The goal of cleft palate (CP) repair is to restore normal speech, however, rates of velopharyngeal insufficiency (VPI) after palatoplasty remain high. We present a modified straight-line palate repair (SLR) technique that facilitates velum length to alleviate VPI. The technique releases nasal mucosa with the levator muscle off the hard palate. This study assesses speech outcomes of this modified SLR technique. Secondary aims are to assess fistula outcomes., Methods: A retrospective review evaluated non-syndromic patients with Veau III or IV CP ± cleft lip who underwent SLR from 1993-2023. Patients undergoing modified SLR were compared to those receiving traditional SLR. Outcomes included postoperative palatal fistula, fistula location, fistula repair rates, and velopharyngeal insufficiency (VPI) correcting surgery rates. Multivariable logistic regression was performed., Results: Overall, 343 patients were included (160 modified SLR, 183 traditional SLR). Average length of follow-up from palatoplasty was 6.4±5.3 years. Modified SLR was associated with fewer fistulas than traditional SLR (3.1% vs 15.3%, Odds Ratio [OR]: 0.19; p=0.001), lower fistula repair rates (0.6% vs 13.1%, OR: 0.26; p=0.022), and lower secondary speech surgery rates (0.8% vs 16.0%, OR: 0.046; p=0.003)., Conclusion: The modified SLR technique resulted in lower rates of VPI surgery, as well as fewer fistulas and lower rates of fistula repairs compared to traditional SLR at six years postoperatively. We hypothesize that releasing the nasal mucosa off the hard palate facilitates more posterior positioning of the levator muscle and less restricted medial mobilization of the oral mucosa, which lengthens the velum to alleviate VPI., (Copyright © 2024 by the American Society of Plastic Surgeons.)
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- 2024
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28. Premaxillary Setback in the Management of Patients With Bilateral Cleft Lip: A 2 Decade Review.
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Jolibois MI, Lasky S, Stanton EW, Roohani I, Moshal T, Foster L, Husain F, Munabi NC, Urata MM, Magee WP 3rd, and Hammoudeh JA
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Objective: This study analyzes indications and outcomes of premaxillary setback (PS) and presents an algorithm for its use in patients with bilateral cleft lip and/or palate (BCL ± P)., Design: Retrospective review., Setting: Children's Hospital Los Angeles., A retrospective review was conducted evaluating patients with BCL ± P undergoing lip repair from 2003-2023. Patients were categorized as undergoing repair with (BCL + PS) or without (BCL-PS) simultaneous PS. Presurgical nasoalveolar molding (NAM), indications for PS, timing of surgery, and complications were collected., Interventions: BCL with PS, BCL + PS., Main Outcome Measures(s): Primary outcomes included rates of postoperative complications and revision surgeries. Secondary outcome was the need for orthognathic surgery to correct midface hypoplasia in patients at least 14 years old at their most recent follow-up., Results: Of 1193 patients, 262 met inclusion criteria. One hundred forty-nine patients (56.9%) were referred for NAM. Fifty-one patients (19.5%) underwent PS during primary BCL repair. Patients who failed repositioning of the premaxilla following presurgical NAM (n = 12) were not candidates for NAM (n = 31) or presented late with a protruding premaxilla (n = 8, 12.977 ± 8.196 months) underwent PS. Median age at surgery was 4.29 months. Complications included wound dehiscence (n = 3) and abscess formation (n = 2). No premaxillary necrosis occurred. Overall revision rates were 9.9%. Of 41 patients over 14 years old, 53.6% needed orthognathic surgery. BCL + PS had comparable rates of wound dehiscence (2.0% vs 4.0%; P = .790), lip revisions (7.8% vs 10.4%; P = .770), and orthognathic surgery (50.0% vs 56.3%; P > .999)., Conclusion: PS is a safe and effective method to facilitate BCL repair in patients who are not candidates for NAM., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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29. STOPTHEBURN: A Randomized Controlled Trial of Death Cafés for Burnout Prevention in Intensive Care Unit Employees.
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Bateman ME, Chung CH, Mascarenhas E, Hammer R, Ravindran N, Panjshiri F, Mehta P, Byrne A, Lasky S, Denson R, Brown M, Halton B, Chiurco J, Ferrell S, Ruiz B, Wentowski C, Shukla I, Bauer H, Sarma A, Bhyravabhotla K, Zu Y, Peacock E, Lefante J, Epere J, and Denson JL
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- Humans, Female, Male, Adult, Louisiana, Depression prevention & control, Adaptation, Psychological, Death, Burnout, Professional prevention & control, Intensive Care Units
- Abstract
Rationale: Effective interventions to prevent burnout among intensive care unit (ICU) clinicians are urgently needed. Death cafés, group discussions about death, build a sense of community and create a space for reflection on distressing events. Objective: To assess whether participation in regular death cafés can prevent burnout in ICU clinicians (physicians, nurses, pharmacists, therapists). Methods: A randomized clinical trial was conducted from July 2020 to December 2022 in 10 ICUs in Louisiana. Subjects were randomized to attend four psychotherapist-facilitated virtual death cafés or to a control arm. The primary outcome was burnout defined by the Maslach Burnout Inventory-Human Services Survey at 6 months. Depression and anxiety scores were measured, as were qualitative data on stressors, coping, and death café experience. Results: Among 340 clinicians who were screened and gave consent (171 physicians, 169 nonphysicians), 251 participated (mean age, 31.0 ± 6.8 years; 63% female; 72% White; 37% nurses, 27% residents, 25% interns, 11% other). Burnout prevalence was 19% at baseline. Of 136 participants who completed the 6-month follow-up, no significant differences were found between intervention and control for the primary outcome (18% vs. 25%; unadjusted odds ratio, 0.64; 95% confidence interval, 0.26-1.57; P = 0.33). There were no differences in anxiety or depression. Notably, the study was limited by an inability to achieve target enrollment and a high attrition rate (46%). Conclusions: Virtual death cafés were unable to reduce burnout, although the study was underpowered to detect differences between groups. Clinical trial registered with clinicaltrials.gov (NCT04347811).
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- 2024
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30. Skeletal and Soft Tissue Surgeries in the Long-term Management of Patients With Syndromic Craniosynostosis: A 20-Year Review.
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Moshal T, Roohani I, Jolibois M, Lasky S, Stanton EW, Vallurupalli M, Wolfe EM, Munabi NCO, Hammoudeh JA, and Urata MM
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- Humans, Retrospective Studies, Male, Female, Infant, Child, Preschool, Child, Treatment Outcome, Craniosynostoses surgery, Plastic Surgery Procedures methods
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Background: Soft tissue procedures are often crucial for normalizing the long-term facial appearance in patients with syndromic craniosynostosis, yet they are underrepresented in the literature and existing treatment algorithms. This study evaluated secondary soft tissue surgeries in relation to skeletal operations in patients with syndromic craniosynostosis., Methods: A retrospective review evaluated patients with syndromic craniosynostosis treated at a tertiary children's hospital from 2003 to 2023. Craniofacial skeletal and soft tissue procedures were assessed for timing and frequency. Skeletal surgeries included redo fronto-orbital advancements, monobloc advancement/distraction ± facial bipartition, and LeFort III or III/I advancement/distraction. Soft tissue surgeries encompassed oculoplastic procedures, scalp reconstruction, fat grafting, and septorhinoplasty., Results: Of 106 patients with syndromic craniosynostosis, 57 (57.8%) underwent ≥1 secondary skeletal operation, and 101 (95.3%) underwent ≥1 soft tissue procedures, averaging 3.7 ± 3.3 soft tissue procedures per patient. Patients who underwent secondary forehead advancement had significantly higher rates of subsequent lateral canthopexy (71.4% vs 25.6, P < 0.001), ptosis reconstruction (17.9% vs 7.7%, P = 0.025), and frontotemporal fat grafting (50.0% vs 15.4%, P < 0.001) than those who did not. Patients who underwent midface advancement surgery had significantly higher rates of subsequent lateral canthopexy (65.4% vs 11.1%, P < 0.001), medial canthopexy (7.7% vs 0.0%, P = 0.038), scalp reconstruction (36.5% vs 16.7%, P = 0.020), frontotemporal fat grafting (34.6% vs 14.8%, P = 0.018), malar fat grafting (11.5% vs 0.0%, P = 0.010), and septorhinoplasty (26.9% vs 1.9%, P < 0.001) than those who did not. Specifically, LeFort III or III/I advancement/distractions were significantly associated with higher rates of subsequent septorhinoplasties (33.3% vs 1.6%, P < 0.001). The mean follow-up was 10.2 ± 7.0 years., Conclusions: This study revealed an intricate interplay between skeletal and soft tissue surgery in patients with syndromic craniosynostosis. Exploring techniques to reduce the need for further corrective surgery and anticipating necessary secondary interventions may improve patient counseling and outcomes., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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31. The Risk of Medication-Related Osteonecrosis of the Jaw in Children: Guidance for Antiresorptive Use in Pediatric Patients.
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Lasky S, Moshal T, Shakoori P, Roohani I, Jolibois M, Youn S, Urata MM, and Hammoudeh JA
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- Humans, Retrospective Studies, Child, Female, Male, Adolescent, Risk Factors, Child, Preschool, Denosumab therapeutic use, Denosumab adverse effects, Bone Density Conservation Agents adverse effects, Bone Density Conservation Agents therapeutic use, Bisphosphonate-Associated Osteonecrosis of the Jaw, Diphosphonates adverse effects, Diphosphonates therapeutic use, Diphosphonates administration & dosage
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Background: Antiresorptive targeted cancer therapies, such as denosumab and bisphosphonates, are used in adults, but their application in pediatric cancer is more recent. Side effects such as osteonecrosis of the jaw (ONJ) observed in adults have curtailed use of these medications in the pediatric population., Purpose: This study assesses the frequency of ONJ, other side effects, and the indications for use of denosumab versus bisphosphonates in pediatric subjects., Study Design, Setting, Sample: A retrospective cohort study of pediatric subjects who underwent bisphosphonate or denosumab therapy at our institution from 2007-2023 was conducted. Subjects aged ≥ 18 years at therapy initiation were excluded., Independent Variable: The independent variable was antiresorptive therapy divided into 2 groups, treatment with intravenous bisphosphonates or denosumab., Main Outcome Variable(s): Primary outcomes were development of bisphosphonate-related and denosumab-related ONJ. Secondary outcomes included additional side effects., Covariates: ONJ risk factors, subject demographics, indications for use, timing, duration, and cumulative dose of antiresorptive therapy were abstracted., Analyses: Univariate and bivariate statistics were computed to describe the sample and measure associations between antiresorptive therapy and outcomes. P values < .05 conferred statistical significance., Results: The sample was composed of 178 subjects with a mean age of 11.7 ± 6.1 years. There were 14 (7.9%) and 164 (92.1%) subjects treated with denosumab and bisphosphonate therapies, respectively. There were 0 cases of ONJ across all subjects. The most common indication for treatment was adjuvant targeted therapy for aggressive tumors and malignancy (39.3%) followed by osteoporosis (14.6%). Subjects treated with denosumab had higher frequencies of hypercalcemia and severe bone pain than subjects treated with bisphosphonates, 28.6% versus 1.2% (P < .001) and 14.3% versus 0.00% (P < .001), respectively., Conclusion and Relevance: While invasive dental procedures are ideally performed before antiresorptive treatment, our data suggest that bisphosphonates may be used safely in the pediatric population with low concern for ONJ. Our data also demonstrated bisphosphonates may have a more tolerable side effect profile than denosumab. If the perceived benefits are similar, we recommend using bisphosphonates as first-line therapy in children while reserving denosumab for refractory cases. Future studies will help determine long-term side effects and differences in efficacies of these medications., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2024
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32. Expanding Accessibility in Cleft Care: The Role of Artificial Intelligence in Improving Literacy of Alveolar Bone Grafting Information.
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Manasyan A, Lasky S, Jolibois M, Moshal T, Roohani I, Munabi N, Urata MM, and Hammoudeh JA
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Objective: The American Medical Association (AMA) recommends patient education materials (PEMs) be written at or below a sixth grade reading level. This study seeks to determine the quality, readability, and content of available alveolar bone grafting (ABG) PEMs and determine if artificial intelligence can improve PEM readability., Design: Review of free online PEMs., Setting: Online ABG PEMs were retrieved from different authoring body types (hospital/academic center, medical society, or private practice)., Patients, Participants: None., Interventions: Content was assessed by screening PEMs for specific ABG-related topics. Quality was evaluated with the Patient Education Material Assessment Tool (PEMAT), which has measures of understandability and actionability. Open-access readability software (WebFX) determined readability with Flesch Reading Ease, Flesch-Kincaid Grade Level, and Gunning-Fog Index. PEMs were rewritten with ChatGPT, and readability metrics were reassessed., Main Outcome Measure(s): Quality, readability, and content of ABG PEMs., Results: 34 PEMs were analyzed. Regarding quality, the average PEMAT-understandability score was 67.0 ± 16.2%, almost at the minimum acceptable score of 70.0% (p = 0.281). The average PEMAT-actionability score was low at 33.0 ± 24.1%. Regarding readability, the average Flesch Reading Ease score was 64.6 ± 12.8, categorized as "standard/plain English." The average Flesch-Kincaid Grade Level was 8.0 ± 2.3, significantly higher than AMA recommendations (p < 0.0001). PEM rewriting with ChatGPT improved Flesch-Kincaid Grade Level to 6.1 ± 1.3 (p < 0.0001)., Conclusions: Available ABG PEMs are above the recommended reading level, yet ChatGPT can improve PEM readability. Future studies should improve areas of ABG PEMs that are most lacking, such as actionability., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics StatementThe research was conducted with full adherence to the ethical principles outlined by Children's Hospital Los Angeles. All data was collected with respect for the rights and privacy of patients and families (IRB exempt and not directly involving human subjects). Measures were taken to ensure the accuracy and integrity of the research findings. The authors ensure that this research has not been published or submitted elsewhere for consideration.
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- 2024
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33. Resources on lymphedema surgery: How effective are they for patients?
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Manasyan A, Lasky S, Stanton EW, Cannata B, Moshal T, Roohani I, Koesters E, and Daar DA
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- Humans, Internet, Lymphedema surgery, Patient Education as Topic
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Online patient education materials (PEMs) on lymphedema surgery were assessed for quality, readability, and content. A total of 37 PEMs were identified, primarily authored by academic/medical organizations. Readability scores indicated materials were difficult to read, with an average Flesch-Kincaid Grade Level of 10.4. PEM Assessment Tools showed acceptable understandability (72.3%) but poor actionability (28.5%). PEMs often lacked information on surgical risks, postoperative care, and long-term follow-up. Simplifying language and adding visual aids could improve PEM effectiveness., (© 2024 Wiley Periodicals LLC.)
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- 2024
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34. Sociodemographic Factors Associated with Delayed Presentation in Craniosynostosis Surgery at a Tertiary Children's Hospital.
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Jolibois MI, Roohani I, Moshal T, Lasky S, Urata M, Munabi NCO, Johns AL, Sader N, Durham SR, and Urata MM
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Background: Craniosynostosis is a common diagnosis requiring early referral to a pediatric plastic surgeon; however, disparities in healthcare may influence presentation timing and affect treatment options and outcomes. This study aimed to explore sociodemographic factors contributing to delay in craniosynostosis surgical consultation., Methods: A retrospective cohort study of 694 California-based craniosynostosis patients at a tertiary children's hospital was performed from 2006 to 2023. State-specific Area Deprivation Index (ADI) and distance to the hospital were calculated using ZIP codes. Multivariate linear and logistic regressions considered race, insurance type, syndromic status, suture type, and ZIP code-based socioeconomic factors., Results: Median age of presentation was 4.5 [interquartile range: 2.6-7.6] months with racial/ethnic breakdown of Hispanic/Latinx (41.2%), White (23.6%), Asian (3.7%), Black/African American (2.0%), or other/unreported (29.5%) with 58.4% having public insurance and an average distance to the hospital of 48.3 km. Median ADI was 5.4 [interquartile range: 4.0-7.1]. By linear regression, public insurance ( P < 0.001) and higher ADI decile ( P < 0.001) independently contributed to an older age of presentation. Patients with public insurance (odds ratio 1.90; P = 0.002) were more likely to present after 4 months of age., Conclusions: Patients who had public insurance or resided in more disadvantaged areas presented later for craniosynostosis surgical consultation. Eliminating disparities in these populations ensures more equitable access to surgical options and can improve patient outcomes., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)
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- 2024
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35. Orthognathic Surgery Rates in Furlow Double-Opposing Z-Plasty Versus Straight-Line Repair: A Review of Three Decades of Experience.
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Lasky S, Moshal T, Jolibois M, Roohani I, Manasyan A, Husain F, Harris S, Nagengast ES, Urata MM, Magee WP, and Hammoudeh JA
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Objective: The influence of different surgical techniques on maxillary growth remains unclear. This study investigates the long-term impact of Furlow double-opposing Z-plasty versus straight-line repair (SLR) techniques on midface growth and subsequent orthognathic surgery., Design: Retrospective cohort study., Setting: Tertiary children's hospital., Patients/participants: This study evaluated patients who underwent primary palatoplasty with Furlow or SLR techniques from 1994-2023. Patients were >14 years old at their most recent follow-up., Interventions: No interventions were performed., Main Outcome Measure(s): Primary outcomes were orthognathic surgery and orthognathic surgery recommendation rates to correct midface hypoplasia (MFH). Cephalometrics at the time of orthognathic surgery recommendation were traced to validate MFH., Results: In total, 1857 patients underwent palatoplasty, of which 335 met inclusion criteria (49 SLR, 286 Furlow). Average age at last follow-up was 18.5±2.6 years. Patients who underwent Furlow versus SLR showed no significant difference in orthognathic surgery rates (p=0.428) or recommendation for orthognathic surgery rates (p=0.900). Patients recommended to undergo orthognathic surgery had more negative ANB angles (p<0.001) and smaller SNA angles (p<0.001) than patients not recommended for orthognathic surgery, demonstrating maxillary hypoplasia. Upon multivariate regression, patients with Veau III and IV clefts had an increased need for orthognathic surgery, p=0.047 and p=0.008, respectively., Conclusions: Our findings suggest that higher cleft severity contributes to future orthognathic surgery. However, palatoplasty technique did not influence orthognathic surgery rates. Our results provide valuable data when surgeons are considering the impact of palatoplasty technique on sagittal growth restriction., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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36. Polysomnogram Findings and Psychosocial and Academic Concerns in Children With Cleft Palate With or Without Cleft Lip.
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Riklin E, Choi DG, Trotter C, Lasky S, Kato RM, Davidson Ward SL, Magee WP 3rd, Hammoudeh JA, Urata MM, and Johns AL
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Children born with a cleft palate with or without a cleft lip (CP±L) are at risk for sleep-disordered breathing, particularly obstructive sleep apnea (OSA). While OSA and CP±L have both been associated with higher risk for psychosocial and academic concerns, their combined risk has been understudied. This paper aimed to describe polysomnography findings and psychosocial and academic concerns among children with isolated (iCP±L) and syndrome-associated (sCP±L) clefts who had undergone primary palatoplasty. Medical records were reviewed from 2004 to 2022 for demographics, medical history, polysomnography results, and family-reported psychosocial and academic variables. Of the 694 patients with CP±L who had a palatoplasty, 147 had a polysomnogram and 82 had at least one follow-up polysomnogram. Across time points, only 19% to 27% of participants had normal polysomnograms and the most frequent finding was mild OSA for 30% to 35% of patients. For children with iCP±L, more frequent oxygen desaturations were significantly associated with receiving special education services and family-reported academic concerns and OSA was associated with a history of receiving mental health services. Children with sCP±L had a significantly higher Obstructive Apnea-Hypopnea Index and a greater proportion of all-day special education classroom placements relative to youth with iCP±L. Study results suggest that cleft providers should monitor for OSA and sleep-disordered breathing symptoms, collaborate with pulmonologists for evaluation and treatment of sleep concerns, and address possible sleep-associated psychosocial and academic issues., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)
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- 2024
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37. Simulated outcomes for durotomy repair in minimally invasive spine surgery.
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Balu A, Kugener G, Pangal DJ, Lee H, Lasky S, Han J, Buchanan I, Liu J, Zada G, and Donoho DA
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- Humans, Educational Status, Spine surgery, Artificial Intelligence, Models, Anatomic
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Minimally invasive spine surgery (MISS) is increasingly performed using endoscopic and microscopic visualization, and the captured video can be used for surgical education and development of predictive artificial intelligence (AI) models. Video datasets depicting adverse event management are also valuable, as predictive models not exposed to adverse events may exhibit poor performance when these occur. Given that no dedicated spine surgery video datasets for AI model development are publicly available, we introduce Simulated Outcomes for Durotomy Repair in Minimally Invasive Spine Surgery (SOSpine). A validated MISS cadaveric dural repair simulator was used to educate neurosurgery residents, and surgical microscope video recordings were paired with outcome data. Objects including durotomy, needle, grasper, needle driver, and nerve hook were then annotated. Altogether, SOSpine contains 15,698 frames with 53,238 annotations and associated durotomy repair outcomes. For validation, an AI model was fine-tuned on SOSpine video and detected surgical instruments with a mean average precision of 0.77. In summary, SOSpine depicts spine surgeons managing a common complication, providing opportunities to develop surgical AI models., (© 2024. The Author(s).)
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- 2024
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38. Lessons Learned from a Single Institution's Eight Years of Experience with Early Cleft Lip Repair.
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Roohani I, Trotter C, Shakoori P, Moshal TA, Lasky S, Manasyan A, Wolfe EM, Magee WP 3rd, and Hammoudeh JA
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- Infant, Child, Humans, Infant, Newborn, Nose surgery, Retrospective Studies, Preoperative Care methods, Treatment Outcome, Cleft Lip surgery, Cleft Palate surgery
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Background and Objectives : The traditional approach in managing wide cleft lip deformities involves presurgical nasoalveolar molding (NAM) therapy followed by surgical cleft lip repair between three and six months of age. This institution has implemented an early cleft lip repair (ECLR) protocol where infants undergo primary cleft lip repair between two and five weeks of age without NAM. This study aims to present this institution's ECLR repair protocol over the past eight years from 188 consecutive patients with unilateral or bilateral CL/P deformity. Materials and Methods : Retrospective review was conducted at Children's Hospital Los Angeles evaluating patients who underwent ECLR before three months of age and were classified as American Society of Anesthesiologists (ASA) class I or II from 2015-2022. Anthropometric analysis was performed, and pre- and postoperative photographs were evaluated to assess nasal and lip symmetry. Results : The average age at cleft lip repair after correcting for gestational age was 1.0 ± 0.5 months. Mean operative and anesthetic times were 120.3 ± 33.0 min and 189.4 ± 35.4, respectively. Only 2.1% (4/188) of patients had postoperative complications. Lip revision rates were 11.4% (20/175) and 15.4% (2/13) for unilateral and bilateral repairs, respectively, most of which were minor in severity (16/22, 72.7%). Postoperative anthropometric measurements demonstrated significant improvements in nasal and lip symmetry ( p < 0.001). Conclusions : This analysis demonstrates the safety and efficacy of ECLR in correcting all unilateral cleft lip and nasal deformities of patients who were ASA classes I or II. At this institution, ECLR has minimized the need for NAM, which is now reserved for patients with bilateral cleft lip, late presentation, or comorbidities that preclude them from early repair. ECLR serves as a valuable option for patients with a wide range of cleft severity while reducing the burden of care.
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- 2023
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39. Assessment of Cranial Sexual Dimorphism Using 3D Reconstruction: Implications for Gender-Affirming Surgery.
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Goli R, Lasky S, Ray E, and Chen H
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- Male, Female, Humans, Imaging, Three-Dimensional methods, Sex Characteristics, Retrospective Studies, Face, Gender-Affirming Surgery
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Background: As more centers offer gender-affirming procedures, dissemination of best practices is critical to ensuring quality care. This study is the first to use advanced 3-dimensional visualization software to characterize cranial differences between natal males and females, as they relate to planning for facial gender-affirming operations., Materials and Methods: A retrospective analysis was conducted on randomly selected patients with facial computed tomography imaging performed at a single institution between February 2020 and July 2021. Patients with acquired bony deformity on computed tomography or documented history of hormone replacement therapy were excluded. The images were retrieved and analyzed using advanced 3-dimensional visualization software (Vitrea). Independent sample t tests were performed to analyze variation in typically sexually dimorphic facial features between natal males and females., Results: We identified 50 patients (25 natal males and 25 natal females) who met the inclusion criteria. Ages ranged from 19 to 91. Natal males were found to have significantly greater frontosellar distances (difference between means, SEM: 2.7±1.2; P =0.03) and mandible volumes (difference between means, SEM: 14.0±4.2; P =0.002) than natal females. Statistical analysis revealed no significant differences in gonial angle, chin width, nasofrontal angle, or nasolabial angle between natal males and females., Conclusion: In this diverse sample of natal males and females, statistical analysis revealed that the sexually dimorphic facial characteristics most relevant to the planning of facial gender-affirming surgery are frontosellar distance and mandible volume. When planning facial gender-affirming surgery, we recommend that these characteristics be considered to achieve optimum results., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)
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- 2023
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40. Tympanostomy Tubes: Are They Necessary? A Systematic Review on Implementation in Cleft Care.
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Stanton E, Kondra K, Brahme I, Lasky S, Munabi NCO, Jimenez C, Jacob L, Urata MM, Hammoudeh JA, and Magee WP 3rd
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- Humans, Infant, Middle Ear Ventilation adverse effects, Retrospective Studies, Cleft Palate complications, Cleft Lip complications, Otitis Media with Effusion etiology, Dental Implants
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Objective: To understand the indication for and the effects of early ventilation tube insertion (VTI) on hearing and speech for patients with cleft lip and/or palate (CLP)., Design: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review of relevant literature., Setting: Setting varied by geographical location and level of clinical care across studies., Patients, Participants: Patients with CLP who underwent VTI were included., Interventions: No interventions were performed., Main Outcome Measure(s): Primary outcome measures were hearing and speech following VTI. Secondary outcome measures were tube-related and middle ear complications. Early VTI occurred before or at time of palatoplasty while late VTI occurred after palatoplasty., Results: Twenty-three articles met inclusion criteria. Articles varied among study design, outcome measures, sample size, follow-up, and quality. Few studies demonstrated support for early VTI. Many studies reported no difference in hearing or speech between early and late VTI. Others reported worse outcomes, greater likelihood of complications, or needing repeat VTI following early tympanostomy placement. Several studies had significant limitations, including confounding variables, small sample size, or not reporting on our primary outcome., Conclusions: No consistency was found regarding which patients would benefit most from early VTI. Given the aforementioned variability and sub-optimal methodologies, additional studies are warranted to provide stronger evidence regarding VTI timing in cleft care.
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- 2023
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41. Assessing Local Public Health Agency Alignment With Public Health 3.0: A Content Analysis of Illinois Community Health Improvement Plans.
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Welter CR, Herrera Y, Uskali AL, Seweryn S, Call L, Lasky S, Agbodo N, and Ezike NO
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- Humans, Illinois, Public Health Administration, Social Determinants of Health, Community Health Planning, Public Health
- Abstract
Context: Public Health 3.0 described the need for public health agencies and the public health workforce to transform and obtain new skills and approaches to address the social determinants of health (SDOH) through cross-sectoral partnerships and collective action., Objective: To assess the current state of local health departments' Public Health 3.0 alignment through interventions and initiatives documented in community health improvement plans (CHIPs)., Method: We conducted a content analysis of Illinois CHIPs from July to November 2020. A coding framework aligned with Public Health 3.0 concepts was developed on the basis of constructs from the literature, faculty expertise, and preliminary reviews of the CHIPs. Two researchers deductively coded for health priorities and interventions in Microsoft Excel 2016 and calculated the number of CHIPs in which each code appeared., Results: Ninety CHIPs representing 98 counties across the state were analyzed; 2 CHIPs were excluded because of a lack of strategies. Our content analysis found that 13% (n = 12) of CHIPs had explicit priorities related to SDOH and 12% (n = 11) included interventions that addressed socioeconomic factors. Ten percent (n = 9) of CHIPs proposed multilevel multicomponent interventions. Eighty-nine percent (n = 80) of CHIPs included community-level interventions, and 53% (n = 48) of CHIPs included policy, systems, and environmental strategies focused on specific health content. The majority of CHIPs (96%; n = 86) had at least 1 partnership strategy. Thirty-two percent (n = 29) of CHIPs mentioned the use of an evidence-based strategy., Conclusions: Our content analysis found opportunities to improve Illinois public health agencies' Public Health 3.0 capacities and capability. Findings are limited to this data source and definitions of the Public Health 3.0 attributes, leaving room for practice and research opportunities to develop operational definitions of Public Health 3.0; capacity building to improve the public health workforce readiness; and research and evaluation to measure improvements., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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42. Utility of the Simulated Outcomes Following Carotid Artery Laceration Video Data Set for Machine Learning Applications.
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Kugener G, Pangal DJ, Cardinal T, Collet C, Lechtholz-Zey E, Lasky S, Sundaram S, Markarian N, Zhu Y, Roshannai A, Sinha A, Han XY, Papyan V, Hung A, Anandkumar A, Wrobel B, Zada G, and Donoho DA
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- Carotid Arteries, Humans, Machine Learning, Neural Networks, Computer, Lacerations surgery, Surgeons
- Abstract
Importance: Surgical data scientists lack video data sets that depict adverse events, which may affect model generalizability and introduce bias. Hemorrhage may be particularly challenging for computer vision-based models because blood obscures the scene., Objective: To assess the utility of the Simulated Outcomes Following Carotid Artery Laceration (SOCAL)-a publicly available surgical video data set of hemorrhage complication management with instrument annotations and task outcomes-to provide benchmarks for surgical data science techniques, including computer vision instrument detection, instrument use metrics and outcome associations, and validation of a SOCAL-trained neural network using real operative video., Design, Setting, and Participants: For this quailty improvement study, a total of 75 surgeons with 1 to 30 years' experience (mean, 7 years) were filmed from January 1, 2017, to December 31, 2020, managing catastrophic surgical hemorrhage in a high-fidelity cadaveric training exercise at nationwide training courses. Videos were annotated from January 1 to June 30, 2021., Interventions: Surgeons received expert coaching between 2 trials., Main Outcomes and Measures: Hemostasis within 5 minutes (task success, dichotomous), time to hemostasis (in seconds), and blood loss (in milliliters) were recorded. Deep neural networks (DNNs) were trained to detect surgical instruments in view. Model performance was measured using mean average precision (mAP), sensitivity, and positive predictive value., Results: SOCAL contains 31 443 frames with 65 071 surgical instrument annotations from 147 trials with associated surgeon demographic characteristics, time to hemostasis, and recorded blood loss for each trial. Computer vision-based instrument detection methods using DNNs trained on SOCAL achieved a mAP of 0.67 overall and 0.91 for the most common surgical instrument (suction). Hemorrhage control challenges standard object detectors: detection of some surgical instruments remained poor (mAP, 0.25). On real intraoperative video, the model achieved a sensitivity of 0.77 and a positive predictive value of 0.96. Instrument use metrics derived from the SOCAL video were significantly associated with performance (blood loss)., Conclusions and Relevance: Hemorrhage control is a high-stakes adverse event that poses unique challenges for video analysis, but no data sets of hemorrhage control exist. The use of SOCAL, the first data set to depict hemorrhage control, allows the benchmarking of data science applications, including object detection, performance metric development, and identification of metrics associated with outcomes. In the future, SOCAL may be used to build and validate surgical data science models.
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- 2022
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43. Use of surgical video-based automated performance metrics to predict blood loss and success of simulated vascular injury control in neurosurgery: a pilot study.
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Pangal DJ, Kugener G, Cardinal T, Lechtholz-Zey E, Collet C, Lasky S, Sundaram S, Zhu Y, Roshannai A, Chan J, Sinha A, Hung AJ, Anandkumar A, Zada G, and Donoho DA
- Abstract
Objective: Experts can assess surgeon skill using surgical video, but a limited number of expert surgeons are available. Automated performance metrics (APMs) are a promising alternative but have not been created from operative videos in neurosurgery to date. The authors aimed to evaluate whether video-based APMs can predict task success and blood loss during endonasal endoscopic surgery in a validated cadaveric simulator of vascular injury of the internal carotid artery., Methods: Videos of cadaveric simulation trials by 73 neurosurgeons and otorhinolaryngologists were analyzed and manually annotated with bounding boxes to identify the surgical instruments in the frame. APMs in five domains were defined-instrument usage, time-to-phase, instrument disappearance, instrument movement, and instrument interactions-on the basis of expert analysis and task-specific surgical progressions. Bounding-box data of instrument position were then used to generate APMs for each trial. Multivariate linear regression was used to test for the associations between APMs and blood loss and task success (hemorrhage control in less than 5 minutes). The APMs of 93 successful trials were compared with the APMs of 49 unsuccessful trials., Results: In total, 29,151 frames of surgical video were annotated. Successful simulation trials had superior APMs in each domain, including proportionately more time spent with the key instruments in view (p < 0.001) and less time without hemorrhage control (p = 0.002). APMs in all domains improved in subsequent trials after the participants received personalized expert instruction. Attending surgeons had superior instrument usage, time-to-phase, and instrument disappearance metrics compared with resident surgeons (p < 0.01). APMs predicted surgeon performance better than surgeon training level or prior experience. A regression model that included APMs predicted blood loss with an R2 value of 0.87 (p < 0.001)., Conclusions: Video-based APMs were superior predictors of simulation trial success and blood loss than surgeon characteristics such as case volume and attending status. Surgeon educators can use APMs to assess competency, quantify performance, and provide actionable, structured feedback in order to improve patient outcomes. Validation of APMs provides a benchmark for further development of fully automated video assessment pipelines that utilize machine learning and computer vision.
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- 2021
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44. Death Cafés for prevention of burnout in intensive care unit employees: study protocol for a randomized controlled trial (STOPTHEBURN).
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Bateman ME, Hammer R, Byrne A, Ravindran N, Chiurco J, Lasky S, Denson R, Brown M, Myers L, Zu Y, and Denson JL
- Subjects
- Anxiety diagnosis, Anxiety epidemiology, Awareness physiology, Burnout, Professional epidemiology, COVID-19 epidemiology, COVID-19 virology, Case-Control Studies, Communication, Critical Illness mortality, Critical Illness psychology, Depression diagnosis, Depression epidemiology, Humans, Occupational Stress epidemiology, Patient Health Questionnaire statistics & numerical data, Patient Safety statistics & numerical data, Personnel Turnover statistics & numerical data, Surveys and Questionnaires, User-Computer Interface, Burnout, Professional prevention & control, Intensive Care Units statistics & numerical data, Occupational Stress psychology, SARS-CoV-2 genetics, Terminal Care psychology
- Abstract
Background: Burnout is an occupational syndrome that leads to mental health problems, job turnover, and patient safety events. Those caring for critically ill patients are especially susceptible due to high patient mortality, long hours, and regular encounters with trauma and ethical issues. Interventions to prevent burnout in this population are needed. Preliminary studies suggest debriefing sessions may reduce burnout. This study aims to assess whether participation in regular debriefing can prevent burnout in intensive care unit (ICU) clinicians., Methods: A randomized controlled trial will be conducted in two large academic medical centers. Two hundred ICU clinicians will be recruited with target enrollment of 100 physicians and 100 non-physicians (nurses, pharmacists, therapists). Participants must have worked in the ICU for the equivalent of at least 1 full time work week in the preceding 4 weeks. Enrolled subjects will be randomized to virtually attend biweekly debriefing sessions facilitated by a psychotherapist for 3 months or to a control arm without sessions. Our debriefs are modeled after Death Cafés, which are informal discussions focusing on death, dying, loss, grief, and illness. These sessions allow for reflection on distressing events and offer community and collaboration among hospital employees outside of work. The primary outcome is clinician burnout as measured by the Maslach Burnout Inventory (MBI) Score. Secondary outcomes include depression and anxiety, as measured by the Patient Health Questionnaire 8 (PHQ-8) and Generalized Anxiety Disorder 7-item scale (GAD-7), respectively. Questionnaires will be administered prior to the intervention, at 1 month, at 3 months, and at 6 months after enrollment. These values will be compared between groups temporally. Qualitative feedback will also be collected and analyzed., Discussion: With ICU clinician burnout rates exceeding 50%, Death Café debriefing sessions may prove to be an effective tool to avert this debilitating syndrome. With COVID-19 limiting social interactions and overloading ICUs worldwide, the virtual administration of the Death Café for ICU clinicians provides an innovative strategy to potentially mitigate burnout in this vulnerable population., Trial Registration: ClinicalTrials.gov NCT04347811 . Registered on 15 April 2020.
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- 2020
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45. Hydronephrosis in infants and children: natural history and risk factors for persistence in children followed by a medical service.
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Vandervoort K, Lasky S, Sethna C, Frank R, Vento S, Choi-Rosen J, Goilav B, and Trachtman H
- Abstract
Background: Infants with neonatal hydronephrosis and a normal voiding cystourethrogram (VCUG) are presumed to have ureteropelvic junction obstruction (UPJO). There is little current information about the natural history of children with hydronephrosis or clinical factors that predict resolution of the radiological abnormality., Objective: To determine the time course until spontaneous resolution of neonatal hydronephrosis and define risk factors for persistence of the abnormality., Methods: This retrospective single center review examined infants and children <5 years of age with hydronephrosis who were followed for at least 12 months., Results: 136 children were identified (96 male:40 female). The mean age at diagnosis of hydronephrosis was 3.3 ± 9.7 months and 76% of the patients were diagnosed at birth. The hydronephrosis was unilateral in 98 (72%) of cases, and hydronephrosis was at least moderate in severity in 22% of affected kidneys. At last follow-up at 30 ± 10 months, the abnormality had resolved in 77 out of 115 (67%) available patients, 30 (26%) had been referred to urology, and 12 (10%) had persistent hydronephrosis. Severity of hydronephrosis was the only clinical feature that predicted persistence of the abnormality (P < 0.001). There was an association between detection at birth and lack of resolution of hydronephrosis., Conclusions: Children with hydronephrosis and presumed UPJO and normal kidney parenchyma can be followed for at least 2 years to allow for spontaneous resolution before referral to urology. Serial sonography can be performed at 6 month intervals in uncomplicated cases. More severe hydronephrosis and presence of the lesion at birth may predict infants and children requiring closer observation and referral for possible surgical correction of the hydronephrosis.
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- 2009
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46. Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study.
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Seeff LB, Hollinger FB, Alter HJ, Wright EC, Cain CM, Buskell ZJ, Ishak KG, Iber FL, Toro D, Samanta A, Koretz RL, Perrillo RP, Goodman ZD, Knodell RG, Gitnick G, Morgan TR, Schiff ER, Lasky S, Stevens C, Vlahcevic RZ, Weinshel E, Tanwandee T, Lin HJ, and Barbosa L
- Subjects
- Aged, Cohort Studies, Female, Follow-Up Studies, Hepatitis C complications, Hepatitis C epidemiology, Hepatitis C immunology, Hepatitis C Antibodies analysis, Hepatitis, Viral, Human epidemiology, Hepatitis, Viral, Human immunology, Humans, Incidence, Liver Cirrhosis virology, Male, Middle Aged, Survival Analysis, Viremia epidemiology, Hepatitis C etiology, Hepatitis C mortality, Hepatitis, Viral, Human etiology, Hepatitis, Viral, Human mortality, Transfusion Reaction
- Abstract
Persons with non-A, non-B hepatitis (cases) identified in 5 transfusion studies in the early 1970s have been followed ever since and compared for outcome with matched, transfused, non-hepatitis controls from the same studies. Previously, we reported no difference in all-cause mortality but slightly increased liver-related mortality between these cohorts after 18 years follow-up. We now present mortality and morbidity data after approximately 25 years of follow-up, restricted to the 3 studies with archived original sera. All-cause mortality was 67% among 222 hepatitis C-related cases and 65% among 377 controls (P = NS). Liver-related mortality was 4.1% and 1.3%, respectively (P =.05). Of 129 living persons with previously diagnosed transfusion-associated hepatitis (TAH), 90 (70%) had proven TAH-C, and 39 (30%), non-A-G hepatitis. Follow-up of the 90 TAH-C cases revealed viremia with chronic hepatitis in 38%, viremia without chronic hepatitis in 39%, anti-HCV without viremia in 17%, and no residual HCV markers in 7%. Thirty-five percent of 20 TAH-C patients biopsied for biochemically defined chronic hepatitis displayed cirrhosis, representing 17% of all those originally HCV-infected. Clinically evident liver disease was observed in 86% with cirrhosis but in only 23% with chronic hepatitis alone. Thirty percent of non-A, non-B hepatitis cases were unrelated to hepatitis viruses A,B,C, and G, suggesting another unidentified agent. In conclusion, all-cause mortality approximately 25 years after acute TAH-C is high but is no different between cases and controls. Liver-related mortality attributable to chronic hepatitis C, though low (<3%), is significantly higher among the cases. Among living patients originally HCV-infected, 23% have spontaneously lost HCV RNA.
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- 2001
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47. Genome sequence of Halobacterium species NRC-1.
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Ng WV, Kennedy SP, Mahairas GG, Berquist B, Pan M, Shukla HD, Lasky SR, Baliga NS, Thorsson V, Sbrogna J, Swartzell S, Weir D, Hall J, Dahl TA, Welti R, Goo YA, Leithauser B, Keller K, Cruz R, Danson MJ, Hough DW, Maddocks DG, Jablonski PE, Krebs MP, Angevine CM, Dale H, Isenbarger TA, Peck RF, Pohlschroder M, Spudich JL, Jung KW, Alam M, Freitas T, Hou S, Daniels CJ, Dennis PP, Omer AD, Ebhardt H, Lowe TM, Liang P, Riley M, Hood L, and DasSarma S
- Subjects
- Biological Evolution, Cell Membrane metabolism, DNA Repair, DNA Replication, Energy Metabolism, Halobacterium metabolism, Lipid Bilayers, Molecular Sequence Data, Protein Biosynthesis, Recombination, Genetic, Signal Transduction, Transcription, Genetic, Genome, Bacterial, Halobacterium genetics
- Abstract
We report the complete sequence of an extreme halophile, Halobacterium sp. NRC-1, harboring a dynamic 2,571,010-bp genome containing 91 insertion sequences representing 12 families and organized into a large chromosome and 2 related minichromosomes. The Halobacterium NRC-1 genome codes for 2,630 predicted proteins, 36% of which are unrelated to any previously reported. Analysis of the genome sequence shows the presence of pathways for uptake and utilization of amino acids, active sodium-proton antiporter and potassium uptake systems, sophisticated photosensory and signal transduction pathways, and DNA replication, transcription, and translation systems resembling more complex eukaryotic organisms. Whole proteome comparisons show the definite archaeal nature of this halophile with additional similarities to the Gram-positive Bacillus subtilis and other bacteria. The ease of culturing Halobacterium and the availability of methods for its genetic manipulation in the laboratory, including construction of gene knockouts and replacements, indicate this halophile can serve as an excellent model system among the archaea.
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- 2000
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48. FVB/N (H2(q)) mouse is resistant to arthritis induction and exhibits a genomic deletion of T-cell receptor V beta gene segments.
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Osman GE, Hannibal MC, Anderson JP, Lasky SR, Ladiges WC, and Hood L
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- Amino Acid Sequence, Animals, Arthritis etiology, Base Sequence, Collagen immunology, DNA Primers genetics, Disease Models, Animal, Humans, Mice, Mice, Inbred Strains, Molecular Sequence Data, Polymorphism, Genetic, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Species Specificity, T-Lymphocytes immunology, Arthritis genetics, Arthritis immunology, Receptors, Antigen, T-Cell, alpha-beta genetics, Sequence Deletion
- Abstract
Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced arthritis (CIA) in mice is an autoimmune disease model of rheumatoid arthritis. Susceptibility to CIA in mice is linked to genes of the major histocompatibility complex (MHC). CD4(+) T cells that express the T-cell receptor (TCR) Tcra-V11.1 and/or Tcrb-V8.2 play a key role in the pathogenesis of arthritis in the DBA/1 mouse (H2(q)). We identified an inbred mouse strain, FVB/NJ (H2(q)), that is resistant to arthritis induction and exhibits a genomic deletion of certain Tcrb-V gene segments. We report a novel polymerase chain reaction-based method for the rapid identification of new mouse strains that exhibit germline Tcrb-V gene deletions. We mapped for the first time both the 5' and 3' breakpoints of the Tcrb-V deletion in the FVB/NJ, SWR, SJL, C57L, and C57BR strains to within 1.1 kilobases. Since there is an association between a particular Tcra-V allele (Tcra-V11.1(d)) and arthritis susceptibility in H2(q) mouse strains, we examined the allelic polymorphisms of the Tcra-V11 gene subfamily members between the arthritis-susceptible DBA/1 mouse and the arthritis-resistant FVB/NJ mouse strain. The amino acid sequences of the Tcra-V11.1 alleles differ at two positions (codons 18 and 68). Therefore, the resistance of FVB/NJ mouse to arthritis induction may be due in part to Tcra-V11.1 coding sequence polymorphism and Tcrb-V8.2 gene segment deletion, as we have recently demonstrated in the case of SWR mouse strain.
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- 1999
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49. T-cell receptor vbeta deletion and valpha polymorphism are responsible for the resistance of SWR mouse to arthritis induction.
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Osman GE, Hannibal MC, Anderson JP, Cheunsuk S, Lasky SR, Liggitt HD, Ladiges WC, and Hood LE
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- Animals, Arthritis pathology, B-Lymphocytes immunology, Collagen immunology, Epitopes, Gene Deletion, Genetic Predisposition to Disease, Immunoglobulin Variable Region metabolism, Joints pathology, Mice, Mice, Inbred DBA, Mice, Inbred Strains, Mice, Transgenic, Molecular Sequence Data, Polymorphism, Genetic, Arthritis genetics, Receptors, Antigen, T-Cell, alpha-beta genetics
- Abstract
Collagen type II-induced arthritis (CIA) develops in susceptible mouse strains after intradermal injections of type II collagen (CII) in complete Freund's adjuvant (CFA). Susceptibility to CIA in mice is linked to genes of the major histocompatibility complex (MHC). Although the SWR mouse has a susceptible MHC haplotype (H2q), it is resistant to CIA. SWR exhibits at least two known immunological defects: (1) it contains a germline deletion of about 50% of T-cell receptor (TCR) Vbeta-chain gene segments, and (2) SWR is deficient in complement component C5. It has been shown that T cells that express TCRValpha11.1 and TCRVbeta8.2 play a substantial role in the pathogenesis of arthritis in the DBA/1 mouse (H2q). We generated SWR transgenic (tg) mice to determine whether the expression of pathogenic Valpha11.1 and/or Vbeta8.2 transgenes would confer arthritis susceptibility. Arthritis was induced in the SWR TCRalphabeta tg mice, but not in SWR TCRbeta tg mice. To address the role of Valpha11.1 in arthritis susceptibility, we examined the allelic polymorphisms of the Tcra-V11-gene subfamily members between the arthritis susceptible DBA/1 mouse and the arthritis-resistant SWR mouse strain. The amino acid sequences of the Valpha11.1 alleles differ at two positions (codons 18 and 68). Accordingly, these two amino acid changes are sufficient to allow the production of pathogenic T cells in SWR mice. This is the first demonstration of the association of a particular Tcra-V allele and arthritis susceptibility in mice.
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- 1999
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50. Differential regulation of vitamin D receptors in clonal populations of a chronic myelogenous leukemia cell line.
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Iwata K, Kouttab N, Ogata H, Morgan JW, Maizel AL, and Lasky SR
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- Base Sequence, Carboxylesterase, Carboxylic Ester Hydrolases metabolism, Cell Differentiation, Clone Cells, DNA metabolism, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lipopolysaccharide Receptors metabolism, Macrophage-1 Antigen metabolism, Molecular Sequence Data, Nitroblue Tetrazolium metabolism, Oligodeoxyribonucleotides, Tumor Cells, Cultured, Cholecalciferol pharmacology, Receptors, Calcitriol metabolism
- Abstract
RWLeu4 is a chronic myelogenous leukemia cell line that is sensitive to the antiproliferative and differentiation-inducing actions of 1alpha,25(OH)2-vitamin D3 (VD3). The JMRD3 cell line is a VD3-resistant variant of RWLeu4 that was selected by continuous passage of RWLeu4 in the presence of VD3. The isolation of a spontaneous VD3-resistant variant suggests that phenotypically different cells exist within the RWLeu4 cell population. Therefore, single-cell clones of RWLeu4 cells were isolated and characterized. Four clonal cell populations that fall into three groups differing in response to the antiproliferative and differentiation-inducing actions of VD3 were examined. Surprisingly, the extent of response of the clones to VD3 does not show a correlation with the basal level of the vitamin D receptor (VDR). RWLeu4-3 and RWLeu4-4 are the clones most sensitive to the antiproliferative actions of VD3 (ED50 approximately equal to 1 nM); however, RWLeu4-3 expresses basal levels of VDRs similar to those found in the parental cells and the RWLeu4-2 clone, while in RWLeu4-4, VD3 binding and VDR protein are below the limits of detection. Furthermore, RWLeu4-10 expresses the highest basal level of VDR protein but is relatively resistant to the antiproliferative actions of VD3 (ED50 > or = 30 nM). Like JMRD3, RWLeu4-10 is still capable of differentiating in response to VD3, as judged by the induction of biochemical processes and cell-surface antigen expression. Although VD3 treatment increases VDR protein levels and DNA-binding activity in all clones, altered DNA-protein complexes are detected in RWLeu4-4. Our results suggest that sensitivity to the antiproliferative and differentiation-inducing actions of VD3 is not dependent solely upon the level of VDR expressed, but may also require posttranslational modification of the VDR or complex interactions with other nuclear transcription factors.
- Published
- 1996
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