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Article ; Online: Ketotifen directly modifies the fibrotic response of human skin fibroblasts.

Leong, Edwin / Al-Bitar, Haya / Marshall, Jean S / Bezuhly, Michael

2024 Volume 14, Issue 1, Page(s) 7076

Abstract: Fibrosis is a destructive, end-stage disease process. In the skin, it is associated with systemic sclerosis and scarring with considerable health burden. Ketotifen is a clinical antihistamine and mast cell stabilizer. Studies have demonstrated mast cell- ... ...

Abstract	Fibrosis is a destructive, end-stage disease process. In the skin, it is associated with systemic sclerosis and scarring with considerable health burden. Ketotifen is a clinical antihistamine and mast cell stabilizer. Studies have demonstrated mast cell-dependent anti-fibrotic effects of ketotifen but direct effects on fibroblasts have not been determined. Human dermal fibroblasts were treated with pro-fibrotic transforming growth factor-β1 (TGFβ) followed by ketotifen or control treatments to determine direct effects on fibrotic fibroblasts. Ketotifen impaired TGFβ-induced α-smooth muscle actin gene and protein responses and decreased cytoskeletal- and contractility-associated gene responses associated with fibrosis. Ketotifen reduced Yes-associated protein phosphorylation, transcriptional coactivator with PDZ binding motif transcript and protein levels, and phosphorylation of protein kinase B. In a fibroblast-populated collagen gel contraction assay, ketotifen reduced the contractile activity of TGFβ-activated fibroblasts. In a murine model of bleomycin-induced skin fibrosis, collagen density and dermal thickness were significantly decreased in ketotifen-treated mice supporting in vitro findings. These results support a novel, direct anti-fibrotic activity of ketotifen, reducing pro-fibrotic phenotypic changes in fibroblasts and reducing collagen fibres in fibrotic mouse skin. Together, these findings suggest novel therapeutic potential and a novel mechanism of action for ketotifen in the context of fibrosis.
MeSH term(s)	Humans ; Mice ; Animals ; Ketotifen/pharmacology ; Ketotifen/metabolism ; Ketotifen/therapeutic use ; Fibrosis ; Skin/metabolism ; Scleroderma, Systemic/metabolism ; Collagen/metabolism ; Fibroblasts/metabolism ; Bleomycin/pharmacology ; Transforming Growth Factor beta1/metabolism ; Cells, Cultured ; Transforming Growth Factor beta/metabolism
Chemical Substances	Ketotifen (X49220T18G) ; Collagen (9007-34-5) ; Bleomycin (11056-06-7) ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta
Language	English
Publishing date	2024-03-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-57776-7
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Article ; Online: Sternal cleft reconstruction with acellular dermal matrix and full-thickness calvarial graft.

Ching, Carmen / Sett, Suvro / Walling, Simon / Bezuhly, Michael

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2023 Volume 63, Issue 4

Abstract: We describe reconstruction of a sternal cleft in a neonate using acellular dermal matrix, full-thickness calvarial bone graft and myocutaneous pectoralis flaps. ...

Abstract	We describe reconstruction of a sternal cleft in a neonate using acellular dermal matrix, full-thickness calvarial bone graft and myocutaneous pectoralis flaps.
MeSH term(s)	Humans ; Infant, Newborn ; Acellular Dermis ; Musculoskeletal Abnormalities ; Sternum/abnormalities
Language	English
Publishing date	2023-04-01
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezad126
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Zs.A 2303: Show issues

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Article ; Online: The Role of ACE-Inhibitors and ARBs in reducing hypertrophic scarring following bilateral breast reduction.

Dow, Todd / Selman, Tamara / Williams, Jason / Bezuhly, Michael

Journal of plastic, reconstructive & aesthetic surgery : JPRAS

2023 Volume 78, Page(s) 1–3

Abstract: Background: The angiotensin-renin system (ARS) has been shown to play a role in the promotion of tissue fibrosis through angiotensin II activation of the angiotensin-receptor 1 and subsequently transforming growth factor beta-1 (TGF- β1). Breast ... ...

Abstract	Background: The angiotensin-renin system (ARS) has been shown to play a role in the promotion of tissue fibrosis through angiotensin II activation of the angiotensin-receptor 1 and subsequently transforming growth factor beta-1 (TGF- β1). Breast reduction surgery is known to have a potential complication of hypertrophic scarring. The primary objective of this study is to assess whether the use of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blockers (ARBs) by patients undergoing bilateral reduction mammoplasty is correlated with a reduction in hypertrophic scarring complications post-operatively. Methods: A retrospective chart review of all patients who received bilateral breast reduction surgery in our province over a 10-year period was performed. Patient charts were reviewed for post-operative hypertrophic scarring as well as medications being used around the time of surgery. The rate of hypertrophic scarring within patients treated with an ACEi or ARB for existing hypertension were compared with the rest of the population. Results: A total of 981 patients met the inclusion criteria of the study. The overall incidence of hypertrophic scarring was 6%. Within the population, 132 (14%) of patients had a clinical diagnosis of hypertension. Of the patients who were managed with an ACEi or ARB, one (2%) patient developed hypertrophic scarring post-operatively. This was significantly less than the total population and the remainder of the population with hypertension treated with a medication other than an ACEi or ARB. Conclusions: This study investigated the impact of routine ACEi or ARB use by patients undergoing bilateral reduction mammoplasty and demonstrated a statistically significant reduction in the incidence of hypertrophic scarring. This study is one of the first to investigate ACEi or ARB use in humans to reduce rates of unsightly scarring. Level of evidence: Level III.
MeSH term(s)	Humans ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Retrospective Studies ; Cicatrix/etiology ; Cicatrix/prevention & control ; Hypertension/epidemiology ; Mammaplasty/adverse effects ; Angiotensins/therapeutic use
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Angiotensin Receptor Antagonists ; Angiotensins
Language	English
Publishing date	2023-01-12
Publishing country	Netherlands
Document type	Letter
ZDB-ID	2217750-4
ISSN	1878-0539 ; 1748-6815 ; 0007-1226
ISSN (online)	1878-0539
ISSN	1748-6815 ; 0007-1226
DOI	10.1016/j.bjps.2022.11.032
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Article ; Online: Physician Scientists Of Yesterday, Today And Tomorrow - Published 44(3) September 2021.

Hollenberg, Morley D / Bezuhly, Michael Bezuhly

Clinical and investigative medicine. Medecine clinique et experimentale

2021 Volume 44, Issue 3, Page(s) E80–81

Abstract: In this issue, Ryan Kirkpatrick and Gordon Boyd speculated on the reasons for the dwindling number of physician scientists in Canada. To help stimulate discussion on this important issue, Clinical and Investigative Medicine invited two distinguished ... ...

Abstract	In this issue, Ryan Kirkpatrick and Gordon Boyd speculated on the reasons for the dwindling number of physician scientists in Canada. To help stimulate discussion on this important issue, Clinical and Investigative Medicine invited two distinguished scientists to present their views on this issue.
MeSH term(s)	Canada ; Humans ; Physicians
Language	English
Publishing date	2021-10-03
Publishing country	Canada
Document type	Editorial ; Comment
ZDB-ID	434004-8
ISSN	1488-2353 ; 0147-958X
ISSN (online)	1488-2353
ISSN	0147-958X
DOI	10.25011/cim.v44i3.37244
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Zs.A 1389: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 345: Show issues

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Article ; Online: Systematic Review of Patient Safety and Quality Improvement Initiatives in Breast Reconstruction.

Paffile, Julia / McGuire, Connor / Bezuhly, Michael

Annals of plastic surgery

2022 Volume 89, Issue 1, Page(s) 121–136

Abstract: Background: Improving patient care and safety requires high-quality evidence. The objective of this study was to systematically review the existing evidence for patient safety (PS) and quality improvement initiatives in breast reconstruction.: Methods! ...

Abstract	Background: Improving patient care and safety requires high-quality evidence. The objective of this study was to systematically review the existing evidence for patient safety (PS) and quality improvement initiatives in breast reconstruction. Methods: A systematic review of the published plastic surgery literature was undertaken using a computerized search and following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Publication descriptors, methodological details, and results were extracted. Articles were assessed for methodological quality and clinical heterogeneity. Descriptive statistics were completed, and a meta-analysis was considered. Results: Forty-six studies were included. Most studies were retrospective (52.2%) and from the third level of evidence (60.9%). Overall, the scientific quality was moderate, with randomized controlled trials generally being higher quality. Studies investigating approaches to reduce seroma (28.3% of included articles) suggested a potential benefit of quilting sutures. Studies focusing on infection (26.1%) demonstrated potential benefits to prophylactic antibiotics and drain use under 21 days. Enhanced recovery after surgery protocols (10.9%) overall did not compromise PS and was beneficial in reducing opioid use and length of stay. Interventions to increase flap survival (10.9%) demonstrated a potential benefit of nitroglycerin on mastectomy skin flaps. Conclusions: Overall, studies were of moderate quality and investigated several worthwhile interventions. More validated, standardized outcome measures are required, and studies focusing on interventions to reduce thromboembolic events and bleeding risk could further improve PS.
MeSH term(s)	Breast Neoplasms/surgery ; Female ; Humans ; Mammaplasty/methods ; Mastectomy/methods ; Patient Safety ; Quality Improvement ; Retrospective Studies
Language	English
Publishing date	2022-01-24
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	423835-7
ISSN	1536-3708 ; 0148-7043
ISSN (online)	1536-3708
ISSN	0148-7043
DOI	10.1097/SAP.0000000000003062
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Zs.A 1419: Show issues

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Article ; Online: Reply: Alternatively Activated M2 Macrophages Improve Autologous Fat Graft Survival in a Mouse Model through Induction of Angiogenesis.

Bezuhly, Michael

Plastic and reconstructive surgery

2015 Volume 136, Issue 2, Page(s) 278e

MeSH term(s)	Adipose Tissue/transplantation ; Animals ; Autografts/immunology ; Graft Survival/immunology ; Macrophages/physiology ; Male
Language	English
Publishing date	2015-03-26
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	208012-6
ISSN	1529-4242 ; 0032-1052 ; 0096-8501
ISSN (online)	1529-4242
ISSN	0032-1052 ; 0096-8501
DOI	10.1097/PRS.0000000000001462
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Uk I Zs.142: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 293: Show issues

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Article ; Online: Combining vascularized lymph node transfer with autologous breast reconstruction: A Surveillance, Epidemiology and End Results (SEER) Database cost-utility analysis.

Corkum, Joseph P / Bezuhly, Michael

Journal of plastic, reconstructive & aesthetic surgery : JPRAS

2020 Volume 73, Issue 10, Page(s) 1879–1888

Abstract: Background: The cost effectiveness of combining vascularized lymph node transfer (VLNT) with autologous breast reconstruction has not been established. Herein we describe the use of Markov modeling to evaluate the cost utility of VLNT with delayed ... ...

Abstract	Background: The cost effectiveness of combining vascularized lymph node transfer (VLNT) with autologous breast reconstruction has not been established. Herein we describe the use of Markov modeling to evaluate the cost utility of VLNT with delayed autologous breast reconstruction for patients with breast cancer related lymphedema (BCRL). Methods: We conducted a cost effectiveness analysis using a Markov model with microsimulation. The characteristics and associated life expectancy of the hypothetical patients were derived from the Surveillance, Epidemiology, and End Results database. Costs of were derived from the publicly available sources and health economics literature. The utilities were based on the best available literature. The relative effectiveness of VLNT was derived from a meta-analysis of the literature. A specific strategy is considered attractive if the estimate of incremental cost effectiveness ratio (ICER) is less than the amount decision makers are willing to pay for an additional quality-adjusted life-year (QALY) gain. A baseline willingness to pay of $50,000 USD per additional QALY was used for analysis. Results: The base case situation demonstrated an overall ICER of $13898.76/QALY for adding VLNT to delayed autologous abdominally based breast reconstruction in the situation where lymphedema is already present, which suggests it is cost-effective at the chosen willingness to pay. Discussion: This cost-utility simulation demonstrates that it is cost effective to combine delayed breast reconstruction with VLNT in patients with existing lymphedema. This could have implications for the application of the evolving technique of VLNT in the treatment of different subpopulations of breast cancer patients, and future clinical research.
MeSH term(s)	Adolescent ; Adult ; Aged ; Breast Neoplasms/economics ; Breast Neoplasms/surgery ; Combined Modality Therapy/economics ; Cost-Benefit Analysis ; Databases, Factual ; Female ; Humans ; Lymph Nodes/blood supply ; Lymph Nodes/transplantation ; Mammaplasty/economics ; Mammaplasty/methods ; Middle Aged ; SEER Program ; Young Adult
Language	English
Publishing date	2020-05-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2217750-4
ISSN	1878-0539 ; 1748-6815 ; 0007-1226
ISSN (online)	1878-0539
ISSN	1748-6815 ; 0007-1226
DOI	10.1016/j.bjps.2020.05.027
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Article ; Online: Rapid intraoperative fabrication of an inexpensive, reliable nasal stent for use after primary cleft nasal repair.

Bezuhly, Michael

The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association

2014 Volume 51, Issue 5, Page(s) e110–2

Abstract: Nasal stents are frequently used to maintain corrected nostril shape following primary cleft lip and nasal repair. Various stents have been described, but they are often cumbersome to generate, expensive, or difficult to retain. The author describes a ... ...

Abstract	Nasal stents are frequently used to maintain corrected nostril shape following primary cleft lip and nasal repair. Various stents have been described, but they are often cumbersome to generate, expensive, or difficult to retain. The author describes a rapid, effective, and inexpensive alternative to previously described commercially available or molded nasal stents whereby a nasal stent is fabricated from a pediatric nasal oxygen cannula. All patients in whom this stent has been used to date tolerated it well with no complication and with good maintenance of nostril shape at a minimum of 6 months follow-up.
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1069409-2
ISSN	1545-1569 ; 0009-8701 ; 1055-6656
ISSN (online)	1545-1569
ISSN	0009-8701 ; 1055-6656
DOI	10.1597/13-205
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Zs.A 451: Show issues

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Article ; Online: Comparison of two Specialized Cleft Palate Feeders.

Penny, Cameron / Nugent, Kendra-Ann / Gilgan, Holly / Bezuhly, Michael

The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association

2022 Volume 61, Issue 3, Page(s) 443–449

Abstract: Objective: To evaluate feeding efficiency and weight gain in infants with cleft palate fed using 1 of the 2 specialty feeders.: Design: Retrospective cohort study.: Setting: Cleft palate clinic in a tertiary pediatric hospital.: Participants: ... ...

Abstract	Objective: To evaluate feeding efficiency and weight gain in infants with cleft palate fed using 1 of the 2 specialty feeders. Design: Retrospective cohort study. Setting: Cleft palate clinic in a tertiary pediatric hospital. Participants: Infants with cleft palate (with or without cleft lip) fed using the Medela SpecialNeeds® Feeder (n = 39) or the Dr. Brown's® Specialty Feeding System (n = 16) and who had documented feeding and growth data available from the time of initial assessment in the first month of life and at subsequent follow-up between 2 and 4 months. Primary outcome measure: Feeding velocity (mL/min). Secondary outcomes measures: Calorie velocity (kcal/min), weight gain, and complications associated with poor feeding. Results: No statistically significant differences in feeding or calorie velocities were identified between infants with cleft palate fed with the Medela SpecialNeeds® feeder and those fed with the Dr. Brown's® feeder. Mean weight z-scores by month did not differ significantly between the 2 bottle groups at the time of initial assessment (P = .84) and follow-up (P = .20). Mean weight z-scores by month for the infants included in this study fell below the 50th percentile. The proportion of infants who developed otitis media, reflux requiring treatment, or who required hospital admission for nasogastric (NG) feeds did not differ significantly between the 2 groups. Conclusions: Despite being adequately powered for the primary outcome, no significant differences were identified between infants fed with the Medela or the Dr. Brown's feeders in terms of feeding velocity, calorie velocity, weight gain, or complications.
MeSH term(s)	Infant ; Humans ; Child ; Cleft Palate/complications ; Retrospective Studies ; Cleft Lip/complications ; Weight Gain
Language	English
Publishing date	2022-10-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1069409-2
ISSN	1545-1569 ; 0009-8701 ; 1055-6656
ISSN (online)	1545-1569
ISSN	0009-8701 ; 1055-6656
DOI	10.1177/10556656221129977
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Zs.A 451: Show issues

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Article ; Online: Patient Safety and Quality Improvement Initiatives in Cleft Lip and Palate Surgery: A Systematic Review.

Grue, Brendan / McGuire, Connor / Hong, Paul / Bezuhly, Michael

The Journal of craniofacial surgery

2022 Volume 34, Issue 3, Page(s) 979–986

Abstract: Background: Cleft lip and/or palate repair techniques require continued reevaluation of best practice through high-quality evidence. The objective of this systematic review was to highlight the existing evidence for patient safety and quality ... ...

Abstract	Background: Cleft lip and/or palate repair techniques require continued reevaluation of best practice through high-quality evidence. The objective of this systematic review was to highlight the existing evidence for patient safety and quality improvement (QI) initiatives in cleft lip and palate surgery. Methods: A systematic review of published literature evaluating patient safety and QI in patients with cleft lip and/or palate was conducted from database inception to June 9, 2022, using Preferred Reporting Items for Systematic Reviews guidelines. Quality appraisal of included studies was conducted using Methodological Index for Non-Randomized Studies, Cochrane, or a Measurement Tool to Assess Systematic Reviews (AMSTAR) 2 instruments, according to study type. Results: Sixty-one studies met inclusion criteria, with most published between 2010 and 2020 (63.9%). Randomized controlled trials represented the most common study design (37.7%). Half of all included studies were related to the topic of pain and analgesia, with many supporting the use of infraorbital nerve block using 0.25% bupivacaine. The second most common intervention examined was use of perioperative antibiotics in reducing fistula and infection (11.5%). Other studies examined optimal age and closure material for cleft lip repair, early recovery after surgery protocols, interventions to reduce blood loss, and safety of outpatient surgery. Conclusions: Patient safety and QI studies in cleft surgery were of moderate quality overall and covered a wide range of interventions. To further enhance PS in cleft repair, more high-quality research in the areas of perioperative pharmaceutical usage, appropriate wound closure materials, and optimal surgical timing are needed.
MeSH term(s)	Humans ; Cleft Lip/surgery ; Cleft Palate/surgery ; Patient Safety ; Quality Improvement ; Pain
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Systematic Review ; Journal Article
ZDB-ID	1159501-2
ISSN	1536-3732 ; 1049-2275
ISSN (online)	1536-3732
ISSN	1049-2275
DOI	10.1097/SCS.0000000000009094
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Zs.MO 175: Show issues

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