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1.
Ann Surg ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38726665

RESUMEN

OBJECTIVE: Despite politically charged media coverage and legislation surrounding gender affirming care (GAC), many organizations have released position statements to provide scientifically backed clinical practice standards, combat misinformation, and inform medicolegal policies. The purpose of this study is to objectively assess the availability and the content of the official position statements of relevant medical professional organizations regarding GAC. SUMMARY BACKGROUND DATA: A list of U.S. medical professional organizations with likely involvement in GAC based on medical or surgical specialties was compiled. METHODS: For included organizations, we evaluated the availability, content, and publication year of positions on GAC through October 2023. When available, formal positions were categorized as supportive or unsupportive. RESULTS: A total of 314 professional medical organizations were screened for our study based on specialty, relevance to GAC, and issuance of patient guidelines or position statements. Inclusion criteria were met by 55 organizations. Most organizations (35, 63.6%) had formal position statements on GAC. Support for GAC was described in 97.1% (n=34). Further, 94.2% (n=33) of available statements explicitly addressed GAC in individuals less than 18 years old and were largely supportive (96.9%, n=32). CONCLUSIONS: This cross-sectional analysis demonstrates that a majority of multidisciplinary professional medical organizations with relevance to GAC have issued formal position statements on the topic. Available positions were overwhelmingly supportive of individualized access to gender-affirming therapies in adult and adolescent populations. However, silence from some organizations continues to represent a modifiable disparity in the provision of GAC.

3.
Eplasty ; 24: e13, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38685992

RESUMEN

Background: OpenAI's ChatGPT can generate novel ideas for a number of applications. The aim of this study was to prompt the chatbot to generate possible innovations in aesthetic surgery relating to rhinoplasty. Methods: ChatGPT was prompted to develop rhinoplasty patents. The resulting outputs were tabulated and categorized based on technology domain and anatomic location. A Google Patents search was conducted to find uses of the term "rhinoplasty" between 2021 and 2023. Patents not pertaining to rhinoplasty were excluded. Filed patents were compared with those generated by ChatGPT to determine predictive power. Results: A total of 40 patents resulted from ChatGPT and 42 Google Patents from 2021 to 2023 were included. Patents generated without a detailed description command were related to preoperative planning (35%), intraoperative tools (30%), functional evaluation (15%), and 3D printing and implants (10%). Patents with a detailed description command resulted in the majority being postoperative tools (40%), followed by intraoperative tools (30%), 3D printing and implants (10%), and nonsurgical (10%) categories. The anatomic locations included the airway, dorsum, septum, and nasal tip. ChatGPT's predictive power yielded 45% for the detailed prompting, which was higher than the prompt without the detail command. Conclusions: ChatGPT has reasonable potential to generate ideas for innovations in plastic surgery with the assistance of an experienced surgeon-innovator. With new artificial intelligence generations and updates, chatbots will continue to improve. Determining whether these technologies can assist in the later portions of the patent process beyond idea generation will be crucial.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38668643

RESUMEN

OBJECTIVES: To assess potential risk factors influencing diet outcomes after reconstruction of subtotal hypopharyngeal defects using free patch- or tube-shaped anterolateral thigh (ALT) fasciocutaneous flaps. STUDY DESIGN: Retrospective cohort study. SETTING: First-level referral hospital. METHODS: Between January 2011 and December 2020, we studied hypopharyngeal cancer patients who underwent the reconstruction of hypopharyngeal defects using free patch- or tube-shaped ALT fasciocutaneous flaps. The choice between patch- or tube-shaped ALT flaps depended on the defect's nature, favoring patch-shaped for subtotal defects and tube-shaped for circumferential defects. A restricted diet was characterized by a history of enterostomy or endoscopic esophageal dilation treatment postreconstruction. We analyzed patients with restricted diets at 1- and 3-year follow-up visits. RESULTS: Ninety-eight patients were enrolled; 39 patch-shaped flaps, and 59 tube-shaped flaps. No significances were noted in demographics, postoperative radiotherapy (RT) or chemotherapy, rates of free flap reoperation/salvage, or complications. However, a significant difference emerged in diet outcomes at the 1-year follow-up (P = .005). The rate of a restricted diet was 6.08 times higher in patients with tube-shaped flaps compared to patch-shaped flaps (95% confidence interval [CI]: 1.95-18.94). Stratifying based on postoperative RT revealed a 5.47 times higher rate of a restricted diet in tube-shaped flap recipients compared to patch-shaped flap recipients (95% CI: 1.44-20.48). No significances were observed in 5-year survival rates. CONCLUSION: Concerning postoperative RT, patch-shaped flaps exhibited a lower incidence of a restricted diet compared to tube-shaped flaps. Preservation of the posterior mucosa may play a crucial role in preventing RT-induced esophageal stricture.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38584330

RESUMEN

Body mass index (BMI) requirements for gender-affirming surgeries (GAS) present an obstacle to gender transition for many transgender and gender diverse (TGD) people. Furthermore, TGD people have unique barriers and preferences in managing their weight that must be considered. TGD patients frequently present to their endocrinologists for individualized, gender-affirming support to meet BMI cutoffs for GAS. This Approach to the Patient article combines expertise from several disciplines, including gender-affirming hormone management, weight management, mental health, gynecology, and plastic surgery. Multidisciplinary management considerations are offered for clinicians to assist TGD patients with obesity navigate BMI requirements to access GAS.

6.
Oral Maxillofac Surg Clin North Am ; 36(2): 221-236, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38458858

RESUMEN

For some patients, feminine facial features may cause significant gender dysphoria. Multiple nonsurgical and surgical techniques exist to masculinize facial features. Nonsurgical techniques include testosterone supplementation and dermal fillers. Surgical techniques include soft tissue manipulation, synthetic implants, regenerative scaffolding, or bony reconstruction. Many techniques are derived from experience with cisgender patients, but are adapted with special considerations to differing anatomy between cisgender and transgender men and women. Currently, facial masculinization is less commonly sought than feminization, but demand is likely to increase as techniques are refined and made available.


Asunto(s)
Implantes Dentales , Procedimientos de Cirugía Plástica , Cirugía de Reasignación de Sexo , Personas Transgénero , Masculino , Humanos , Femenino , Cirugía de Reasignación de Sexo/métodos , Cara/cirugía
7.
Transgend Health ; 9(1): 83-91, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38312453

RESUMEN

Purpose: The transgender community utilizes online platforms to view and share postoperative masculinizing top surgery photographs. However, the quantitative and qualitative nature of these photographs is unknown. We aimed to conduct an analysis of postoperative online photographs for nipple-areolar complex (NAC) shape and location, and compare social media platforms to World Professional Association for Transgender Health (WPATH) surgeons' websites and published cis-male chest proportions. Methods: In a cross-sectional analysis (April to May 2019), social media (Instagram and Reddit) and WPATH surgeon website postoperative top surgery photographs were analyzed. Areola height (AH):areola width (AW), NAC horizontal (inter-nipple distance [IND]:chest width [CW]) and vertical placement (sternal notch to nipple line [SN-NL]:sternal notch to umbilicus [SN-U]), and vertical scar placement (sternal notch to scar line [SN-SL]:SN-U) ratios were assessed on MATLAB. Data were compared to published cis-male proportions. Photograph skin color, soft tissue redundancy, and scar location were also analyzed. Results: We analyzed 304 social media and 192 surgeons' website photographs qualitatively, and 139 social media and 189 surgeons' photographs quantitatively. Means (standard deviation) for postoperative photographs were AH:AW 1.12±0.24, IND:CW 0.68±0.07, SN-NL:SN-U 0.37±0.06. Most ratios significantly differed from published cis-male ratios (p<0.001). Photographs from WPATH surgeons' websites differed from social media platforms in SN-NL:SN-U and SN-SL:SN-U (p<0.001), and in scar location and soft tissue redundancy (p=0.012). Conclusion: Postoperative top surgery photographs on online platforms showed more vertically oval, caudally positioned, and in many cases wider-spaced NACs than cis-male proportions. Our study highlights variability in results of masculinizing top surgery as it relates to an emerging source of information; online photographs.

8.
Aesthet Surg J Open Forum ; 6: ojad066, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38196964

RESUMEN

Background: Bard is a conversational generative artificial intelligence (AI) platform released by Google (Mountain View, CA) to the public in May 2023. Objectives: This study investigates the performance of Bard on the American Society of Plastic Surgeons (ASPS) In-Service Examination to compare it to residents' performance nationally. We hypothesized that Bard would perform best on the comprehensive and core surgical principles portions of the examination. Methods: Google's 2023 Bard was used to answer questions from the 2022 ASPS In-Service Examination. Each question was asked as written with the stem and multiple-choice options. The 2022 ASPS Norm Table was utilized to compare Bard's performance to that of subgroups of plastic surgery residents. Results: A total of 231 questions were included. Bard answered 143 questions correctly corresponding to an accuracy of 62%. The highest-performing section was the comprehensive portion (73%). When compared with integrated residents nationally, Bard scored in the 74th percentile for post-graduate year (PGY)-1, 34th percentile for PGY-2, 20th percentile for PGY-3, 8th percentile for PGY-4, 1st percentile for PGY-5, and 2nd percentile for PGY-6. Conclusions: Bard outperformed more than half of the first-year integrated residents (74th percentile). Its best sections were the comprehensive and core surgical principle portions of the examination. Further analysis of the chatbot's incorrect questions might help improve the overall quality of the examination's questions.

9.
Vet Comp Orthop Traumatol ; 37(1): 50-56, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37696299

RESUMEN

OBJECTIVE: The aim of this study is to describe the use of String of Pearls (SOP) plates for the surgical management of feline pelvic fractures, including surgical technique, proposed indications, complications, and outcomes in a cohort of cats. STUDY DESIGN: This study is a single-center retrospective clinical case series. METHODS: Medical records (2015-2019) of cats presenting for pelvic fractures (n = 33) were reviewed. Type of fracture, preoperative and postoperative imaging, and complications were retrospectively retrieved. Owners were contacted via questionnaire for medium- and long-term follow-up. RESULTS: A total of 20 cats met the inclusion criteria. Minor intraoperative complications were encountered in three patients. One patient suffered a major intraoperative complication. Five major complications were encountered postoperatively. These included two greater trochanter osteotomy fixation implant removal and three SOP plate removal. Full function was recovered in all patients according to the owners' assessment. CLINICAL SIGNIFICANCE: The use of SOP plates in feline pelvic fractures appears to yield a consistently good outcome with a very low incidence of canal narrowing and screw loosening. SOP plates are easy to contour and to apply along the entire pelvic length.


Asunto(s)
Enfermedades de los Gatos , Fracturas Óseas , Huesos Pélvicos , Gatos , Animales , Estudios Retrospectivos , Fracturas Óseas/cirugía , Fracturas Óseas/veterinaria , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/cirugía , Fijación Interna de Fracturas/veterinaria , Pelvis , Placas Óseas/veterinaria , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/cirugía
10.
Surgery ; 174(6): 1376-1383, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37839968

RESUMEN

BACKGROUND: Gender-affirming surgery is unequally distributed across the United States due to resource allocation, state-based regulations, and the availability of trained physicians. Many individuals seeking gender-affirming surgery travel vast distances to receive care. This study aims to quantify the distances that individuals travel to receive gender-affirming surgery based on procedure type and patient home-of-record location. METHODS: Patients in the Optum Clinformatics Data Mart who underwent gender-affirming surgery were identified via Current Procedural Terminology codes. Data on patient demographics, procedural care, and location of patient and provider were collected. To be included, a patient had to meet diagnostic criteria to receive gender-affirming surgery and have a recorded surgical procedure reimbursed as part of gender-affirming surgery per the Centers for Medicare and Medicaid Services guidelines. Patients residing or receiving care outside the continental United States were excluded. Distances between the ZIP Code of each patient's home of record and the location where the gender-affirming surgery was performed were calculated via the Google Maps Distance Matrix API. Distance traveled for gender-affirming surgery by patient state and gender-affirming surgery procedure were determined. Multivariate linear regression analysis determined predictors of distance traveled for gender-affirming surgery, whereas multivariate logistic regression identified variables associated with an increased likelihood of out-of-state travel to gender-affirming surgery. RESULTS: Across 86 million longitudinal patient records, the study population included 2,743 records corresponding to 1,735 patients who received gender-affirming surgery between January 2003 and June 2020. The median distance traveled for gender-affirming surgery was 191 miles (mean: 391.5), and 36.0% of patients traveled out of their state of residence. Every patient from West Virginia, Wyoming, South Dakota, Mississippi, and Delaware traveled out of state for gender-affirming surgery. Patients with homes of record in California (18.4%), Massachusetts (20.7%), and Oregon (19.0%) were the least likely to travel out-of-state for gender-affirming surgery out of states with more than 10 gender-affirming surgery encounters. The main predictors for out-of-state travel included both feminizing and masculinizing genital surgery, as well as an insurance coverage with increased provider options. Additionally, patients traveled shorter distances for gender-affirming surgery after the post-2014 Affordable Care Act expansion compared to pre-2014. CONCLUSION: Patients receiving gender-affirming surgery in the United States travel great distances for their care, often receiving their care from out-of-state providers. Restrictive guidelines imposed by state laws on both the access to and provision of gender-affirming surgery compound the myriad of common difficulties that patients face. It is imperative to discuss potential factors that may mitigate these barriers for those who require gender-affirming surgery.


Asunto(s)
Cirugía de Reasignación de Sexo , Humanos , Estados Unidos , Anciano , Patient Protection and Affordable Care Act , Medicare , Viaje , Massachusetts , Accesibilidad a los Servicios de Salud
11.
Ann Surg ; 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37870257

RESUMEN

OBJECTIVE: To analyze the impact of Body Mass Index (BMI) on clinical and patient-reported outcomes following gender-affirming mastectomy (GM). BACKGROUND: BMI is a barrier for obese patients seeking GM despite increasing evidence that it is safe in this population. Currently little is known about the impact of BMI on chest-specific body image and satisfaction following GM. METHODS: This single-center, cross-sectional study included individuals 18 years and older who underwent GM between 1990-2020 and were at least 2 years post-operative. Patient-reported chest-specific body image was measured using the BODY-Q and Gender Congruence and Life Satisfaction (GCLS) chest subscales. Satisfaction was measured using the Holmes-Rovner Satisfaction with Decision (SWD) scale. Clinical and demographic variables were identified from chart review. Bivariate analysis was performed to determine if BMI was associated with chest-specific body image, satisfaction, complications within 30 days or revisions in GM. RESULTS: Two hundred twenty-seven individuals meeting eligibility criteria were contacted to participate and one hundred thirty-seven responded (60.4% response rate). The mean age was 29.1 (SD=9.0) and mean BMI was 30.9 (SD=8.0), with 26.4% (N=60) of the cohort having a BMI>35. Chest-specific body image, and satisfaction with decision did not vary by BMI or breast resection weight. Complications and revisions were not associated with BMI. CONCLUSION: Individuals undergoing GM reported high rates of satisfaction following GM regardless of BMI. Complication and revision rates did not vary significantly by BMI or breast resection weight. Surgeons should re-evaluate the role BMI plays in patient selection and counseling for GM.

12.
Plast Reconstr Surg Glob Open ; 11(10): e5306, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37817924

RESUMEN

Background: As visibility of the transgender patient population and utilization of online resources increases, it is imperative that web-based gender-affirming surgery (GAS) materials for patients are readable, accessible, and of high quality. Methods: A search trends analysis was performed to determine frequency of GAS-related searches over time. The top 100 most common results for GAS-related terms were analyzed using six readability formulas. Accessibility of patient-facing GAS sources was determined by categorizing types of search results. Frequency of article types was compared in low- and high-population dense areas. Quality was assigned to GAS web-based sources using the DISCERN score. Results: Search engine trend data demonstrates increasing occurrence of searches related to GAS. Readability scores of the top 100 online sources for GAS were discovered to exceed recommended levels for patient proficiency. Availability of patient-facing online information related to GAS was found to be 60%, followed by information provided by insurance companies (17%). Differences in availability of online resources in varying dense cities were found to be minimal. The average quality of sources determined by the DISCERN score was found to be 3, indicating "potential important shortcomings." Conclusions: Despite increasing demand for web-based GAS information, the readability of online resources related to GAS was found to be significantly greater than the grade level of proficiency recommended for patients. A high number of nonpatient-facing search results appear in response to GAS search terms. Quality sources are still difficult for patients to find, as search results have a high incidence of low-quality resources.

13.
Ann Plast Surg ; 91(5): 518-523, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37823617

RESUMEN

BACKGROUND: As the demand for gender affirmation grows, teaching gender-affirming surgery (GAS) in plastic and reconstructive surgery (PRS) programs has become increasingly important. Residency applicants interested in GAS often use program web sites to explore potential training opportunities. Our study aimed to quantify the GAS training opportunities promoted on residency program web sites and determine the characteristics of programs likely to promote GAS training. METHODS: An assessment of 88 integrated PRS residency programs' web sites was conducted between 2021 and 2022. Plastic and reconstructive surgery residency and institutional webpages were queried for geographical location, training opportunities in GAS through residency or fellowship, and the number of faculty performing GAS. Descriptive statistics and multivariable regressions were used to describe and identify factors associated with increased GAS residency training opportunities. RESULTS: Twenty-six percent of PRS residencies mentioned training opportunities for GAS on their web sites. Gender-affirming surgery fellowships were offered at 7% of institutions, and an additional 7% were available via adjunct academic programs. Programs with faculty practicing GAS were 54% more likely to mention GAS on their residency page (odds ratio, 1.54; 95% confidence interval, 1.14-2.21; P = 0.009). CONCLUSIONS: Few PRS residency programs mention GAS on their web sites. As GAS becomes a more robust component of plastic surgery, appropriate information about the extent of GAS training should be available for applicants. Determining how local, state, and federal policies impact programs' abilities to highlight GAS should be investigated in future studies.


Asunto(s)
Internado y Residencia , Cirugía de Reasignación de Sexo , Cirugía Plástica , Humanos , Cirugía Plástica/educación , Educación de Postgrado en Medicina , Escolaridad
14.
JAMA Surg ; 158(10): 1070-1077, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37556147

RESUMEN

Importance: There has been increasing legislative interest in regulating gender-affirming surgery, in part due to the concern about decisional regret. The regret rate following gender-affirming surgery is thought to be approximately 1%; however, previous studies relied heavily on ad hoc instruments. Objective: To evaluate long-term decisional regret and satisfaction with decision using validated instruments following gender-affirming mastectomy. Design, Setting, and Participants: For this cross-sectional study, a survey of patient-reported outcomes was sent between February 1 and July 31, 2022, to patients who had undergone gender-affirming mastectomy at a US tertiary referral center between January 1, 1990, and February 29, 2020. Exposure: Decisional regret and satisfaction with decision to undergo gender-affirming mastectomy. Main Outcomes and Measures: Long-term patient-reported outcomes, including the Holmes-Rovner Satisfaction With Decision scale, the Decision Regret Scale, and demographic characteristics, were collected. Additional information was collected via medical record review. Descriptive statistics and univariable analysis using Fisher exact and Wilcoxon rank sum tests were performed to compare responders and nonresponders. Results: A total of 235 patients were deemed eligible for the study, and 139 responded (59.1% response rate). Median age at the time of surgery was 27.1 (IQR, 23.0-33.4) years for responders and 26.4 (IQR, 23.1-32.7) years for nonresponders. Nonresponders (n = 96) had a longer postoperative follow-up period than responders (median follow-up, 4.6 [IQR, 3.1-8.6] vs 3.6 [IQR, 2.7-5.3] years, respectively; P = .002). Nonresponders vs responders also had lower rates of depression (42 [44%] vs 94 [68%]; P < .001) and anxiety (42 [44%] vs 97 [70%]; P < .001). No responders or nonresponders requested or underwent a reversal procedure. The median Satisfaction With Decision Scale score was 5.0 (IQR, 5.0-5.0) on a 5-point scale, with higher scores noting higher satisfaction. The median Decision Regret Scale score was 0.0 (IQR, 0.0-0.0) on a 100-point scale, with lower scores noting lower levels of regret. A univariable regression analysis could not be performed to identify characteristics associated with low satisfaction with decision or high decisional regret due to the lack of variation in these responses. Conclusions and Relevance: In this cross-sectional survey study, the results of validated survey instruments indicated low rates of decisional regret and high levels of satisfaction with decision following gender-affirming mastectomy. The lack of dissatisfaction and regret impeded the ability to perform a more complex statistical analysis, highlighting the need for condition-specific instruments to assess decisional regret and satisfaction with decision following gender-affirming surgery.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Humanos , Femenino , Estudios Transversales , Toma de Decisiones , Neoplasias de la Mama/cirugía , Satisfacción del Paciente , Emociones
15.
AMA J Ethics ; 25(6): E421-430, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37285296

RESUMEN

Patient-reported outcome measures (PROMs) are questionnaires that assess how patients feel and function. PROMs should be developed and validated using a mixed methods, multistep approach with extensive patient input to ensure that they are easy to understand, comprehensive, and relevant. PROMs that are specific to gender-affirming care (including surgery), such as the GENDER-Q, can be used to educate patients, align patients' goals and preferences with realistic expectations about the surgical procedures' purposes and outcomes, and conduct comparative effectiveness research. PROM data can contribute to evidence-based, shared decision making and just access to gender-affirming surgical care.


Asunto(s)
Medición de Resultados Informados por el Paciente , Cirugía de Reasignación de Sexo , Calidad de Vida , Personas Transgénero
17.
Facial Plast Surg Clin North Am ; 31(3): 381-392, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37348981

RESUMEN

For patients with gender dysphoria, gender-affirming surgery of the face has been shown to vastly improve quality of life. The mandible is one area of the face that has distinct feminine and masculine presentations. This article will review gender-affirming surgery of the lower jaw, both for feminization and masculinization. Techniques for bony contouring and soft tissue manipulation will be discussed.


Asunto(s)
Cirugía de Reasignación de Sexo , Masculino , Humanos , Feminización/cirugía , Calidad de Vida , Mandíbula/cirugía
18.
Plast Reconstr Surg Glob Open ; 11(5): e5033, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37255762

RESUMEN

Penile inversion vaginoplasty is the most common gender-affirming genital surgery performed around the world. Although individual centers have published their experiences, expert consensus is generally lacking. Methods: Semistructured interviews were performed with 17 experienced gender surgeons representing a diverse mix of specialties, experience, and countries regarding their patient selection, preoperative management, vaginoplasty techniques, complication management, and postoperative protocols. Results: There is significant consistency in practices across some aspects of vaginoplasty. However, key areas of clinical heterogeneity are also present and include use of extragenital tissue for vaginal canal/apex creation, creation of the clitoral hood and inner labia minora, elevation of the neoclitoral neurovascular bundle, and perioperative hormone management. Pathway length of stay is highly variable (1-9 days). Lastly, some surgeons are moving toward continuation or partial reduction of estrogen in the perioperative period instead of cessation. Conclusions: With a broad study of surgeon practices, and encompassing most of the high-volume vaginoplasty centers in Europe and North America, we found key areas of practice variation that represent areas of priority for future research to address. Further multi-institutional and prospective studies that incorporate patient-reported outcomes are necessary to further our understanding of these procedures.

20.
J Allergy Clin Immunol ; 152(3): 711-724.e14, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37100120

RESUMEN

BACKGROUND: Mast cell activation is critical for the development of allergic diseases. Ligation of sialic acid-binding immunoglobin-like lectins (Siglecs), such as Siglec-6, -7, and -8 as well as CD33, have been shown to inhibit mast cell activation. Recent studies showed that human mast cells express Siglec-9, an inhibitory receptor also expressed by neutrophils, monocytes, macrophages, and dendritic cells. OBJECTIVE: We aimed to characterize Siglec-9 expression and function in human mast cells in vitro. METHODS: We assessed the expression of Siglec-9 and Siglec-9 ligands on human mast cell lines and human primary mast cells by real-time quantitative PCR, flow cytometry, and confocal microscopy. We used a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing approach to disrupt the SIGLEC9 gene. We evaluated Siglec-9 inhibitory activity on mast cell function by using native Siglec-9 ligands, glycophorin A (GlycA), and high-molecular-weight hyaluronic acid, a monoclonal antibody against Siglec-9, and coengagement of Siglec-9 with the high-affinity receptor for IgE (FcεRI). RESULTS: Human mast cells express Siglec-9 and Siglec-9 ligands. SIGLEC9 gene disruption resulted in increased expression of activation markers at baseline and increased responsiveness to IgE-dependent and IgE-independent stimulation. Pretreatment with GlycA or high-molecular-weight hyaluronic acid followed by IgE-dependent or -independent stimulation had an inhibitory effect on mast cell degranulation. Coengagement of Siglec-9 with FcεRI in human mast cells resulted in reduced degranulation, arachidonic acid production, and chemokine release. CONCLUSIONS: Siglec-9 and its ligands play an important role in limiting human mast cell activation in vitro.


Asunto(s)
Ácido Hialurónico , Mastocitos , Humanos , Ligandos , Ácido Hialurónico/metabolismo , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/genética , Inmunoglobulina E/metabolismo
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