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1.
Ann Plast Surg ; 92(4S Suppl 2): S210-S217, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556676

RESUMO

ABSTRACT: Current literature demonstrates a lack of racial diversity in plastic surgery media. However, to our knowledge, no study has yet examined the racial diversity of Webpage content as if from a patient-search perspective. The objective of this study is to determine if there is a racial discrepancy between the US Census, American Society of Plastic Surgeons (ASPS) statistics, and the media featuring implied patients on US plastic surgeons' Webpages from a patient-focused approach. A Google search was completed using the term "(state) plastic surgeon." The first 10 relevant Web sites were collected for each state, and homepages were analyzed. In line with previous studies, the implied patients in media were classified into 1 of 6 skin tone categories: I, ivory; II, beige; III, light brown; IV, olive; V, brown; and VI, dark brown. These correlate to Fitzpatrick phototypes; however, the Fitzpatrick scale measures skin's response to UV exposure. Skin tone was used as a guide to measure racial representation in the media, with the caveat that skin tone does not absolutely correlate to racial identity. Categories I-III were further classified as "white" and IV-VI as "nonwhite." These data were compared with the 2020 ASPS demographics report and US Census. Four thousand eighty individuals were analyzed from 504 Webpages, the majority of which were those of private practice physicians. A total of 91.62% of individuals were classified as "white" and 8.38% "nonwhite." The distribution by category was as follows: I = 265, II = 847, III = 2626, IV = 266, V = 71, and VI = 5. Using χ2 analyses, a statistically significant difference was found between the racial representation within this sample and that of the 2020 US Census nationally (P < 0.001), regionally (P < 0.001), and subregionally (P < 0.001); the 2020 ASPS Cosmetic Summary Data (P < 0.001); and the 2020 ASPS Reconstructive Summary Data (P < 0.001). This study highlights the significant difference between racial representation on plastic surgeons' Webpages and the demographics of patients they serve. Further analyses should identify the impact of these representational disparities on patient care and clinical outcomes, as well as examine how best to measure racial diversity and disparities in patient-oriented media.


Assuntos
Procedimentos de Cirurgia Plástica , Cirurgiões , Cirurgia Plástica , Humanos , Estados Unidos , Prática Privada
4.
Laryngoscope ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554009

RESUMO

OBJECTIVE: To evaluate the literature and summarize cochlear implantation (CI) outcomes after intralabyrinthine schwannoma (ILS) excision and tumor observation with CI. DATA SOURCES: OVID Medline, Embase, Web of Science; conception to 2024. REVIEW METHODS: A literature review was performed using subject headings, MeSH terms, and keywords. Abstracts and full texts were reviewed by two independent reviewers and adjudicated by a third. Inclusion criteria included studies with ILS and CI with reported audiologic outcomes. Subjects were analyzed into two groups, ILS resection with CI and in situ ILS with CI. Patients with NF2 were included. The main outcome of interest was CI audiometric performance level, with secondary outcomes of CI user status and open-set speech attainment. RESULTS: There were 29 articles with a total of 93 patients who met inclusion criteria. The resection group had 17% low performers, 44% intermediate performers, and 38% high performers. The in situ group had 40% low performers, 32% intermediate performers, 27% high performers. The resection group had 69 patients with 97% maintaining user status and 92% with open-set speech recognition. The observation group had 24 patients, with 87% user rate and 86% achieving open-set speech recognition. There was a greater percentage of NF2 diagnosis seen in the in situ group. CONCLUSION: There is a paucity of literature on CI and ILS. Patients are managed with both resection of tumor and implantation in situ. Early data are limited, with improvement in hearing outcomes and high user rates in both populations. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

6.
Int J Dermatol ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251749

RESUMO

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder that may be drug-induced or paraneoplastic. We aim to characterize features of LABD and determine differentiating factors among idiopathic, drug-induced, or malignancy-associated diseases. METHODS: We conducted a single-center retrospective chart review of adult patients with linear IgA bullous dermatosis at a large tertiary referral center and a literature review of adult linear IgA bullous dermatosis. RESULTS: Eighty-one patients were included in the study. Ten patients (12.3%) had comorbid malignancy and nine (11.1%) had inflammatory bowel disease. Median disease duration was significantly shorter in both drug-induced (1.2 vs. 48.8 months; P < 0.001) and malignancy-associated (1.7 vs. 48.8 months; P < 0.001) LABD compared with idiopathic LABD. Recurrent episodes occurred significantly more often in idiopathic LABD compared to those with drug-induced (76.1 vs. 11.5%; P < 0.001) or malignancy-associated disease (76.1 vs. 33.3%; P = 0.019). Time to diagnosis was significantly shorter in the drug-induced (0.2 vs. 5.4 months; P < 0.001) and malignancy-associated groups (0.7 vs. 5.4 months; P = 0.049) compared with idiopathic; similarly, time to improvement was significantly shorter in both drug-induced (0.4 vs. 3.0 months; P < 0.001) and malignancy-associated disease (1.1 vs. 3.0 months; P = 0.016). Clinical morphology was indistinguishable between groups. Limitations included retrospective data collection, data from tertiary referral centers, and limited racial and ethnic diversity. CONCLUSION: Screening for underlying malignancy, as well as for a predisposing medication or possibly inflammatory bowel disease, may be advisable in patients with LABD, particularly when it is newly diagnosed.

7.
J Hand Surg Glob Online ; 5(6): 757-762, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38106944

RESUMO

Purpose: The increasing incidence of both distal radius fractures (DRFs) and chronic conditions that necessitate long-term steroid use has resulted in a growing intersection between the patient populations of the two. Chronic steroid use is known to increase bone frailty and the likelihood of fractures but may also contribute to poorer outcomes following the repair of DRF. The purpose of this study was to investigate the association between preoperative chronic steroid use, postoperative complications, and readmission after open reduction internal fixation (ORIF) of DRF. Methods: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients who underwent DRF ORIF between 2015 and 2021. However, 30-day postoperative complications after DRF ORIF were collected. Multivariate logistic regression analysis was conducted to investigate the relationship among preoperative chronic steroid use, postoperative complications, and patient factors associated with readmission. Results: The postoperative complications associated with the steroid cohort were categorized as major, minor, and overall complications. Additionally, pneumonia, stroke, myocardial infarction, bleeding transfusions, deep vein thrombosis, pulmonary embolism, readmission, non-home discharge, and mortality were recorded. Chronic steroid use was found to be independently associated with major , minor, and overall complications, deep vein thrombosis, and readmission. Further investigation of readmission showed that male sex and comorbid chronic obstructive pulmonary disease were the only two patient factors independently associated with a greater likelihood of readmission after DRF ORIF. Conclusions: Preoperative chronic steroid use was associated with an increasing rate of postoperative complications after DRF ORIF. Male sex and comorbid chronic obstructive pulmonary disease were characteristics of chronic steroid-use patients independently associated with increased risk of readmission after DRF ORIF. A better understanding of preoperative chronic steroid use as a risk factor for postoperative complications may allow surgeons to improve preoperative risk stratification and patient counseling in the management of DRF. Type of study/level of evidence: Prognostic III.

8.
J Hand Surg Glob Online ; 5(6): 787-792, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38106953

RESUMO

Purpose: Carpometacarpal (CMC) arthroplasty is an effective surgical treatment to relieve pain and improve function for osteoarthritis of the CMC joint. The association between body mass index (BMI) and postoperative complications has been studied for other orthopedic procedures, including total knee arthroplasty, total hip arthroplasty, and total shoulder arthroplasty. However, BMI has not been studied as a risk factor for postoperative complications following CMC arthroplasty. The purpose of this study was to determine the postoperative complications associated with different categories of BMI following CMC arthroplasty. We hypothesized that increasing BMI is associated with more severe complications. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent CMC arthroplasty between 2015 and 2020. Patient demographics, comorbidities, surgical characteristics, and 30-day postoperative complication data were collected. Patients were stratified into cohorts based on BMI as follows: underweight (BMI < 18.5 kg/m2), normal/reference (18.5 kg/m2 ≤ BMI < 30.0 kg/m2), obese (30.0 kg/m2 ≤ BMI < 35.0 kg/m2), severely obese (35.0 kg/m2 ≤ BMI < 40.0 kg/m2), and morbidly obese (BMI ≥ 40.0 kg/m2). Multivariate logistic regression was used to identify postoperative complications associated with each cohort. Results: In total, 6,432 patients were included in this study: 3,622 (56.3%) patients were included in the normal/reference cohort, 77 (1.2%) patients were included in the underweight cohort, 1,479 (23.0%) patients were included in the obese cohort, 718 (11.2%) patients were included in the severely obese cohort, and 536 (8.3%) patients were included in the morbidly obese cohort. The obese cohort was independently associated with a higher rate of superficial incisional surgical-site infection (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.00-4.44; P = .050). The morbidly obese cohort was independently associated with readmission (OR, 3.35; 95% CI, 1.15-9.74; P = .026) and reoperation (OR, 3.40; 95% CI, 1.04-1.11; P = .043). Conclusions: Morbid obesity is a clinically significant predictor for readmission and reoperation within 30 days following CMC arthroplasty. Obesity is a clinically significant predictor for superficial incisional surgical-site infection within 30 days following CMC arthroplasty. Clinical relevance: A better understanding of BMI as a risk factor for postoperative complications may allow surgeons to improve preoperative risk stratification and patient counseling. Type of study/level of evidence: Prognostic III.

9.
PLoS One ; 18(12): e0295546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38127915

RESUMO

The purpose of this study was to analyze secondary resiliency and user experience outcomes from a novel, 8-week website-based mind-body intervention (NF-Web) for adults (18+) with neurofibromatosis (NF1, NF2, and schwannomatosis), a genetic, neurocutaneous disorder characterized by nerve sheath tumors of the central and peripheral nervous system. The study design was a secondary data analysis of a single-arm, early feasibility pilot study (September 2020-May 2021) for adults with NF (N = 28). Across participants, the mean age was 46 (SD = 13.67) and included 22 females and 6 males. Participants completed baseline and posttest assessments (t-tests), as well as exit interviews (exploratory rapid data analysis). Results demonstrated that participation was associated with pre-to-post improvements in gratitude, coping, and mindfulness (p < .05). Exit interviews indicated participant enjoyment and that many would recommend NF-Web to a friend. Participants found the website easy to navigate and enjoyed NF-Web's video format. Many found transcripts useful if they had hearing differences or if English was their second language. NF-Web demonstrated initial signals of improvement in resiliency outcomes and positive user experience. Future pilot RCTs will explore these changes by NF type.


Assuntos
Neurilemoma , Neurofibromatoses , Neurofibromatose 1 , Neurofibromatose 2 , Resiliência Psicológica , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Neurofibromatoses/terapia , Internet
10.
JSES Int ; 7(6): 2467-2472, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37969519

RESUMO

Background: The purpose of this study was to investigate the association between in-hospital length of stay (LOS) and postoperative complication rates within 30 days of total shoulder arthroplasty (TSA). Methods: All patients who underwent either anatomic or reverse TSA between 2015 and 2019 were queried from the American College of Surgeons National Surgical Quality Improvement database. The study population was stratified into three cohorts as follows: LOS 0 (same-day discharge), LOS 1 (next-day discharge), and LOS 2-3 (LOS of 2-3 days). Patient demographics and comorbidities were compared between cohorts using bivariate analysis. Multivariate logistic regression analysis was conducted to investigate the relationship between LOS and postoperative complications. Results: In comparison to the LOS 0 day cohort, LOS 2-3 day cohort had a greater likelihood of developing overall complication (OR, 2.598; P < .001), major complication (OR, 1.885; P < .001), minor complication (OR: 3.939; P < .001), respiratory complication (OR: 12.979; P = .011), postoperative anemia requiring transfusion (OR, 23.338; P < .001), non-home discharge (OR, 10.430; P < .001), and hospital readmission (OR, 1.700; P = .012). Similarly, in comparison to the LOS 1 cohort, LOS 2-3 cohort had a greater likelihood of developing overall complication (OR: 2.111; P < .001), major complication (OR, 1.423; P < .001), minor complication (OR, 3.626; P < .001), respiratory complication (OR, 2.057; P < .001), sepsis or septic shock (OR: 2.795; P = .008), urinary tract infection (OR, 1.524; P = .031), postoperative anemia requiring transfusion (OR, 10.792; P < .001), non-home discharge (OR: 10.179; P < .001), hospital readmission (OR, 1.395; P < .001), and return to the operating room (OR. 1.394; P = .014). There was no significant difference in the risk of developing postoperative complications between LOS 0 day and LOS 1 day cohort. On baseline, the LOS 1 and LOS 2-3 day cohort had a higher proportion of patients with the following demographics and comorbidities compared to LOS 0 day cohort: advanced age, higher body mass index, female gender, positive smoking status, insulin-dependent diabetes, noninsulin-dependent diabetes, dyspnea at rest and moderate exertion, partially dependent functional status, an American Society of Anesthesiologists classification of 3 or higher, a history of severe chronic obstructive pulmonary disease, a history of congestive heart failure, the use of hypertension medication, disseminated cancer, wound infection, the use of steroids, and a history of bleeding disorder. Conclusion: Patients who were discharged on the same and next day following TSA demonstrated a reduced probability of experiencing respiratory complications, infections, postoperative anemia requiring transfusion, non-home discharge, and readmission in comparison to those with a LOS of 2-3 days. There was no difference in postoperative complications between same and nextday discharged patients. Patients who underwent outpatient arthroplasty were healthier at baseline compared to those who underwent inpatient arthroplasty.

11.
Aesthetic Plast Surg ; 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644187

RESUMO

BACKGROUND: The incidence of obesity is on the rise around the globe. Outside of the massive weight loss (MWL) patient population, knowledge of risk factors associated with abdominal body contouring (BC) is limited. This systematic review and meta-analysis assesses the impact of obesity has on cosmetic abdominal BC outcomes. METHODS: A systematic review conducted in accordance with PRISMA 2020 was done. PubMed, Embase, Scopus, and COCHRANE databases were reviewed under search syntax "obesity," "abdominoplasty," "panniculectomy," and "body contouring" for articles. Cosmetic was defined as abdominoplasty or panniculectomy outside the context of MWL. Obesity was defined as BMI ≥ 30 kg/m2. Studies reporting postoperative outcomes with less than 50% of their population involving MWL patients were included. Postoperative outcomes were assessed by pooled analysis and meta-analysis. RESULTS: Of 3088 initial studies, 16 met inclusion criteria, and nine were used for pooled and meta-analysis. Meta-analysis demonstrated that obesity was associated with more seromas (OR 1.45, 1.06-1.98, p = 0.02), hematomas (OR 2.21, 1.07-4.57, p = 0.03), and total surgical site occurrences (OR 1.99, 1.30-3.04, p = 0.0016). There was no significant difference in odds of any other complications. Analysis by obesity class showed no significant increase in odds in seromas or wound dehiscence. CONCLUSIONS: This review demonstrates obesity increased odds of postoperative complications following cosmetic abdominal BC. However, risk of complications does not continue to increase with higher obesity class. A BMI ≥ 30 kg/m2 should not be a strict contraindication to cosmetic abdominal BC. Instead, plastic surgeons should evaluate patients on a case-by-case basis. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

12.
Ann Plast Surg ; 90(6S Suppl 5): S667-S673, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37399487

RESUMO

BACKGROUND: As reduction mammoplasty rises in popularity, it will become increasingly important to understand the patient-reported outcome measurements associated with a successful operation. There has been a growing body of literature on BREAST-Q outcomes for patients undergoing reduction mammoplasty, but meta-analyses of patient factors and BREAST-Q Reduction Module scores are lacking. This study sought to ascertain which patient factors were associated with improvements in BREAST-Q scores compared with preoperative levels. METHODS: A literature review through August 6, 2021, was conducted using the PubMed database to select publications using the BREAST-Q questionnaire to evaluate outcomes after reduction mammoplasty. Studies examining breast reconstruction, breast augmentation, oncoplastic reduction, or breast cancer patients were excluded. BREAST-Q data were stratified by comorbidities, age, body mass index (BMI), complication rate, and resection weight. RESULTS: Among 14 articles and 1816 patients, the mean age ranged from 15.8 to 55 years, mean BMI ranged from 22.5 to 32.4 kg/m2, and bilateral mean resected weight ranged from 323 to 1845.96 g. Overall complication rate was 19.9%. On average, satisfaction with breasts improved by 52.1 ± 0.9 points (P < 0.0001), psychosocial well-being improved by 43.0 ± 1.0 points (P < 0.0001), sexual well-being improved by 38.2 ± 1.2 points (P < 0.0001), and physical well-being improved by 27.9 ± 0.8 points (P < 0.0001). The mean age was positively correlated with preoperative sexual well-being (Spearman rank correlation coefficient [SRCC]: 0.61, P < 0.05). Body mass index was negatively correlated with preoperative physical well-being (SRCC: -0.78, P < 0.01) and positively correlated with postoperative satisfaction with breasts (SRCC: 0.53, P < 0.05). The mean bilateral resected weight was significantly positively correlated with postoperative satisfaction with breasts (SRCC: 0.61, P < 0.05). No significant correlations were observed between complication rate and preoperative, postoperative, or mean change in BREAST-Q scores. CONCLUSIONS: Reduction mammoplasty improves patient satisfaction and quality of life as reflected by the BREAST-Q. Although preoperative or postoperative BREAST-Q scores may be individually influenced by age and BMI, these variables demonstrated no statistically significant effect on the average change between these scores. This literature review suggests that reduction mammoplasty delivers high satisfaction across a diverse range of patient populations, and additional prospective cohort or comparative studies gathering robust data on other patient factors would benefit this area of research.


Assuntos
Neoplasias da Mama , Mamoplastia , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Qualidade de Vida , Estudos Prospectivos , Mama/cirurgia , Neoplasias da Mama/cirurgia , Satisfação do Paciente , Resultado do Tratamento
13.
Ann Plast Surg ; 90(6S Suppl 5): S538-S542, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36880790

RESUMO

PURPOSE: Data after enhanced recovery after surgery (ERAS) with same-day discharge in breast reconstruction is limited. This study evaluates early postoperative outcomes after same-day discharge in tissue-expander immediate breast reconstruction (TE-IBR) and oncoplastic breast reconstruction. METHODS: A single-institution retrospective review of TE-IBR patients from 2017 to 2022 and oncoplastic breast reconstruction patients from 2014 to 2022 was performed. Patients were divided by procedure and recovery pathway: group 1 (TE-IBR, overnight admission), group 2 (TE-IBR, ERAS), group 3 (oncoplastic, overnight admission), and group 4 (oncoplastic, ERAS). Groups 1 and 2 were subdivided by implant location: groups 1a (prepectoral) and 1b (subpectoral), and groups 2a (prepectoral) and 2b (subpectoral). Demographics, comorbidities, complications, and reoperations were analyzed. RESULTS: A total of 160 TE-IBR patients (group 1, 91; group 2, 69) and 60 oncoplastic breast reconstruction patients (group 3, 8; group 4, 52) were included. Of the 160 TE-IBR patients, 73 underwent prepectoral reconstruction (group 1a, 25; group 2a, 48), and 87 underwent subpectoral reconstruction (group 1b, 66; group 2b, 21). There were no differences in demographics and comorbidities between groups 1 and 2. Group 3 had a higher average body mass index than group 4 (37.6 vs 32.2, P = 0.022). There was no significant difference between groups 1a and 2a or between groups 1b and 2b in rates of for rates of infection, hematoma, skin necrosis, wound dehiscence, fat necrosis, implant loss, or reoperations. Group 3 and group 4 showed no significant difference in any complications or in reoperations. Notably, no patients in same-day discharge groups required unplanned hospital admission. CONCLUSIONS: Many surgical subspecialities have successfully adopted ERAS protocols into their patient care and have shown both its safety and feasibility. Our research shows that same-day discharge in both TE-IBR and oncoplastic breast reconstruction does not increase risk for major complications or reoperations.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Recuperação Pós-Cirúrgica Melhorada , Mamoplastia , Humanos , Feminino , Implantes de Mama/efeitos adversos , Alta do Paciente , Mamoplastia/métodos , Dispositivos para Expansão de Tecidos/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Implante Mamário/métodos
14.
Ann Plast Surg ; 90(6S Suppl 5): S659-S666, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36913563

RESUMO

BACKGROUND: Despite the commonly recognized benefits and drawbacks of each surgical technique for reduction mammoplasty, data on the influence of each surgical approach on patient quality of life and satisfaction remains limited. Our study aims to evaluate the association between surgical factors and BREAST-Q scores for reduction mammoplasty patients. METHODS: A literature review through August 6, 2021, was conducted using the PubMed database to select publications that used the BREAST-Q questionnaire to evaluate outcomes after reduction mammoplasty. Studies examining breast reconstruction, breast augmentation, oncoplastic reduction, or breast cancer patients were excluded. The BREAST-Q data were stratified by incision pattern and pedicle type. RESULTS: We identified 14 articles that met selection criteria. Among 1816 patients, the mean age ranged from 15.8 to 55 years, mean body mass index ranged from 22.5 to 32.4 kg/m 2 , and bilateral mean resected weight ranged from 323 to 1845.96 g. Overall complication rate was 19.9%. On average, satisfaction with breasts improved by 52.1 ± 0.9 points ( P < 0.0001), psychosocial well-being improved by 43.0 ± 1.0 points ( P < 0.0001), sexual well-being improved by 38.2 ± 1.2 points ( P < 0.0001), and physical well-being improved by 27.9 ± 0.8 points ( P < 0.0001). No significant correlations were observed when mean difference was modeled against complication rates or prevalence of superomedial pedicle use, inferior pedicle use, Wise pattern incision, or vertical pattern incision. Complication rates were not correlated with preoperative, postoperative, or mean change in BREAST-Q scores. A negative correlation was noted between the prevalence of superomedial pedicle use and postoperative physical well-being (Spearman rank correlation coefficient [SRCC], -0.66742; P < 0.05). The prevalence of Wise pattern incision was negatively correlated with postoperative sexual well-being (SRCC, -0.66233; P < 0.05) and physical well-being (SRCC, -0.69521; P < 0.05). CONCLUSIONS: Although either preoperative or postoperative BREAST-Q scores may be individually influenced by pedicle or incision type, there was no statistically significant effect of surgical approach or complication rates on the average change of these scores, and overall satisfaction and well-being scores improved. This review suggests that any of the main surgical approaches to reduction mammoplasty provide equally substantial improvements in patient-reported satisfaction and quality of life, but more robust comparative studies would strengthen this area of research.


Assuntos
Mamoplastia , Qualidade de Vida , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Mamoplastia/métodos , Mama/cirurgia , Satisfação do Paciente
15.
J Pharmacol Exp Ther ; 385(2): 95-105, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36849411

RESUMO

Leucine-rich repeat-containing G-protein-coupled receptor (LGR5) and LGR6 mark epithelial stem cells in normal tissues and tumors. They are expressed by stem cells in the ovarian surface and fallopian tube epithelia from which ovarian cancer arises. High-grade serous ovarian cancer is unique in expressing unusually high levels of LGR5 and LGR6 mRNA. R-spondins are the natural ligands for LGR5 and LGR6 to which they bind with nanomolar affinity. To target stem cells in ovarian cancer, we used the sortase reaction to site-specifically conjugate the potent cytotoxin monomethyl auristatin E (MMAE) via a protease sensitive linker to the two furin-like domains of RSPO1 (Fu1-Fu2) that mediate its binding to LGR5 and LGR6 and their co-receptors Zinc And Ring Finger 3 and Ring Finger Protein 43 via a protease-cleavable linker. An immunoglobulin Fc domain added to the N-terminal end served to dimerize the receptor-binding domains so that each molecule carries two MMAE. The resulting molecule, FcF2-MMAE, demonstrated: 1) selective LGR5-dependent low nanomolar cytotoxicity against ovarian cancer cells in vitro; 2) selectivity that was dependent on binding to both the LGR receptors and ubiquitin ligase co-receptors; 3) favorable stability and plasma pharmacokinetic properties when administered intravenously with an elimination half-life of 29.7 hours; 4) selective inhibition of LGR5-rich as opposed to isogenic LGR5-poor tumors in vivo; and, 5) therapeutic efficacy in three aggressive wild-type human ovarian cancer xenograft models. These results demonstrate the successful use of the Fu1-Fu2 domain of RSPO1 as a drug carrier and the ability of FcF2-MMAE to target cells in tumors that express stem cell markers. SIGNIFICANCE STATEMENT: FcF2-MMAE is a novel cancer therapeutic that exploits the high-affinity binding domains of RSPO1 to target monomethyl auristatin E to tumor stem cells that express LGR5. FcF2-MMAE has low nanomolar LGR5-dependent cytotoxicity in vitro, favorable pharmacokinetics, and differential efficacy in an isogenic LGR5-poor versus LGR5-rich ovarian cancer xenograft model when given on a weekly schedule.


Assuntos
Neoplasias Ovarianas , Receptores Acoplados a Proteínas G , Feminino , Humanos , Leucina , Neoplasias Ovarianas/tratamento farmacológico , Peptídeo Hidrolases , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Células-Tronco/metabolismo , Trombospondinas/metabolismo
16.
Cogn Behav Neurol ; 36(1): 19-27, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36651958

RESUMO

BACKGROUND: Emotional distress can lead to suicidal ideation and potentially suicide completion, yet there is very little literature on suicidal ideation in individuals with a diagnosis of neurofibromatosis (NF; NF1, NF2, and schwannomatosis). OBJECTIVE: To examine the baseline occurrence, severity, and clinical correlates of suicidal ideation in adults with NF. METHOD: Individuals with NF (N = 220) completed assessments measuring depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), perceived stress (Perceived Stress Scale-10), pain (Graded Chronic Pain Scale and PROMIS Pain Interference Short Form 8a), and general quality of life (World Health Organization Quality of Life-Brief version) before beginning a two-arm, single-blind randomized control trial of a live-video mind-body program for stress management and resiliency. RESULTS: Nineteen percent (n = 42) of the individuals experienced suicidal ideation (ie, >0; ideation present several days or greater). More individuals with NF2 experienced suicidal ideation compared with those with NF1 or schwannomatosis. All of the clinical variables except pain intensity were significantly correlated ( P < 0.01) with greater suicidal ideation. Suicidal ideation in individuals with NF was comparable to or higher than that in other medical populations (eg, cancer, dermatological, neurologic). Depression and poor psychological quality of life significantly increased the risk for suicidal ideation. CONCLUSION: Suicidal ideation was relatively prevalent in individuals with NF seeking participation in a mind-body randomized controlled trial. NF clinicians should be prepared to discuss these concerns and provide resources when suicidal ideation is present. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT03406208).


Assuntos
Neurofibromatoses , Ideação Suicida , Humanos , Adulto , Qualidade de Vida , Método Simples-Cego , Dor , Depressão/psicologia
17.
Front Pharmacol ; 14: 1337319, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38273829

RESUMO

Colorectal cancer (CRC) stands as a leading cause of death worldwide, often arising from specific genetic mutations, progressing from pre-cancerous adenomas to adenocarcinomas. Early detection through regular screening can result in a 90% 5-year survival rate for patients. However, unfortunately, only a fraction of CRC cases are identified at pre-invasive stages, allowing progression to occur silently over 10-15 years. The intricate interplay between the immune system and tumor cells within the tumor microenvironment plays a pivotal role in the progression of CRC. Immune cell clusters can either inhibit or facilitate tumor initiation, growth, and metastasis. To gain a better understanding of this relationship, we conducted N-glycomic profiling using matrix-assisted laser desorption-ionization mass spectrometry imaging (MALDI-MSI). We detected nearly 100 N-glycan species across all samples, revealing a shift in N-glycome profiles from normal to cancerous tissues, marked by a decrease in high mannose N-glycans. Further analysis of precancerous to invasive carcinomas showed an increase in pauci-mannose biantennary, and tetraantennary N-glycans with disease progression. Moreover, a distinct stratification in the N-glycome profile was observed between non-mucinous and mucinous CRC tissues, driven by pauci-mannose, high mannose, and bisecting N-glycans. Notably, we identified immune clusters of CD20+ B cells and CD3/CD44+ T cells distinctive and predictive with signature profiles of bisecting and branched N-glycans. These spatial N-glycan profiles offer potential biomarkers and therapeutic targets throughout the progression of CRC.

18.
Front Cell Infect Microbiol ; 12: 1029178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329823

RESUMO

Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted infections worldwide. Since the symptoms of Ct infection are often subtle or absent, most people are unaware of their infection until they are tested or develop severe complications such as infertility. It is believed that the primary culprit of Ct-associated tissue damage is unresolved chronic inflammation, resulting in aberrant production of cytokines, chemokines, and growth factors, as well as dysregulated tissue influx of innate and adaptive immune cells. A member of the IL-6 cytokine family, leukemia inhibitory factor (LIF), is one of the cytokines induced by Ct infection but its role in Ct pathogenesis is unclear. In this article, we review the biology of LIF and LIF receptor (LIFR)-mediated signaling pathways, summarize the physiological role of LIF in the reproductive system, and discuss the impact of LIF in chronic inflammatory conditions and its implication in Ct pathogenesis. Under normal circumstances, LIF is produced to maintain epithelial homeostasis and tissue repair, including the aftermath of Ct infection. However, LIF/LIFR-mediated signaling - particularly prolonged strong signaling - can gradually transform the microenvironment of the fallopian tube by altering the fate of epithelial cells and the cellular composition of epithelium. This harmful transformation of epithelium may be a key process that leads to an enhanced risk of infertility, ectopic pregnancy and cancer following Ct infection.


Assuntos
Infecções por Chlamydia , Infertilidade , Gravidez , Feminino , Humanos , Fator Inibidor de Leucemia/metabolismo , Chlamydia trachomatis/metabolismo , Receptores de OSM-LIF , Infertilidade/complicações
19.
SICOT J ; 8: 43, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36367405

RESUMO

BACKGROUND: Early failure of uncemented femoral stems associated with incorrect sizing is a known postoperative complication. Surgeons are often faced with the question of whether an uncemented stem of adequate stability or a larger-sized stem should be implanted, especially when the proximal femoral cancellous bone is adequate. The biomechanical effect of sub-optimal stem sizing in the femur remains unclear. This study investigated the mechanical behaviour of two sequential sized uncemented stems of the same type. METHODS: Six laboratory models of synthetic non-osteoporotic femora were randomly divided into two groups and implanted with either a nominal or oversized uncemented hydroxyapatite-coated nonporous titanium collarless stem. Stiffness, uniaxial strain, and pattern of strain distribution were measured under an anatomical one-legged stance. RESULTS: Oversized stems demonstrated a higher overall stiffness compared to nominal; however, this was not statistically significant. The nominal stem showed a higher strain in the neck and the proximal medial diaphyseal region. The oversized stem showed higher strains in the distal region around the implant tip. CONCLUSION: Opting to use a larger stem may potentially increase primary stability, thus allowing safer early mobility. However, higher stiffness may lead to stress shielding, bone loss, and thigh pain in the long term. In addition, strains in the diaphysis and the tip of the stem may predispose to periprosthetic fractures, especially in osteoporotic bones, making this a relatable aspect for users and biomechanical loading. Given the wide range of complex factors that need to be considered when choosing stem size in uncemented THA surgery, this study's results should be interpreted cautiously.

20.
Knee Surg Sports Traumatol Arthrosc ; 30(5): 1836-1845, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34626228

RESUMO

PURPOSE: To compare patients with a concomitant full-thickness cartilage lesion and anterior cruciate ligament (ACL) injury to patients with an isolated ACL injury at 10-15 years post ACL reconstruction. METHODS: This is a longitudinal follow-up of a cohort of 89 patients that were identified in the Norwegian National Knee Ligament Registry and included in the index study in 2007. The study group consisted of 30 patients that underwent ACL reconstruction and had a concomitant, isolated full-thickness cartilage lesion (International Cartilage Repair Society [ICRS] grade 3-4). Each study patient was matched with two control patients who underwent ACL reconstruction but had no cartilage lesions (ICRS grade 1-4) (n = 59). At a median follow-up of 10.2 years (range 9.9-15.6), 65 patients (74%) completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), which was the main outcome measure, resulting in 23 pairs after matching. RESULTS: At a follow-up of 10-15 years after ACL reconstruction, no significant differences in KOOS were found between patients with a concomitant full-thickness cartilage lesion and patients without cartilage lesions. There was also no significant difference between the two groups when comparing the change over time in KOOS scores from preoperative to follow-up. Both groups showed significant improvement in all KOOS subscales from preoperative to follow-up, except for in the Symptoms subscale for the control group. The greatest improvement was in the QoL subscale for the study group. CONCLUSION: ACL-reconstructed patients with a full-thickness cartilage lesion did not report worse outcomes at 10-15 years after surgery compared with patients with an isolated ACL injury. Our findings support that there is no long-term negative effect of a concomitant cartilage lesion in an ACL-reconstructed knee. These findings should be considered when discussing treatment and informing about the expected long-term outcome after ACL reconstruction to patients with such combined injuries. LEVEL OF EVIDENCE: II.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/cirurgia , Cartilagem , Seguimentos , Humanos , Traumatismos do Joelho/complicações , Traumatismos do Joelho/cirurgia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida
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