Bringing an end to diabetes stigma and discrimination: an international consensus statement on evidence and recommendations.

People with diabetes often encounter stigma (ie, negative social judgments, stereotypes, prejudice), which can adversely affect emotional, mental, and physical health; self-care, access to optimal health care; and social and professional opportunities. To accelerate an end to diabetes stigma and discrimination, an international multidisciplinary expert panel (n=51 members, from 18 countries) conducted rapid reviews and participated in a three-round Delphi survey process. We achieved consensus on 25 statements of evidence and 24 statements of recommendations. The consensus is that diabetes stigma is driven primarily by blame, perceptions of burden or sickness, invisibility, and fear or disgust. On average, four in five adults with diabetes experience diabetes stigma and one in five experience discrimination (ie, unfair and prejudicial treatment) due to diabetes, such as in health care, education, and employment. Diabetes stigma and discrimination are harmful, unacceptable, unethical, and counterproductive. Collective leadership is needed to proactively challenge, and bring an end to, diabetes stigma and discrimination. Consequently, we achieved unanimous consensus on a pledge to end diabetes stigma and discrimination.

Person-first language in diabetes and obesity scientific publications.

AIMS: We aimed to quantify the use of person-first language (PFL) among scholarly articles focusing on diabetes or obesity. METHODS: PFL and condition-first language (CFL) terms for diabetes and obesity (e.g. diabetic, obese) were identified from existing guidelines and a review of the literature. Exact phrase literature searches were conducted between 2011 and 2020 and results were categorised as PFL, CFL or both. RESULTS: Among diabetes articles, 43% used PFL, 40% used CFL and 17% contained both. Among obesity articles, 0.5% used PFL, 99% used CFL and 0.2% used both. The use of PFL increased by 3% per year for diabetes articles, compared to 117% for obesity articles. The rate of adoption of PFL in diabetes articles was unchanged in 2018-2020 compared to the 3 years prior. CONCLUSIONS: While the use of person-first language in diabetes articles had increased over the review period, its rate of adoption has started to slow. Conversely, the use of PFL in obesity articles is nascent and increasing.

Gender Affirming Surgery: A Comprehensive, Systematic Review of All Peer-reviewed Literature and Methods of Assessing Patient-centered Outcomes (Part 1: Breast/Chest, Face, and Voice).

OBJECTIVE: To perform the first systematic review of all available gender-affirming surgery (GAS) publications across all procedures to assess both outcomes reported in the literature and the methods used for outcome assessment. SUMMARY OF BACKGROUND DATA: Rapidly increasing clinical volumes of gender-affirming surgeries have stimulated a growing need for high-quality clinical research. Although some procedures have been performed for decades, each individual procedure has limited data, necessitating synthesis of the entire literature to understand current knowledge and guide future research. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify all outcomes measures in GAS cohorts, including PCOs, complications, and functional outcomes. Outcome data were pooled to assess currently reported complication, satisfaction, and other outcome rates. RESULTS: Overall, 15,186 references were identified, 4162 papers advanced to abstract review, and 1826 underwent full-text review. After review, there were 406 GAS cohort publications. Of non-genitoplasty titles, 35 were mastectomy, 6 mammoplasty, 21 facial feminization, and 31 voice/cartilage. Although 59.1% of non-genitoplasty papers addressed PCOs in some form, only 4.3% used instruments partially-validated in transgender patients. Overall, data were reported heterogeneously and were biased towards high-volume centers. CONCLUSIONS: This study represents the most comprehensive review of GAS literature. By aggregating all previously utilized measurement instruments, this study offers a foundation for discussions about current methodologic limitations and what dimensions must be included in assessing surgical success. We have assembled a comprehensive list of outcome instruments; this offers an ideal starting basis for emerging discussions between patients and providers about deficiencies which new, better instruments and metrics must address. The lack of consistent use of the same outcome measures and validated GAS-specific instruments represent the 2 primary barriers to high-quality research where improvement efforts should be focused.

Gender Affirming Surgery: A Comprehensive, Systematic Review of All Peer-reviewed Literature and Methods of Assessing Patient-centered Outcomes (Part 2: Genital Reconstruction).

OBJECTIVE: To perform the first systematic review of all available GAS publications across all procedures to assess outcomes reported in the literature and the methods used for outcome assessment. SUMMARY OF BACKGROUND DATA: Assessment of GAS results is complex and multidimensional, involving not only complication rates but also anatomic (eg, vaginal depth), functional (eg, urinary), and psychosocial outcomes. A fully comprehensive aggregation of all prior research would offer an essential cornerstone for continued progress. METHODS: A systematic review was performed after PRISMA guidelines to identify all outcomes measures in GAS cohorts, including patient-centered outcomes, complications, and functional outcomes. Data were aggregated to assess pooled rates of complications, satisfaction, and other outcomes. RESULTS: Overall, 15,186 references were identified, 4162 papers advanced to abstract review, and 1826 underwent full-text review. After review, there were 406 GAS cohort publications, including 171 vaginoplasty, 82 phalloplasty, 16 metoidioplasty, 23 oophorectomy/vaginectomy, and 21 with multiple procedures.Although 68.7% of genitoplasty papers addressed patient-centered outcomes, only 1.0% used metrics validated in the transgender population. Forty-three different outcome instruments were used. No instrument was used in more than 15% of published series and 38 were used in only 1 or 2 publications. CONCLUSIONS: Our review found high patient satisfaction for genital procedures but little concordance between study methods, with almost 90% of patient-focused outcome metrics appearing only once or twice. Standardization of outcome instruments and measurement methods through patient-inclusive, multidisciplinary consensus efforts is the essential next step for quality improvement. As GAS continues to mature, building on current foundations with the goal of improving both surgical and patient-reported outcomes is essential.

Human fibroblast-macrophage tissue spheroids demonstrate ratio-dependent fibrotic activity for in vitro fibrogenesis model development.

Fibrosis is a pathological accumulation of excessive collagen that underlies many of the most common diseases, representing dysfunction of the essential processes of normal tissue healing. Fibrosis research aims to limit this response without ameliorating the essential role of fibrogenesis in organ function. However, the absence of a realistic in vitro model has hindered investigation into mechanisms and potential interventions because the standard 2D monolayer culture of fibroblasts has limited applicability. We sought to develop and optimize fibrosis spheroids: a scaffold-free three-dimensional human fibroblast-macrophage spheroid system representing an improved benchtop model of human fibrosis. We created, characterized and optimized human fibroblast-only spheroids, demonstrating increased collagen deposition compared to monolayer fibroblasts, while spheroids larger than 300 µm suffered from progressively increasing apoptosis. Next, we improved the spheroid system with the addition of human macrophages to more precisely recapitulate the environment during fibrogenesis, creating a hybrid spheroid system with different ratios of fibroblasts and macrophages ranging from 2 : 1 to 64 : 1. We found that in the hybrid spheroids (particularly the 16 : 1 [F16] ratio) more fibroblasts were activated, with greater macrophage polarization towards a pro-inflammatory M1 phenotype. Hybrid spheroids containing higher ratios of macrophages showed greater macrophage heterogeneity and less fibrogenesis, while low macrophage ratios limited macrophage-induced effects and yielded less collagen deposition. The F16 group also had the highest expression levels of fibrosis-related genes (Col-1a1, Col-3a1 and TGF-ß) and inflammation-related genes (TNF, IL1ß and IL6). IF staining demonstrated that F16 spheroids had the highest levels of αSMA, collagen-1 and collagen-3 deposition among all groups as well as formation of a dense collagen rim surrounding the spheroid. Future studies exploring the greater fibrotic activity of F16 spheroids may provide new mechanistic insights into diseases involving excessive fibrotic activity. Microtissue fibrosis models capable of achieving greater clinical fidelity have the potential to combine the relevance of animal models with the scale, cost and throughput of in vitro testing.

Complete Human Penile Scaffold for Composite Tissue Engineering: Organ Decellularization and Characterization.

Reconstruction for total penile defects presents unique challenges due to its anatomical and functional complexity. Standard methods suffer from high complication rates and poor functional outcomes. In this work we have developed the first protocol for decellularizing whole-organ human penile specimens for total penile tissue engineering. The use of a hybrid decellularization scheme combining micro-arterial perfusion, urethral catheter perfusion and external diffusion enabled the creation of a full-size scaffold with removal of immunogenic components. Decellularization was complete as assessed by H&E and immunohistochemistry, while quantification of residual DNA showed acceptably low levels (<50 ng/mg). An intact ECM was maintained with histologic architecture preservation on H&E and SEM as well as preservation of key proteins such as collagen-1, laminin and fibronectin and retention of growth factors VEGF (45%), EGF (57%) and TGF-beta1 (42%) on ELISA. Post-decellularization patency of the cavernosal arteries for future use in reseeding was demonstrated. Scaffold biocompatibility was evaluated using human adipose-derived stromal vascular cells. Live/Dead stains showed the scaffold successfully supported cell survival and expansion. Influence on cellular behavior was seen with significantly higher expression of VWF, COL1, SM22 and Desmin as compared to cell monolayer. Preliminary evidence for regional tropism was also seen, with formation of microtubules and increased endothelial marker expression in the cavernosa. This report of successful decellularization of the complete human phallus is an initial step towards developing a tissue engineered human penile scaffold with potential for more successfully restoring cosmetic, urinary and sexual function after complete penile loss.