Outcomes in facial transplantation - A systematic review.

Facial transplantations have become a clinical reality as the last reconstructive option in severely disfigured patients. To date, clinical outcomes remain unclear. The purpose of this paper was to analyse the outcomes in facial transplantation (FT) and determine the risks and benefits of FT based on short- and long-term outcomes. An electronic literature search was performed across PubMed, EMBASE and the Cochrane Central Register for Controlled Trials (CENTRAL) databases to capture all the relevant records relating to outcomes in FTs from 2005 to 2021. Articles for inclusion were decided upon pre-defined inclusion and exclusion criteria. A total of 48 FTs has been performed to date. A total of 90 studies met the eligibility criteria and were included in the outcome analysis. Studies were analysed based on each of the 48 cases and outcomes categorised into short-term (<36 months) and long-term (>36 months) outcomes. Primary outcomes included patient and graft survival and secondary outcomes included functional, surgical revision events, immunological, medical complications, aesthetics, psychosocial and quality of life. Mortality rate, infection and malignancy incidence remain high, and patients should be fully informed of the potential life-threatening complications. FTs improve outcomes such as quality of life and psychosocial recovery in the short- and long-term. Outcomes remain under-reported in peer-review journals.

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning.

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-ß, TGF-ß1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-ß induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-ß1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

Correlation between oral and oropharyngeal resection subsites and impact of reconstruction on speech and swallowing function in head and neck cancer patients: A systematic review.

This review aims to provide a correlation between oral and oropharyngeal subsites and type of reconstruction used in the management of head and neck cancer patients. A literature search of PubMed, Embase and Web of Science was conducted. All study types describing long-term speech and swallow outcomes of adults following head and neck oncological reconstruction, which used a subsite classification, were included. Risk of bias was assessed using the Robbins-1 tool. A total of 2270 patients were found in 26 studies. The number of subsites/studies ranged from 2 to 18. Subsites were predominantly divided on an anatomical basis. Other classifications included functionally grouped subsites. Seven articles considered combinations, unilateral and bilateral defects. Base of tongue, FOM, and defects crossing the midline are negatively correlated with post-operative speech and swallow. Lateral distributions were associated with superior outcomes. The University of Washington Quality of Life Questionnaire (UW-QOL) was the most prevalent tool for speech and swallow assessment. Other factors that significantly affect speech and swallow outcomes include adjuvant therapy, size, type of reconstruction (free flap compared to pedicled or local). The role of neoadjuvant therapy remains unknown. A consistent and formalised approach including risk stratification for multiple contributing factors would be useful in clinical pre- and post-operative management.

Scarring and Skin Fibrosis Reversal with Regenerative Surgery and Stem Cell Therapy.

Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body's natural ability to repair damaged tissue. Adipose-derived stem cells (ASCs) represent an optimal choice for practical regenerative medicine due to their abundance, autologous tissue origin, non-immunogenicity, and ease of access with minimal morbidity for patients. This review of the literature explores the current body of evidence around the use of ASCs-based regenerative strategies for the treatment of scarring and skin fibrosis, exploring the different surgical approaches and their application in multiple fibrotic skin conditions. Human, animal, and in vitro studies demonstrate that ASCs present potentialities in modifying scar tissue and fibrosis by suppressing extracellular matrix (ECM) synthesis and promoting the degradation of their constituents. Through softening skin fibrosis, function and overall quality of life may be considerably enhanced in different patient cohorts presenting with scar-related symptoms. The use of stem cell therapies for skin scar repair and regeneration represents a paradigm shift, offering potential alternative therapeutic avenues for fibrosis, a condition that currently lacks a cure.

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review.

AIM: Radiation-induced fibrosis is a recognised consequence of radiotherapy, especially after multiple and prolonged dosing regimens. There is no definitive treatment for late-stage radiation-induced fibrosis, although the use of autologous fat transfer has shown promise. However, the exact mechanisms by which this improves radiation-induced fibrosis remain poorly understood. We aim to explore existing literature on the effects of autologous fat transfer on both in-vitro and in-vivo radiation-induced fibrosis models, and to collate potential mechanisms of action. METHOD: PubMed, Cochrane reviews and Scopus electronic databases from inception to May 2023 were searched. Our search strategy combined both free-text terms with Boolean operators, derived from synonyms of adipose tissue and radiation-induced fibrosis. RESULTS: The search strategy produced 2909 articles. Of these, 90 underwent full-text review for eligibility, yielding 31 for final analysis. Nine conducted in-vitro experiments utilising a co-culture model, whilst 25 conducted in-vivo experiments. Interventions under autologous fat transfer included adipose-derived stem cells, stromal vascular function, whole fat and microfat. Notable findings include downregulation of fibroblast proliferation, collagen deposition, epithelial cell apoptosis, and proinflammatory processes. Autologous fat transfer suppressed hypoxia and pro-inflammatory interferon-γ signalling pathways, and tissue treated with adipose-derived stem cells stained strongly for anti-inflammatory M2 macrophages. Although largely proangiogenic initially, studies show varying effects on vascularisation. There is early evidence that adipose-derived stem cell subgroups may have different functional properties. CONCLUSION: Autologous fat transfer functions through pro-angiogenic, anti-fibrotic, immunomodulatory, and extracellular matrix remodelling properties. By characterising these mechanisms, relevant drug targets can be identified and used to further improve clinical outcomes in radiation-induced fibrosis. Further research should focus on adipose-derived stem cell sub-populations and augmentation techniques such as cell-assisted lipotransfer.

The efficacy of negative-pressure wound therapy for head and neck wounds: A systematic review and update.

Despite the established benefits of negative-pressure wound therapy (NPWT) in various wound healing contexts, its application in head and neck surgical cases remains under-explored. This study aimed to systematically review its effectiveness, safety, and comparative efficacy. Thirty-one studies from a systematic literature search were identified and analyzed for wound healing response, overall success rate, improvements compared to conventional wound care, and variation in pressure settings, treatment lengths, and dressing change frequency. NPWT showed enhanced outcomes across diverse head and neck wounds, particularly complex post-reconstructive wounds and severe infections. Despite the predominantly case report/series evidence and lack of standardized NPWT protocols, its benefits over conventional care were clear. NPWT emerges as a promising approach for head and neck wound management, potentially improving patient outcomes and reducing complications. More randomized controlled trials are needed to solidify the evidence and standardize NPWT application protocols.

A comparison of commercially available synthetic skin substitutes for surgical simulation training.

Objective: Simulation training provides an important opportunity to accelerate surgical skills acquisition whilst safeguarding patients. This study compares the suitability of different synthetic skin substitutes for use in surgical simulation training. Design: Data was collected for eight commercially available synthetic skin substitutes and included cost, delivery time, subjective assessment of fidelity by surgeons and trainees, and objective comparison with the biomechanics of human skin was made through cutometry and durometry measurements. Cutometry and durometry data was collected from three healthy adults from the forearm, forehead and back, with measurements being repeated in triplicate. Subjective assessment of skin pad quality was collected using an 8-criteria questionnaire, graded using a 5-point Likert scale for fidelity to normal skin. Results: The questionnaire assessment was completed by 30 trainees and practitioners. Overall, felt pads received the poorest outcomes in all criteria; cutometry and durometry results demonstrate poor similarity to skin, and felt received the lowest scores in the questionnaire, although the cheapest. Foam dressings were similar in both cutometric and durometric properties to skin of the face, back and arm. Clinical outcomes of foam dressings were similar to the most expensive commercial skin pad. Conclusions: Bilaminar foam-based dressings provide a low cost, high fidelity non-biological simulation of skin for surgical training, which is non-inferior to more expensive specifically designed products. Many products designed to act as skin substitutes for surgical simulation fail to adequately replicate the anatomical and mechanical properties of skin.

Application of fluorescence lifetime imaging microscopy to monitor glucose metabolism in pancreatic islets in vivo.

Glucose stimulated insulin secretion is mediated by glucose metabolism via oxidative phosphorylation generating ATP that triggers membrane depolarization and exocytosis of insulin. In stressed beta cells, glucose metabolism is remodeled, with enhanced glycolysis uncoupled from oxidative phosphorylation, resulting in the impaired glucose-mediated insulin secretion characteristic of diabetes. Relative changes in glycolysis and oxidative phosphorylation can be monitored in living cells using the 3-component fitting approach of fluorescence lifetime imaging microscopy (FLIM). We engrafted pancreatic islets onto the iris to permit in vivo FLIM monitoring of the trajectory of glucose metabolism. The results show increased oxidative phosphorylation of islet cells (∼90% beta cells) in response to hyperglycemia; in contrast red blood cells traversing the islets maintained exclusive glycolysis as expected in the absence of mitochondria.

Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin.

Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand-receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour.

Phalangeal and Metacarpal Fractures in Children: A 10-Year Comparison of Factors Affecting Functional Outcomes in 313 Patients.

Introduction It is widely believed that fractures in children have excellent clinical outcomes due to their capacity to remodel. There are, however, certain fractures that require careful management to avoid long-lasting functional impairment. Functional outcomes following hand fractures in children are poorly studied. Materials and Methods We performed a retrospective cohort study of consecutive children and adolescents who had operative treatment for metacarpal and phalangeal fractures (2008-2018). Tuft fractures and replantations were excluded. Functional outcomes were measured by total active motion (TAM) scoring, where a "good" outcome = TAM > 75%. Fractures were categorized by location, classification, and by the fixation they required. Results Three hundred thirteen children were included. For proximal phalangeal fractures, those treated by manipulation under anesthesia, had a higher proportion of "good" functional outcomes than Kirschner-wire or open reduction internal fixation at discharge from hand therapy ( p = 0.043). Middle phalanx fractures had excellent functional outcomes, with no difference between fixation methods ( p = 0.81). For metacarpals, there was no statistically significant difference in functional outcomes across all managements ( p = 0.134). Fractures in the thumb had poorer postoperative function at mean 7.26 weeks than those in the long fingers ( p < 0.0001), and the data suggested a trend toward worse outcomes in the distal phalanx, pediatric Bennett fractures, Seymour fractures, and oblique fractures. Conclusions Fractures in the thumb and phalangeal fractures that require percutaneous or open fixation may need closer early postoperative monitoring in children to optimize their potential for good function.

Efficacy of IAPP suppression in mouse and human islets by GLP-1 analogue conjugated antisense oligonucleotide.

Insulin resistance is the major risk factor for Type 2 diabetes (T2D). In vulnerable individuals, insulin resistance induces a progressive loss of insulin secretion with islet pathology revealing a partial deficit of beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP). IAPP is co-expressed and secreted with insulin by beta cells, expression of both proteins being upregulated in response to insulin resistance. If IAPP expression exceeds the threshold for clearance of misfolded proteins, beta cell failure occurs exacerbated by the action of IAPP toxicity to compromise the autophagy lysosomal pathway. We postulated that suppression of IAPP expression by an IAPP antisense oligonucleotide delivered to beta cells by the GLP-1 agonist exenatide (eGLP1-IAPP-ASO) is a potential disease modifying therapy for T2D. While eGLP1-IAPP-ASO suppressed mouse IAPP and transgenic human IAPP expression in mouse islets, it had no discernable effects on IAPP expression in human islets under the conditions studied. Suppression of transgenic human IAPP expression in mouse islets attenuated disruption of the autophagy lysosomal pathway in beta cells, supporting the potential of this strategy.

The intraoperative use of augmented and mixed reality technology to improve surgical outcomes: A systematic review.

BACKGROUND: This systematic review aims to critically appraise the intraoperative use of augmented and mixed reality technology to improve surgical outcomes. METHOD: A literature search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and WHO ICTRP was performed in accordance with Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: This review included 94 studies on 2473 patients, comprising 78 studies on augmented reality and 16 on mixed reality. This technology has seen broad intraoperative application. Augmented and mixed reality can reduce operative duration, blood loss, and the duration of inpatient care. Current evidence shows that they achieve this most in percutaneous surgery. CONCLUSIONS: Augmented and mixed reality technology improve surgical outcomes by increasing navigational speed and reducing navigational error intraoperatively. However, they have technical limitations which are the subject of ongoing research. Further studies are necessary to define how this technology is best applied intraoperatively. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020205892.

Executive Involvement in Governing Boards and Hospital and Health System Performance.

Governing boards and executive leaders play important roles ensuring that their organizations work toward their missions and maintain their visions, while also meeting compliance and performance goals. The level of executive involvement in hospital governing boards varies across organizations, with little evidence to suggest whether and to what degree executive involvement influences hospital performance. The aim of this study is to determine the influence of executive involvement in governance on health system performance. The sample analyzed in this study were organizations responding to The Governance Institute's (TGI) Biennial Survey of Hospital and Health Systems in 2017. Bivariate and multivariate analyses were used to examine associations between self-reported executive leadership team involvement in governing boards and a composite metric of health system performance calculated by Truven Analytics as part of the "Top 100" program. Results indicate executive involvement is associated with several organizational characteristics, including whether an institution was defined as a hospital or health system, whether or not the board was appointed by the parent/system, and whether the board was accountable to the parent/system board. Although no significant direct relationship was found between executive team involvement in governance and overall health system performance, several promising pathways for future study were identified and are discussed, including examining specific organizational performance outcomes rather than composite measures.

Portable three-dimensional imaging to monitor small volume enhancement in face, vulva, and hand: A comparative study.

Multiple handheld three-dimensional (3D) systems are available on the market, but data regarding their use in detecting small volumes are limited. The aim of this study was to compare different portable 3D technologies in detecting small volumetric enhancement on a mannequin model and a series of patients. Five portable 3D systems (Artec Eva, Crisalix, Go!Scan, LifeViz Mini, and Vectra H1) were tested in a controlled environment with standardised volumes and in a clinical setting with patients undergoing small volume fat grafting to face, vulva, and hand. Accuracy was assessed with absolute and relative technical error measurement (TEM and rTEM); precision with intra- and inter-observer reliability (rp and ICC); and usability in clinical practice with the following parameters: portability, suitability of use in operating theatre/clinic, ease of use of hardware and software, speed of capture, image quality, patient comfort, and cost. All tested devices presented overall good accuracy in detecting small volumetric changes ranging from 0.5 to 4 cc. Structured-light laser scanners (Artec Eva and Go!Scan) showed high accuracy, but their use in clinical practice was limited by longer capture time, multiple wiring, and complex software for analysis. Crisalix was considered the most user-friendly, less bothering for patients, and truly portable, but its use was limited to the face because the software does not include vulva and hand. Three-dimensional technologies exploiting the principle of passive stereophotogrammetry such as LifeViz Mini and Vectra H1 were the most versatile for assessing accurately multiple body areas, representing overall the best long-term value for money. Therefore, 3D portable technology is a non-invasive, accurate, and reproducible method to assess the volumetric outcome after facial, vulval, and hand injectables. The choice of the 3D system should be based on the clinical need and resources available.

Ectopic extramammary Paget's disease of the abdominal wall with abdominoplasty reconstruction.

Ectopic extramammary Paget's disease describes an exceedingly rare intraepithelial adenocarcinoma arising within non-apocrine tissues. We present a case report of E-EPMD arising on the lower abdomen without underlying secondary malignancy in a 56-year-old female patient. We performed a wide local excision of the lesion with subsequent mini abdominoplasty reconstruction.

IAPP-induced beta cell stress recapitulates the islet transcriptome in type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by islet amyloid and toxic oligomers of islet amyloid polypeptide (IAPP). We posed the questions, (1) does IAPP toxicity induce an islet response comparable to that in humans with type 2 diabetes, and if so, (2) what are the key transcriptional drivers of this response? METHODS: The islet transcriptome was evaluated in five groups of mice: beta cell specific transgenic for (1) human IAPP, (2) rodent IAPP, (3) human calpastatin, (4) human calpastatin and human IAPP, and (5) wild-type mice. RNA sequencing data was analysed by differential expression analysis and gene co-expression network analysis to establish the islet response to adaptation to an increased beta cell workload of soluble rodent IAPP, the islet response to increased expression of oligomeric human IAPP, and the extent to which the latter was rescued by suppression of calpain hyperactivation by calpastatin. Rank-rank hypergeometric overlap analysis was used to compare the transcriptome of islets from human or rodent IAPP transgenic mice vs humans with prediabetes or type 2 diabetes. RESULTS: The islet transcriptomes in humans with prediabetes and type 2 diabetes are remarkably similar. Beta cell overexpression of soluble rodent or oligomer-prone human IAPP induced changes in islet transcriptome present in prediabetes and type 2 diabetes, including decreased expression of genes that confer beta cell identity. Increased expression of human IAPP, but not rodent IAPP, induced islet inflammation present in prediabetes and type 2 diabetes in humans. Key mediators of the injury responses in islets transgenic for human IAPP or those from individuals with type 2 diabetes include STAT3, NF-κB, ESR1 and CTNNB1 by transcription factor analysis and COL3A1, NID1 and ZNF800 by gene regulatory network analysis. CONCLUSIONS/INTERPRETATION: Beta cell injury mediated by IAPP is a plausible mechanism to contribute to islet inflammation and dedifferentiation in type 2 diabetes. Inhibition of IAPP toxicity is a potential therapeutic target in type 2 diabetes.

A transparent low intensity pulsed ultrasound (LIPUS) chip for high-throughput cell stimulation.

We report an on-chip platform for low-intensity pulsed ultrasound (LIPUS) stimulation of cells directly cultured on a biocompatible surface of a transparent ultrasound transducer (TUT) fabricated using lithium niobate. The high light transmittance (>80%) and compact size (3 mm × 3 mm × 2 mm) of TUTs allowed easy integration with powerful optical microscopy techniques with no additional acoustic coupling and risk for contamination. TUTs were excited with varying acoustic excitation parameters (voltage amplitude and duty cycle) and resulting live cell calcium signaling was simultaneously imaged using time-lapse confocal microscopy, while the temperature change was measured by a thermocouple. Quantitative single-cell fluorescence analysis revealed the dynamic calcium signaling responses and together with the temperature measurements elucidated the optimal stimulation parameters for non-thermal and thermal effects. The fluorescence change profile was distinct from the recorded temperature change (<1 degree Celsius) profile under LIPUS treatment conditions. Cell dead assay results confirmed cells remain viable after the LIPUS treatment. These results confirmed that the TUT platform enables controllable, safe, high-throughput, and uniform mechanical stimulation of all plated cells. The on-chip LIPUS stimulation using TUTs has the potential to attract several in vitro and in vivo biomedical applications such as controlling stem cell differentiation and proliferation, studying biomechanical properties of cancer cells, and gaining fundamental insights into mechanotransduction pathways when integrated with state-of-the-art high-speed and high-resolution microscopy techniques.