A set of genes previously implicated in the hypoxia response might be an important modulator in the rat ear tissue response to mechanical stretch

<p>Abstract</p> <p>Background</p> <p>Wounds are increasingly important in our aging societies. Pathologies such as diabetes predispose patients to chronic wounds that can cause pain, infection, and amputation. The vacuum assisted closure device shows remarkable outcomes in wound healing. Its mechanism of action is unclear despite several hypotheses advanced. We previously hypothesized that micromechanical forces can heal wounds. To understand better the biological response of soft tissue to forces, rat ears in vivo were stretched and their gene expression patterns over time obtained. The absolute enrichment (AE) algorithm that obtains a combined up and down regulated picture of the expression analysis was implemented.</p> <p>Results</p> <p>With the use of AE, the hypoxia gene set was the most important at a highly significant level. A co-expression network analysis showed that important co-regulated members of the hypoxia pathway include a glucose transporter (slc2a8), heme oxygenase, and nitric oxide synthase2 among others.</p> <p>Conclusion</p> <p>It appears that the hypoxia pathway may be an important modulator of response of soft tissue to forces. This finding gives us insights not only into the underlying biology, but also into clinical interventions that could be designed to mimic within wounded tissue the effects of forces without all the negative effects that forces themselves create.</p

Absolute Enrichment: Gene Set Enrichment Analysis for Homeostatic Systems

The Gene Set Enrichment Analysis (GSEA) identifies sets of genes that are differentially regulated in one direction. Many homeostatic systems will include one limb that is upregulated in response to a downregulation of another limb and vice versa. Such patterns are poorly captured by the standard formulation of GSEA. We describe a technique to identify groups of genes (which sometimes can be pathways) that include both up- and down-regulated components. This approach lends insights into the feedback mechanisms that may operate, especially when integrated with protein interaction databases

Patient Satisfaction and Surgeon Experience: A Follow-Up to the Reduction Mammaplasty Learning Curve Study

Background: While it is known that increasing surgeon experience is correlated with improved efficiency and safety in the reduction mammaplasty procedure, it is unclear whether these improvements lead to an erosion in patient satisfaction. Methods: The authors distributed the Breast-Q questionnaire to all patients who underwent bilateral reduction mammaplasty at their institution between 1995 and 2007. Univariate and multivariate analyses were performed to assess the relationship between postoperative patient satisfaction scores and surgeon experience, as well as to characterize those patients with particularly high or low satisfaction scores, in general. Results: A total of 279 (26.1%) completed surveys were analyzed. No statistically significant erosion in either Satisfaction with Breasts (SWB) or Satisfaction with Outcomes (SWO) scores were witnessed with increasing surgeon experience or efficiency. Patients older than 40 years demonstrated significantly higher SWB scores than younger patients (P = .004), while patients who suffered postoperative soft tissue necrosis demonstrated significantly lower SWB (P = .003) and SWO (P = .010) scores. Conclusions: Gains in operative efficiency with increasing surgeon experience do not appear to come at the expense of patient satisfaction in the reduction mammaplasty procedure. Younger patients and those who experience postoperative soft tissue necrosis appear to be at higher risk for reporting lower postoperative patient satisfaction scores

Patient- and surgeon-adjusted control charts for monitoring performance

Objectives: To determine whether an innovative graphical tool for accurate measurement of individual surgeon performance metrics, adjusted for both surgeon-specific and patient-specific factors, significantly alters interpretation of performance data. Design: Retrospective analysis of all total knee replacements (TKRs) conducted at the host institution between 1996 and 2009. The database was randomly divided into training and testing datasets. Using multivariate generalised estimating equation regression models, the training dataset enabled generation of patient-risk and surgeon-experience adjustment factors. To simulate prospective monitoring of individual surgeon outcomes, the testing dataset was mapped on control charts. Weighted κ statistics were calculated to measure the agreement between patient-risk adjusted and fully adjusted control charts. Setting: Tertiary care academic hospital. Participants: All patients undergoing TKR at the host institution 1996–2009. Main outcome measure Operative efficiency. Results: 5313 procedures were analysed. Adjusted control charts were generated using a training dataset comprising 3756 procedures performed by 13 surgeons. The operative time gradually declined by 121 min with 25 years of experience (p<0.0001). Charts were tested by monitoring four other surgeons, performing an average of 389 procedures each. Adjustment for surgeon experience significantly altered the interpretation of operative efficiency (κ=0.29 (95% CI 0.11 to 0.47)), and enhanced assessment of a surgeon's improvement or diminishment in efficiency over time. Specifically, experience adjustment inverted the interpretation of surgeon efficiency from above average to below average, or from improving to declining performance. Conclusions: Adjustment for surgeon experience is necessary for accurate interpretation of metrics over the course of a surgeon's career. Patient-adjusted and surgeon-adjusted control charts provide an accurate method of monitoring individual operative efficiency

Randomised controlled trials in plastic surgery: a systematic review of reporting quality

Background: We recently conducted a systematic review of the methodological quality of randomised controlled trials (RCTs) in plastic surgery. In accordance with convention, we are here separately reporting a systematic review of the reporting quality of the same RCTs. Methods: MEDLINE® and the Cochrane Database of Systematic Reviews were searched by an information specialist from 1 January 2009 to 30 June 2011 for the MESH heading ‘Surgery, Plastic’. Limitations were entered for English language, human studies and randomised controlled trials. Manual searching for RCTs involving surgical techniques was performed within the results. Scoring of the eligible papers was performed against the 23-item CONSORT Statement checklist. Independent secondary scoring was then performed and discrepancies resolved through consensus. Results: Fifty-seven papers met the inclusion criteria. The median CONSORT score was 11.5 out of 23 items (range 5.3–21.0). Items where compliance was poorest included intervention/comparator details (7 %), randomisation implementation (11 %) and blinding (26 %). Journal 2010 impact factor or number of authors did not significantly correlate with CONSORT score (Spearman rho = 0.25 and 0.12, respectively). Only 61 % declared conflicts of interest, 75 % permission from an ethics review committee, 47 % declared sources of funding and 16 % stated a trial registry number. There was no correlation between the volume of RCTs performed in a particular country and reporting quality. Conclusions: The reporting quality of RCTs in plastic surgery needs improvement. Better education, awareness amongst all stakeholders and hard-wiring compliance through electronic journal submission systems could be the way forward. We call for the international plastic surgical community to work together on these long-standing problems

Political Prioritisation for Performance-Based Financing at the County Level in Kenya: 2015 to 2018

Background: Performance based financing was introduced to Kilifi county in Kenya in 2015. This study investigates how and why political and bureaucratic actors at the local level in Kilifi county influenced the extent to which PBF was politically prioritised at the sub-national level. Methods: The study employed a single-case study design. The Shiffman and Smith political priority setting framework with adaptations proposed by Walt and Gilson was applied. Data was collected through document review (n=19) and in-depth interviews (n=8). Framework analysis was used to analyse data and generate findings. Results: In the period 2015-2018, the political prioritisation of PBF at the county level in Kilifi was influenced by contextual features including the devolution of power to sub-national actors and rigid public financial management structures. It was further influenced by interpretations of the idea of ‘pay-for-performance’, its framing as ‘additional funding’, as well as contestation between actors at the sub national level about key PBF design features. Ultimately PBF ceased at the end of 2018 after donor funding stopped. Conclusion: Health reformers must be cognisant of the power and interests of national and sub national actors in all phases of the policy process, including both bureaucratic and political actors in health and non-health sectors. This is particularly important in devolved public governance contexts where reforms require sustained attention and budgetary commitment at the sub national level. There is also need for early involvement of critical actors to develop shared understandings of the ideas on which interventions are premised, as well as problems and solutions

Diffusion and Perfusion: The Keys to Fat Grafting

Background: Fat grafting is now widely used in plastic surgery. Long-term graft retention can be unpredictable. Fat grafts must obtain oxygen via diffusion until neovascularization occurs, so oxygen delivery may be the overarching variable in graft retention. Methods: We studied the peer-reviewed literature to determine which aspects of a fat graft and the microenvironment surrounding a fat graft affect oxygen delivery and created 3 models relating distinct variables to oxygen delivery and graft retention. Results: Our models confirm that thin microribbons of fat maximize oxygen transport when injected into a large, compliant, well-vascularized recipient site. The “Microribbon Model” predicts that, in a typical human, fat injections larger than 0.16 cm in radius will have a region of central necrosis. Our “Fluid Accommodation Model” predicts that once grafted tissues approach a critical interstitial fluid pressure of 9 mm Hg, any additional fluid will drastically increase interstitial fluid pressure and reduce capillary perfusion and oxygen delivery. Our “External Volume Expansion Effect Model” predicts the effect of vascular changes induced by preoperative external volume expansion that allow for greater volumes of fat to be successfully grafted. Conclusions: These models confirm that initial fat grafting survival is limited by oxygen diffusion. Preoperative expansion increases oxygen diffusion capacity allowing for additional graft retention. These models provide a scientific framework for testing the current fat grafting theories

Current and future applications of artificial intelligence in surgery: implications for clinical practice and research

Surgeons are skilled at making complex decisions over invasive procedures that can save lives and alleviate pain and avoid complications in patients. The knowledge to make these decisions is accumulated over years of schooling and practice. Their experience is in turn shared with others, also via peer-reviewed articles, which get published in larger and larger amounts every year. In this work, we review the literature related to the use of Artificial Intelligence (AI) in surgery. We focus on what is currently available and what is likely to come in the near future in both clinical care and research. We show that AI has the potential to be a key tool to elevate the effectiveness of training and decision-making in surgery and the discovery of relevant and valid scientific knowledge in the surgical domain. We also address concerns about AI technology, including the inability for users to interpret algorithms as well as incorrect predictions. A better understanding of AI will allow surgeons to use new tools wisely for the benefit of their patients

Hair follicle melanocyte cells as a renewable source of melanocytes for culture and transplantation

Objective: Advances in melanocyte culture techniques have not yet led to reliable clinical methods for treating hypopigmentation disorders. We hypothesized that melanocytes harvested from plucked hair follicles may provide a renewable source of melanocytes for the treatment of hypopigmentation. Methods: Hairs with attached cells from the follicles were plucked from Yucatan pigs and implanted in a collagen-glycosaminoglycan matrix for either immediate or delayed implantation into full-thickness excisional porcine wounds. Wounds were allowed to heal and were biopsied at 2 and 4 weeks, respectively. Results: Fully healed wounds with transplanted hair follicles showed central areas of dark pigmentation corresponding to the location of implanted hair follicles. Corresponding collagen-glycosaminoglycan matrix wounds showed no central areas of pigmentation. Conclusions: Hair follicle--derived melanocytes may potentially serve as a renewable source of pigment-producing cells for treating hypopigmentation disorders

Use of the parabiotic model in studies of cutaneous wound healing to define the participation of circulating cells

Previous experimental studies to assess the contribution of blood-borne circulating (BBC) cells to cutaneous wound healing have relied on discontinuous pulsing of labeled BBC elements or bone marrow transplant protocols. Such approaches do not allow the examination of stable BBC cells that have matured in a physiologically normal host. We have used a parabiotic murine model for cutaneous wound healing to evaluate the relative contribution of stable populations of peripheral blood cells expressing the green fluorescent protein (GFP) transgene in otherwise normal animals. Circulating cells (mature and immature) expressing the GFP transgene were easily detected and quantified in wounds of GFP− parabiotic twins during all evaluated stages of the healing response. Using multiple antibody probes, the relative contribution of various subsets of BBC cells could be comparatively assessed. In early wounds, some cells expressing mesenchymal epitopes were documented to be of hematopoietic origin, indicating the utility of this model in assessing cell plasticity in the context of tissue regeneration and repair. Application of this approach enables further investigation into the contribution of peripheral blood in normal and abnormal healing responses.National Institutes of Health (U.S.) (NIH 5 T32 HL007627- 22 Physician-Scientist Training Grant)National Institutes of Health (U.S.) (NIH/NIDDK (5 P30 DK36836-20))Brigham and Women’s Hospital (Program in Dermatopathology core grant (SDRC))National Institutes of Health. (U.S.). Department of Health and Human Services (Brigham and Women’s Hospital’s Program in Dermatopathology core grant (SPORE)