Systematic review of therapeutic nipple-sparing versus skin-sparing mastectomy.

Background: The use of nipple-sparing mastectomy (NSM) is increasing, despite unproven oncological safety in the therapeutic setting. The aim of this systematic review was to determine the safety and efficacy of NSM compared with skin-sparing mastectomy (SSM). Methods: A literature search of all original studies including RCTs, cohort studies and case-control studies comparing women undergoing therapeutic NSM or SSM for breast cancer was undertaken. Primary outcomes were oncological outcomes; secondary outcomes were clinical, aesthetic, patient-reported and quality-of-life outcomes. Data analysis was undertaken to explore the relationship between NSM and SSM, and preselected outcomes. Heterogeneity was assessed using the Cochrane tests. Results: A total of 690 articles were identified, of which 14 were included. There was no statistically significant difference in 5-year disease-free survival and mortality for NSM and SSM groups, where data were available. Local recurrence rates were also similar for NSM and SSM (3·9 versus 3·3 per cent respectively; P = 0·45). NSM had a partial or complete nipple necrosis rate of 15·0 per cent, and a higher complication rate than SSM (22·6 versus 14·0 per cent respectively). The higher overall complication rate was due to the rate of nipple necrosis in the NSM group (15·0 per cent). Conclusion: In carefully selected cases, NSM is a viable choice for women with breast cancer who need to have a mastectomy. More research is needed to help further refine which surgical approaches to NSM optimize outcomes.

Impact of frailty on outcomes in surgical patients: A systematic review and meta-analysis.

IMPORTANCE: Age has historically been used to predict negative post-surgical outcomes. The concept of frailty was introduced to explain the discrepancies that exist between patients' chronological and physiological age. The efficacy of the modified frailty index (mFI) to predict surgical risk is not clear. OBJECTIVE: We sought to synthesize the current literature to quantify the impact of frailty as a prognostic indicator across all surgical specialties. DATA SOURCES: Pubmed and Cochrane databases were screened from inception to 1 January 2018. STUDY SELECTION: Studies utilizing the modified Frailty Index (mFI) as a post-operative indicator of any type of surgery. The mFI was selected based on a preliminary search showing it to be the most commonly applied index in surgical cohorts. DATA EXTRACTION AND SYNTHESIS: Articles were selected via a two-stage process undertaken by two reviewers (AP and DS). Statistical analysis was performed in Revman (Review manager V5.3). The random-effects model was used to calculate the Risk Ratios (RR). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes: post-operative complications, re-admission, re-operation, discharge to a skilled care facility, and mortality. RESULTS: This meta-analysis of 16 studies randomizes 683,487 patients, 444,885 frail, from gastrointestinal, vascular, orthopedic, urogenital, head and neck, emergency, neurological, oncological, cardiothoracic, as well as general surgery cohorts. Frail patients were more likely to experience complications (RR 1.48, 95%CI 1.35-1.61; p < 0.001), major complications (RR 2.03, 95%CI 1.26-3.29; p = 0.004), and wound complications (RR 1.52, 95%CI 1.47-1.57; p < 0.001). Furthermore, frail patients had higher risk of readmission (RR 1.61, 95%CI 1.44-1.80; p < 0.001) and discharge to skilled care (RR 2.15, 95%CI 1.92-2.40; p < 0.001). Notably, the risk of mortality was 4.19 times more likely in frail patients (95% CI 2.96-5.92; p < 0.001). CONCLUSIONS: and Relevance: This study is the first to synthesize the evidence across multiple surgical specialties and demonstrates that the mFI is an underappreciated prognostic indicator that strongly correlates with the risk of post-surgical morbidity and mortality. This supports that formal incorporation of pre-operative frailty assessment improves surgical decision-making.

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery.

In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations; surgical transfer intrinsically impairs metabolic supply to tissues placing a risk of ischemia-related complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) can limit postsurgical ischemic complications and improve outcomes, but very few preconditioning strategies have successfully been translated to clinical practice due to the invasiveness of most proposed approaches, their suboptimal effects, and their challenging regulatory approval. We optimized a method that adopts noninvasive external suction to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model, we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized repeated short-intermittent applications of intermediate suction induced a 1.7-fold increase in tissue vascular density after only 5 days of treatment (p < 0.05); foam interfaces showed the same effectiveness and caused less complications. In a second separate experiment, our model showed that the optimized technique significantly improves survival of transferred tissues. Here we demonstrate that noninvasive external suction can successfully, safely, and promptly enhance vascularity of soft tissues: these translational principles can help design effective preconditioning strategies, transform best clinical practice in surgery, and improve patient outcomes.

Impact of the SCARE guideline on the reporting of surgical case reports: A before and after study.

INTRODUCTION: The SCARE guideline was developed in 2016 through an expert Delphi consensus exercise. It aimed to improve the quality of reporting of surgical case reports. The aim of this study was to assess the impact of introducing the SCARE guideline for surgical on reporting of case reports submitted to a single journal. METHODS: A total of 20 case reports published in the International Journal of Surgery Case Reports (IJSCR) and Annals of Medicine and Surgery (AMS) in July and August 2016, prior to the introduction of the SCARE guideline (the pre-SCARE period), were randomly identified and scored against the SCARE criteria. Two independent teams performed the scoring giving a total score out of a theoretical maximum of 34 for each case report, the 'SCARE score' (expressed as a percentage). The scores for the two teams were then compared and consensus was reached to achieve a final sore set. This process was repeated for the January and February 2017 issues of the journal, post implementation of the guideline (the post-SCARE period). SCARE scores were compared between the pre- and post-SCARE periods. RESULTS: The mean pre-SCARE score was 75.0% (standard deviation ± 6.29, Range 62-84), and the mean post-SCARE score was 82.6% (standard deviation ± 8.02, range 66-99), a 10% relative increase in compliance which was statistically significant (P < 0.001). The Cohen's Kappa score between teams A and B was 0.871, implying very substantial agreement. CONCLUSION: Implementation of the SCARE guideline resulted in a 10% improvement in the reporting quality of surgical case reports published in a single journal. Adherence to SCARE reporting guidelines by authors, reviewers and editors should be improved to boost reporting quality. Journals should develop their policies, submission processes and guide for authors to incorporate the guideline.

Impact of the PROCESS guideline on the reporting of surgical case series: A before and after study.

INTRODUCTION: The PROCESS guideline was developed in 2016 through expert Delphi consensus. It aimed to improve the quality of reporting of surgical case series. This study assessed the impact of the introduction of the PROCESS guideline on reporting for surgical case series submitted to three journals. METHODS: 20 case series published in the International Journal of Surgery Case Reports (IJSCR), the International Journal of Surgery (IJS) or the Annals of Medicine and Surgery (AMS) in September to December 2016, prior to the introduction of the PROCESS guideline (the pre-PROCESS period), were randomly identified and scored against the PROCESS criteria. Two authors independently scored each article a total score out of 29, the 'PROCESS score' (expressed as a percentage). Scores for the two researchers were compared and consensus was reached to achieve a final score set. The process was repeated for the January 2017 to April 2017 issues of the three journals, post PROCESS implementation (the post-PROCESS period). RESULTS: The mean PROCESS score was 80% (range 66-90%) for the pre-PROCESS period and 84% (range 72-95%) for the post-PROCESS period, a 4% relative increase [STATS]. The Cohen's Kappa score between researchers was 0.907 implying very substantial agreement. CONCLUSION: Implementation of the PROCESS guideline resulted in a 5% improvement in the reporting quality of surgical case series published in three journals. Further research is needed to identify and successfully navigate existing barriers to greater compliance. Authors, reviewers and editors should adhere to the guidelines to boost reporting quality. Journals should develop their policies and guide for authors to incorporate the guideline and mandate compliance.

Systematic review of the methodological and reporting quality of case series in surgery.

BACKGROUND: Case series are an important and common study type. No guideline exists for reporting case series and there is evidence of key data being missed from such reports. The first step in the process of developing a methodologically sound reporting guideline is a systematic review of literature relevant to the reporting deficiencies of case series. METHODS: A systematic review of methodological and reporting quality in surgical case series was performed. The electronic search strategy was developed by an information specialist and included MEDLINE, Embase, Cochrane Methods Register, Science Citation Index and Conference Proceedings Citation index, from the start of indexing to 5 November 2014. Independent screening, eligibility assessments and data extraction were performed. Included articles were then analysed for five areas of deficiency: failure to use standardized definitions, missing or selective data (including the omission of whole cases or important variables), transparency or incomplete reporting, whether alternative study designs were considered, and other issues. RESULTS: Database searching identified 2205 records. Through the process of screening and eligibility assessments, 92 articles met inclusion criteria. Frequencies of methodological and reporting issues identified were: failure to use standardized definitions (57 per cent), missing or selective data (66 per cent), transparency or incomplete reporting (70 per cent), whether alternative study designs were considered (11 per cent) and other issues (52 per cent). CONCLUSION: The methodological and reporting quality of surgical case series needs improvement. The data indicate that evidence-based guidelines for the conduct and reporting of case series may be useful.

Systematic review of methodological quality of individual performance measurement in surgery.

BACKGROUND: Calls for greater transparency with improved quality, safety and outcomes have led to performance tracking of individual surgeons. This study evaluated the methodology of studies investigating individual performance in surgery. METHODS: MEDLINE, Embase, PsycINFO, AMED and the Cochrane Database of Systematic Reviews (from their inception to July 2014) were searched. Two authors independently reviewed citations using predetermined inclusion and exclusion criteria; 91 data points per study were extracted. RESULTS: The search strategy yielded 8514 citations; 101 were eligible, comprising 1 006 037 procedures by 14 455 surgeons. Thirty-four studies were prospective and 66 were retrospective. The aim of the studies was either to assess individual performance and describe the learning curve of a procedure, to describe factors influencing performance, or to describe methods for routine performance monitoring. Some 51·5 per cent of the studies investigated 500 or fewer procedures. Most (77 of 101) were single-centre studies. Less than half of the studies (42, 41·6 per cent) employed statistical modelling or stratification to adjust performance measures. Forty studies (39·6 per cent) adjusted outcomes for case mix. Seventeen (16·8 per cent) adjusted metrics for surgeon-specific factors. Thirteen studies (12·9 per cent) considered clustering in their analyses. The most frequent outcome studied was duration of operation (59·4 per cent), followed by complication rate (45·5 per cent) and reoperation rate (29·7 per cent); 15·8 per cent of studies recorded mortality, and 4·0 per cent explored patient satisfaction. Only 48·5 per cent of studies displayed procedural learning curves using a graph. CONCLUSION: There exist substantial shortcomings in methodological quality, outcome measurements and quality improvement evaluation among current studies of individual surgical performance. Methodological guidelines should be established to ensure that assessments are valid.

The wound watch: an objective staging system for wounds in the diabetic (db/db) mouse model.

As in cancer biology, in wound healing there is a need for objective staging systems to decide for the best treatment and predictors of outcome. We developed in the diabetic (db/db) wound healing model, a staging system, the "wound watch," based on the quantification of angiogenesis and cell proliferation in open wounds. In chronic wounds, there is often a lack of cellular proliferation and angiogenesis that leads to impaired healing. The wound watch addresses this by quantifying the proliferative phase of wound healing in two dimensions (cellular division and angiogenesis). The results are plotted in a two-dimensional graph to monitor the course of healing and compare the response to different treatments.

Restoration of facial form and function after severe disfigurement from burn injury by a composite facial allograft.

Composite facial allotransplantation is emerging as a treatment option for severe facial disfigurements. The technical feasibility of facial transplantation has been demonstrated, and the initial clinical outcomes have been encouraging. We report an excellent functional and anatomical restoration 1 year after face transplantation. A 59-year-old male with severe disfigurement from electrical burn injury was treated with a facial allograft composed of bone and soft tissues to restore midfacial form and function. An initial potent antirejection treatment was tapered to minimal dose of immunosuppression. There were no surgical complications. The patient demonstrated facial redness during the initial postoperative months. One acute rejection episode was reversed with a brief methylprednisolone bolus treatment. Pathological analysis and the donor's medical history suggested that rosacea transferred from the donor caused the erythema, successfully treated with topical metronidazol. Significant restoration of nasal breathing, speech, feeding, sensation and animation was achieved. The patient was highly satisfied with the esthetic result, and regained much of his capacity for normal social life. Composite facial allotransplantation, along with minimal and well-tolerated immunosuppression, was successfully utilized to restore facial form and function in a patient with severe disfigurement of the midface.

The relative thermal stability of tissue macromolecules and cellular structure in burn injury.

When tissue is subjected to higher than physiological temperatures, protein and cell organelle structures can be altered resulting in cell death and subsequent tissue necrosis. A burn injury can be stratified into three main zones, coagulation, stasis and edema, which correlate with the extent of heat exposure and thermal properties of the tissue. While there has been considerable effort to characterize the time-temperature dependence of the injury, relatively little attention has been paid to the other important variable, the thermal susceptibility of the tissue. In the present study, we employ a standard physical chemistry approach to predict the level of denaturation at supraphysiological temperatures of 12 vital proteins as well as RNA, DNA and cell membrane components. Melting temperatures and unfolding enthalpies of the cellular components are used as input experimental parameters. This approach allows us to establish a relation between the level of denaturation of critical cellular components and clinical manifestations of the burn through the characteristic zones of the injury. Specifically, we evaluate the degree of molecular alteration for characteristic temperature profiles at two different depths (Mid-Dermis and Dermis-Fat interface) of 80 degrees C; 20s contact burn. The results of this investigation suggest that the thermal alteration of the plasma membrane is likely the most significant cause of the tissue necrosis. The lipid bilayer and membrane-bound ATPases show a high probability of thermal damage (almost 100% for the former and 85% for the latter) for short heat exposure times. These results suggest that strategies to minimize the damage in a burn injury might focus on the stabilization of the cellular membrane and membrane-bound ATPases. Further work will be required to validate these predictions in an in vivo model.

Stability of cellular proteins under supraphysiological temperatures.

We present quantitative analyses of the kinetics of cellular components confronted with the destabilizing effect of irreversible thermal denaturation. We examine the dependence of the thermal denaturation on the heating rate, relative stability, population and lifetime of the states involved in transition and crowding effects. We propose a mechanism for self-stabilization of proteins during unfolding in tightly packed fibers and membranes. Speaking in terms of vulnerability to thermal denaturation, our results suggest that the thermal alteration of the plasma membrane is likely to be the most significant cause of the tissue necrosis.

The development of an educational web site for burn care: burnsurgery.org.

Advances in burn care are well documented in the literature but often do not reach health care professionals who treat burn patients. The World Wide Web provides instant access to a wide variety of information globally. We describe the development of www.burnsurgery.org, a nonprofit Web site dedicated to the education of burn care professionals. Internet-based medical education is becoming a dominant method of information transfer and we believe that it will help to standardize and improve burn care throughout the world.

A review of computer-aided body surface area determination: SAGE II and EPRI's 3D Burn Vision.

Estimates of percent body surface area (%BSA) burns correlate well with fluid needs, nutritional requirements, and prognosis. Most burn centers rely on the Lund Browder chart and "rule of nines," to calculate the %BSA. Computer-based methods may improve precision and data analysis. We studied two new methods of determining %BSA: a two-dimensional Web-based program (Sage II) and a three-dimensional computer-aided design program (EPRI 3D Burn Vision). Members of our burn team found the Sage II program easy to use and found many of the features useful for patient care. The EPRI program has the advantage of 3D images and different body morphologies but required training to use. Computer-aided methods offer the potential for improved precision and data analysis of %BSA measurements.

Melanocyte repopulation in full-thickness wounds using a cell spray apparatus.

Melanocyte restoration is critical in reconstituting skin color. We developed a spotted (piebald) pig wound model to study methods of restoring melanocytes to the epidermis. Paired, full-thickness, porcine wounds were covered with nonpigmented, fully expanded, 3:1 meshed, split-thickness skin grafts and were sprayed with an epidermal cell suspension. The suspensions were highly pigmented skin (HPS) cell isolates for half of the wounds (n = 16) and nonpigmented skin (NPS) cell isolates for the remaining wounds (n = 16). Histologic sections showed 6.0 +/- 3.0 and 15 +/- 4.0 pigmented melanocytes per high-power field on days 8 and 20 in HPS-treated wounds and no pigmented melanocytes in NPS-treated wounds. Melanin pigment was dispersed in all layers of the epithelium for the HPS group on day 20 compared with a lack of melanin pigment observed in the NPS group. Cell spraying may provide a clinical method to restore color to skin; further work is needed to control the expression of melanin.

Reduction of abdominal adhesions using composite collagen-GAG implants for ventral hernia repair.

Structural biomaterials can restore abdominal wall integrity but may cause adhesions to the underlying viscera. Collagen-glycosaminoglycan (CG) matrices induce the formation of connective tissue and may reduce adhesion formation to permanent biomaterials such as polypropylene (PP) mesh. Composite implants were created by interposing PP mesh within a porous CG matrix created composite implants. The implants were cross-linked with glutaraldehyde one group (CG-G/PP) or left untreated (CG-nG/PP) and compared to PP mesh. At 4 weeks, the abdominal wall was assessed for the degree of adhesions. The composite implants developed a nascent connective tissue-like structure that reduced adhesions to the bowel. The thickest connective tissue developed in the CG-G/PP group (0.7 +/- 0.1 mm) and thinnest in the PP mesh (0.05 +/- 0.01 mm). The surface area covered with adhesions was greatest in the PP group (72 +/- 17%) compared with the CG-G/PP group (28 +/- 15%) or the CG-nG/PP group (21 +/- 8%). Bowel preferentially adhered to the PP mesh, whereas omentum had some adherence to all constructs. Integrating a biodegradable extracellular matrix analog with a permanent structural biomaterial reduced adhesions in this animal model. Alterations in cross-linking of the CG matrix altered the biological response. This technology may be useful in reconstructive surgery by reducing adhesion formation, while maintaining the strength of permanent structural biomaterials.

Perfusion of medium improves growth of human oral neomucosal tissue constructs.

Tissue engineering of the oral mucosa may be useful in congenital cleft palate repairs, defects following extirpative oncologic surgery, and periodontal disease. One of the limitations of in vitro growth of oral mucosal constructs is central necrosis of 3-dimensional tissues. We tested the hypothesis that medium perfusion would enhance oral mucosal histogenesis in vitro. Normal human oral keratinocytes were obtained from young to middle-aged adults. Porous 3-dimensional matrices were prepared from collagen and chondroitin sulfate with some crosslinked with glutaraldehyde. Each device was seeded with 5.0 x 10(5) human oral keratinocytes. The seeded matrices were cultured with or without perfusion of medium at 1.3 ml/min. Histologic analysis of samples cultured for 3, 7, or 14 days showed superior viability and proliferation when perfused. At day 7, the average number of cell layers of the neoepithelium of sponges in the perfused culture system (9.4 +/- 1.0) was 88% greater than for the nonperfused culture system (5.0 +/- 0.9, p<0.005). Glutaraldehyde crosslinking did not influence cellular proliferation or the extent of matrix's shrinkage in either culture system. This study shows that medium perfusion enhanced cell viability and proliferation of human oral keratinocytes cultured in porous 3-dimensional matrices.

The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury.

PURPOSE: Severe burn injury leads to marked catabolism and decreased lean mass, which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site. MATERIALS AND METHODS: Patients with burns between 40% and 70% of body surface were studied. A randomized double-blinded placebo-controlled study design was used. Patients were given oxandrolone 20 mg/day (n = 11) or a placebo 20 mg/day (n = 9) beginning between days 2 and 3 post burn. Net nitrogen balance and the healing time of a standardized donor site were measured. Patients were monitored until transferred to a burn rehabilitation facility, an average time period of 33 +/- 9 days. RESULTS: Mean burn size was 49 +/- 8% for placebo and 53 +/- 9% of total body surface for the oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8 +/- 3.1 kg in the placebo group compared with 3 +/- 1.9 kg in the oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3-week period (days 7 to 28) was 13 +/- 4 g in placebo treated compared with 4 +/- 1.9 g for the oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13 +/- 3 days to 9 +/- 2 days for oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group. CONCLUSION: We found the anabolic agent, oxandrolone, significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared with placebo controls. We noted no complications with the use of oxandrolone.

Sprayed keratinocyte suspensions accelerate epidermal coverage in a porcine microwound model.

Keratinocyte suspensions can potentially treat a variety of epidermal defects, but the mechanism of action has not been fully determined. We developed a porcine model to study the effect of sprayed cell suspensions delivered on small wounds within a meshed autograft. Paired full-thickness surgically excised wounds were covered with a fully expanded 3:1 meshed split-thickness autograft. A keratinocyte cell suspension was sprayed onto half of the wounds at a seeding density of 2.8 x 10(3) cells/cm2; the remaining wounds were sprayed with cell culture medium alone. Histologic analysis at days 5 and 8 showed an increase in average epidermal thickness, confluence, keratin cysts, and blood vessels in the keratinocyte cell suspension group compared with the cell culture medium control group. Wounds sprayed with the cell suspension showed faster and better quality of epithelialization than wounds sprayed with cell culture medium alone.