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Introduction: The lack of attention to transgender and gender diverse (TGD) people in undergraduate medical education (UME) is a point of concern, particularly among medical students. A project was undertaken to develop a UME curriculum framework for teaching the healthcare needs of TGD people., Methods: Using a modified Delphi methodology, four rounds of surveys were presented to an expert stakeholder group that included content experts, generalist physicians, UME teaching faculty, and medical students. Questions covered what content should be taught, who should teach the content, and how much time should be dedicated for this teaching. Once the Delphi process was complete, feedback on the provisional framework was sought from members of the TGD community to ensure it represented their needs and perspectives., Results: 71 panel members and 56 community members participated in the study. Core values included the scope of the framework, and topics such as inclusivity, and safety in practice and in teaching. The framework included terminology, epidemiology, medical and surgical treatment, mental health, sexual and reproductive health, and routine primary care. There was also guidance on who should teach, time to be allocated, and the learning environment., Discussion: There is a clear need to train tomorrow's doctors to provide competent and respectful healthcare services to and for TGD patients. Although local factors will likely shape the way in which this framework will be implemented in different contexts, this paper outlines a core UME-level curriculum framework for Canada and, potentially, for use in other parts of the world., (© 2021. The Author(s).)

Despite the success of composite tissue allograft (CTA) such as face and hand transplant at improving recipients' quality of life, organ donors' hesitation needs to be better understood. The aim of the study was to assess Canadian organ donors' willingness to donate their face and hands, and the efficacy of an educational intervention., Methods: Canadians registered for organ donation were invited to complete an online survey about CTA. An interactive vignette was introduced part way through to clarify transplant-related concepts, with repeat of questions post-vignette exposure to assess attitudes pliability., Results: A total of 942 participants completed the survey. Fifty-two percent of donors were willing to donate their face after passing, whereas 80% were willing to donate their hands. Reasons to refuse CTA donation included the risk of upsetting their family, having someone look like them, and wanting their body to remain intact. Donors' willingness to donate their face (38%, P < 0.001) and hands (79%, P = 0.67) decreased following vignette exposure. Comparative analysis of our interventional vignette with a similar study where donors' donation readiness increased after an educational intervention revealed that our vignette lacked a strong enough emotional component to positively impact donors' attitude to CTA, and may have exposed participants to alternatives to transplant they were not previously aware of., Conclusions: Canadian organ donors surveyed were willing to donate their face and hands following death, a willingness reduced after watching our informative vignette. Further qualitative work is required to better understand the educational needs and areas to address to increase donors' acceptance of CTA., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Major improvements in breast cancer treatment in the last decade include advancements in postmastectomy breast reconstruction (PMBR). Unfortunately, the studies in PMBR are primarily researcher or industry led with minimal input from patients and caregivers. The aim of this study is to use the James Lind Alliance (JLA) approach to bring together the patients, caregivers and clinicians in a priority setting partnership to identify the most important unanswered research questions in PMBR., Methods: The JLA priority setting methodology involved four key stages: gathering research questions on PMBR from patients, caregivers and clinicians; checking these research questions against existing evidence; interim prioritisation and a final consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology., Results: In stage 1, 3168 research questions were submitted from 713 respondents across Canada, of which 73% of the participants were patients or caregivers. Stage 2 confirmed that there were a total of 48 unique unanswered questions. In stage three, 488 individuals completed the interim prioritisation survey and the top 25 questions were taken to a final consensus meeting. In the final stage, the top 10 unanswered research questions were determined. They cover a breadth of topics including personalised surgical treatment, safety of implants and newer techniques, access to PMBR, breast cancer recurrence and rehabilitation., Interpretation: Identification of the top 10 unanswered research questions is an important first step to generating relevant and impactful research that will ultimately improve the PMBR experience for patients with breast cancer., Competing Interests: Competing interests: ‘Yes, there are competing interests for one or more authors and I have provided a Competing Interests statement in my manuscript and in the box below’, (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intralesional injection of interleukin-2 (IL-2) for in-transit melanoma (ITM) is associated with a high rate of complete response. However, there is a paucity of data on treatment durability and long-term outcomes., Objectives: To provide long-term data on patients with a complete response to IL-2 therapy for ITM., Methods: Consecutive patients with ITM, treated with intralesional IL-2 therapy, at the Tom Baker Cancer Center were identified from April 2009 to August 2019. All patients received at least 4 cycles (every 2 weeks) of IL-2 (5 MIU/mL). Complete response was defined as sustained (ie, 3 months) clinical complete remission of all known in-transit disease., Results: Sixty-five patients were treated with curative intent for in-transit disease with intralesional IL-2. Complete clinical response was identified in 44.6% (29/65). In this subset of patients, the median number of lesions per patient was 9 (range 1-40). The median total dose of IL-2 was 0.8 mL (IQR 0.4-1.5) per lesion. One patient received isolated limb infusion and 13.8% (4/29) received systemic immunotherapy as part of their initial management. At a median follow-up of 27 months (IQR 16-59), 34.5% (10/29) developed recurrent disease. Of these patients, 50.0% (5/10) presented with synchronous in-transit and distant metastases. The median time to recurrence was 10.5 months (IQR 5.8-16.3)., Conclusion: With long-term follow-up, 65.5% of complete responders have a durable response to intralesional IL-2 therapy. In this cohort of patients, local in-transit recurrence is most likely to occur within 12 months and is often associated with concomitant distant disease.

Competing Interests: Competing interests: ML reports personal fees from JnJ/Ethicon, outside the submitted work, and is an ad hoc speaker for Intuitive Surgical Inc. GN reports personal fees from Abbott and Medtronic, outside the submitted work.

Introduction The COVID 19 pandemic has affected education at all levels. Surgical fellows have faced unique challenges., Problems: The authors address aspects of Canadian surgical fellowships that have been impacted by the pandemic. These include case volumes, training objectives, funding models, burden of stress and research productivity., Solutions: Solutions are proposed including varying the mix of cases to meet objectives, pursuing alternative finance structures and leveraging technology for both research and advancing surgical technique., Conclusion: These solutions are offered to help mitigate the effects of future pandemics for both current and future surgical fellows., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Intra-lesional interleukin 2 (IL-2) therapy trials for the treatment of in-transit melanoma using different treatment protocols have been published reporting varied results. This study assesses the results of IL-2 therapy in our institution and to evaluate the reproducibility of our response rates when using the same treatment protocol as another Canadian centre., Methods: A retrospective review was undertaken of patients with in-transit melanoma who were treated with intralesional IL-2 in a single institution from 2010 to 2016. Responses were evaluated using RECIST criteria. Demographic data, tumour characteristics, follow-up data, in-transit-free interval, and survival data were collected and analysed., Results: Forty-nine patients were identified. Overall tumour response rate was 72%, including complete response in 23 patients (47%) and partial response in 12 patients (24%). Stable disease was observed in 4% of patients and progressive disease in 25%. The main side effects were minor discomfort with injections and auto-limited flu-like symptoms. The presence of tumour-infiltrating lymphocytes may be a predictor of better response., Conclusion: This study confirms prior experience with intra-lesional IL-2, demonstrating it to be an effective, safe, and well-tolerated therapy for in-transit melanoma. Tumour-infiltrating lymphocytes as a predictor of better response warrant further study., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2020 The Author(s).)

Background: Some women with breast implants express concern about the safety of implants, fearing the possibility of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and breast implant-related illness., Methods: A qualitative analysis was performed to examine the perceived challenges, barriers, and worries experienced by these women. Convenience sampling was used to elicit responses from members of Canadian BIA-ALCL Facebook advocacy groups. Three independent coders read and reread the transcripts, using thematic analysis to identify emerging themes., Results: Sixty-four women answered questions posed by the president of the Canadian Society of Plastic Surgeons regarding concerns about their breast implants. Five themes were identified: informing, listening, acknowledging, clarifying, and moving forward. Patients desire improved communication about possible risks before implantation and as new information becomes available (informing), sincere listening to their concerns (listening), acknowledgement that these disease entities may be real and have psychosocial/physical impact on patients (acknowledging), clarification of implant-related problems and their treatment (clarifying), and improved processes for monitoring and treatment of patients with identified problems (moving forward). Consideration of these themes in the context of the five domains of trust theory (i.e., fidelity, competence, honesty, confidentiality, and global trust) suggests significant breakdown in the doctor-patient relationship for a subset of concerned women., Conclusions: Concerns related to BIA-ALCL and breast implant-related illnesses have undermined some women's trust in plastic surgeons. Consideration of these five themes and their impact on the five domains of trust can guide strategies for reestablishing patients' trust in the plastic surgery community., Competing Interests: Disclosure:The authors have no financial disclosures or conflicts of interest to report., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Purpose: To determine the type of information women want to be provided in order to make an informed decision as to whether, when, and using what technique to proceed with breast reconstruction., Method: Using purposeful sampling, 19 patients who had recently undergone various breast reconstruction procedures were recruited to each participate in a 30- to 45-minute semi-structured interview. Participants shared their insights and beliefs regarding the type of breast reconstruction information they most valued prior to undergoing breast reconstruction surgery. Participants were also queried as to perceived information gaps. In some cases, the participants' partners or support persons were also interviewed. Grounded theory and thematic analysis assisted in interview transcript analysis., Results: Eight topics were identified relating to women's informational needs around breast reconstruction. Examples include how to weigh the pros and cons of various breast reconstruction options to decide between flap or implant reconstruction, whether there are safety concerns with immediate breast reconstruction or nipple-sparing reconstruction, and expectations and advice on how to manage possibly unexpected intimacy issues after breast reconstruction., Conclusions: Using mixed methods research methodology, 19 women reported on preoperative informational gaps relating to their recent breast reconstruction experiences. Patients report that adequate breast reconstruction information prior to breast reconstruction surgery helps them to manage their expectations, prepare for surgery and recovery, and improve postoperative satisfaction., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2020 The Author(s).)

Purpose: To examine common themes and synthesize data surrounding pregnancy and parenthood during surgical residency training., Method: The authors conducted a systematic search of the literature in March 2019. They searched MEDLINE, EMBASE, and Scopus, seeking articles published from 2003 to 2018 that focused on pregnancy, parenthood, and the experience of surgical residents. They excluded articles that examined nonsurgical programs, as well as editorials, abstracts, and commentaries. Two investigators independently reviewed all citations, selected articles for full-text review, and extracted data from the selected articles., Results: Of 523 titles and abstracts screened, 27 were included. Overall, female surgical residents had fewer children during residency training than their male counterparts (18%-28% vs 32%-54%). As compared with the general population, surgical residents had their first child later in life (30-34 vs 25 years old), and had fewer children overall (0.6-2.1 vs 2.7). Infertility rates were higher among female surgeons than in the general population (30%-32% vs 11%), as were assisted reproductive technology rates (8%-13% vs 1.7%). Pregnant surgical residents experienced a high rate of obstetrical complications; working more than 6 overnight calls shifts per month or 60 hours per week were predictors of increased complication rates. The authors noted no differences in attrition, caseload, or exam pass rates amongst female surgical residents who had become pregnant as compared with other residents. Despite these similar academic outcomes, negative attitudes and perceptions toward pregnancy during residency were consistently identified., Conclusions: Female surgical residents experience high rates of infertility and obstetrical complications, contend with negative attitudes and stigma during their pregnancies, and voluntarily delay childbearing. Formal maternity policies, a shift in surgical culture, and ongoing discussion with all stakeholders are needed to attract and retain female surgical residents.

Background: This study aimed to determine the current state of oncology education in Canadian family medicine postgraduate medical education programs (FM PGME) and examine opinions regarding optimal oncology education in these programs., Methods: A survey was designed to evaluate ideal and current oncology teaching, educational topics, objectives, and competencies in FM PGMEs. The survey was sent to Canadian family medicine (FM) residents and program directors (PDs)., Results: In total, 150 residents and 17 PDs affiliated with 16 of 17 Canadian medical schools completed the survey. The majority indicated their programs do not have a mandatory clinical rotation in oncology (79% residents, 88% PDs). Low rates of residents (7%) and PDs (13%) reported FM residents being adequately prepared for their role in caring for cancer patients (p = 0.03). Residents and PDs believed the most optimal method of teaching oncology is through clinical exposure (65% residents, 80% PDs). Residents and PDs agreed the most important topics to learn (rated ≥4.7 on 5-point Likert scale) were: performing pap smears, cancer screening/prevention, breaking bad news, and approach to patient with increased cancer risk. According to residents, other important topics such as appropriate cancer patient referrals, managing cancer complications and post-treatment surveillance were only taught at frequencies of 52, 40 and 36%, respectively., Conclusions: Current FM PGME oncology education is suboptimal, although the degree differs in the opinion of residents and PDs. This study identified topics and methods of education which could be focussed upon to improve FM oncology education.

Background: The purpose of this article is to illuminate differences in published clinical practice guideline recommendations for breast reconstruction after prophylactic and therapeutic mastectomy., Methods: Ten guidelines were identified through a systematic search of websites and databases of reputable oncology guideline developers, and key differences and gaps in recommendations were noted. Quality assessment of the guidelines was conducted by three reviewers using the AGREE II tool, focusing on breast reconstruction specific documents rather than the general breast cancer guidelines., Results: The most comprehensive guidelines were published by Alberta Health Services, Cancer Care Ontario, the American Society of Plastic Surgeons, and the Association of Breast Surgery/British Association of Plastic Reconstructive and Aesthetic Surgeons. AGREE II scores in the domains of "Scope and Purpose" and "Clarity and Presentation" were ranked relatively high for all four guidelines while "Applicability" and "Editorial Independence" were ranked relatively low. The Alberta and Ontario guidelines were the overall highest ranked guidelines across all domains., Conclusion: Overall, these guidelines provide consistent recommendations on who should receive breast reconstruction education, who is a candidate for postmastectomy breast reconstruction, and the appropriate timing of reconstruction and extent of mastectomy. Future updates from all should focus on expanding to include alloplastic and autologous forms of reconstruction and should include a broad scope of relevant questions., Competing Interests: Declaration of competing interest None declared., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Skin flap necrosis (SFN) is a morbid complication that is disfiguring, leads to acute and chronic wound issues, often requires further surgery, and can delay adjuvant chemotherapy. Although most surgeons rely on the clinical examination, near-infrared (NIR) spectroscopy can extrapolate tissue oxygenation and may serve as an important tool to assess flap perfusion intraoperatively. This cohort study was undertaken to evaluate the capacity of NIR spectroscopy to detect clinically relevant differences in tissue perfusion intraoperatively., Methods: Patients undergoing oncologic resection of breast cancer, sarcomas, and cutaneous tumors requiring flap reconstruction (local, regional, or free) between January 2018 and January 2019 were analyzed in this study. Clinicians were blinded to device tissue oxygen saturation (S t O 2 ) measurements taken intraoperatively after closure and at follow-up appointments in the first 30 days. Measurements were categorized as (1) control areas not affected by the procedure, (2) areas at risk, and (3) areas of necrosis. These areas were retrospectively demarcated by 2 blinded assessors on follow-up images and transposed onto anatomically correlated intraoperative S t O 2 measurements. Mean S t O 2 values were compared using a single-sample t test and analysis of variance (ANOVA) to determine differences in oxygenation., Results: Forty-two patients were enrolled, and 51 images were included in the analysis. Oncologic procedures were predominantly breast (22), postextirpative melanoma (13), and sarcoma (3) reconstructions. Flap reconstruction involved 30 regional skin flaps, 3 pedicled flaps, and 3 free flaps. Nine patients (20.9%) and 11 surgical sites developed SFN. Mean intraoperative S t O 2 measurements for control areas, areas at risk, and areas of SFN were 74.9%, 71.1%, and 58.3%, respectively. Relative to control areas, mean intraoperative S t O 2 measurements were lower by 17.5% ( P = 0.01) in ultimate areas of SFN and in areas at risk by 5.8% ( P = 0.003). Relative to areas at risk, mean S t O 2 measurements from areas of ultimate SFN were lower by 8.3% ( P = 0.04)., Conclusion: These preliminary data suggest that measuring skin flap tissue oxygenation intraoperatively, with NIR spectroscopy, can differentiate objective variations in perfusion that are associated with clinical outcomes., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Pediatric hand fractures are common and approximately 10% require surgery., Methods: This retrospective cohort study reports on hand fractures in a large pediatric population and identifies the characteristics and patterns of fractures that required surgical correction. A χ 2 analysis was done to evaluate the association between individual fracture variables and surgery. The STROBE checklist was applied., Results: One thousand one-hundred seventy-three hand fractures were reviewed. Peak age was 16 years for boys and 14 years for girls. Most fractures were closed (96.0%) and nonrotated (91.3%), and had no concomitant soft tissue injury (72.7%). More than half (56.3%) were nonepiphyseal plate fractures; yet as a single diagnosis, Salter-Harris II fractures were most common (30.2%). The following variables were significantly associated with surgery: open fractures, rotational deformity, distal phalangeal fracture location, multiple fractures, oblique pattern, comminution, displacement >2 mm, intra-articular involvement, and angulation >15°. Most fractures required only immobilization and early range of motion (64.3%). Closed reduction was required in 22.7%. Minor surgery by the primary provider was performed in 3.2% of fractures. Surgery by a hand surgeon was performed in 9.8%. The most common patterns requiring surgery were proximal or middle phalanx head or neck fractures (38.2%) and metacarpal midshaft fractures (20.9%). The most common operation was open reduction internal fixation (52.2%)., Conclusions: Pediatric hand fractures are common, but 90.2% do not require surgery and, as such, primary providers play a key role in management. Certain fracture variables and patterns are more likely to lead to surgery., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Little is known with regard to patient-reported outcomes (PROs) in the setting of implant-based reconstruction (IBR) with post-mastectomy radiation therapy (PMRT)., Methods: We identified patients who underwent immediate IBR from a prospectively compiled database. The Breast Reconstruction Satisfaction Questionnaire (BRECON-31) was scored and compared between patients with and without PMRT., Results: Sixty-four women met the study criteria. Forty-eight did not receive PMRT and 16 did. Nine women had an unanticipated indication for PMRT. The PMRT group was similar to the control group with regard to baseline characteristics (ie, age, marital status, body mass index, tobacco use, and comorbidities). However, treatment and oncologic characteristics (eg, diagnosis, tumour characteristics, systemic therapy use) differed. Of all complications, only capsular contracture rates differed (1.2% vs 13%; P = .01). Of the 9 subscales, 7 showed no difference in satisfaction between the groups. Radiated women scored lower in the arm concerns and breast appearance subscales. Scores were similar whether the indication for PMRT had been anticipated or not., Discussion: Women with immediate IBR scored similarly to their nonradiated counterparts across 7 of 9 domains of satisfaction. Arm concerns and breast appearance scores are lower with PMRT, likely secondarily to more extensive nodal procedures in higher stage patients and to the side effect profile of radiotherapy. Our findings are in line with the few available studies using other PRO tools to evaluate the impact of PMRT on patient satisfaction and studies objectively measuring the effect of PMRT on arm morbidity and cosmetic outcomes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In many cultures, the female breast is a potent symbol of beauty, motherhood, and vitality. When such breasts become diseased and a woman is faced with a mastectomy, multiple competing discourses converge to complicate the decision for or against breast reconstruction. This process can be fraught with tension and ambivalence. Women, along with surgeons working in the field of breast reconstruction, should be aware of the cultural history that shapes the understanding of breasts. When a woman considers her options, she is influenced by the personal and the evolving social and cultural discourse., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Enhanced recovery after surgery pathways are well established in other surgical specialties but are relatively new in plastic surgery. These guidelines focus on improving patient care by incorporating evidence-based recommendations. Length of stay is shorter, and overall hospital costs are lower without compromising patient satisfaction. When care is standardized, ambiguity is removed and physician acceptance is improved. Yet, implementation can be challenging on an institutional level. The Johns Hopkins microsurgical breast reconstruction team identified areas of dogmatic dissonance during 3 focus groups to formalize an enhanced recovery pathway for microsurgical breast reconstruction. Six microsurgeons used nominal group technique to reach consensus. Four discussion points were identified: multidisciplinary buy-in, venous thromboembolism (VTE) chemophylaxis, early feeding, and dietary restrictions. Evidence-based recommendations and our enhanced recovery after surgery protocol are provided.

Purpose: The purpose of this study was to examine the perceived satisfaction and barriers to care for transgender patients after they decide to undergo gender-affirming surgery (GAS)., Method: A survey consisting of 21 multiple-choice and short-answer questions was distributed to transgender organizations and online forums across Canada and the United States. The data were then analyzed using descriptive statistics., Results: There were 32 participants, 12 who identified as female to male and 20 as male to female. The mean age was 36 years, with a range of 18 to 81 years. The mean age of their first GAS was 33 years, and the range of wait time was 6 months to 7 years. Most of the participants received information about GAS from transgender websites and transgender surgery clinics (91% and 50%, respectively). Most participants (74%) felt like they had access to appropriate care and 89% felt like their surgeons provided enough information about GAS. There were 38% of participants who would change their experience with GAS. Participants stated several barriers toward receiving GAS: financial (73%), finding a physician (65%), and access to information (63%). Surgical transition was important to the quality of life for 91% of participants and 100% were happy with their decision to undergo GAS., Conclusions: Transgender participants demonstrated that GAS is important to their quality of life and this study showed significant barriers to GAS., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Transgender men or Female-to-Male (FtM) patients' risk of breast cancer and screening recommendations remain unclear. The objective of this study is to perform a systematic review of the literature and document all reported cases of FtM breast cancer as well as provide research recommendations. Following PRISMA guidelines, MEDLINE, ProQuest, PubMed, and Cochrane Database of Systematic Reviews were searched from inception until September 15, 2016. Screening and data extraction were performed in duplicate by two independent reviewers (RH and JS). Study quality was assessed using a component-based system. Study characteristics, patient demographics, breast cancer characteristics, presentation and management are reported. Eight articles met inclusion criteria representing 17 transgender men with breast cancer. Median age at diagnosis was 44.5 years. Breast cancer types included: 8 invasive ductal carcinomas, two tubular carcinomas and seven unrecorded. Twelve of the 14 known hormone status tumours were estrogen receptor positive (85.7%), of which nine were also progesterone positive. The most common was breast lump (n = 6) and four patients had local regional or distant disease at presentation. Management was reported for ten patients: six patients underwent mastectomy (60.0%), three radiation (30.0%), and five chemotherapy (50.0%). Breast cancer is present in transgender men and the risk is dependent on top surgery; those with top surgery appear to be lower risk than natal females. More longitudinal studies and better population data are required to contribute to evidence-based screening recommendations., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Male-to-Female (MtF) breast cancer events have been reported since 1968 however, MtF patients' risk of breast cancer remain unclear. Following PRISMA guidelines, electronic databases and grey literature were searched April 2018 to identify breast cancer events in MtF transgender persons. Screening and data extraction were independently performed in duplicate by two reviewers. Study quality was assessed using a component-based system. Qualitative analysis was performed on study characteristics, patient demographics, breast cancer characteristics, and breast cancer presentation and management. Eighteen articles met inclusion criteria representing 22 breast cancer events. Median age at breast cancer diagnosis was 51.5 years. The most common breast cancer type was adenocarcinomas (59.1%) and half of the breast cancers were hormone sensitive, with estrogen receptor positive status in 10 of 19 tested and progesterone receptor positive status in 5 of 14 tested. The most common presentation was breast lump (n = 6, 42.9%), two patients had palpable lymph nodes at presentation (14.3%), and six patients eventually developed metastases (42.9%). Seven patients had a recorded positive breast cancer family history and one was BRCA2 positive. Breast cancers were treated with mastectomies (simple, modified radical, and radical), wide local excision, lumpectomy, or were unclear. Four patients received hormone therapy (23.5%), two received radiation (11.8%), and seven received chemotherapy (41.2%). Breast cancer is present in MtF patients and commonly presents at a younger age with a palpable mass. Major gaps in the literature include lack of transgender population data and long term follow-up. This work highlights the need for screening recommendations., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: The Wolf motor function test (WMFT) evaluates the upper extremity performance of patients with neurological disorders and traumatic brain injuries by assessing time and functional capacity. It was later modified to also measure the quality of the performed movements. This study aimed to adapt the WMFT for patients with shoulder injuries and to evaluate the inter-rater and intra-rater reliability of this adapted version., Subjects and Methods: A total of 20 individuals with a median age of 80.5 years were assessed using a test-retest design after surgical or conservative treatment of shoulder injuries. Two raters rated performance to determine inter-rater reliability. One rater rated the performance again to determine intra-rater reliability. Both inter-rater and intra-rater agreement were determined by weighted Cohen's kappa statistics with corresponding confidence intervals. Cronbach's alpha was calculated to determine internal consistency., Results: The inter-rater Cohen's kappa values ranged from 0.84-1.00 for functional capacity and from 0.79-1.00 for quality of movement. For intra-rater reliability the Cohen's kappa ranged from 0.71-1.00. Cronbach's alpha was >0.94 for functional capacity and >0.96 for quality of movement., Conclusion: The adapted version of the WMFT shows high intra-rater and inter-rater reliability for patients with shoulder injuries.

Purpose: To discover missed opportunities for providing information to women undergoing breast reconstruction in an effort to decrease regret and improve patient education, teaching modalities, and satisfaction., Method: Thirty- to 45-minute semi-structured interviews were conducted exploring patient experiences with information provision on breast reconstruction. Purposeful sampling was used to include women with a variety of reconstruction types at different time points along their recovery. Using grounded theory methodology, 2 independent reviewers analyzed the transcripts and generated thematic codes based on patient responses. BREAST-Q scores were also collected to compare satisfaction scores with qualitative responses., Results: Patients were interested in a wide variety of topics related to breast reconstruction including the pros and cons of different options, nipple-sparing mastectomies, immediate breast reconstruction, oncological safety/monitoring and the impact of chemotherapy and radiotherapy, secondary procedures (balancing, nipple reconstruction), post-operative recovery, and long-term expectations. Patients valued accessing information from multiple sources, seeing numerous photographs, being guided to reliable information online, and having access to a frequently asked questions file or document. Information delivery via interaction with medical personnel and previously reconstructed patients was most appreciated. Compared with BREAST-Q scores for satisfaction with the plastic surgeon (mean: 95.7, range: 60-100), informational satisfaction scores were lower at 74.7 (50-100), confirming the informational gaps expressed by interviewees., Conclusions: Women having recently undergone breast reconstruction reported key deficiencies in information provided prior to surgery and identified preferred information delivery options. Addressing women's educational needs is important to achieve appropriate expectations and improve satisfaction.

Background: The aim of this study was to develop, implement, and evaluate a standardized perioperative enhanced recovery after surgery (ERAS) clinical care pathway in microsurgical abdominal-based breast reconstruction., Methods: Development of a clinical care pathway was informed by the latest ERAS guideline for breast reconstruction. Key features included shortened preoperative fasting, judicious fluids, multimodal analgesics, early oral nutrition, early Foley catheter removal, and early ambulation. There were 3 groups of women in this cohort study: (1) traditional historical control; (2) transition group with partial implementation; and (3) ERAS. Narcotic use, patient-reported pain scores, antiemetic use, time to regular diet, time to first walk, hospital length of stay, and 30-day postoperative complications were compared between the groups., Results: After implementation of the pathway, the use of parenteral narcotics was reduced by 88% (traditional, 112 mg; transition, 58 mg; ERAS, 13 mg; P < 0.0001), with no consequent increase in patient-reported pain. Patients in the ERAS cohort used less antiemetics (7.0, 5.3, 2.2 doses, P < 0.0001), returned to normal diet 19 hours earlier (46, 39, 27 hours, P < 0.0001), and walked 25 hours sooner (75, 70, 50 hours, P < 0.0001). Overall, hospital length of stay was reduced by 2 days in the ERAS cohort (6.6, 5.6, 4.8 days, P < 0.0001), without an increase in rates of major complications (9.5%, 10.1%, 8.3%, P = 0.9)., Conclusions: A clinical care pathway in microsurgical breast reconstruction using the ERAS Society guideline promotes successful early recovery.

Background: To compare enhanced recovery after surgery (ERAS) with traditional recovery after surgery (TRAS) for patients undergoing alloplastic breast reconstruction., Methods: A retrospective chart review of 2 patient groups (ERAS and TRAS) undergoing alloplastic breast reconstruction was performed. Data were collected from 2012 to 2013 (TRAS) and from 2013 to 2016 (ERAS). The ERAS protocol included day surgery, multimodal analgesia, and preoperative anti-emetic. The TRAS pathway involved overnight admission, narcotic-based analgesia, and no preoperative anti-emetic. Demographics, operative variables, and complications were compared between groups., Results: Seventy-eight ERAS patients and 78 TRAS patients were included. Length of stay was shorter for ERAS patients (0.38 nights ERAS and 1.45 nights TRAS; P < .001). The ERAS patients underwent significantly more bilateral surgery (80.8% ERAS and 55.1% TRAS; P < .001), immediate reconstruction (98.6% ERAS and 89.3% TRAS; P = .004), and had more implants versus expanders placed (66% [93/141] ERAS and 24.8% TRAS; P < .001). There were no differences in the number of post-operative emergency department visits (8% ERAS and 14% TRAS; P = .2) and readmissions (8% ERAS and 3.8% TRAS; P = .3) between the groups. There was no difference in the rate of hematoma (0.7% ERAS and 0% TRAS; P = .35), infection requiring explantation (1.4% ERAS and 0.8% TRAS; P = .65), infection requiring outpatient IV antibiotics (1.4% ERAS and 2.5% TRAS; P = .53), and infection requiring IV antibiotics and readmission (2.1% ERAS and 1.7% TRAS; P = .78) between the groups. There were no differences in the number of minor complications (22% ERAS and 23% TRAS; P = .82)., Conclusion: The ERAS protocol for alloplastic breast reconstruction is safe, without increased readmission or complication rates compared to TRAS, and significantly decreased length of stay., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Enhanced recovery following surgery can be achieved through the introduction of evidence-based perioperative maneuvers. This review aims to present a consensus for optimal perioperative management of patients undergoing breast reconstructive surgery and to provide evidence-based recommendations for an enhanced perioperative protocol., Methods: A systematic review of meta-analyses, randomized controlled trials, and large prospective cohorts was conducted for each protocol element. Smaller prospective cohorts and retrospective cohorts were considered only when higher level evidence was unavailable. The available literature was graded by an international panel of experts in breast reconstructive surgery and used to form consensus recommendations for each topic. Each recommendation was graded following a consensus discussion among the expert panel. Development of these recommendations was endorsed by the Enhanced Recovery after Surgery Society., Results: High-quality randomized controlled trial data in patients undergoing breast reconstruction informed some of the recommendations; however, for most items, data from lower level studies in the population of interest were considered along with extrapolated data from high-quality studies in non-breast reconstruction populations. Recommendations were developed for a total of 18 unique enhanced recovery after surgery items and are discussed in the article. Key recommendations support use of opioid-sparing perioperative medications, minimal preoperative fasting and early feeding, use of anesthetic techniques that decrease postoperative nausea and vomiting and pain, use of measures to prevent intraoperative hypothermia, and support of early mobilization after surgery., Conclusion: Based on the best available evidence for each topic, a consensus review of optimal perioperative care for patients undergoing breast reconstruction is presented., Clinical Question/level of Evidence: Therapeutic, V.

A hallmark of HIV-1 infection is the continuously declining number of the virus' predominant target cells, activated CD4+ T cells. With diminishing CD4+ T cell levels, the capacity to utilize alternate cell types and receptors, including cells that express low CD4 receptor levels such as macrophages, thus becomes crucial. To explore evolutionary paths that allow HIV-1 to acquire a wider host cell range by infecting cells with lower CD4 levels, we dissected the evolution of the envelope-CD4 interaction under in vitro culture conditions that mimicked the decline of CD4high target cells, using a prototypic subtype B, R5-tropic strain. Adaptation to CD4low targets proved to severely alter envelope functions including trimer opening as indicated by a higher affinity to CD4 and loss in shielding against neutralizing antibodies. We observed a strikingly decreased infectivity on CD4high target cells, but sustained infectivity on CD4low targets, including macrophages. Intriguingly, the adaptation to CD4low targets altered the kinetic of the entry process, leading to rapid CD4 engagement and an extended transition time between CD4 and CCR5 binding during entry. This phenotype was also observed for certain central nervous system (CNS) derived macrophage-tropic viruses, highlighting that the functional perturbation we defined upon in vitro adaptation to CD4low targets occurs in vivo. Collectively, our findings suggest that CD4low adapted envelopes may exhibit severe deficiencies in entry fitness and shielding early in their evolution. Considering this, adaptation to CD4low targets may preferentially occur in a sheltered and immune-privileged environment such as the CNS to allow fitness restoring compensatory mutations to occur.

Background: Enhanced recovery after surgery was compared with traditional recovery after surgery for postmastectomy alloplastic breast reconstruction., Methods: Length of stay, emergency room visits, and complications within 30 days of surgery were compared among three groups: traditional recovery after surgery, transition (some elements of enhanced recovery protocol, not transitioned to outpatient care), and enhanced recovery after surgery (day surgery, provided with standardized perioperative education and multimodal analgesia). Prospective data collection allowed quality-of-recovery assessment using a validated questionnaire for enhanced recovery/transition groups. Results were statistically analyzed (analysis of variance/chi-square)., Results: The traditional recovery, transition, and enhanced recovery cohorts comprised 29, 11, and 29 patients, respectively. No significant differences were present regarding age, smoking status, preoperative radiation, single stage direct-to-implant versus tissue expander, bilateral versus unilateral surgery, or immediate versus delayed reconstruction among groups. Average length of stay was 1.6 nights in both the traditional recovery and transition groups, compared with 0 nights in the enhanced recovery group (p < 0.001). Enhanced recovery patients had less severe pain (p = 0.02) and nausea (p = 0.01), and better enjoyed their food (p = 0.0002) and felt more rested (p = 0.02) than their transition counterparts. There were no differences in the number of emergency room visits among the three groups (p = 0.88). There was no difference in the rate of hematoma (p = 0.36), infection requiring intravenous antibiotics (p = 0.36), or infection requiring explantation (p = 0.36) among the three groups., Conclusion: An enhanced recovery protocol for alloplastic breast reconstruction treated patients safely, with improved patient satisfaction and same-day discharge and with no increase in complications., Clinical Question/level of Evidence: Therapeutic, III.

Objective: The purpose of this study is to determine the utility of self-assessment in microsurgical training using a previously validated rating scale., Design: A prospective study of surgical residents taking a hands-on 5-day microsurgical training course. Learners completed multiple self-assessments of their technical skills using the University of Western Ontario Microsurgical Acquisition/Assessment instrument. Simultaneously, preceptors assessed the learners using the same scale. Self-assessment and preceptor scores were compared using the Pearson correlation coefficient (PCC)., Results: There was a significant agreement noted between the 32 preceptor assessments and 36 self-assessments that were completed. Correlation between scores for the knot-tying (PCC = 0.62) and anastomosis modules (PCC = 0.77) was good and excellent, respectively. Preceptor scores and self-scores improved over the duration of the course: for preceptors, knot-tying scores increased from 58% on day 1 to 78% on day 5 (p = 0.02) and anastomosis scores improved from 56% to 82% (p = 0.004); for self-scores, knot-tying scores increased from 44% to 81% (p = 0.001) and anastomosis scores from 49% to 84% (p = 0.001). Learners with greater experience (higher postgraduate year level) tended to have higher self as well as preceptor ratings, albeit not statistically significant., Conclusion: Self-assessment using the University of Western Ontario Microsurgical Acquisition/Assessment instrument has good to excellent agreement with preceptor-assessment scores suggesting good interrater reliability. Self-assessment using such tools may, therefore, be used along with preceptor supervision and assessment to potentially improve self-directed learning during these courses., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The progression from classroom to clinical setting can be a difficult transition for medical students. Experience in the operating room is anticipated as one of the most challenging environments for a novel medical learner. We sought to identify common concerns before exposure in this learning environment and examine the experience of final-year medical students on their surgical clerkship rotation in an effort to identify areas where improvements can be made., Methods: A 20-question survey was developed after a focus group met to identify potential issues that medical students encounter during their surgical clerkship. Personal and anecdotal experiences guided the development of the survey. It was distributed to final-year medical students and recent graduates (350 individuals) using SurveyMonkey. A quality improvement ethics application was completed before the commencement of the survey, as were participant consent forms. Responses were grouped and common themes were identified in the experiences reported by 2 investigators., Results: A total of 72 individuals responded to the survey, providing a 21% response rate. Subjects were asked how confident they were in their understanding of what was expected during a surgical rotation. Of them, 52 (72%) responded that they were "unsure" or "very unsure," whereas only 12 and 3 felt "somewhat confident" and "very confident," respectively. Most of the learners felt nervous (96%) and feared appearing incompetent (89%). Common concerns included insufficient knowledge and technical skill, anticipated negative experiences, and feelings of uncertainty regarding medical student expectations., Conclusion: We present common themes stemming from medical student experiences during their surgical clerkship. We comment on perception of intimidation and abuse, the rationalization behind such behavior, and perceived lack of guidance. The intention of this analysis was to identify weaknesses in our surgical training so that a quality improvement plan can be implemented., (Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Isolated limb infusion (ILI) delivers low-flow chemotherapy via percutaneous catheters to treat melanoma in-transit metastases., Objective: To describe the experience of two regional referral centres with ILI., Methods: A retrospective review of patients who underwent ILI between 2002 and 2012 was performed. Outcomes were measured using the WHO criteria for response, the Wieberdink toxicity score and long-term limb function using the Toronto Extremity Salvage Score (TESS)., Results: Fifty-two patients (mean age 66 years [range 27 to 90 years], female sex 65%, and lower [treated] limb in 86%) with 54 ILIs were reviewed. Wieberdink toxicity score was ≥3 in 21 (39%) procedures. Median follow-up was 18 months (range one to 117 months). Initial complete response (CR) was 29%, partial response 27%, stable disease 18% and progressive disease 27%. Predictors of better initial response were low disease burden and previous treatment. One or more treatments after ILI were common (65%). At 12 months, 19% of ILI patients had died from melanoma but 44% of surviving patients experienced limb CR. At 24 months, 57% of surviving patients experienced limb CR. The quality of life in the surviving, contactable patients according to the Toronto Extremity Salvage Score was 89%., Conclusion: Even if ILI does not result in CR for melanoma intransit metastases. it may slow disease progression as a single therapy, but more frequently in combination with other modalities.

Objectives: To systematically review literature pertaining to microsurgical skill assessment tools to determine those specific to, and validated for, microsurgery training., Design: Multiple databases were searched with preset terms. The search dates included all years up to May 2014. The eligibility criteria included the presence of statistical comparison with a control group and the presence of a measure of validation. The articles and their references were independently reviewed by 2 assessors. Each assessment tool was evaluated for content, construct, face, and criterion validities as well observation/expectant bias and interrater/intrarater reliability. For individual studies, we screened for expectant and selection bias., Results: Of the 261 articles reviewed, 10 articles and 1 abstract were included. Those excluded were predominantly assessment tools that did not evaluate microsurgical skill or articles where no assessment tool was described. The assessment tools identified in this review include a self-assessment tool where trainees rate their skill confidence from 1 to 5, stereoscopic visual acuity as a predictor for microsurgical performance, an objective motion-tracking electronic device--the Imperial College of Surgical Assessment Device, and 6 global rating scales. Content, construct, and face validities were consistently demonstrated in addition to observation/expectant bias and interrater reliability. Criterion validity was only demonstrated for half of the instruments and intrarater reliability for only 1., Conclusions: Overall, 10 articles and 1 abstract described validated methods. Reliability and validity were demonstrated by 6 global rating scales (University of Western Ontario microsurgical skills acquisition, structured assessment of microsurgery skills, and video-based objective structured assessment of technical skill). Motion analysis using the Imperial College of Surgical Assessment Device is a valid objective measure of skill., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression., Methods: We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption)., Results: Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+ cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40)., Conclusion: The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Background: A person-centered approach to co-decision-making using tailored information respects each woman's preferences and may heighten breast reconstruction satisfaction., Methods: Women seeking breast reconstruction underwent initial and follow-up consultations wherein suitable options were discussed, and take-away material, balanced website links, and access to a nurse specialist and peer volunteers was provided. After reconstruction, the BRECON-31(©) was administered and analyzed in three groups: autologous, alloplastic, and latissimus dorsi (LD)/implant. BRECON-31(©) subscale scores were compared between the groups, and multiple regression used to determine if the type of reconstruction independently predicted satisfaction., Results: One hundred twenty three of 176 (70%) women completed the questionnaire (43% autologous, 47% alloplastic, and 10% LD/implant reconstructions). The LD/implant group had a low rate of immediate reconstruction (8.3%, P = 0.04), and the highest rate of chemotherapy (91.7%, P = 0.002) and radiation (100%, P = 0.003). The alloplastic group had a high rate of bilateral reconstruction (86.8%, P = 0.01). All groups scored well on the self-image, arm concerns, intimacy, satisfaction, and expectations subscales. All groups scored moderately on the self-consciousness, appearance, and nipple subscales. The autologous group scored the lowest on recovery (51 vs. 68 and 65, P < 0.0001) and only moderately well on the abdomen subscale (67). Multiple regression analysis showed that satisfaction was not driven by type of reconstruction (P > 0.05)., Conclusion: High satisfaction can be achieved using a person-centered approach by providing detailed information, appreciating each woman's unique features, and tailoring the reconstruction plan to the individual. Recovery remains a particular challenge, especially for women undergoing autologous reconstruction., (© 2014 Wiley Periodicals, Inc.)

Background: Family physicians (FPs) have an opportunity to diagnose pigmented lesions early with a timely biopsy., Objective: To assess current biopsy practices used by FPs in diagnosing melanoma., Methods: A computer-generated random sample of 200 practicing FPs from large and small communities in Southwestern Ontario was identified from the College of Physicians and Surgeons of Ontario physician directory. Paper-based surveys exploring practice setting, basic melanoma knowledge, biopsy practices and referral wait times were mailed using a modified Dillman protocol., Results: The response rate was 50% and respondents reflected the demographic characteristics of FPs nationwide as per the National Physician Survey. Knowledge testing revealed reasonable mean (± SD) scores (3.2±1.03 of 5). Twenty percent of respondents would always perform an excisional biopsy of skin lesions suspicious for melanoma. The remaining 80% would avoid an excisional biopsy in an aesthetically sensitive area and if there was risk of failure to close the defect primarily, among other reasons. If an excisional biopsy were not performed, one-half of respondents would perform an incisional biopsy (eg, punch biopsy). In large communities, 24% of patients were not seen by a surgeon within six months when referred without a tissue biopsy, leading to delayed diagnosis., Discussion: Educating and supporting FPs to perform incisional biopsies in cases for which excisional biopsies are inappropriate should result in earlier diagnosis of melanoma., Conclusion: FPs appropriately recognize that excisional biopsies are ideal in melanoma management and one-half will move on to an incisional biopsy when excision is not appropriate.

The side effects of mastectomy can be significant. Breast reconstruction may alleviate some distress; however, there are currently no provincial recommendations regarding the integration of reconstruction with breast cancer therapy. The purpose of the present article is to provide evidence-based strategies for the management of patients who are candidates for reconstruction. A systematic review of meta-analyses, guidelines, clinical trials and comparative studies published between 1980 and 2013 was conducted using the PubMed and EMBASE databases. Reference lists of publications were manually searched for additional literature. The National Guidelines Clearinghouse and SAGE directory, as well as guideline developers' websites, were also searched. Recommendations were developed based on the available evidence. Reconstruction consultation should be made available for patients undergoing mastectomy. Tumour characteristics, cancer therapy, patient comorbidities, body habitus and smoking history may affect reconstruction outcomes. Although immediate reconstruction should be considered whenever possible, delayed reconstruction is acceptable when immediate is not available or appropriate. The integration of reconstruction and postmastectomy radiotherapy should be addressed in a multidisciplinary setting. The decision as to which type of procedure to perform (autologous or alloplastic with or without acellular dermal matrices) should be left to the discretion of the surgeons and the patient after providing counselling. Skin-sparing mastectomy is safe and appropriate. Nipple-sparing is generally not recommended for patients with malignancy, but could be considered for carefully selected patients. Immediate reconstruction requires resources to coordinate operating room time between the general and plastic surgeons, to provide supplies including acellular dermal matrices, and to develop the infrastructure needed to facilitate multidisciplinary discussions.

Objectives: The purpose of this study is to (1) systematically review all the literature pertaining to microsurgical training models and to (2) determine which of these are specific to and validated for microsurgery training., Design: PubMed, MEDLINE (OVID/EBSCO), Google Scholar, and Cochrane Central Register of Controlled Trials were searched using preset terms. The last search date was in July 2012. Articles of all languages, years of publication, sample sizes, and model types pertaining to microsurgery were included. The eligibility criteria included the use of a microsurgical training model on a subject group with statistical analysis and measures of validation. Two assessors independently reviewed the articles and their references., Results: Of the 238 articles reviewed, 9 articles met the criteria. Those excluded were predominantly model descriptions that had not been validated in a set of learners. The 9 models whose performances were assessed in a group of learners included an online curriculum, nonliving prosthetics and biologics, and the live rat femoral artery model. Each model was evaluated for content, construct, face, and criterion (concurrent and predictive) validity, as well as selection and observation/expectant bias. Content, construct, concurrent, and face validities were consistently demonstrated for all 9 models. Selection bias was also reliably well controlled with random allocation of participants to each study group. Observation/expectant bias was controlled in 6 of the 8 papers. Predictive validity, an arguably more difficult factor to measure, was only present in 1 article., Conclusions: Despite a plethora of papers describing microsurgical learning tools, only 9 were discovered that provided validation of the proposed method of microsurgical skills acquisition. This review depicts the need for basic, yet well-designed studies that substantiate the effectiveness of microsurgical training models by using a subject group and demonstrating a statistical improvement with employment of the model. Ease of access, cost, and assessment tools used also require attention., (© 2013 Published by Association of Program Directors in Surgery on behalf of Association of Program Directors in Surgery.)

Background: The two-stage tissue expander/implant (TE/I) reconstruction is currently the gold standard method of implant-based immediate breast reconstruction in North America. Recently, however, there have been numerous case series describing the use of one-stage direct to implant reconstruction with the aid of acellular dermal matrix (ADM). In order to rigorously investigate the novel application of ADM in one-stage implant reconstruction, we are currently conducting a multicentre randomized controlled trial (RCT) designed to evaluate the impact on patient satisfaction and quality of life (QOL) compared to the two-stage TE/I technique., Methods/designs: The MCCAT study is a multicenter Canadian ADM trial designed as a two-arm parallel superiority trial that will compare ADM-facilitated one-stage implant reconstruction compared to two-stage TE/I reconstruction following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) at 2 weeks, 6 months, and 12 months. The source population will be members of the mastectomy cohort with stage T0 to TII disease, proficient in English, over the age of 18 years, and planning to undergo SSM or NSM with immediate implant breast reconstruction. Stratified randomization will maintain a balanced distribution of important prognostic factors (study site and unilateral versus bilateral procedures). The primary outcome is patient satisfaction and QOL as measured by the validated and procedure-specific BREAST-Q. Secondary outcomes include short- and long-term complications, long-term aesthetic outcomes using five standardized photographs graded by three independent blinded observers, and a cost effectiveness analysis., Discussion: There is tremendous interest in using ADM in implant breast reconstruction, particularly in the setting of one-stage direct to implant reconstruction where it was previously not possible without the intermediary use of a temporary tissue expander (TE). This unique advantage has led many patients and surgeons alike to believe that one-stage ADM-assisted implant reconstruction should be the procedure of choice and should be offered to patients as the first-line treatment. We argue that it is crucial that this technique be scientifically evaluated in terms of patient selection, surgical technique, complications, aesthetic outcomes, cost-effectiveness, and most importantly patient-reported outcomes before it is promoted as the new gold standard in implant-based breast reconstruction., Trial Registration: ClinicalTrials.gov: NCT00956384.

Background: The incidence of cancer in patients with neurological diseases, who have been treated with LiCl, is below average. LiCl is a well-established inhibitor of Glycogen synthase kinase-3, a kinase that controls several cellular processes, among which is the degradation of the tumour suppressor protein p53. We therefore wondered whether LiCl induces p53-dependent cell death in cancer cell lines and experimental tumours., Results: Here we show that LiCl induces apoptosis of tumour cells both in vitro and in vivo. Cell death was accompanied by cleavage of PARP and Caspases-3, -8 and -10. LiCl-induced cell death was not dependent on p53, but was augmented by its presence. Treatment of tumour cells with LiCl strongly increased TNF-α and FasL expression. Inhibition of TNF-α induction using siRNA or inhibition of FasL binding to its receptor by the Nok-1 antibody potently reduced LiCl-dependent cleavage of Caspase-3 and increased cell survival. Treatment of xenografted rats with LiCl strongly reduced tumour growth., Conclusions: Induction of cell death by LiCl supports the notion that GSK-3 may represent a promising target for cancer therapy. LiCl-induced cell death is largely independent of p53 and mediated by the release of TNF-α and FasL.Key words: LiCl, TNF-α, FasL, apoptosis, GSK-3, FasL.

Caspases are the most important effectors of apoptosis, the major form of programmed cell death (PCD) in multicellular organisms. This is best reflected by the appearance of serious development defects in mice deficient for caspase-8, -9, and -3. Meanwhile, caspase-independent PCD, mediated by other proteases or signaling components has been described in numerous publications. Although we do not doubt that such cell death exists, we propose that it has evolved later during evolution and is most likely not designed to execute, but to amplify and speed-up caspase-dependent cell death. This review shall provide evidence for such a concept.

The intranasal lethal mousepox model employing the A/Ncr mouse strain is used to evaluate anti-orthopoxvirus therapies. These infections mimic large droplet transmission and result in 100% mortality within 7-10 days with as little as 1 PFU of ectromelia virus. Unlike the A/Ncr model, humans are less susceptible to lethal respiratory infections with variola virus and monkeypox virus as demonstrated by their lower mortality rates. In this study we show that a low dose intranasal infection of C57BL/6 mice results in 60-80% mortality and better models smallpox. Comparing CMX001 (HDP-cidofovir) efficacy in the A/Ncr strain and the C57BL/6 strain revealed that delayed treatment with CMX001 is more efficacious at preventing severe disease in the C57BL/6 strain. The increased efficacy of CMX001 in C57BL/6 over A/Ncr following an intranasal infection with ectromelia appears to be mediated by a stronger Th1 cell mediated response. Following footpad infection we show that the C57BL/6 strain has earlier and more robust transcriptional activity, Th1 cytokine secretions, antigen presenting activity and IFNgamma splenic CD8+ T cell responses as compared to the A/Ncr strain. As a result of the enhanced immune response in the C57BL/6 strain, non-lethal intradermal ectromelia infections can therapeutically protect up to 3 days following a homologous, lethal intranasal infection - much like how smallpox vaccination can protect humans for up to 4 days following intranasal variola infection.

Several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (SARS-CoV) replication and pathogenesis. Syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. Cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after SARS-CoV infection. In addition, there was a significant weight loss, expanded tissue tropism, and increased viral pathology in the lung, heart, kidney, and nasal turbinate tissues. Infection with recombinant SARS-CoV viruses bearing disruptions in the gene 7 coding region showed no significant change in replication kinetics, tissue tropism, morbidity, or mortality suggesting that the ORF7a (7a) and ORF7b (7b) proteins are not required for virus replication in immunosuppressed hamsters. This modified hamster model may provide a useful tool for SARS-CoV pathogenesis studies, evaluation of antiviral therapy, and analysis of additional SARS-CoV mutants.

Background: The emergence of human monkeypox and the potential use of recombinant variola and monkeypox viruses as biological terrorist agents have necessitated the development of therapeutic and prophylactic therapies. The primary, or index, cases of smallpox and/or human monkeypox will likely be identified by a characteristic rash. Effective biomarkers will be required to monitor disease progression, guide the choice of therapeutic intervention strategies and evaluate their efficacies. To address this we have evaluated several biomarkers of disease in a lethal mousepox model., Methods: The efficacy of a single dose of a hexadecyloxypropyl ester of cidofovir (CMX001) at 20, 25 and 30 mg/kg doses administered on days 4, 5, 6 and 7 post-infection was evaluated in A/Ncr mice intranasally infected with low doses of ectromelia virus (<20 plaque-forming units). Mice were monitored for weight loss, blood interferon-gamma levels, alanine aminotransferase (ALT), aspartate aminotransferase, viral DNA copies and neutrophilia levels to stage disease progression., Results: We have used these biomarkers to establish the optimal dosing regimen for treatment and reveal that a single dose of 25 mg/kg of CMX001 can be efficacious at treating lethal mousepox when administered on days 4 or 5 post-infection. This dose significantly reduces ALT, interferon-gamma and DNA copies found in the blood of infected animals., Conclusions: A single dose regimen of CMX001 is efficacious at treating mousepox. Disease progression and antiviral efficacy can be monitored using several biomarkers that could readily be used in the case of a human monkeypox or smallpox outbreak.

In the 21st century we are faced with the potential use of natural or recombinant VARV and MPXV as biological weapons, and the emergence of human MPXV. Such an occurrences would require therapeutic and prophylactic intervention with antivirals. Cidofovir, an antiviral approved for the treatment of cytomegalovirus retinitis in AIDS patients, has activity against poxviruses, but must be administered intravenously and is associated with nephrotoxicity. An ether-lipid analogue of CDV, CMX001 (HDP-CDV), has potent antiviral activity against a range of DNA viruses including poxviruses, excellent oral bioavailability and minimal nephrotoxicity. CMX001 and CDV are equally efficacious at protecting mice from mortality following high ectromelia virus doses (10,000 x LD(50)) introduced by the intra-nasal route or small particle aerosol. Using CMX001 at a 10mg/kg dose followed by 2.5mg/kg doses every other-day for 14 days provided solid protection against mortality and weight loss following an intra-nasal challenge of (100-200) x LD(50) of ectromelia virus. Furthermore, complete protection against mortality was achieved when administration was delayed until as late as 5 days post-infection, which is 3-4 days prior to the death of the untreated controls. This therapeutic window would be equivalent to intervening during the rash stage of ordinary smallpox.

Alkylphosphocholines (APCs) represent a new and very encouraging class of antitumour agents that have also been shown to induce apoptosis in tumour cells, but their exact mode of action has still not been elucidated. The APC compound presented here, S-1-O-phosphocholine-2- N-acetyl-octadecane (S-NC-2) induces apoptosis in a variety of cancer cells. To define the molecular requirements for S-NC-2-induced apoptosis, activation of caspase-8 and -3 and the cleavage of death substrates, such as poly(ADP-ribose) polymerase (PARP), were investigated in Jurkat, BJAB, SKW6.4 and K562 cells. The signalling pathway seems to be initiated at the death receptor level. Cells that are defective in Fas-receptor signalling (e.g., FADDdn BJAB), as well as cells lacking the Fas receptor (K562), were resistant to S-NC-2 treatment. Furthermore, the treatment of Jurkat cells with S-NC-2 resulted in the clustering of death receptor molecules and co-localisation of the Fas receptor with caveolin, a marker for lipid rafts. In addition, the involvement of mitochondria was detected, since S-NC-2 induces the breakdown of the mitochondrial membrane potential. Overexpression of the anti-apoptotic protein Bcl-2 prevented the loss of delta psi(m) in type II (Jurkat) but not in type I cells (SKW6.4). Moreover, cleavage of Bid was found, which points to a possible linkage between the receptor-dependent and the mitochondrial pathways.

This study focused on the role of eggshell matrix proteins as a function of potential natural antimicrobial defenses of avian eggs. The electrophoretic profile of SDS-PAGE showed that the soluble eggshell matrix proteins had three major bands of 15 000, 36 000, and 66 000 and several minor bands comprising 17 000, 25 000, 30 000, and 75 000, while insoluble matrix proteins were consisting of various bands comprising at least 16 distinct migration bands between 10 000 and 200 000. Three bacteria species, Pseudomonas aureginosa, Bacillus cereus, and Staphylococcus aureus, were found to be inhibited in the presence of soluble eggshell matrix proteins (100 microg/mL). On the other hand, Escherichia coli and Salmonella enteritidis were weakly inhibited at only an early stage of incubation time (up to 4 h). Scanning electron microscopy revealed that eggshell matrix proteins might interact and disrupt the membrane integrity of bacteria. The present study clearly indicated that avian eggshell matrix proteins possess a potential of novel antimicrobial defensin mechanism.