Outcomes of Women Undergoing Mastectomy for Unilateral Breast Cancer Who Elect to Undergo Contralateral Mastectomy for Symmetry: A Systematic Review.

BACKGROUND: Breast reconstruction (BR) is routinely offered to restore symmetry after mastectomy for breast cancer. Not all women, however, may want reconstructive surgery. A contralateral mastectomy (CM) to achieve "flat symmetry" can be an excellent alternative, but surgeons are often reluctant to offer this procedure. This systematic review aimed to summarize the available evidence regarding the outcomes of CM as the first step to developing guidelines in this area. METHODS: PubMed, MEDLINE, CINAHL and PsycINFO were searched to identify primary research studies, published in English between 1 January 2000 and 30 August 2022, evaluating clinical or patient-reported outcomes for women who underwent a CM without reconstruction after a mastectomy for unilateral breast cancer. Simple descriptive statistics summarized quantitative data, and content analysis was used for qualitative data. RESULTS: The study included 15 studies (13 quantitative, 1 qualitative, and 1 mixed-methods) evaluating outcomes for at least 1954 women who underwent a bilateral mastectomy without reconstruction (BM) after unilateral breast cancer. The risk of surgical complications after BM was higher than after unilateral mastectomy without reconstruction (UM) but significantly less than after BR. Satisfaction with the decision for BM was high in all the studies. Key themes relating to flat denial, stigma, and gender-based assumptions were identified. CONCLUSION: Women electing to undergo BM reported high levels of satisfaction with their decision and complication rates similar to those for UM. Further study is needed to comprehensively explore the outcomes for women seeking BM, but these data should give surgeons confidence to offer the procedure as an alternative option for symmetry after unilateral mastectomy for breast cancer. REGISTRATION: This systematic review was prospectively registered on the PROSPERO database (CRD42022353689).

Patterns of mental health service use among perpetrators of domestic homicide: descriptive study of Domestic Homicide Reviews in England and Wales.

AIMS AND METHOD: We used data from Domestic Homicide Reviews (DHRs) to describe the patterns of mental health service use by perpetrators of domestic homicide in England and Wales. In 186 DHR reports we compared the characteristics of perpetrators who accessed mental health services with those of perpetrators who did not. Separate analyses were conducted for perpetrators of intimate partner homicide (IPH) and family homicide. RESULTS: Over two-thirds (64.5%, n = 120) of the perpetrators had accessed mental healthcare before the homicide. Perpetrators of IPH who had used mental health services compared with those who had not were more likely to have a history of substance misuse, contact with the criminal justice system and a history of self-harm or suicide attempts. CLINICAL IMPLICATIONS: Our findings support the need for health services, particularly mental health, addictions and primary care, to take an assertive role in the prevention of domestic violence and abuse by identifying patients who are potential perpetrators of domestic violence and abuse.

Surgical management of pes planus in children with cerebral palsy: A systematic review.

Purpose: Pes planus (or flatfoot) is the most common deformity in children with cerebral palsy. There are several surgical interventions used to treat it: single calcaneal osteotomies, extra-articular arthrodesis, double calcaneal osteotomy, calcaneo-cuboid-cuneiform osteotomy, intra-articular arthrodesis, and arthroereisis. There is currently no evidence on optimal treatment for flatfoot in children with cerebral palsy. Our purpose is to systematically review studies reporting complications, recurrence rates, and radiological outcomes of the surgical management of flatfoot in children with cerebral palsy. Methods: Five databases were searched to identify studies published from inception until July 2021, with keywords relating to flatfoot, cerebral palsy, and surgical interventions. We included prospective, retrospective, and comparative study designs in the English language. Data was extracted and tabulated in duplicate into Excel, and analysis was conducted using Python SciPy. Results: In total, 1220 studies were identified of which 44 met the inclusion criteria, comprising 2234 feet in 1364 patients with a mean age of 10.3 years and mean follow-up of 55.9 months. Radiographic outcomes showed improvement with all procedures; complications and recurrence rates were too poorly reported to compare. Only 6 (14%) studies were assessed as a low risk of bias. There was substantial heterogeneity of outcome measures. Conclusion: There is a lack of high-quality, comparative studies assessing the radiological outcomes, complications, and recurrence rates of surgical alternatives to treat flatfoot in children with cerebral palsy. There is currently no clear evidence on optimal surgical treatment. Level of evidence: IIa based on Oxford Centre for Evidence-based Medicine.

Non-technical skills for urological surgeons (NoTSUS): development and evaluation of curriculum and assessment scale.

OBJECTIVE: In the last decade non-technical skills (NTS) have emerged as a vital area for improvement within surgery. This study aims to develop and evaluate a Non-technical Skills for Urological Surgeons (NoTSUS) training curriculum and assessment scale. METHODS: This international, longitudinal and observational study began with a 3-round Delphi methodology to refine curriculum contents and rating scale. Sessions with up to four participants were delivered where each candidate undertook an independent scenario within the validated full immersion simulation environment. Candidates were assessed using both the NoTSS (Non-technical Skills for Surgeons) and NoTSUS rating scales by NTS-trained and non-trained experts. A post-training evaluation survey was distributed. RESULTS: 62 participants comprising trainees (n = 43) and specialists (n = 19) undertook the NoTSUS course. The NoTSS and NoTSUS scales correlated well, with a mean difference of 3.3 in the overall total (p = 0.10, r = 0.53). However, there was significant differences in scores between the NoTSS-trained and non-trained raters (n = 28, p = 0.03). A one-way ANOVA test revealed significant improvement throughout the four simulation scenarios in each session (p = 0.02). The NoTSUS curriculum received positive feedback from participants and demonstrated educational value and acceptability. CONCLUSIONS: The NoTSUS curriculum has demonstrated high educational value for NTS training aimed at urologists, with marked improvement throughout sessions. Correlation of NoTSUS and NoTSS scales proves its suitability for evaluating NTS in future training. Demonstration of inter-rater reliability indicates that the scale is reliable for use in assessment by expert faculty members. Furthermore, qualitative feedback from participants suggests gain of transferrable skills over the course.

Non-technical skills: a review of training and evaluation in urology.

PURPOSE: With non-technical skills (NTS) deficits being recognised as a major cause for error in surgery, there is an increasing interest in their training and evaluation. A growing number of training courses are emerging and some NTS curricula have also been created. Many different training methods are described in the literature but there is still uncertainty with regards to their optimum combination within a curriculum. METHODS: A literature review of the electronic database Medline was performed. All articles published before December 2018 were screened by abstract and included if deemed relevant by the author. The included articles' reference lists were also screened for further relevant studies. RESULTS: Simulation training is accepted as the most effective way to train NTS. Within simulation training, it is shown that the 'igloo' full immersion/distributed simulation environment is appropriate for teaching NTS in urological scenarios where a designated operating room or space is not available. The use of multiple settings, for example wards and clinics as well as the operating room, is advantageous, as is training in an interprofessional team. Classroom teaching also plays a role in NTS training as an adjunct to simulation, with evidence that it improves some parameters of NTS. All levels, including qualified surgeons, benefit from NTS training; however, adaptation to both trainee level and specialty is important. Although less time consuming, training juniors and seniors together mainly benefits juniors, and training NTS at the same time as technical skills detracts from the quality of teaching. Debriefing is an important part of training and should be well structured; there are many debriefing models in existence, allowing for choice of method based on examiner preference and participant demographic. Furthermore, examiners should be well briefed in their task and trained in NTS assessment. CONCLUSION: To move forward, studies should combine tried and tested learning techniques into a curriculum covering all training levels, which should then be validated and followed up long term to ensure a positive impact on patient safety.

Modulation of natural killer cells by human cytomegalovirus.

Human cytomegalovirus (HCMV) causes lifelong, persistent infections and its survival is under intense, continuous selective pressure from the immune system. A key aspect of HCMV's capacity for survival lies in immune avoidance. In this context, cells undergoing productive infection exhibit remarkable resistance to natural killer (NK) cell-mediated cytolysis in vitro. To date, six genes encoding proteins (UL16, UL18, UL40, UL83, UL141 and UL142) and one encoding a microRNA (miR-UL112) have been identified as capable of suppressing NK cell recognition. Even though HCMV infection efficiently activates expression of ligands for the NK cell activating receptor NKG2D, at least three functions (UL16, UL142 and miR-UL112) act in concert to suppress presentation of these ligands on the cell surface. Although HCMV downregulates expression of endogenous MHC-I, it encodes an MHC-I homologue (UL18) and also upregulates the expression of cellular HLA-E through the action of UL40. The disruption of normal intercellular connections exposes ligands for NK cell activating receptors on the cell surface, notably CD155. HCMV overcomes this vulnerability by encoding a function (UL141) that acts post-translationally to suppress cell surface expression of CD155. The mechanisms by which HCMV systematically evades (or, more properly, modulates) NK cell recognition constitutes an area of growing understanding that is enhancing our appreciation of the basic mechanisms of NK cell function in humans.

The human cytomegalovirus MHC class I homolog UL18 inhibits LIR-1+ but activates LIR-1- NK cells.

The inhibitory leukocyte Ig-like receptor 1 (LIR-1, also known as ILT2, CD85j, or LILRB1) was identified by its high affinity for the human CMV (HCMV) MHC class I homolog gpUL18. The role of this LIR-1-gpUL18 interaction in modulating NK recognition during HCMV infection has previously not been clearly defined. In this study, LIR-1(+) NKL cell-mediated cytotoxicity was shown to be inhibited by transduction of targets with a replication-deficient adenovirus vector encoding UL18 (RAd-UL18). Fibroblasts infected with an HCMV UL18 mutant (DeltaUL18) also exhibited enhanced susceptibility to NKL killing relative to cells infected with the parental virus. In additional cytolysis assays, UL18-mediated protection was also evident in the context of adenovirus vector transduction and HCMV infection of autologous fibroblast targets using IFN-alpha-activated NK bulk cultures derived from a donor with a high frequency of LIR-1(+) NK cells. A single LIR-1(high) NK clone derived from this donor was inhibited by UL18, while 3 of 24 clones were activated. CD107 mobilization assays revealed that LIR-1(+) NK cells were consistently inhibited by UL18 in all tested donors, but this effect was often masked in the global response by UL18-mediated activation of a subset of LIR-1(-) NK cells. Although Ab-blocking experiments support UL18 inhibition being induced by a direct interaction with LIR-1, the UL18-mediated activation is LIR-1 independent.

Characterization of a highly glycosylated form of the human cytomegalovirus HLA class I homologue gpUL18.

Human cytomegalovirus (HCMV) gpUL18 is a HLA class I (HLA-I) homologue with high affinity for the inhibitory receptor LIR-1/ILT2. The previously described 67 kDa form of gpUL18 is shown here to be sensitive to endoglycosidase-H (EndoH). A novel form of gpUL18 with a molecular mass of approximately 160 kDa and resistance to EndoH was identified in cells infected with HCMV strain AD169 or the low passage HCMV isolates Merlin and Toledo. The 67 kDa EndoH-sensitive gpUL18 glycoform was detected earlier in a productive infection (from 24 h post-infection) than the slower-migrating EndoH-resistant glycoform (from 72 h post-infection). Deletion of the US2-US11 region from the HCMV genome was associated with a substantial up-regulation of endogenous HLA-I in infected cells, but had no obvious effect on the gpUL18 expression pattern. Vaccinia virus and adenovirus vectors were used to further analyse gpUL18 expression. Depending on the delivery vector system, differences in the electrophoretic motility of the EndoH-resistant >105 kDa form of gpUL18, but not the EndoH-sensitive 67 kDa form, were observed; post-translational modification of the higher molecular mass glycoform appears to be influenced by active virus infection and vector delivery. The EndoH-sensitive 67 kDa gpUL18 had a rapid turnover, while the maturation to the EndoH-resistant >105 kDa form was relatively slow and inefficient. However, synthesis of the EndoH-resistant >105 kDa form was enhanced with elevated levels of beta2-microglobulin. When expressed by using an adenovirus vector, both the EndoH-sensitive 67 kDa and the EndoH-resistant >105 kDa gpUL18 forms could be detected on the cell surface.

Downregulation of natural killer cell-activating ligand CD155 by human cytomegalovirus UL141.

Natural killer (NK) cells are crucial in the control of cytomegalovirus infections in mice and humans. Here we show that the viral UL141 gene product has an immunomodulatory function that is associated with low-passage strains of human cytomegalovirus. UL141 mediated efficient protection of cells against killing by a wide range of human NK cell populations, including interferon-alpha-stimulated bulk cultures, polyclonal NK cell lines and most NK cell clones tested. Evasion of NK cell killing was mediated by UL141 blocking surface expression of CD155, which was previously identified as a ligand for NK cell-activating receptors CD226 (DNAM-1) and CD96 (TACTILE). The breadth of the UL141-mediated effect indicates that CD155 has a key role in regulating NK cell function.