Breast Cancer Surgery: A Qualitative Exploration of Concerns Over Time.

INTRODUCTION: As outcomes for breast cancer patients improve, addressing the side effects and distress of treatment can optimize survivorship. Although distress in breast cancer is well known in literature, there is a lack of information on how these concerns change through the phases of the cancer care continuum. Therefore, this study investigates the longitudinal trajectory of worry in patients with nonmetastatic breast cancer. METHODS: Female patients with newly diagnosed stage I-III breast cancer comprised a mixed-methods, longitudinal study at a cancer center from June 2019 to June 2023. Patients completed an open-ended survey regarding their top three concerns. Responses were obtained before surgery and two weeks, three, six, nine months, and one year postoperatively. Responses were qualitatively coded and analyzed to determine themes of cancer-related distress. RESULTS: Participants (n = 262) were aged an average 57.53 y (±12.54), 65.8% had stage I disease at diagnosis, and 91.1% were White. Responses revealed that patients' top three sources of concerns varied by treatment phase. Overall, patients were worried about their cancer diagnosis and the risk of recurrence. Preoperatively, patients were worried about treatment timeline, while postoperative concerns transitioned to physical appearance and surgical side effects. CONCLUSIONS: Breast cancer patients consistently reported worries about cancer diagnosis, recurrence, and metastasis as well as the side effects and fear of treatments. However, patient worry appeared to be intrinsically linked with their treatment phase. Therefore, support and interventions should be catered to reflect the changing patterns of patients' sources of distress to optimize breast cancer patients' quality of life.

CRIMP: a CRISPR/Cas9 insertional mutagenesis protocol and toolkit.

Site-directed insertion is a powerful approach for generating mutant alleles, but low efficiency and the need for customisation for each target has limited its application. To overcome this, we developed a highly efficient targeted insertional mutagenesis system, CRIMP, and an associated plasmid toolkit, CRIMPkit, that disrupts native gene expression by inducing complete transcriptional termination, generating null mutant alleles without inducing genetic compensation. The protocol results in a high frequency of integration events and can generate very early targeted insertions, during the first cell division, producing embryos with expression in one or both halves of the body plan. Fluorescent readout of integration events facilitates selection of successfully mutagenized fish and, subsequently, visual identification of heterozygous and mutant animals. Together, these advances greatly improve the efficacy of generating and studying mutant lines. The CRIMPkit contains 24 ready-to-use plasmid vectors to allow easy and complete mutagenesis of any gene in any reading frame without requiring custom sequences, modification, or subcloning.

A Randomized Controlled Trial of the Implementation of BREASTChoice, a Multilevel Breast Reconstruction Decision Support Tool With Personalized Risk Predictiona.

OBJECTIVE: To implement the BREASTChoice decision tool into the electronic health record and evaluate its effectiveness. BACKGROUND: BREASTChoice, is a multilevel decision tool that: 1) educates patients about breast reconstruction; 2) estimates personalized risk of complications; 3) clarifies patient preferences; and 4) informs clinicians about patients' risk and preferences. METHODS: A multisite randomized controlled trial enrolled adult women with stage 0-III breast malignancy undergoing mastectomy. Participants were randomized to BREASTChoice or a control website. A survey assessed knowledge, preferences, decisional conflict, shared decision-making, preferred treatment, and usability. We conducted intent-to-treat (ITT), per-protocol (PP) analyses (those randomized to BREASTChoice who accessed the tool), and stratified analyses. RESULTS: 23/25 eligible clinicians enrolled. 369/761 (48%) contacted patients enrolled and were randomized. Patients' average age was 51 years; 15% were older than 65. BREASTChoice participants had higher knowledge than control participants (ITT: mean 70.6 vs. 67.4, P=0.08; PP: mean 71.4 vs. 67.4, P=0.03), especially when stratified by site (ITT: P=0.04, PP: P=0.01), age (ITT: P=0.04, PP: P=0.02), and race (ITT: P=0.04, PP: P=0.01). BREASTChoice did not improve decisional conflict, match between preferences and treatment, or shared decision-making. In PP analyses, fewer high-risk patients using BREASTChoice chose reconstruction. BREASTChoice had high usability. CONCLUSIONS: BREASTChoice is a novel decision tool incorporating risk prediction, patient education, and clinician engagement. Patients using BREASTChoice had higher knowledge; older adults and those from racially minoritized backgrounds especially benefitted. There was no impact on other decision outcomes. Future studies should overcome implementation barriers and specifically examine decision outcomes among high-risk patients.

"Peace of Mind" After Mastectomy: A Scoping Review.

BACKGROUND: Many women eligible for breast conservation therapy (BCT) elect unilateral mastectomy (UM) with or without contralateral prophylactic mastectomy (CPM) and cite a desire for "peace of mind." This study aimed to characterize how peace of mind is defined and measured and how it relates to surgical choice. METHODS: Nine databases were searched for relevant articles through 8 October 2023, and data were extracted from articles meeting the inclusion criteria. RESULTS: The inclusion criteria were met by 20 studies. Most were prospective cohort studies (65%, 13/20). In the majority of the studies (72%, 13/18), Non-Hispanic white/Caucasian women comprised 80 % or more of the study's sample. Almost half of the studies used the phrase "peace of mind" in their publication (45%, 9/20), and few directly defined the construct (15%, 3/20). Instead, words representing an absence of peace of mind were common, specifically, "anxiety" (85%, 17/20), "fear" (75%, 15/20), and "concern" (75%, 15/20). Most of the studies (90%, 18/20) measured peace of mind indirectly using questionnaires validated for anxiety, fear, worry, distress, or concern, which were administered at multiple postoperative time points (55%, 11/20). Most of the studies (95%, 18/19) reported at least one statistically significant result showing no difference in peace of mind between BCT, UM, and/or CPM at their latest time of assessment. CONCLUSION: Peace of mind is largely framed around concepts that suggest its absence, namely, anxiety, fear, and concern. Existing literature suggests that peace of mind does not differ among average-risk women undergoing BCT, UM, or CPM. Shared surgical decisions should emphasize at least comparable emotional and/or psychosocial well-being between CPM and breast conservation.

Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model.

Mutations in DNAJB6 are a well-established cause of limb girdle muscular dystrophy type D1 (LGMD D1). Patients with LGMD D1 develop progressive muscle weakness with histology showing fibre damage, autophagic vacuoles, and aggregates. Whilst there are many reports of LGMD D1 patients, the role of DNAJB6 in the muscle is still unclear. In this study, we developed a loss of function zebrafish model in order to investigate the role of Dnajb6. Using a double dnajb6a and dnajb6b mutant model, we show that loss of Dnajb6 leads to a late onset muscle weakness. Interestingly, we find that adult fish lacking Dnajb6 do not have autophagy or myofibril defects, however, they do show mitochondrial changes and damage. This study demonstrates that loss of Dnajb6 causes mitochondrial defects and suggests that this contributes to muscle weakness in LGMD D1. These findings expand our knowledge of the role of Dnajb6 in the muscle and provides a model to screen novel therapies for LGMD D1.

Scoping review of experiences of sexual minority women treated for breast cancer.

PURPOSE: To summarize and critique research on the experiences and outcomes of sexual minority women (SMW) treated with surgery for breast cancer through systematic literature review. METHODS: A comprehensive literature search identified studies from the last 20 years addressing surgical experiences and outcomes of SMW breast cancer survivors. Authors performed a quality assessment and thematic content analysis to identify emergent themes. RESULTS: The search yielded 121 records; eight qualitative studies were included in the final critical appraisal. Quality scores for included studies ranged 6-8 out of 10. Experiences and outcomes of SMW breast cancer survivors were organized by major themes: 1) Individual, 2) Interpersonal, 3) Healthcare System, and 4) Sociocultural and Discursive. CONCLUSIONS: SMW breast cancer survivors have unique experiences of treatment access, decision-making, and quality of life in survivorship. SMW breast cancer survivors' personal values, preferences, and support network are critical considerations for researchers and clinicians.

Reported Variability in General Surgery Training Across Integrated Plastic Surgery Residency Programs.

BACKGROUND: Since their development, integrated plastic and reconstructive surgery (PRS) residency training programs have established diverse methods of incorporating general surgery training into graduate medical education. Programs have questioned the necessary duration and timing of such training. The aim of this study is to assess the landscape of general surgery exposure in integrated PRS residency programs. METHODS: Thirty-six integrated PRS residency programs were included based on the availability of postgraduate year (PGY)-level rotation data. Rotations were measured in units of weeks with descriptive titles maintained as advertised by the program. Individual general surgery rotations were also categorized as being either PRS-aligned, American Board of Plastic Surgery (ABPS) Required Clinical (RC) or ABPS Strongly Suggested (SS). Statistical analyses were carried out on the relative proportions of each subcategory in the 2 parent groups. RESULTS: All 36 programs evaluated required general surgery rotations in years PGY- 1 to -2. By PGY-3, 69% of programs required general surgery, and by PGY-6, 25%, and these were limited to 4- to 6-week rotations in burn, breast, or trauma. Looking across all 6 years, with 312 weeks of training total, the minimum number of weeks spent in general surgery rotations was 32, and the maximum number was 119, with an average of 61 weeks (±21).Programs were subcategorized into 2 groups based on whether they spent more (n = 16) or less (n = 20) than the net average number of weeks in ABPS RC + SS rotations. No significant difference was found in the relative proportion of PRS-aligned general surgery across groups. Programs with <60 weeks of general surgery had a relatively greater proportion of ABPS RC and SS rotations. CONCLUSIONS: These data demonstrate that there exists significant variability in overall duration of general surgery training across integrated PRS training programs. When controlling overall general surgery exposure for variables of interest like PRS-aligned exposure or compatibility with ABPS requirements, we found no discernable educational model or patterns to explain the observed range in exposure. These results warrant reexamination of an ideal general surgery track within the integrated plastic surgery training model that optimizes training for the PRS resident.

Executive functions underlie word reading and reading fluency in Chinese children with attention deficit/hyperactivity disorder, reading disabilities, and comorbid attention deficit/hyperactivity disorder and reading disabilities.

The current study examined the executive function (EF) deficits and their roles in reading in one hundred and four Cantonese-speaking children with typical development, reading disabilities (RD), ADHD, and comorbid ADHD and RD (ADHD + RD). Children's EF and reading skills were measured. Analysis of variance results showed that all children with disorders manifested deficits in verbal and visuospatial short-term and working memory and behavioral inhibition. Moreover, children with ADHD and ADHD + RD also exhibited deficits in inhibition (IC and BI) and cognitive flexibility. These findings demonstrated that the EF deficits in Chinese children with RD, ADHD, and ADHD + RD are similar to those in their counterparts using alphabetic languages. However, children with ADHD + RD displayed more severe deficits in visuospatial working memory compared to children with RD and ADHD, which was inconsistent with that observed in children using alphabetic languages. Regression analysis results showed that verbal short-term memory was a significant predictor for both word reading and reading fluency in children with RD and ADHD + RD. Moreover, behavioral inhibition significantly predicted reading fluency in children with ADHD. These findings also agreed with previous studies. Collectively, the results of the current study showed that the EF deficits and their roles in reading found in Chinese children with RD, ADHD, and ADHD + RD are mainly consistent with children using alphabetic languages. However, more studies are still needed to confirm these findings, especially comparing the severity of working memory among these three disorders.

Processing Speed Deficit and Its Relationship with Math Fluency in Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: (1) To determine the processing speed (PS) deficit in children with ADHD; and (2) To investigate if PS deficit was the primary cause of daily dysfunction in ADHD by testing the direct and indirect effects via working memory (WM) of PS on math fluency (MF). METHOD: Seventy-eight children (52 children with ADHD and 26 controls) were tested on their motor, perceptual, cognitive, and verbal PS, WM, and MF. RESULTS: Children with ADHD performed worse than controls on all PS, suggesting a general PS deficit. Moreover, cognitive PS was a significant predictor for MF. Mediation analysis showed that cognitive PS had direct and indirect effects via WM on MF, suggesting PS deficit might be the primary cause of MF difficulties in ADHD. CONCLUSION: Findings of this study suggested a general PS deficit in ADHD. Due to the importance of PS in MF, interventions for MF underachievers should include assessment and training of PS.

Patient-driven decisions and perceptions of the 'safest possible choice': insights from patient-provider conversations about how some breast cancer patients choose contralateral prophylactic mastectomy.

OBJECTIVE: Observe patient-clinician communication to gain insight about the reasons underlying the choice of patients with unilateral breast cancer to undergo contralateral prophylactic mastectomy (CPM), despite lack of survival benefit, risk of harms, and cautions expressed by surgical guidelines and clinicians. METHODS & MEASURES: WORDS is a prospective study that explored patient-clinician communication and patient decision making. Participants recorded clinical visits through a downloadable mobile application. We analyzed 44 recordings from 22 patients: 9 who chose CPM, 8 who considered CPM but decided against it, and 5 who never considered CPM. We used abductive analysis combined with constructivist grounded theory methods. RESULTS: Decisions to undergo CPM are patient-driven and motivated by perceptions that CPM is the most aggressive, and therefore safest, treatment option available. These decisions are shaped not primarily by the content of conversations with clinicians, but by the history of cancer in patients' families, their own first-hand experiences with cancers among loved ones, fear for their children, and anxiety about cancer recurrence. CONCLUSION: The perception that CPM is the safest, most aggressive option strongly influences patients, despite scientific evidence to the contrary. Future efforts to address high CPM rates should focus on patient-driven decision making and cancer-related fears.

Current Trends in Mortality Attributable to Racial or Ethnic Disparities in Post-Surgical Population in The United States: A Population-Based Study.

Background: No study has contextualized the excess mortality attributable to racial and ethnic disparities in surgical outcomes. Further, not much effort has been made to quantify the effort needed to eliminate these disparities. Objective: We examined the current trends in mortality attributable to racial or ethnic disparities in the US postsurgical population. We then identified the target for mortality reduction that would be necessary to eliminate these disparities by 2030. Methods: We performed a population-based study of 1,512,974 high-risk surgical procedures among adults (18-64 years) performed across US hospitals between 2000 and 2020. Results: Between 2000 and 2020, the risk-adjusted mortality rates declined for all groups. Nonetheless, Black patients were more likely to die following surgery (adjusted relative risk 1.42; 95% CI, 1.39-1.46) driven by higher Black mortality in the northeast (1.60; 95% CI, 1.52-1.68), as well as the West (1.53; 95% CI, 1.43-1.62). Similarly, mortality risk remained consistently higher for Hispanics compared with White patients (1.21; 95% CI, 1.19-1.24), driven by higher mortality in the West (1.26; 95% CI, 1.21-1.31). Overall, 8364 fewer deaths are required for Black patients to experience mortality on the same scale as White patients. Similar figures for Hispanic patients are 4388. To eliminate the disparity between Black and White patients by 2030, we need a 2.7% annualized reduction in the projected mortality among Black patients. For Hispanics, the annualized reduction needed is 0.8%. Conclusions: Our data provides a framework for incorporating population and health systems measures for eliminating disparity in surgical mortality within the next decade.

A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients with Cancer.

Background: Tumor genomic testing (TGT) has become standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is variable or frequently omitted. The purpose of this study was to evaluate the impact of a concise (3-4 minute) video for patient education prior to TGT. Methods: Based on a quality improvement cycle, an animated video was created to be applicable to any cancer type, incorporating culturally diverse images, available in English and Spanish. Patients undergoing standard-of care TGT were enrolled at a tertiary academic institution and completed validated survey instruments immediately prior to video viewing (T1) and immediately post-viewing (T2). Instruments included: 1) 10-question objective genomic knowledge/understanding; 2) 10-question video message-specific knowledge/recall; 3) 11-question Trust in Physician/Provider; 4) attitudes regarding TGT. The primary objective was change in outcomes from before to after the video was assessed with Wilcoxon signed rank test. Results: From April 2022 to May 2023, a total of 150 participants were enrolled (MBC n=53, LC n=38, OC n=59). For the primary endpoint, there was a significant increase in video message-specific knowledge (median 10 point increase; p<0.0001) with no significant change in genomic knowledge/understanding (p=0.89) or Trust in Physician/Provider (p=0.59). Results for five questions significantly improved, including the likelihood of TGT impact on treatment decision, incidental germline findings, and cost of testing. Improvement in video message-specific knowledge was consistent across demographic groups, including age, income, and education. Individuals with less educational attainment had had greater improvement from before to after video viewing. Conclusions: A concise, 3-4 minute, broadly applicable video incorporating culturally diverse images administered prior to TGT significantly improved video message-specific knowledge across all demographic groups. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice. Clinical Trial Registration: ClinicalTrials.gov NCT05215769.

Patient Preferences for Postmastectomy Breast Reconstruction.

Importance: Up to 40% of women experience dissatisfaction after breast reconstruction due to unexpected outcomes that are poorly aligned with personal preferences. Identifying what attributes patients value when considering surgery could improve shared decision-making. Adaptive choice-based conjoint (ACBC) analysis can elicit individual-level treatment preferences. Objectives: To identify which attributes of breast reconstruction are most important to women considering surgery and to describe how these attributes differ by those who prefer flap vs implant reconstruction. Design, Setting, and Participants: This web-based, cross-sectional study was conducted from March 1, 2022, to January 31, 2023, at Duke University and between June 1 and December 31, 2022, through the Love Research Army with ACBC analysis. Participants were 105 women at Duke University with a new diagnosis of or genetic predisposition to breast cancer who were considering mastectomy with reconstruction and 301 women with a history of breast cancer or a genetic predisposition as identified through the Love Research Army registry. Main Outcomes and Measures: Relative importance scores, part-worth utility values, and maximum acceptable risks were estimated. Results: Overall, 406 women (105 from Duke University [mean (SD) age, 46.3 (10.5) years] and 301 from the Love Research Army registry [mean (SD) age, 59.2 (11.9) years]) participated. The attribute considered most important was the risk of abdominal morbidity (mean [SD] relative importance [RI], 28% [11%]), followed by chance of major complications (RI, 25% [10%]), number of additional operations (RI, 23% [12%]), appearance of the breasts (RI, 13% [12%]), and recovery time (RI, 11% [7%]). Most participants (344 [85%]) preferred implant-based reconstruction; these participants cared most about abdominal morbidity (mean [SD] RI, 30% [11%]), followed by the risk of complications (mean [SD], RI, 26% [11%]) and additional operations (mean [SD] RI, 21% [12%]). In contrast, participants who preferred flap reconstruction cared most about additional operations (mean [SD] RI, 31% [15%]), appearance of the breasts (mean [SD] RI, 27% [16%]), and risk of complications (mean [SD] RI, 18% [6%]). Factors independently associated with choosing flap reconstruction included being married (odds ratio [OR], 2.30 [95% CI, 1.04-5.08]; P = .04) and higher educational level (college education; OR, 2.43 [95% CI, 1.01-5.86]; P = .048), while having an income level of greater than $75 000 was associated with a decreased likelihood of choosing the flap profile (OR, 0.45 [95% CI, 0.21-0.97]; P = .01). Respondents who preferred flap appearance were willing to accept a mean (SD) increase of 14.9% (2.2%) chance of abdominal morbidity (n = 113) or 6.4% (4.8%) chance of complications (n = 115). Conclusions and Relevance: This study provides information on how women value different aspects of their care when making decisions for breast reconstruction. Future studies should assess how decision aids that elicit individual-level preferences can help tailor patient-physician discussions to focus preoperative counseling on factors that matter most to each patient and ultimately improve patient-centered care.

Turning the Page on Breast Cancer in Ohio: Lessons learned from implementing a multilevel intervention to reduce breast cancer mortality among Black women.

BACKGROUND: Turning the Page on Breast Cancer (TPBC) uses a multilevel approach to reduce breast cancer (BC) mortality among Black women. TPBC intervenes by (1) improving health care facilities' ability to conduct effective BC screening, follow-up, and treatment; (2) involving community-based organizations; and (3) providing education and personal risk information through a culturally relevant website. Ohio has among the worst BC mortality rates in the United States for Black women. TPBC is in its third year of providing targeted interventions in 12 Ohio counties with particularly high BC rates among Black women. METHODS: TPBC enrolls health care facilities, collects organizational and patient data, and conducts key informant interviews to inform the provision of appropriate evidence-based interventions. TPBC engages Black communities through community-based organizations and social media advertising. The TPBC website offers BC information, connects Black women to community BC resources, and provides access to a risk-assessment tool. RESULTS: TPBC has provided tailored information packets, evidence-based interventions, and systematic support for improving the tracking and follow-up of breast health care among patients in 10 clinical partnerships. The project has provided education at community events monthly since mid-2021. The TPBC website (http://endbreastcancerohio.org) is promoted through social media (primarily Facebook) and community events to reach Black women aged 25-70 years. To date, 4108 unique users have visited the website, of whom 15.9% completed the risk assessment. CONCLUSIONS: Novel strategies are needed to address persistent disparities in BC outcomes among Black women. TPBC demonstrates the potential effectiveness of multiple methods of community-based, clinic-based, and web-based engagement. PLAIN LANGUAGE SUMMARY: Turning the Page on Breast Cancer (TPBC) aims to reduce breast cancer mortality among Black women in Ohio by conducting multilevel, community-engaged interventions in 12 counties. Women are provided risk information and education at virtual and in-person community events and through a community-friendly website that was launched in November 2020. Almost 4000 women have visited the website, which offers community-targeted information, urges screening for individuals at elevated risk, and offers access to patient navigation services; 655 users have used a breast cancer risk-assessment tool on the site. Community-based organizations conduct educational efforts. TPBC partners with health care facilities, which are taught to improve their ability to conduct effective breast cancer screening, follow-up, and treatment. So far, TPBC has provided educational information, evidence-based intervention lists, tailored information packets, and ongoing quarterly support to partners in 10 counties. Evaluation will focus on aggregated data for screening and genetic testing referral at the clinic level.