Association of early menarche with breast tumor molecular features and recurrence.

BACKGROUND: Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. METHODS: We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses' Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952). RESULTS: Early menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFN α and IFN γ ). Replication in TCGA confirmed these trends. Early menarche was associated with significantly higher PAM50 proliferation scores (ß = 0.082 [0.02-0.14]), odds of aggressive molecular tumor subtypes (basal-like, OR = 1.84 [1.18-2.85] and HER2-enriched, OR = 2.32 [1.46-3.69]), and PAM50 risk of recurrence score (ß = 4.81 [1.71-7.92]). Our NHS-derived early menarche gene expression signature was significantly associated with worse 10-year disease-free survival in METABRIC (N = 952, HR = 1.58 [1.10-2.25]). CONCLUSIONS: Early menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.

Where you live matters: Area deprivation predicts poor survival and liver transplant waitlisting.

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

Shifting Mindsets: The Impact of a Patient Portal on Functioning and Recovery in a Mental Health Setting.

OBJECTIVE: This study aims to understand whether higher use of a patient portal can have an impact on mental health functioning and recovery. METHOD: A mixed methods approach was used for this study. In 2019-2021, patients with mental health diagnoses at outpatient clinics in an academic centre were invited to complete World Health Organization Disability Assessment Scale 12 (WHODAS-12) and Mental Health Recovery Measure surveys at baseline, 3 months, and 6 months after signing up for the portal. At the 3-month time point, patients were invited to a semistructured interview with a member of the team to contextualize the findings obtained from the surveys. Analytics data was also collected from the platform to understand usage patterns on the portal. RESULTS: Overall, 113 participants were included in the analysis. There was no significant change in mental health functioning and recovery scores over the 6-month period. However, suboptimal usage was observed as 46% of participants did not complete any tasks within the portal. Thirty-five participants had low use of the portal (1-9 interactions) and 18 participants had high usage (10+ interactions). There were also no differences in mental health functioning and recovery scores between low and high users of the portal. Qualitative interviews highlighted many opportunities where the portal can support overall functioning and mental health recovery. CONCLUSIONS: Collectively, this study suggests that higher use of a portal had no impact, either positive or negative, on mental health outcomes. While it may offer convenience and improved patient satisfaction, adequate support is needed to fully enable these opportunities for patient care. As the type of interaction with the portal was not specifically addressed, future work should focus on looking at ways to support patient engagement and portal usage throughout their care journey.

Making respiratory care safe for neonatal and paediatric intensive care unit staff: mitigation strategies and use of filters.

Background: Many medical devices in pediatric and newborn intensive care units can potentially expose healthcare workers (HCWs) and others to transmission of respiratory and other viruses and bacteria. Such fomites include ventilators, nebulizers, and monitoring equipment. Approach: We report the general, novel approach we have taken to identify and mitigate these risks and to protect HCWs, visitors and patients from exposure while maintaining the optimal performance of such respiratory equipment. Findings: The approach combined a high level of personal protective equipment (PPE), strict hand hygiene, air filtration and air conditioning and other relevant viral risk mitigation guidelines. This report describes the experiences from the SARS-CoV-2 pandemic to provide a reference framework that can be applied generally. The steps we took consisted of auditing our equipment and processes to identify risk through sources of potentially contaminated gas that may contain aerosolized virus, seeking advice and liaising with suppliers/manufacturers, devising mitigation strategies using indirect and direct approaches (largely filtering), performing tests on equipment to verify proper function and the absence of negative impacts and the development and implementation of relevant procedures and practices. We had a multidisciplinary team to guide the process. We monitored daily for hospital-acquired infections among staff caring for SARS-CoV-2 patients. Conclusion: Our approach was successful as we have continued to offer optimal intensive care to our patients, and we did not find any healthcare worker who was infected through the course of caring for patients at the bedside. The lessons learnt will be of benefit to future local outbreaks or pandemics.

The impact of social and environmental factors on cancer biology in Black Americans.

Low socioeconomic status (SES) is associated with early onset of chronic diseases and reduced life expectancy. The involvement of neighborhood-level factors in defining cancer risk and outcomes for marginalized communities has been an active area of research for decades. Yet, the biological processes that underlie the impact of SES on chronic health conditions, such as cancer, remain poorly understood. To date, limited studies have shown that chronic life stress is more prevalent in low SES communities and can affect important molecular processes implicated in tumor biology such as DNA methylation, inflammation, and immune response. Further efforts to elucidate how neighborhood-level factors function physiologically to worsen cancer outcomes for disadvantaged communities are underway. This review provides an overview of the current literature on how socioenvironmental factors within neighborhoods contribute to more aggressive tumor biology, specifically in Black U.S. women and men, including the impact of environmental pollutants, neighborhood deprivation, social isolation, structural racism, and discrimination. We also summarize commonly used methods to measure deprivation, discrimination, and structural racism at the neighborhood-level in cancer health disparities research. Finally, we offer recommendations to adopt a multi-faceted intersectional approach to reduce cancer health disparities and develop effective interventions to promote health equity.

Sex Hormone Levels in Lesbian, Bisexual, and Heterosexual Women: Systematic Review and Exploratory Meta-Analysis.

Lesbian and bisexual women may have different levels of sex hormones compared to heterosexual women. We systematically reviewed comparative studies measuring any sex hormones. A protocol was prospectively registered (PROSPERO-CRD42017072436) and searches conducted in six databases. Any relevant empirical studies published within the last 50 years reporting any circulating sex hormones in sexual minority women compared to heterosexual women were included, with no language or setting restrictions. Inclusions, data extraction, and quality assessment were conducted in duplicate. Random-effects meta-analyses of hormone levels, using standardized-mean-differences (SMD) were conducted where five or more studies reported results. From 1236 citations, 24 full papers were examined and 14 studies of mixed designs included, 12 in women without known ovarian problems. Hormones were measured in plasma (n = 9), saliva (n = 4), and urine (n = 2) and included androstenedione, luteinizing hormone, estradiol, pregnanediol, progesterone, testosterone, and several other hormones. Most studies were small, biased, and had considerable heterogeneity. Few found statistically significant differences between groups. All-sample meta-analysis showed increased testosterone in sexual minority women compared to heterosexual women (n = 9; SMD = 0.90; 95% Confidence interval (CI) 0.22, 1.57, I2 = 84%). This was the only difference found. We conclude that the small amount of heterogeneous research, from 50 years to date, suggests little discernable difference in sex hormone levels between lesbian, bisexual, and heterosexual women excepting possibly higher testosterone. A large-scale primary study would be required before placing any certainty in the findings or their implications.

Assessing multiparametric drug response in tissue engineered tumor microenvironment models.

The tumor microenvironment is important in promoting treatment resistance of tumor cells via multiple mechanisms. However, studying this interaction often proves difficult. In vivo animal models are costly, time-consuming, and often fail to adequately predict human response to treatment. Conversely, testing drug response on human tumor cells in vitro in 2D cell culture excludes the important contribution of stromal cells and biophysical forces seen in the in vivo tumor microenvironment. Here, we present tissue-engineered models of both human brain and breast tumor microenvironments incorporating key stromal cell populations for assessing multiple mechanisms of therapeutic response using flow cytometry. We show our physiologically-relevant systems used to interrogate a variety of parameters associated with chemotherapeutic efficacy, including cell death, proliferation, drug uptake, and invasion of cancer and stromal cell populations. The use of flow cytometry allows for single cell, quantitative, and fast assessments of multiple outcomes affecting anti-tumor therapy failure. Our system can be modified to add and remove cellular components with ease, thereby enabling the study of individual cellular contributions in the tumor microenvironment. Together, our models and analysis methods illustrate the importance of developing fast, cost-effective, and reproducible methods to model complex human systems in a physiologically-relevant manner that may prove useful for drug screening efforts in the future.

Docetaxel facilitates lymphatic-tumor crosstalk to promote lymphangiogenesis and cancer progression.

BACKGROUND: Infiltration into lymphatic vessels is a critical step in breast cancer metastasis. Lymphatics undergo changes that facilitate metastasis as a result of activation of the cells lining lymphatic vessels, lymphatic endothelial cells (LECs). Inhibition of activation by targeting VEGFR3 can reduce invasion toward lymphatics. To best benefit patients, this approach should be coupled with standard of care that slows tumor growth, such as chemotherapy. Little is known about how chemotherapies, like docetaxel, may influence lymphatics and conversely, how lymphatics can alter responses to therapy. METHODS: A novel 3D in vitro co-culture model of the human breast tumor microenvironment was employed to examine the contribution of LECs to tumor invasion and viability with docetaxel and anti-VEGFR3, using three cell lines, MDA-MB-231, HCC38, and HCC1806. In vivo, the 4T1 mouse model of breast carcinoma was used to examine the efficacy of combinatorial therapy with docetaxel and anti-VEGFR3 on lymph node metastasis and tumor growth. Lymphangiogenesis in these mice was analyzed by immunohistochemistry and flow cytometry. Luminex analysis was used to measure expression of lymphangiogenic cytokines. RESULTS: In vitro, tumor cell invasion significantly increased with docetaxel when LECs were present; this effect was attenuated by inhibition of VEGFR3. LECs reduced docetaxel-induced cell death independent of VEGFR3. In vivo, docetaxel significantly increased breast cancer metastasis to the lymph node. Docetaxel and anti-VEGFR3 combination therapy reduced lymph node and lung metastasis in 4T1 and synergized to reduce tumor growth. Docetaxel induced VEGFR3-dependent vessel enlargement, lymphangiogenesis, and expansion of the LEC population in the peritumoral microenvironment, but not tumor-free stroma. Docetaxel caused an upregulation in pro-lymphangiogenic factors including VEGFC and TNF-α in the tumor microenvironment in vivo. CONCLUSIONS: Here we present a counter-therapeutic effect of docetaxel chemotherapy that triggers cancer cells to elicit lymphangiogenesis. In turn, lymphatics reduce cancer response to docetaxel by altering the cytokine milieu in breast cancer. These changes lead to an increase in tumor cell invasion and survival under docetaxel treatment, ultimately reducing docetaxel efficacy. These docetaxel-induced effects can be mitigated by anti-VEGFR3 therapy, resulting in a synergism between these treatments that reduces tumor growth and metastasis.

Leading nursing to achieve organizational performance: Consider the role of nursing intellectual capital [corrected].

The success and performance of healthcare organizations relies on the strategic management of knowledge. Nursing Intellectual Capital (NIC) has emerged as a concept involving nursing knowledge resources that create value in healthcare organizations. This article aims to discuss the importance of considering knowledge resources in the context of healthcare performance, with specific reference to NIC. Reflections are then provided on how leaders can look to advance NIC for improved performance.

Cost, Quality, and Utilization After Hospital-Physician and Hospital-Post Acute Care Vertical Integration: A Systematic Review.

Vertical integration of health systems-the common ownership of different aspects of the health care system-continues to occur at increasing rates in the United States. This systematic review synthesizes recent evidence examining the association between two types of vertical integration-hospital-physician (n = 43 studies) and hospital-post-acute care (PAC; n = 10 studies)-and cost, quality, and health services utilization. Hospital-physician integration is associated with higher health care costs, but the effect on quality and health services utilization remains unclear. The effect of hospital-PAC integration on these three outcomes is ambiguous, particularly when focusing on hospital-SNF integration. These findings should raise some concern among policymakers about the trajectory of affordable, high-quality health care in the presence of increasing hospital-physician vertical integration but perhaps not hospital-PAC integration.

Communities with an anchor institution have higher coronavirus vaccination rates.

PURPOSE: Anchor institutions ("anchors") are large employers, rooted in a community by reason of mission, capital, or relationships. Many anchors have encouraged coronavirus vaccination for employees and their families. Our objective was to determine whether the presence of an anchor was associated with a higher county-level vaccination rate. METHODS: A cross-sectional study focused on 745 small- and mid-sized US counties. We used data from the Centers for Disease Control and Prevention, Reference USA's US Business Database, Economic Innovation Group's Distressed Communities Index database, 2021 County Health Ratings and Rankings, 2020 US Presidential Election popular vote data, and National Center for Health Statistics urban-rural classification data. We constructed 3 explanatory variables of interest: a binary variable indicating whether the county had an anchor; a continuous variable representing the number of anchors within a county; and the percent of all workers in the county who were employed by an anchor. Multivariable linear regression models were adjusted for race/ethnicity, political party allegiance, rurality, economic distress, and prevalence of smoking and adult obesity. FINDINGS: Counties with an anchor had vaccination rates 2.31 (P<.01) percentage points higher than those without an anchor. The number of anchors in a county was also significantly associated with higher vaccination rates. CONCLUSIONS: Efforts by anchors to encourage vaccination may have been successful, and that anchors may be well positioned to amplify public health messages. However, the influence and efforts of anchors to increase vaccination did not fully mitigate disparities in vaccination rates by race, ethnicity, and political party allegiance.

For-Profit Businesses as Public Health Partners to Promote COVID-19 Vaccination: A Multiple Case Study.

OBJECTIVE: This study aimed to describe the actions used by health professionals employed by large, for-profit businesses to promote uptake of COVID-19 vaccines, and factors that facilitated and hindered coordination with local public health leaders. METHODS: In this qualitative multiple case study, we conducted telephone interviews with health professionals from businesses, health department leaders, and others who could provide information about local vaccination efforts (e.g., emergency managers, reporters). RESULTS: Businesses' self-interest (i.e., need to keep employees working), vaccine mandates, and characteristics of the businesses (e.g., ownership, expertise) facilitated leadership in COVID-19 vaccination efforts. Coordination with local health departments was influenced by the resources of the local health department and history of collaboration. CONCLUSIONS: Health professionals employed by large businesses can serve as key public health partners, but their role is shaped by characteristics of the businesses and communities.

Racial and Ethnic Differences in the Use of Electronic Medical Record Messaging Among Patients With Breast Cancer: A Quality Improvement Study.

INTRODUCTION: Despite evidence that use of electronic medical record (EMR) messaging positively impacts patients with cancer, there is little research on utilization patterns. The objective of this study is to describe the use of EMR messaging among breast cancer patients so that future interventions may be developed and targeted appropriately. MATERIALS AND METHODS: Sociodemographic and MyChart usage data were collected. Study eligibility included patients who completed a visit at an academic breast center and sent at least one message to a provider during the study period (May 2021-May 2022). Chi-square and t-tests were used to describe differences between users and nonusers of EMR messaging. ANOVA and chi-square were used to describe differences between race/ethnicity. RESULTS: A total of 4069 patients with activated MyChart accounts were included in the analysis. About 3575 (87.9%) were messaging users and 494 (12.1%) were nonusers. The mean age of users was significantly lower compared to the nonusers (57.7 vs 61.2, P< .001). Compared to non-Hispanic White (NHW) individuals, non-Hispanic Black (NHB) (odds ratio [OR]: 0.38, CI [0.21, 0.37]) and Hispanic individuals (OR: 0.35, CI [0.22, 0.57]) were significantly less likely to use electronic messaging. There were statistically significant racial/ethnic differences in the types of messages sent among EMR users. CONCLUSION: Our study shows disparate EMR messaging utilization based on age, race, and primary language. As the availability of patient portals and electronic messaging increase, it is important to understand the barriers that patients face so that they can be addressed.

A budget impact analysis of cost to implement a whole child health focused, family-based intervention in primary care for children with elevated BMI.

BACKGROUND: Although the cost of implementing evidence-based interventions (EBIs) is a key determinant of adoption, lack of cost information is widespread. We previously evaluated the cost of preparing to implement Family Check-Up 4 Health (FCU4Health), an individually tailored, evidence-based parenting program that takes a whole child approach, with effects on both behavioral health and health behavior outcomes, in primary care settings. This study estimates the cost of implementation, including preparation. METHODS: We assessed the cost of FCU4Health across the preparation and implementation phases spanning 32 months and 1 week (October 1, 2016-June 13, 2019) in a type 2 hybrid effectiveness-implementation study. This family-level randomized controlled trial took place in Arizona with n = 113 predominantly low-income, Latino families with children ages > 5.5 to < 13 years. Using electronic cost capture and time-based activity-driven methods, budget impact analysis from the perspective of a future FCU4Health adopting entity-namely, ambulatory pediatric care clinicians-was used to estimate the cost of implementation. Labor costs were based on 2021 Bureau of Labor Statistics Occupational Employment Statistics, NIH-directed salary cap levels or known salaries, plus fringe benefits at a standard rate of 30%. Non-labor costs were based on actual amounts spent from receipts and invoices. RESULTS: The cost of FCU4Health implementation to 113 families was $268,886 ($2380 per family). Actual per family cost varied widely, as individual tailoring resulted in families receiving a range of 1-15 sessions. The estimated cost of replicating implementation for future sites ranged from $37,636-$72,372 ($333-$641 per family). Using our previously reported preparation costs (i.e., $174,489; $1544 per family), with estimated replication costs of $18,524-$21,836 ($164-$193 per family), the total cost of delivering FCU4Health was $443,375 ($3924 per family), with total estimated replication costs of $56,160-$94,208 ($497-$834 per family). CONCLUSIONS: This study provides a baseline for costs associated with implementation of an individually tailored parenting program. Results provide critical information for decision makers and a model for future economic analysis and can be used to inform optimization thresholds for implementation and, when necessary, benchmarks for program adaptation to promote scale-up. TRIAL REGISTRATION: This trial was prospectively registered on January 6, 2017, at ClinicalTrials.gov (NCT03013309).

Chromatin Accessibility Landscape of Human Triple-negative Breast Cancer Cell Lines Reveals Variation by Patient Donor Ancestry.

African American (AA) women have an excessive risk of developing triple-negative breast cancer (TNBC). We employed Assay for Transposase-Accessible Chromatin using sequencing to characterize differences in chromatin accessibility between nine commonly used TNBC cell lines derived from patients of European and African ancestry. Principal component and chromosome mapping analyses of accessibility peaks with the most variance revealed separation of chromatin profiles by patient group. Motif enrichment and footprinting analyses of disparate open chromatin regions revealed differences in transcription factor activity, identifying 79 with ancestry-associated binding patterns (FDR < 0.01). AA TNBC cell lines exhibited increased accessibility for 62 transcription factors associated with epithelial-to-mesenchymal transition, cancer stemness/chemotherapeutic resistance, proliferation, and aberrant p53 regulation, as well as KAISO, which has been previously linked to aggressive tumor characteristics in AA patients with cancer. Differential Assay for Transposase-Accessible Chromatin signal analysis identified 1,596 genes located within promoters of differentially open chromatin regions in AA-derived TNBC, identifying DNA methyltransferase 1 as the top upregulated gene associated with African ancestry. Pathway analyses with these genes revealed enrichment in several pathways, including hypoxia. Culturing cells under hypoxia showed ancestry-specific stress responses that led to the identification of a core set of AA-associated transcription factors, which included members of the Kruppel-like factor and Sp subfamilies, as well as KAISO, and identified ZDHHC1, a gene previously implicated in immunity and STING activation, as the top upregulated AA-specific gene under hypoxia. Together, these data reveal a differential chromatin landscape in TNBC associated with donor ancestry. The open chromatin structure of AA TNBC may contribute to a more lethal disease. SIGNIFICANCE: We identify an ancestry-associated open chromatin landscape and related transcription factors that may contribute to aggressive TNBC in AA women. Furthermore, this study advocates for the inclusion of diversely sourced cell lines in experimental in vitro studies to advance health equity at all levels of scientific research.

Effects of the energy balance transition on bone mass and strength.

Chronic positive energy balance has surged among societies worldwide due to increasing dietary energy intake and decreasing physical activity, a phenomenon called the energy balance transition. Here, we investigate the effects of this transition on bone mass and strength. We focus on the Indigenous peoples of New Mexico in the United States, a rare case of a group for which data can be compared between individuals living before and after the start of the transition. We show that since the transition began, bone strength in the leg has markedly decreased, even though bone mass has apparently increased. Decreased bone strength, coupled with a high prevalence of obesity, has resulted in many people today having weaker bones that must sustain excessively heavy loads, potentially heightening their risk of a bone fracture. These findings may provide insight into more widespread upward trends in bone fragility and fracture risk among societies undergoing the energy balance transition.

Population-specific Mutation Patterns in Breast Tumors from African American, European American, and Kenyan Patients.

Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole-exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients. Our analysis of the sequencing data revealed an elevated tumor mutational burden in both Kenyan and African American patients, when compared with European American patients. TP53 mutations were most prevalent, particularly in African American patients, followed by PIK3CA mutations, which showed similar frequencies in European American, African American, and the Kenyan patients. Mutations targeting TBX3 were confined to European Americans and those targeting the FBXW7 tumor suppressor to African American patients whereas mutations in the ARID1A gene that are known to confer resistance to endocrine therapy were distinctively enriched among Kenyan patients. A Kyoto Encyclopedia of Genes and Genomes pathway analysis could link FBXW7 mutations to an increased mitochondrial oxidative phosphorylation capacity in tumors carrying these mutations. Finally, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures in tumors correlated with the occurrence of driver mutations, immune cell profiles, and neighborhood deprivation with associations ranging from being mostly modest to occasionally robust. To conclude, we found mutational profiles that were different between these patient groups. The differences concentrated among genes with low mutation frequencies in breast cancer. SIGNIFICANCE: The study describes differences in tumor mutational profiles between African American, European American, and Kenyan breast cancer patients. It also investigates how these profiles may relate to the tumor immune environment and the neighborhood environment in which the patients had residence. Finally, it describes an overrepresentation of ARID1A gene mutations in breast tumors of the Kenyan patients.

Revisiting Short-term Outcomes of Conventional and Computer-Assisted Total Knee Arthroplasty: A Population-based Study.

BACKGROUND: Population-based studies showing the advantage of computer-assisted total knee arthroplasty (CATKA) over conventional total knee arthroplasty (TKA) are outdated. More recent institution-based studies with relatively small sample sizes may hinder wider adoption. This cohort-based study aimed to compare postoperative CATKA and TKA in-hospital complications and 90-day all-cause readmissions using 2017-2018 data. METHODS: Patients who underwent a primary unilateral CATKA or TKA were identified in the New York Statewide Planning and Research Cooperative System database. In-hospital complications were defined based on the 2020 Centers for Medicare & Medicaid Services total hip arthroplasty and TKA complications measure. Ninety-day readmissions were identified using unique patient identifiers. Logistic regression with a generalized estimating equation was used to assess associations of computer assistance with in-hospital complications and 90-day all-cause readmissions. RESULTS: A total of 80,468 TKAs were identified during the study period, of which 7,395 (9.2%) were CATKAs. Significantly fewer complications occurred among patients who had CATKAs compared with conventional TKAs (0.4% of total CATKAs vs 2.6% of total conventional TKAs, P < 0.001); patients who had CATKAs had fewer 90-day all-cause readmissions compared with those who underwent TKAs (363 vs 4,169 revisits, P < 0.01). Computer assistance was associated with significantly lower odds of in-hospital complications (odds ratio, 0.15, 95% confidence interval, 0.09 to 0.24; P < 0.05) but not 90-day all-cause readmissions. CONCLUSION: Patients undergoing CATKAs had markedly lower odds of in-hospital complications, compared with patients having TKAs, which has implications for both patient outcomes and hospital reimbursement. These more recent cohort-based findings encourage wider CATKA adoption.

Designing Patient-Driven, Tissue-Engineered Models of Primary and Metastatic Breast Cancer.

The rising survival rate for early-stage breast cancer in the United States has created an expanding population of women in remission at risk for distant recurrence, with metastatic spread to the brain demonstrating an especially poor prognosis. The current standard of care for breast cancer brain metastases is not well defined or differentiated from the treatment of brain metastases from other primary sites. Here, we present tissue-engineered models of the primary and brain metastatic breast cancer microenvironments informed by analysis of patient tumor resections. We find that metastatic resections demonstrate distinct cellular and matrix components compared with primary resections or non-cancerous controls. Using our model systems, we find that the observed deposition of collagen I after metastasis to the brain may enhance breast cancer invasion. Future optimization of these models will present a novel platform to examine tumor-stroma interactions and screen therapeutics for the management of metastatic breast cancer.