Characterizing attitudes related to future child-bearing in young women diagnosed with early-stage breast cancer.

PURPOSE: This study characterizes attitudes and decision-making around the desire for future children in young women newly diagnosed with early-stage breast cancer and assesses how clinical factors and perceived risk may impact these attitudes. METHODS: This is a prospective study in women < 45 years with newly diagnosed stage 1-3 breast cancer. Patients completed a REDCap survey on fertility and family-building in the setting of hypothetical risk scenarios. Patient, tumor, and treatment characteristics were collected through surveys and medical record. RESULTS: Of 140 study patients [median age = 41.4 (range 23-45)], 71 (50.7%) were interested in having children. Women interested in future childbearing were younger than those who were not interested (mean = 35.2 [SD = 5.2] vs 40.9 years [3.90], respectively, p < 0.001), and more likely to be childless (81% vs 31%, p < 0.001). 54 women (77.1% of patients interested in future children) underwent/planned to undergo oocyte/embryo cryopreservation before chemotherapy. Interest in future childbearing decreased with increasing hypothetical recurrence risk, however 17% of patients wanted to have children despite a 75-100% hypothetical recurrence risk. 24.3% of patients wanted to conceive < 2 years from diagnosis, and 35% of patients with hormone receptor positive tumors were not willing to complete 5 years of hormone therapy. CONCLUSION: Many young women diagnosed with early-stage breast cancer prioritize childbearing. Interest in having a biologic child was not associated with standard prognostic risk factors. Interest decreased with increasing hypothetical recurrence risk, though some patients remained committed to future childbearing despite near certain hypothetical risk. Individual risk assessment should be included in family-planning discussions throughout the continuum of care as it can influence decision-making.

Differences in Acute Postoperative Opioid Use by English Proficiency, Race, and Ethnicity After Total Knee and Hip Arthroplasty.

BACKGROUND: There is increasing interest in documenting disparities in pain management for racial and ethnic minorities and patients with language barriers. Previous studies have found differential prescription patterns of opioids for racial and ethnic minority group and patients having limited English proficiency (LEP) after arthroplasty. However, there is a knowledge gap regarding how the intersection of these sociodemographic factors is associated with immediate postoperative pain management. This study aimed to explore language and racial-ethnic disparities in short-term opioid utilization after total hip and knee arthroplasty. METHODS: We conducted a retrospective cohort study of adult patients who underwent total hip and knee arthroplasty from 2015 to 2019 at an urban medical center. The primary predictor variables included LEP status and racial-ethnic category, and the primary outcome variables were oral morphine equivalents (OMEs) during 2 distinct postoperative periods: the first 12 hours after surgery and from the end of surgery to the end of postoperative day (POD) 1. Patient characteristics and perioperative metrics were described by language status, race, and ethnicity using nonparametric tests, as appropriate. We performed an adjusted generalized estimating equation to assess the total effect of the intersection of LEP and racial-ethnic categories on short-term postoperative opioid use in mean ratios (MRs). RESULTS: This study included a total of 4090 observations, in which 7.9% (323) patients had LEP. Patients reported various racial-ethnic categories, with 72.7% (2975) non-Hispanic White, and minority groups including non-Hispanic Asian and Pacific Islander (AAPI), Hispanic/Latinx, non-Hispanic Black/African American, and Others. Patients self-identifying as non-Hispanic AAPI received fewer OME regardless of LEP status during the first 12 hours postoperatively (MR for English proficient [EP], 0.12 [95% confidence interval, CI, 0.08-0.18]; MR for LEP, 0.22 [95% CI, 0.13-0.37]) and from end of surgery to the end of POD 1 (MR for EP, 0.24 [95% CI, 0.16-0.37]; MR for LEP, 0.42, [95% CI, 0.24-0.73]) than EP non-Hispanic White. Hispanic/Latinx patients with LEP received lower amounts of OME during the first postoperative 12 hours (MR, 0.29; 95% CI, 0.17-0.53) and from end of surgery to the end of POD 1 (MR, 0.42; 95% CI 0.23-0.79) than EP non-Hispanic White. Furthermore, within the non-Hispanic White group, those with LEP received fewer OME within the first 12 hours (MR, 0.33; 95% CI, 0.13-0.83). CONCLUSIONS: We identified an association between LEP, racial-ethnic identity, and short-term postoperative OME utilization after total knee and hip arthroplasty. The observed differences in opioid utilization imply there may be language and racial-ethnic disparities in acute pain management and perioperative care.

C5aR plus MEK inhibition durably targets the tumor milieu and reveals tumor cell phagocytosis.

Plexiform neurofibromas (PNFs) are nerve tumors caused by loss of NF1 and dysregulation of RAS-MAPK signaling in Schwann cells. Most PNFs shrink in response to MEK inhibition, but targets with increased and durable effects are needed. We identified the anaphylatoxin C5a as increased in PNFs and expressed largely by PNF m acrophages. We defined pharmacokinetic and immunomodulatory properties of a C5aR1/2 antagonist and tested if peptide antagonists augment the effects of MEK inhibition. MEK inhibition recruited C5AR1 to the macrophage surface; short-term inhibition of C5aR elevated macrophage apoptosis and Schwann cell death, without affecting MEK-induced tumor shrinkage. PNF macrophages lacking C5aR1 increased the engulfment of dying Schwann cells, allowing their visualization. Halting combination therapy resulted in altered T-cell distribution, elevated Iba1+ and CD169+ immunoreactivity, and profoundly altered cytokine expression, but not sustained trumor shrinkage. Thus, C5aRA inhibition independently induces macrophage cell death and causes sustained and durable effects on the PNF microenvironment.