Citations

ABSTRACT Background and Objectives Among patient with early‐stage breast cancer, breast conservation surgery (BCS) is the most performed surgery, utilized in approximately two‐thirds of patients. While 5‐year overall‐survival rates are strong—typically above 90%—additional re‐excisions can occur in up to 25% of patients who undergo index BCS and some patients will require subsequent surgery for new breast cancer or recurrences. As such, these additional procedures can complicate patients’ pathway to survivorship, negatively impact quality of life, and lead to excess healthcare costs. Methods This retrospective cohort study used linked claims and an electronic healthcare record database to (1) characterize patients at higher risk for additional breast oncologic surgery (aBOS) following BCS, and (2) quantify the long‐term financial impact of aBOS after BCS. In total, 87,190 patients with breast cancer, who had an index BCS between January 1, 2012, to March 31, 2023, were followed for up to 5‐years post‐operatively. Patients with and without aBOS were analyzed, comparing demographics, tumor characteristics, healthcare utilization, and per‐person‐per‐month (PPPM) costs. Results Twenty‐three percent ( n = 20,212) of patients underwent aBOS. These patients were younger, had higher tumor grades and larger tumor sizes, and incurred greater healthcare costs compared to patients who did not undergo a secondary surgery. Conclusion This study highlights significant factors influencing BCS outcomes and healthcare utilization, underscoring the need for tailored therapeutic strategies for patients with breast cancer.

Background Studies have demonstrated neighborhood structural inequities are associated with cardiovascular outcomes among breast cancer survivors. We investigated the associations between bias in mortgage lending practices (contemporary redlining and racial lending bias) and cardiovascular outcomes in women with breast cancer. Methods Using the SEER (Surveillance, Epidemiology, and End Results)–Medicare database, we identified 51 007 Black and White women diagnosed with breast cancer between 2010 and 2014 with follow‐up through 2020. We used Home Mortgage Disclosure Act data to calculate census‐tract contemporary redlining index and racial lending bias index, and assessed indices continuously and categorically (low, moderate, or high). We used Cox proportional hazards regression to estimate multivariable‐adjusted, cause‐specific hazard ratios (HRs) for major adverse cardiovascular events, ischemic heart disease, heart failure, stroke, and cardiovascular death. Results In the overall population, a 10%‐unit increase in redlining was associated with increased risk of major adverse cardiovascular events (HR, 1.04 [95% CI, 1.02–1.06]). Among Black women, those in high redlining neighborhoods had an increased heart failure risk compared with those in low redlining neighborhoods (HR, 1.22 [95% CI, 1.05–1.41]). Similarly, White women in high redlining neighborhoods had an increased risk of ischemic heart disease (HR, 1.23 [95% CI, 1.15–1.30]) and stroke (HR, 1.09 [95% CI, 1.03–1.16]). Black women in high racial lending bias neighborhoods had reduced cardiovascular mortality risk compared with those in low racial lending bias neighborhoods (HR, 0.69 [95% CI, 0.54–0.90]). Conclusions We identified associations between contemporary redlining and cardiovascular outcomes among breast cancer survivors. High racial lending bias was associated with reduced cardiovascular mortality risk among Black women. Bias in mortgage lending practices may serve as a structural driver of cardiovascular disparities.

PURPOSE Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2- 18 F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.

Background. The VPS35 p.D620N variant causes autosomal dominant Parkinson's disease (PD) and has been shown to activate the LRRK2 kinase pathway, resulting in increased Rab substrate phosphorylation in peripheral immune cells and elevated urinary bis(monoacylglycero)phosphate (BMP) levels. Recently, a VPS35 variant of unknown significance (c.959C>T; p.A320V) was described in two late-onset sporadic PD patients. Methods. We ascertained a family from the Canary Islands in which six siblings were chronically exposed to high doses of pesticides. Three siblings developed levodopa-responsive, akinetic-rigid PD, while the other three remained unaffected. Whole-exome sequencing was performed in the three affected siblings. The frequency of the resulting candidate variant was assessed in 23,327 PD patients and 9,235 controls from four independent cohorts. Members of this pedigree and unrelated controls were assessed for LRRK2 kinase activity in monocytes and neutrophils and BMP levels in urine. Results. The three affected siblings were all heterozygous for p.A320V, whereas the three unaffected siblings did not carry the variant. In the combined PD case-control cohort, p.A320V was identified in six patients and one control. However, unlike p.D620N, heterozygous carrier status for p.A320V was not associated with increased LRRK2 kinase activity or elevated urine BMP levels. Conclusions. While VPS35 p.A320V co-segregated with PD in this family, it did not exhibit the characteristic LRRK2-associated biomarker signature observed in VPS35 p.D620N carriers. It is possible that p.A320V exerts a subtle effect on VPS35 function that was not captured by the assays performed and that chronic pesticide exposure contributed to disease penetrance in this pedigree.

Importance Recent case reports suggest that B antigen–containing blood products may be associated with anaphylactic transfusion reactions in recipients with preformed immunoglobulin E to galactose- α -1,3-galactose (alpha-gal). Objective To test the association of local alpha-gal syndrome (AGS) prevalence and allergic transfusion reaction (ATR) in patients with blood type O. Design, Setting, and Participants In this international, multicenter, retrospective cohort study at academic medical centers, sites were assigned to AGS high- or low-prevalence clusters based on the known geographic distribution of AGS. Data were collected on platelet or plasma transfusions and ATRs during 2020 to 2024. Consecutive patients receiving platelet or plasma transfusions were included. Exposures Patients with blood type O who received B or AB units and patients with blood type O who received O units (reference group) in AGS high- and low-prevalence clusters were compared. Main Outcomes and Measures Before data collection, the hypothesis was that if transfusion-related alpha-gal syndrome (TRAGS) is a true clinical entity, excess ATRs to group B or AB units would be detected in AGS high-prevalence regions exclusively. The main measure was the overall risk ratio (RR) for ATRs to B or AB plasma or platelets in AGS high- vs low-prevalence clusters. Results In total, 558 823 platelet and plasma transfusions at 40 sites in 5 countries were analyzed, of which ATRs occurred in 1744 transfusions (0.3%). In the US AGS high-prevalence cluster (9 sites), significantly more ATRs of any severity occurred among patients with blood type O who received B or AB units vs patients with blood type O who received O units (overall RR, 3.93; 95% CI, 2.96-5.21; P < .001). In contrast, in the primary analysis of the AGS low-prevalence cluster (15 sites), excess ATRs to B or AB units were not detected. In subgroup analyses among patients with blood type O receiving B units, the RR for moderate to severe ATRs was 9.14 (95% CI, 5.39-15.52; P < .001) in the AGS high-prevalence cluster vs 2.15 (95% CI, 1.34-3.47; P = .002) in the AGS low-prevalence cluster. Outside the US, a signal consistent with TRAGS was not detected. Conclusions and Relevance This cohort study provides provocative epidemiologic evidence that TRAGS may be a unique manifestation of AGS and a previously unrecognized risk associated with transfusion. In AGS high-prevalence regions, blood collectors and hospital transfusion services should consider approaches to preventing severe ATRs from B or AB plasma or platelet units.

Low protein (LP) diets improve metabolic health in rodents and humans. In rodents, LP diets are typically implemented by replacing protein with carbohydrates like sucrose or cornstarch, keeping diets isocaloric. However, humans can choose from many different types of carbohydrate, and how dietary carbohydrate quality - the precise composition of the dietary sugars - impacts the response to dietary protein remains largely unexplored. Here, mice were fed control (21% protein) or LP (7% protein) diets with four different carbohydrate sources: sucrose, a 1:1 glucose/fructose mixture, glucose, or fructose. While LP diets improved metabolic health across all groups in male mice, carbohydrate quality also significantly altered specific health outcomes, with fructose-fed mice having the lowest body weight and adiposity of all control diets. In female mice, responses to LP diets were influenced by carbohydrate quality, with certain sugars inducing a stronger metabolic response to LP diets than previously seen. Finally, in female APP/PS1 mice, a model of Alzheimer's disease, we find that although LP diets reduce A-beta; plaque burden irrespective of carbohydrate type, dietary sugar type does influence spatial memory. Together, these results demonstrate that while dietary protein is a critical determinant of metabolic and neurological health, carbohydrate quality influences these outcomes in a sex-specific manner.

ABSTRACT Introduction Sustaining interventions implemented as part of pragmatic clinical trials requires proactive planning, but how to approach this process remains understudied. The Non‐pharmacological Options in Hospital‐based and Rehabilitation pain Management stepped‐wedge cluster‐randomized pragmatic trial tested an electronic health record‐based educational bundle (known as the Healing After Surgery [HAS] initiative) that encouraged the incorporation of non‐pharmacological pain care in perioperative pain management. The HAS initiative was implemented in multiple surgical practices and hospital sites. One year prior to trial completion, a sustainment committee was established to support the transition of intervention components to clinical ownership and to support posttrial sustainment of the HAS initiative. Methods We reviewed meeting minutes from biweekly sustainment committee meetings and conducted debriefing sessions with committee members (informed by the Clinical Sustainability Assessment Tool) to identify sustainment strategies and challenges, which were then organized into meaningful themes. Results The following six themes emerged from meeting minutes and debriefings: (1) automation of low‐touch components, (2) reliance on internal champions, (3) intentional handoff communication, (4) institutional attention, (5) relaxed fidelity, and (6) continuous evaluation. Together, they highlight the importance of early, structured planning and adaptable implementation strategies. Conclusions Sustainment of the HAS initiative required extensive communication, adaptation, and stakeholder engagement across diverse institutional contexts. Proactive sustainment planning during trial design may help ensure interventions are successfully integrated into routine clinical practice posttrial.

ABSTRACT Background Post‐pancreatectomy exocrine insufficiency is common after resection for pancreatic cancer and requires pancreatic enzyme replacement therapy (PERT). We sought to determine the out‐of‐pocket cost of PERT and the association between PERT and survival. Methods The SEER‐linked Medicare database was queried for patients with pancreatic cancer who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) from 2010 to 2019. Cumulative out‐of‐pocket costs were calculated and stratified by procedure and radiation. Results 11,854 Medicare beneficiaries with resected pancreatic cancer were identified, 4,653 (39%) required PERT and 7,201 (61%) did not. Median age was 73.0, 50.6% were female and 83.6% White. 25.9% underwent DP and 74.1% underwent PD; 7% received neoadjuvant radiation while 23.5% received adjuvant radiation. Logistic regression demonstrated that female sex (OR 1.25, 95% CI 1.16‐1.35, p < 0.001), neoadjuvant radiation (OR 1.93, 95% CI 1.67‐2.24, p < 0.001), and PD (OR 2.45, 95% CI 2.23‐2.7, p < 0.001) were risk factors for requiring PERT. Patients without subsidies who underwent DP paid a cumulative $4,736 out‐of‐pocket for PERT after 5 years, those who underwent PD paid $5,601 out‐of‐pocket. Conclusions Nearly 40% of Medicare beneficiaries took PERT after resection for pancreatic cancer and paid thousands in out‐of‐pocket costs. While a conservative estimate, these findings highlight the importance of addressing this financial burden to patients.