PURPOSE: To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS: Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION: Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

We have shown that activin A (activin), a TGF-β superfamily member, has pro-metastatic effects in colorectal cancer (CRC). In lung cancer, activin activates pro-metastatic pathways to enhance tumor cell survival and migration while augmenting CD4+ to CD8+ communications to promote cytotoxicity. Here, we hypothesized that activin exerts cell-specific effects in the tumor microenvironment (TME) of CRC to promote anti-tumoral activity of immune cells and the pro-metastatic behavior of tumor cells in a cell-specific and context-dependent manner. We generated an Smad4 epithelial cell specific knockout (Smad4−/−) which was crossed with TS4-Cre mice to identify SMAD-specific changes in CRC. We also performed IHC and digital spatial profiling (DSP) of tissue microarrays (TMAs) obtained from 1055 stage II and III CRC patients in the QUASAR 2 clinical trial. We transfected the CRC cells to reduce their activin production and injected them into mice with intermittent tumor measurements to determine how cancer-derived activin alters tumor growth in vivo. In vivo, Smad4−/− mice displayed elevated colonic activin and pAKT expression and increased mortality. IHC analysis of the TMA samples revealed increased activin was required for TGF-β-associated improved outcomes in CRC. DSP analysis identified that activin co-localization in the stroma was coupled with increases in T-cell exhaustion markers, activation markers of antigen presenting cells (APCs), and effectors of the PI3K/AKT pathway. Activin-stimulated PI3K-dependent CRC transwell migration, and the in vivo loss of activin lead to smaller CRC tumors. Taken together, activin is a targetable, highly context-dependent molecule with effects on CRC growth, migration, and TME immune plasticity.

Up to a third of patients with hemato-oncologic conditions who have received multiply transfusions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence posttransfusion platelet corrected count increments (CCI) in patients with HLA-alloimmune platelet transfusion refractoriness remain less well elucidated. Recent advances in HLA antibody characterization using fluorescent bead-based platforms enable the study of donor-specific antibody (DSA) avidity (as measured by mean fluorescence intensity [MFI]) and its impact on HLA-alloimmune platelet transfusion refractoriness. In this large retrospective study of 2012 platelet transfusions among 73 HLA-alloimmunized patients, we evaluated the impact of cumulative HLA DSA-MFI alongside other donor, platelet component, and patient characteristics on CCI at 2 and 24 hours after transfusion. As part of a quality improvement initiative, we also developed and tested a computerized algorithm to optimize donor–recipient histocompatibility based on cumulative DSA-MFI and sought other actionable predictors of CCI. In multivariate analyses, cumulative HLA DSA-MFI of ≥10 000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively affected 2-hour but not 24-hour posttransfusion CCI. The DSA-MFI threshold of 10 000 was corroborated by greater antibody-mediated complement activation and significantly more CCI failures above this threshold, suggesting the usefulness of this value to inform “permissive platelet mismatching” and to optimize CCI. Furthermore, DSA-MFI decreases were deemed feasible by the computer-based algorithm for HLA-platelet selection in a pilot cohort of 8 patients (122 transfusions) evaluated before and after algorithm implementation. When HLA-selected platelets are unavailable, ABO-identical/minor-mismatched platelet concentrates may enhance 2-hour CCI in heavily HLA-alloimmunized patients with platelet transfusion refractoriness.

Introduction. Preexisting chronic pain has been reported to be a consistent risk factor for severe acute postoperative pain. However, each specific chronic pain condition has unique pathophysiology, and it is possible that the effect of each condition on postoperative pain is different. Methods. This is a retrospective cohort study of pregnant women with preexisting chronic pain conditions (i.e., migraine, chronic back pain, and the combination of migraine + chronic back pain), who underwent cesarean delivery. The effects of the three chronic pain conditions on time-weighted average (TWA) pain score (primary outcome) and opioid dose requirements in morphine milligram equivalents (MME) during postoperative 48 hours were compared. Results. The TWA pain score was similar in preexisting migraine and chronic back pain. Chronic back pain was associated with significantly greater opioid dose requirements than migraine (12.92 MME, 95% CI: 0.41 to 25.43, ). Preoperative opioid use ( ) was associated with a greater TWA pain score. Preoperative opioid use ( ), smoking ( ), and lower postoperative ibuprofen dose ( ) were associated with greater opioid dose requirements. Conclusions. Findings suggest women with chronic back pain and migraine do not report different postpartum pain intensities; however, women with preexisting chronic back pain required 13 MME greater opioid dose than those with migraine during 48 hours after cesarean delivery.

We validated updated National Health Interview Survey questions on mammography indications compared with electronic health records (EHRs). We asked 244 Kaiser Permanente Washington members ages 40-74 years and eligible for breast cancer screening to self-report their most recent mammogram reason by using a series of new hierarchical yes/no questions. We first asked if they had the mammogram because of a health problem, then as a follow-up test, and last for screening. We compared self-reported reasons with 2 EHR datasets: procedure/diagnostic codes and radiologist-defined indications. Self-reported exams for a health problem had 89.2% agreement with codes and 92.2% agreement with radiologist-defined indications. Self-reported exams for follow-up had 87.5% agreement with codes and 89.3% agreement with radiologist-defined indications. Self-reported exams for screening had 91.4% agreement with codes and 95.7% agreement with radiologist-defined indications. Self-reported mammogram indications have good agreement with procedure/diagnostic codes and radiologist-reported indications, when asked using this novel hierarchical approach.