Biostatistical Consulting (United States)

Abstract Background: Patients with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC) have a higher risk of recurrence and worse survival outcomes. Prior studies have shown that higher stromal tumor-infiltrating lymphocytes (sTILs) post-NAC in patients with residual TNBC is associated with improved survival outcomes. In this secondary analysis of EA1131, we evaluated the association between sTILs, intrinsic subtype, and invasive disease-free survival (iDFS), stratified by race in patients with residual TNBC after completion of NAC. Patients and methods: EA1131 enrolled patients with clinical stage II or III TNBC with ≥1.0 cm residual disease (RD) in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine on days 1-14 of a 21-day cycle for six cycles. Stromal TIL density was assessed on full-face hematoxylin and eosin (H&E)-stained tumor sections. Patients were categorized into four groups based on sTILs level (<30% vs. ≥30%) and tumor intrinsic subtype (basal vs. non-basal): (1) low sTILs/basal, (2) low sTILs/non-basal, (3) high sTILs/basal, and (4) high sTILs/non-basal. Cox proportional hazard models were used to examine the association between sTILs and intrinsic subtype group and iDFS, adjusting for available baseline factors. The association between sTILs category and race and intrinsic subtype were examined using Fisher exact test. Results: Among 410 participants with TNBC and RD, H&E slides were available for all 342 who had intrinsic subtype (264 basal, 78 non-basal). Most patients (93%, n=319) had low sTILs (<30%); only 23 (7%) had high sTILs (30-50%: n=17; 51-70%: n=3; >70%: n=3). There was no difference in sTILs by intrinsic subtype (p=0.31) or race (p=0.5). Compared to all groups, patients with low TILs and basal subtype (n=244) had the worst iDFS (p=0.005) and had numerically worse OS (p=0.084). Other significant risk factors for iDFS in this group included high histologic grade (vs intermediate and low), positive lymph node (vs negative), higher pathologic T stage (as a continuous variable). Differences according to race could not be analyzed due to small sample size. Conclusion: In the EA1131 clinical trial, patients with residual basal-like TNBC and low sTILs had the worse iDFS, delineating a particularly high-risk subgroup. These findings underscore the prognostic relevance of post-treatment immune microenvironment characteristics and suggest that patients with basal-like, TIL-low residual TNBC may derive limited benefit from current standard adjuvant therapies. Further investigation is warranted to identify and develop tailored therapeutic approaches for this biologically aggressive subgroup to improve long-term outcomes. Citation Format: S. S. Badve, F. Zhao, S. Reid, Y. Gokmen-Polar, I. Mayer, C. L. Arteaga, W. F. Symmans, B. H. Park, B. L. Burnette, D. F. Makower, M. Block, M. A. Kimberly, C. R. Jani, C. Mescher, S. J. Dewani, B. Tawfik, B. Tawfik, L. E. Flaum, E. L. Mayer, W. M. Sikov, E. T. Rodler, A. M. DeMichele, J. A. Sparano, A. C. Wolff, K. D. Miller, ECOG-ACRIN. Tumor infiltrating lymphocytes in post-NACT residual tumors in ECOG-ACRIN EA1131 - impact of intrinsic subtypes [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF3-06.

The monthly opioid overdose death rate in the US has declined by 50% from its peak in the summer of 2023 through fall of 2024, and the factors associated with this decline are not fully understood. To examine the association between the proportion of fentanyl reports in illicit drug seizures and opioid overdose deaths during periods of rising and falling mortality. This secondary analysis of state-month level panel data from the National Forensic Laboratory Information System and US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) was conducted from January 2018 to September 2024 and included all 50 US states and Washington, DC. CDC WONDER data were collected from recorded death certificates; National Forensic Laboratory Information System data were obtained from drug reports submitted by forensic laboratories. The data were analyzed from July to August 2025. Percentage of illicit drug seizures that contained fentanyl or fentanyl-related compounds. Illicit drug seizures were defined as seizures that contained any of the following: fentanyl or fentanyl-related compounds, heroin, methamphetamine, cocaine, and xylazine. The monthly count of opioid overdose deaths, given by uniform claim descriptor codes X40 to 44, X60 to 64, X85, and Y10 to Y14, with additional multiple cause of death codes of T40.0 to 4 and T40.6. Death rates were calculated using yearly population estimates from the American Community Survey. From a peak in the summer of 2023 through the fall of 2024, the monthly opioid overdose death rate declined by 50%, from 2.2 to 1.1 per 100 000. This decline was was accompanied by a decline in the fentanyl reports as a proportion of total illicit drug seizures from 28.8% to 23.2%. In a 2-way, fixed-effects model, a 1-percentage point reduction in fentanyl prevalence was associated with 0.018 fewer overdose deaths per 100 000 population per month (95% CI, 0.016-0.019; P < .001). There was evidence that the strength of this association has decreased over time. The study results suggest that current decline in the proportion of fentanyl reports in illicit drug seizures is associated with 9.2% of the total observed decline in mortality. Additional contributing factors may include other shifts in the drug supply not captured by fentanyl prevalence in illicit drug seizures, shifts in drug use behavior, and the effect of public health programs, interventions, and policies.

Obesity is a complex, multifactorial disease influenced by genetic, hormonal, and metabolic factors. The fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes have been implicated in body weight regulation through gut–brain signaling and their interactions with adipokines and enteroendocrine hormones. This study investigated the association between gastric expression of FTO and MC4R genes and circulating levels of leptin, adiponectin, and ghrelin in individuals with and without obesity. We conducted a case–control study including 50 patients with obesity undergoing sleeve gastrectomy and 50 controls undergoing diagnostic endoscopy. Gastric tissue gene expression was assessed by qRT-PCR, and serum hormone levels were quantified using ELISA. Inverse propensity score weighting was used to adjust for age and sex. FTO expression was significantly upregulated in patients with obesity (fold-change: 5.8 vs. 1.0, p < 0.001), showing a parallel elevation with adiponectin and BMI at the group level. In contrast, MC4R expression was significantly downregulated (fold-change: 0.1 vs. 1.0, p < 0.001), and positively associated with HOMA-IR and showed a borderline positive trend with fasting blood glucose (p = 0.074). Adiponectin levels were paradoxically elevated in the obesity group and correlated with both BMI and HDL. Leptin and ghrelin levels showed no significant group differences. These findings suggest that altered gastric expression of FTO and MC4R may contribute to obesity-related metabolic disturbances through peripheral adipokine pathways. Further investigation into tissue-specific gene–hormone interactions may inform novel therapeutic strategies for obesity.

We thank Professor Wen X [1] for his methodological comments on our clinical trial, which highlighted that early hemostatic treatment could improve survival in cases of spontaneous rupture of hepatocellular carcinoma (HCC) [2]. We appreciate the opportunity to address the concerns raised. First, we would agree that an immortal time bias could have influenced our results regarding the benefit of subsequent HCC treatments if the overall survival analysis had included only patients who survived long enough to receive them. However, all patients with a ruptured HCC—whether they survived the haemorrhage or not and whether they received subsequent treatment or not—were included in the analysis. We now provide two additional survival analyses: one including patients who survived more than 30 days (first quartile of time to first subsequent treatment: 39 days after bleeding) and another including patients who survived more than 84 days (median time to first subsequent treatment: 84 days). At 30 days or later after bleeding, 38 patients had received a subsequent treatment and 40 had not; at 84 days and beyond, 35 patients had received treatment and 25 had not. In both analyses, subsequent treatment remained a protective factor (Table 1). Second, we acknowledge the limitation related to the imaging diagnosis of HCC rupture. The multicenter retrospective design did not allow centralised rereading, but we applied clear diagnostic criteria to define rupture. Our study aimed to evaluate the real-life management of HCC diagnosed as ruptured, rather than to assess the accuracy of imaging interpretation in guiding hemostatic treatment. A centralised review could have excluded some cases, but doing so would have introduced selection bias for the real-life approach. Finally, as already mentioned, this was a retrospective study with inherent limitations, particularly variability in management across centres. Patients who received hemostatic treatment were more likely to have BCLC stage A/B HCC and higher transfusion rates. However, transfusion was not associated with prognosis, and transfusion rates did not differ between BCLC A/B (22%) and C/D (35%) (p = 0.105). Due to the small sample size and limited number of deaths, neither propensity score matching nor inverse probability weighting was feasible. In conclusion, we thank the reviewer for the constructive feedback and agree that our findings should be interpreted with caution given the retrospective nature of the study. Considering the low incidence of HCC rupture, conducting prospective and randomised studies in this context remains a major challenge. Apolline Commin and Isabelle Ollivier: writing and editing. Chloé Metivier and Remy Morello: statistical analysis and review. We thank all the reviewers for their assistance and support. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. This article is linked to https://doi.org/10.1111/liv.70396. All information required is given in the text.

Background/Objectives: We here describe the impact of navigated care on utilization patterns of pharmacologic and minimally invasive overactive bladder therapies. Methods: This retrospective observational cohort study used electronic medical record data from the Precision Point Specialty Analytics Portal in the United States. Eligible patients were adults (≥18 years) newly diagnosed and treated for non-neurogenic overactive bladder (1 January 2015 to 31 December 2019). Categorical endpoints were analyzed by chi-square test or Fisher exact test. Of 170,000 eligible patients, 8982 (≈5%) were randomly selected and stratified by navigation status (navigated: 1150 [12.8%]; non-navigated: 7832 [87.2%]). Results: Overall, 60.0% of patients were female, 69.9% were White, and 42.7% had Medicare coverage. Navigated care was more common among women, Black patients, and those covered by Medicaid/Medicare. Initial pharmacologic treatment rates were similar between navigated and non-navigated groups (anticholinergic: 57.0% vs. 57.4%; beta-3 agonist: 43.0% vs. 42.6%). Greater percentages of navigated versus non-navigated patients received minimally invasive therapy (23.8% vs. 10.8%, respectively; p &lt; 0.0001). Discontinuation rates were lower for navigated versus non-navigated patients undergoing pharmacologic treatment (62.5% vs. 71.3%; p &lt; 0.0001). Conclusions: Patient navigation for overactive bladder may help increase access to minimally invasive therapies and may be a tool to address treatment disparities.

<h2>Abstract</h2> Precision Medicine, targeted for each person, has presented a major challenge in scaling up to wide use. Reflecting the true behavior of the human body, it requires inquiry across the biomedical scales, from the genome all the way up to the environmental factors impinging on that person. In computation terms, this is a problem of unprecedented complexity. With AI showing its potential, the thoughtful application of advanced machine intelligence, knowledge networks, machine reasoning power and new computational paradigms—guided by human oversight at every stage—can help unlock major advances in treatment and prevention.

South Korea has implemented the National Health Screening Program for Infants and Children (NHSPIC), which includes clinical hip screening with selective hip ultrasonography beginning at 4 months of age. We aimed to investigate the trends in developmental dysplasia of the hip (DDH), associated risk factors, and growth and motor developmental outcomes up to preschool age. We included a retrospective, population-based birth cohort of children born between 2008 and 2015. Patients diagnosed with DDH were stratified by age at detection (early diagnosed [<1 year] vs late diagnosed [≥1 year]) and treatment modalities (major surgery, minor surgery, or nonoperative). Growth and motor developmental outcomes were assessed using NHSPIC data collected up to 6 years of age. Among 2,518,805 children, 4,854 (0.19%) were diagnosed with DDH. The incidence of DDH increased from 1.29 to 2.37 per 1,000 individuals, with the incidence of early diagnosed DDH increased from 0.70 to 1.94 per 1,000. However, the rate of surgical treatment remained unchanged (0.19-0.28 per 1,000). Children who underwent surgical treatment for DDH had a significantly higher incidences of short stature, and delayed gross motor development. After the introduction of the NHSPIC hip screening program, incidences of overall and early diagnosed DDH increased, whereas the surgical treatment rate showed no significant change. Surgical treatment for DDH was significantly associated with both short stature and delayed gross motor development.