Publications by Year: 2026

BACKGROUND: The efficacy of neoadjuvant chemoimmunotherapy in patients with non-metastatic triple-negative inflammatory breast cancer (TN-IBC) remains unclear, as patients with IBC have been poorly represented in pivotal clinical trials.

PATIENTS AND METHODS: We conducted an observational, retrospective/prospective, multicenter cohort study from 2023 to 2024 of patients with non-metastatic TN-IBC who received at least one cycle of neoadjuvant pembrolizumab plus multi-agent chemotherapy from September 2018 to April 2023. The median follow-up was 1.4 years [95% confidence interval (CI) 1.2-1.7 years]. The primary endpoint was pathological complete response (pCR).

RESULTS: Overall, 63 female patients with TN-IBC were included from four cohorts. The most common regimen was pembrolizumab, taxane/carboplatin, and anthracycline/cyclophosphamide (61.9%). Among all patients, 59 (94%) underwent surgery and 4 (6.4%) experienced local and/or distant disease progression during the neoadjuvant treatment. The pCR rate was 31.7% (20/63; 95% CI 20.6% to 44.7%).

CONCLUSIONS: The combination of neoadjuvant chemotherapy and pembrolizumab resulted in a pCR rate of 31.7% in patients with non-metastatic TN-IBC. Compared with triple-negative non-IBC, the lower pCR rate with this combination regimen highlights the need for biomarkers for better patient selection and more active treatment options for this rare and aggressive breast cancer subtype.

INTRODUCTION: Epilepsy surgery remains underutilized despite strong evidence supporting its efficacy for appropriately selected patients with drug-resistant epilepsy (DRE).

CASE PRESENTATION: We describe the case of a 23-year-old woman with a 4-year history of refractory focal impaired awareness seizures, experiencing up to four episodes per week despite multiple trialed antiseizure medications at tolerated doses. Initial investigations including magnetic resonance imaging (MRI), EEG, and paraneoplastic screening were unremarkable, and she was managed as having non-lesional left temporal lobe epilepsy. As part of an artificial intelligence driven research initiative, a natural language processing based random forest algorithm reviewing neurology clinic documentation identified her as a potential surgical candidate. Complementary large language model analysis supported extraction of relevant seizure and imaging information. This prompted re-evaluation of the case, with PET demonstrating left temporal hypometabolism and repeat MRI revealing a previously unrecognized encephalocele. She subsequently underwent left temporal lobe polectomy with encephalocele disconnection. The procedure was successful, and she has remained seizure-free for 1 year postoperatively, allowing initiation of ASM weaning and the possibility of long-term cure.

CONCLUSION: This case illustrates the transformative potential of epilepsy surgery for individuals with DRE and the promising role of artificial intelligence augmented triage systems in reducing delays to surgical referral. Given the morbidity, mortality, and economic burden associated with DRE, timely surgical evaluation should be considered the standard of care for eligible patients. Integrating artificial intelligence tools into clinical workflows may help overcome longstanding barriers to access and ensure that life-changing interventions are offered earlier in the disease course.

BACKGROUND: Effective cardiovascular disease (CVD) risk management is essential for optimal diabetes care. Here, we estimated the prevalence and determinants of CVD risk factor control among individuals with diagnosed diabetes in Mexico.

METHODS: We analyzed data from individuals ≥20 years with diagnosed diabetes from 2016 to 2023 Mexican National Health and Nutrition Surveys. We estimated the prevalence of glycemic, blood pressure, noncurrent smoking, low-density lipoprotein cholesterol, and combined CVD risk factor control. We estimated use of blood pressure-lowering, cholesterol-lowering, and glucose-lowering medication and explored determinants of control achievement using logistic regression.

RESULTS: We analyzed data from 2916 participants, representing 43.2 million adults with diagnosed diabetes during 2016 to 2023. In 2023, glycemic control was 29% (95% CI, 21%-38%), blood pressure control 22.9% (95% CI, 14%-31%), and noncurrent smoking 89% (95% CI, 81%-96%). The prevalence of high or very-high CVD risk using Systematic Coronary Risk Evaluation 2-Diabetes increased from 59.8% (95% CI, 52.1%-67.0%) in 2016 to 68.4% (95% CI, 55.6%-78.9%) in 2023, representing  5.1 million adults. Low-density lipoprotein cholesterol control increased from 2.8% (95% CI, 1.2%-4.4%) in 2016 to 6.6% (95% CI, 1.9%-11.2%) in 2023 and statin use from 5.5% in 2016 to 63% in 2023. Combined risk factor control achievement was low due to suboptimal low-density lipoprotein cholesterol control and was more likely achieved in women, younger individuals, and those with college education or living in states with higher socioeconomic position.

CONCLUSIONS: Despite increasing CVD risk during this period, glycemic and CVD risk factor management for adults with diabetes in Mexico remains suboptimal. Our findings suggest a need for strategies to improve CVD risk management to reduce diabetes-related mortality and complications.

INTRODUCTION: Endogenous measures of impaired kidney tubule secretion are associated with kidney function decline. Whether they associate with future acute kidney injury (AKI) risk is unclear.

METHODS: In 397 participants of the Reasons for Geographic and Racial Differences in Stroke study who underwent coronary artery bypass graft (CABG) surgery (mean age: 66 years, 29% female), we examined the association of a summary secretion score of 11 endogenous secretion markers (measured at a median 5.5 years before CABG) with AKI risk following CABG, adjusting for confounders including estimated glomerular filtration rate (eGFR) and albuminuria.

RESULTS: A total of 177 participants developed AKI (≥ 0.3 mg/dl or 1.5× creatinine increase) following CABG. Individuals who developed AKI were older, more likely to be men, have diabetes, lower eGFR and greater albuminuria at the baseline visit. In models adjusted for age, sex, race, urine creatinine, time from baseline to CABG, diabetes, hypertension, and body mass index, a higher (signifying better) secretion score was associated with lower risk of AKI (risk ratio [RR] comparing 4th to 1st quartile: 0.49, 95% confidence interval [CI]: 0.32-0.74). The results did not meaningfully differ after further adjusting for eGFR and albuminuria (RR: 0.58, 95% CI: 0.38-0.89), or when secretion score was analyzed as a continuous variable (RR per 1 SD higher score: 0.85, 95% CI: 0.71-1.01). Associations were stronger in women (RR: 0.75, 95% CI: 0.59-0.95) than men (RR: 0.89, 95% CI: 0.69-1.16) in fully adjusted models (P interaction = 0.01).

CONCLUSION: In community-based adults, greater estimated tubular secretion at times of relative health is associated with lower risk of AKI following CABG.

BACKGROUND: Living near greenspace is associated with decreased cardiovascular disease (CVD). Greenspace estimates, however, typically represent all types of vegetation using top-down satellite images, which incorporate exposure misclassification and limit policy relevance.

OBJECTIVE: We studied the association between street-view greenspace measures with incident CVD using a large, long-term prospective US cohort of female nurses.

METHODS: We estimated the percentage of streetscapes composed of visible trees, grass, and other green (plants/flowers/fields) from 350 million street-view images using deep learning models. Estimates were applied to Nurses' Health Study participants (N = 88,788) within 500 m of their residential addresses. We used Cox models to estimate associations from 2000 to 2018 between street-view greenspace measures and risk of incident CVD, assessed through self-report, medical record review, or death certificates, and adjusted for individual- and area-level factors.

RESULTS: In adjusted models, higher percentages of visible trees were associated with lower CVD incidence (hazard ratio [HR] per interquartile range [IQR] 0.96 (95% confidence interval 0.93, 1.00]), while higher percentages of visible grass (HR 1.06 [1.02, 1.11]) and other green space types (HR 1.03 [1.01, 1.04]) were associated with higher CVD incidence. We did not observe evidence of effect modification by population density, Census region, air pollution, satellite-based vegetation, or neighborhood socioeconomic status. Findings were robust to adjustment for other spatial and behavioral factors and persisted even after adjustment for traditional satellite-based vegetation indices.

DISCUSSION: Specific greenspace types may be protective or harmful for CVD. Aggregating greenspace into a single exposure category limits epidemiological research and potential interventions to increase health-promoting greenspace.

Glucose hypometabolism is observed in early Alzheimer's disease. However, there are regional discrepancies in hypometabolism and Alzheimer's pathological markers. We examined the local and global contributions of amyloid-β and tau pathology to glucose metabolism and their interplay in memory decline in Presenilin-1 E280A mutation carriers and non-carriers from the largest autosomal-dominant Alzheimer's disease kindred. This cross-sectional study included 43 mutation carriers (6 cognitively impaired) and 39 non-carriers from the Colombia-Boston Biomarker Study. Glucose metabolism was assessed with [18F]fluorodeoxyglucose PET, and memory performance with the Consortium to Establish a Registry for Alzheimer's Disease word list learning. A subgroup of 22 carriers and 26 non-carriers additionally had measures of amyloid-β and tau using 11C-Pittsburgh compound B and 18F-flortaucipir PET, respectively. First, we compared regional glucose metabolism between groups using the Wilcoxon rank-sum test. Then, we studied regional glucose metabolism associations with age, co-localized amyloid-β and tau pathology, and memory using Spearman correlation. Local specificity was assessed by partial correlations controlling for global amyloid-β and tau burden. Finally, we studied whether the link between Alzheimer's pathology and memory was mediated by regional glucose hypometabolism. Mutation carriers exhibited lower glucose metabolism in the precuneus and isthmus cingulate compared to non-carriers. Hypometabolism correlated locally with greater tau accumulation in the medial temporal lobe, inferior temporal gyrus and prefrontal cortex, and with greater amyloid-β accumulation in the inferior temporal gyrus in carriers. These associations were no longer significant when controlled for global pathology, except for the frontal tau-hypometabolism correlation, which was independent of global tau burden, suggesting local specificity. Additionally, lower memory performance in carriers was associated with hypometabolism in regions typically affected by tau. The mediation analysis revealed a region-specific interplay in pathology, with the associations of amyloid-β and tau pathology with memory decline being mediated by hypometabolism in the inferior temporal. Our findings highlight the metabolic vulnerability of the precuneus in early stages, supporting a common pathophysiology between autosomal-dominant and sporadic Alzheimer's disease. The lack of local correlations between amyloid-β, tau and hypometabolism suggests that distant effects may explain the regional discrepancies between pathology accumulation and metabolic alterations. This study describes a model where pathology advances and interacts in a region-specific manner to impact clinical outcomes, underscoring the importance of regional [18F]fluorodeoxyglucose PET as an independent predictor of cognitive decline. Overall, our findings improve understanding of the spatial progression of pathology, which could have important implications in disease management.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation is a leading cause of allograft failure and remains difficult to treat. Standard therapies, including plasma exchange (PEX) and rituximab, are often ineffective and poorly tolerated. Growing evidence implicates immune-mediated circulating factors, such as IgG and IgM autoantibodies, in disease pathogenesis. Given the central role of memory B cells and plasma cells in antibody production, we tested the safety/efficacy profile of a combined B-cell and plasma cell-depleting approach with rituximab and daratumumab in patients with posttransplant FSGS recurrence.

METHODS: This is a retrospective analysis of a multicenter, international cohort of sixteen patients (median age 37 y) with biopsy-proven FSGS recurrence posttransplant who received anti-CD20 plus anti-CD38 monoclonal antibodies or anti-CD38 alone. The majority of patients were resistant to common therapies, including rituximab and PEX.

RESULTS: The treatment achieved complete or partial remission in 5 and 11 patients, respectively. Five experienced proteinuria relapse, and 4 responded to repeated daratumumab alone. At the last follow-up (median 11 [2-18] mo), 13 patients are still in remission and PEX was discontinued in all but 3 cases. Overall, kidney function improved after treatment, and no severe acute or chronic adverse events were reported. Serological analysis revealed a significant decline in IgM, but not in IgG, after treatment.

CONCLUSIONS: Despite the retrospective, nonrandomized design, the temporal association between treatment and remission supports an effect of anti-CD38 monoclonal antibody alone or in combination with anti-CD20. Treatment is safe and may confer enhanced efficacy over standard approaches. Prospective, mechanistic studies are warranted to validate these findings and delineate the immunopathogenesis of FSGS recurrence.

INTRODUCTION: Precision medicine has resulted in improved outcomes for non small cell lung cancer (NSCLC), whereas biomarker testing is considered critical for guiding treatment decisions for advanced-stage NSCLC, and adoption of testing in routine practice is variable. We studied the utilization of biomarker testing in advanced NSCLC.

METHODS: The American Society of Clinical Oncology (ASCO) CancerLinQ Discovery data set was queried to identify patients diagnosed with lung cancer between 2010 and 2018. Data on demographics, tumor stage, histology, and treatments were extracted, and receipt of biomarker testing was investigated as the primary outcome. Univariate association of each clinicopathological variable with the biomarker testing outcome was performed using a chi-square test for categorical variables and an analysis of variance test for numerical variables. A multivariable logistic regression analysis with backward selection at an alpha of 0.05 was reported. All analyses were conducted using SAS 9.4.

RESULTS: A total of 37,925 patients with stage IV NSCLC were analyzed. The patients had a median age of 65 years; meanwhile, 51% of the participants were male individuals, 68% were white, and 33.5% had adenocarcinoma. Approximately 22% of all patients with NSCLC had biomarker testing results. Among the patients with adenocarcinoma, 49% had biomarker testing results available. In the stage IV group, 47% were treated with chemotherapy, 16% with immunotherapy, and 3.5% with targeted therapy. On multivariable analysis, female patients were more likely to have molecular testing compared with male patients (OR = 1.29, 95% confidence interval [CI]: 1.21-1.36, p < 0.001). Compared with white patients, black patients were less likely to have biomarker testing (OR = 0.89, 95% CI: 0.81-0.97, p = 0.009), and Asians were more likely to undergo testing (OR = 2.21, 95% CI: 1.78-2.73, p < 0.001). Hispanic patients were more likely to undergo biomarker testing than non-Hispanic (OR = 1.23, 95% CI: 1.01-1.50, p = 0.03). In addition, treatment with immunotherapy (OR = 1.86, 95% CI: 1.72-2.02, p < 0.001) and targeted therapy (OR = 2.52, 95% CI: 2.21-2.88, p < 0.001) were associated with a significantly higher likelihood of having biomarker testing. These results were also confirmed in a subgroup analysis of patients with adenocarcinoma.

CONCLUSION: In this analysis of a United States-based real-world data set of patients with stage IV NSCLC, the Asian race and female sex were associated with a higher likelihood of having biomarker testing performed. The overall percentage of patients undergoing testing remained suboptimal.