Publications by Year: 2026

BACKGROUND: To assess population-level trends in use of poly (ADP-ribose) polymerase inhibitors (PARPis) among ovarian cancer patients in the years following initial FDA approvals.

METHODS: A national, commercial and Medicare Advantage insurance claims database was used to identify patients with ovarian cancer from 2015 to 2021. Year of ovarian cancer diagnosis was categorized by initial period of PARPi approval for treatment indication (2015-2016) and expanded period of PARPi approval for treatment and maintenance indications (2017-2021). Clinical and demographic characteristics were assessed. The primary outcome was proportion of patients with PARPi dispensings. Time from first observed ovarian cancer diagnosis to first observed PARPi dispensing was calculated.

RESULTS: Of 23,165 patients with ovarian cancer, most were 65 years or older (62.8 %) and had Medicare Advantage insurance (66.2 %). More patients diagnosed in the expanded compared to the initial approval period received PARPi (9.8 % vs. 6.6 %, p < 0.0001) and within less time from diagnosis to PARPi initiation (HR: 2.31, 95 % CI 2.06, 2.59). Age over 65 was associated with lower likelihood of PARPi receipt (OR: 0.85, 95 % CI 0.74, 0.98). In the initial approval period, patients residing in non-white zip codes were more likely to receive a PARPi (OR: 1.61, 95 % CI 1.19, 2.18) and frail patients were less likely to receive a PARPi (OR: 0.41, 95 % CI 0.22, 0.78).

CONCLUSION: Since 2015, PARPi use increased among ovarian cancer patients, and time from diagnosis to PARPi receipt decreased, reflecting expanded PARPi indications over time. Monitoring demographic and clinical characteristics of PARPi recipients may help assess population-level use of novel therapeutics.

Human stem-cell-based embryo models (SCBEMs) imperfectly mimic some-but not all-features of early human development. Yet as these models become increasingly sophisticated, they raise important ethical and regulatory questions. Despite their limitations, SCBEMs already offer powerful platforms to study human embryology, infertility, reproduction, and regenerative medicine. To avoid restrictions that could stall progress for decades, it is essential to proactively establish a clear regulatory framework-one that protects public trust without inhibiting scientific progress. We propose a two-tiered oversight structure anchored in a single fixed ethical principle: no SCBEM should ever attain the capacity for sentience (the ability to experience sensory inputs, such as pain). Tier 1 sets a developmental limit at two criteria: neural tube closure or the appearance of both a defined number of somites and limb buds, corresponding to ∼Day 28 post-fertilization analogue (PFA). Tier 2 allows research requiring a higher level of oversight up to Day 56 PFA, remaining well before the earliest debated threshold of sentience. This framework provides proportionate oversight and enforceable boundaries while acknowledging that concerns beyond sentience will persist for some stakeholders. Our goal is to prepare responsibly for the future, when the models become improved, enabling discovery without compromising ethical integrity.

Interstitial lung diseases (ILD) are characterized by fibrotic scarring of the lung parenchyma with remarkably unfavorable prognosis. Using single-nucleus RNA sequencing and spatial transcriptomics, we generated a comprehensive cellular network of the distal lung and its alterations in fibrosis. Integration with histopathology revealed that the transformation of normal parenchyma into fibrotic tissue is accompanied by ectopic bronchiolization and decellularization. Areas of active fibrosis were characterized by co-localization of pro-fibrotic CTHRC1-hi fibroblasts and aberrant transitional epithelial cells. We modeled this maladaptive differentiation of alveolar epithelial cells using organoids, demonstrating that all three pro-inflammatory ligands present in this pathogenic niche, TGF-β, IL-1β, and TNF-α, are jointly required for their induction. Additionally, we identified a requirement for the transcription factor NFATC4 during myofibroblast differentiation driven by soluble factors or mechanosensing. Collectively, this work identifies essential molecular drivers of the cellular interactions underlying lung fibrosis.

We performed Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) on a cohort of nonpathological human tissues to uncover signatures of aging and senescence in the dorsolateral prefrontal cortex (dlPFC). In doing so, we identified gene expression changes characteristic of aged cortical layers. The cellular composition of the dlPFC also changed with age, with increased homeostatic astrocyte abundance and with decreased somatostatin (SST) inhibitory neurons. Nuclei from dlPFC cell types displayed a strong decline in oxidative phosphorylation- and cytoplasmic translation-related genes with age. Additionally, oligodendrocytes showed several hallmarks of senescence and a linear increase in CDKN2A expression with age. Combined analysis of ST and snRNA-seq datasets revealed astrocyte- and vascular cell-related gene expression programs in the white matter and layer 1 that were strongly enriched with age and for senescence-associated genes. These findings will help facilitate future studies exploring the role of senescent cell subpopulations in the aging brain.

The eye's visual function relies on retinal neural cells that are long-lived, post-mitotic, and possess minimal regenerative capacity. These combined properties render them exceptionally vulnerable to the cumulative damage that drives age-related functional decline. Accumulating evidence now implicates epigenetic alterations, such as aberrant DNA methylation and histone modifications, not merely as correlates of aging but as fundamental drivers of aging and disease. These changes disrupt the stable gene expression programs required to maintain cellular identity and function, thereby contributing to the pathogenesis of irreversible blinding diseases like glaucoma and age-related macular degeneration (AMD). Unlike immutable genetic mutations, the reversible nature of these epigenetic marks offers a novel therapeutic paradigm. Epigenetic reprogramming, a strategy involving the transient expression of Yamanaka factors or chemical cocktails, provides a powerful means to reset this dysregulated epigenetic landscape and restore cells to a more youthful state. Compelling preclinical studies have validated this approach by demonstrating vision restoration in models of optic neuropathy through the rejuvenation of damaged and aged neurons. This review provides a comprehensive overview of ocular aging from an epigenetic perspective, examines the promise and potential concerns of epigenetic reprogramming, and discusses the future of rejuvenation therapies in ophthalmology.

PURPOSE: The incidence of diverticular disease in younger adults has been on the rise over the past decades. This study aimed to evaluate the association between age and postoperative outcomes for patients undergoing colectomy for diverticular disease.

METHODS: A retrospective analysis was performed using the American College of Surgeons National Surgical Quality Improvement Program Participant Use Files between 2016 and 2020. Adults aged ≥18 years who underwent colectomy for diverticular disease were included. Demographic, perioperative, and postoperative variables were analyzed between patients aged <50 and ≥50 years. A multivariable logistic regression was used to identify independent predictors of major intra-abdominal complications, defined as positive when either anastomotic leak or organ/space surgical site infections were present.

RESULTS: A total of 39,729 patients met the inclusion criteria. Younger individuals comprised 23% of the cohort, were less often female (36% vs 61%; P <.001), had a higher mean body mass index (32 vs 29; P <.001), and were more likely to be smokers (28% vs 18%; P <.001). Readmissions were more frequent in older patients (8.5% vs 7.5%; P =.002); however, the median time to first readmission occurred earlier in younger patients (12 vs 15 days; P <.001). In multivariable analysis, among other factors, age younger than 50 years independently increased the risk of major intra-abdominal complications (odds ratio, 1.14; 95% CI, 1.02-1.27).

CONCLUSION: Despite their overall healthier profile, younger patients experience comparable postoperative risk rates with older patients and are at an increased risk of severe intra-abdominal complications. These findings provide insights that add to patient-physician shared decision making.

Kidney transplantation remains the gold standard treatment for end-stage renal disease. The rising prevalence of this condition, at the same time, contributes significantly to the increasing discrepancy between organ supply and demand, impacting the opportunities for treatment while creating challenges for providers and health care systems worldwide. Driven by demographic shifts, the most significant growth in transplant candidates is observed in the older population. Here, we detail characteristics of older recipients who may benefit most from transplantation, with an emphasis on data-driven assessment for candidate selection while also considering the impact of donor organ quality, donation type, and waiting times. Distinguishing between patients with end-stage renal disease who will benefit from transplantation and those who will derive less or no benefit is essential for providing optimal care to older patients while ensuring responsible stewardship of the limited organ supply. We highlight the advantages of preemptive or expedited transplantation to minimize dialysis exposure and address specific considerations for the peri- and postoperative period. Although living donation remains ideal and will shorten the waiting time, kidneys from older or high kidney donor profile index donors show satisfactory outcomes, particularly for older recipients.