Citations

THE 2025 American Society of Clinical Oncology (ASCO) Annual Meeting underscored a key principle: in today’s complex and rapidly evolving cancer landscape, the application of knowledge, not just its acquisition, is our most powerful tool for progress. Robin Zon’s presidential theme, “Driving Knowledge to Action: Building a Better Future,” was brought to life across the plenary sessions and data presentations that spanned tumor types, geographies, and therapeutic modalities. Two dominant motifs emerged from the most practice-changing studies: the use of large-scale, well-designed clinical trials to validate transformative interventions, and a growing effort to repurpose effective therapies earlier in the disease course, challenging historical treatment sequences. These principles reflect the essence of oncology’s future: evidence-powered, patient-centered, and accessible to all.

Objectives The effect of ovarian reserve on expected in vitro fertilisation (IVF) attrition remains controversial. This study analyses IVF attrition rates based on ovarian reserve and stimulation protocol to create customised pre-treatment counselling tools for assisting clinicians in setting accurate patient expectations. Material and Methods We completed a retrospective chart review of 18–44-year-old patients who underwent IVF treatment at a single academic institution between January 1, 2013, and March 23, 2023. Cycle outcomes, number of retrieved oocytes, mature oocytes, fertilised embryos, and blastocysts were analysed for patients with polycystic ovary syndrome (PCOS), unexplained infertility, and diminished ovarian reserve (DOR). A Poisson regression model was used to compare oocyte maturation, fertilisation, and blastulation rates among groups, adjusted for age, body mass index, race, and insemination method. Results Three hundred and thirteen couples underwent a total of 385 IVF cycles analysed in this study. There were 109 patients who underwent 120 cycles in the unexplained infertility group (31% cycles), 133 patients with 143 cycles in the PCOS group (37% cycles), 40 patients with 45 cycles in the DOR antagonist stimulation group (12% cycles), and 39 patients with 77 cycles in the DOR minimal stimulation group (20% cycles). No differences in oocyte maturation, fertilisation, or blastulation rate were seen among PCOS or DOR antagonist cycle groups when compared to unexplained infertility. After adjusting for confounders, blastulation rate was higher for the DOR minimal stimulation group compared to unexplained infertility (1.37-fold change, p = 0.04). Conclusion Rates of oocyte maturation, fertilisation, and blastulation were similar among all antagonist protocol cycles regardless of ovarian reserve. However, patients with DOR who undergo minimal stimulation may have modestly higher blastulation rates compared to DOR patients who undergo the antagonist protocol.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Abstract Background and objective The placenta is crucial for fetal development; altered function is associated with complications and adverse neonatal outcomes. Our goal was to ascertain changes in the placental transcriptome in relation to neonatal outcome and fetal/placental sex. Study design Seventy-two mother-baby dyads were included. Demographic, obstetrical, neonatal, and infant health data were obtained through medical charts. Adverse neonatal outcome was defined as the presence of a pulmonary, cardiac, neurological or other health complication. Bulk RNA-sequencing of placental biopsies was obtained. P-value <0.05 was considered statistically significant. Results Neonates experiencing adverse outcomes were more likely to be premature or have lower birth weights. Analysis of the placental transcriptome revealed a predominant inflammatory profile in pregnancies associated with adverse neonatal outcomes with the top pathways being related to immune and inflammatory responses. Among differently expressed genes (DEGs), 1237 were upregulated and 239 were downregulated in adverse vs no adverse outcomes. Furthermore, sex-specific differences in gene expression were observed and indicated that male and female placentas displayed unique DEGs in association with adverse outcomes. Indeed, no DEG was observed in female placentas when comparing those without vs with adverse neonatal outcomes, as opposed to 1279 DEGs in male placentas, of which 91% were up-regulated in adverse subgroups. Conclusions These findings highlight that inflammatory pathways are upregulated in placentas in association with adverse neonatal outcomes, and showcase the importance of the fetal sex in understanding neonatal health. The placenta provides a unique tool for early identification of high-risk infants rapidly after delivery.

Abstract Astrocytes, the most abundant glial cells in the central nervous system (CNS), play essential roles in maintaining neuronal homeostasis, synaptic regulation, and blood–brain barrier integrity. However, these cells can undergo senescence—a cellular state characterized by irreversible growth arrest and the secretion of proinflammatory factors—in response to aging and pathological stressors, contributing to synaptic dysfunction and neurodegenerative diseases. This review examines the molecular mechanisms driving astrocytic senescence, including oxidative stress, DNA damage, and inflammatory signaling pathways such as NF-κB and the senescence-associated secretory phenotype. A particular focus is placed on the diverse array of known chemical inducers of astrocyte senescence, such as pesticides and heavy metals, which provide critical insights into the processes governing cellular aging in the brain. By analyzing the effects of these inducers, we highlight their implications for neurodegenerative disease progression and brain aging. Understanding astrocytic senescence offers new insights into age-related neuropathology and presents promising avenues for targeted therapies in neurodegenerative disorders induced by environmental toxicants.

Accurate analysis of medical videos remains a major challenge in deep learning (DL) due to the need for effective spatiotemporal feature mapping that captures both spatial detail and temporal dynamics. Despite advances in DL, most existing models in medical AI focus on static images, overlooking critical temporal cues present in video data. To bridge this gap, a novel DL-based framework is proposed for spatiotemporal feature extraction from medical video sequences. As a feasibility use case, this study focuses on gastrointestinal (GI) endoscopic video classification. A 3D convolutional neural network (CNN) is developed to classify upper and lower GI endoscopic videos using the hyperKvasir dataset, which contains 314 lower and 60 upper GI videos. To address data imbalance, 60 matched pairs of videos are randomly selected across 20 experimental runs. Videos are resized to 224 × 224, and the 3D CNN captures spatiotemporal information. A 3D version of the parallel spatial and channel squeeze-and-excitation (P-scSE) is implemented, and a new block called the residual with parallel attention (RPA) block is proposed by combining P-scSE3D with a residual block. To reduce computational complexity, a (2 + 1)D convolution is used in place of full 3D convolution. The model achieves an average accuracy of 0.933, precision of 0.932, recall of 0.944, F1-score of 0.935, and AUC of 0.933. It is also observed that the integration of P-scSE3D increased the F1-score by 7%. This preliminary work opens avenues for exploring various GI endoscopic video-based prospective studies.

ABSTRACT Weight recurrence is a late complication after Roux-en-Y gastric bypass. The transoral outlet reduction (TORe) emerged as an endoscopic alternative to revisional surgery for weight recurrence due to a dilated and incompetent gastrojejunal anastomosis. The procedure has been documented as safe and effective in clinical trials and other high-quality medical literature. Several cases of squamous metaplasia of the gastric pouch after repeated TORe procedures using argon plasma coagulation have been reported. We present a case of a late-onset adenocarcinoma of the gastrojejunal anastomosis after a TORe procedure performed using argon plasma coagulation and suturing.

ABSTRACT Carbapenem‐resistant Acinetobacter baumannii (CRAB) are difficult‐to‐treat pathogens that primarily cause health care‐associated infections. Sulbactam/durlobactam (SUL/DUR) is a novel antibiotic combination that is uniquely formulated to target CRAB isolates. However, investigations of SUL/DUR's pharmacokinetics in obese patients are limited. Here, we report on the successful treatment of CRAB bacteremia in a patient with acute renal failure and severe obesity (weight 273 kg, body mass index 103 kg/m 2 ) with SUL/DUR and meropenem combination therapy. The patient had a calculated creatinine clearance of 25 mL/min and received therapy with intravenous SUL/DUR 1 g/1 g every 8 h over 3 h in combination with intravenous meropenem 500 mg every 8 h to complete 14 days of therapy. Pharmacokinetic analysis revealed target attainment with prolonged half‐life ( T 1/2 ) and volume of distribution (Vd) of 35.3 h and 81.3 L for sulbactam and 30.5 h and 169.1 L for durlobactam, respectively. Susceptibility testing using the broth disk elution test did not show synergy between SUL/DUR and meropenem. No adverse effects were observed, and the patient achieved clinical cure without recurrence of A. baumannii infection.