Citations

Abstract Objective This study was undertaken to evaluate the response to second treatments for infantile epileptic spasms syndrome (IESS). Methods Infants aged 2–24 months with IESS were prospectively enrolled in the National Infantile Spasms Cohort study at 21 pediatric epilepsy centers in the United States from 2012 to 2018. We analyzed data from infants who initially received standard treatment (hormonal therapy [adrenocorticotropic hormone, high‐dose prednisolone] or vigabatrin), had continued or recurring epileptic spasms, and received a second treatment. We excluded those with tuberous sclerosis. Treatment groups included hormonal therapy followed by vigabatrin (reference), hormonal‐to‐hormonal, hormonal‐to‐nonstandard, vigabatrin‐to‐hormonal, and vigabatrin‐to‐nonstandard. Nonstandard treatments included other antiseizure medications and dietary therapy. Treatment groups were tested for differences in 3‐month clinical remission using a binary logistic regression to estimate odds ratios (ORs). Results There were 153 infants with IESS who received second treatments. The highest rates of 3‐month remission were among infants in the hormonal‐to‐vigabatrin (22/65, 34%) and vigabatrin‐to‐hormonal (9/26, 35%) groups, followed by vigabatrin‐to‐nonstandard (3/10, 30%), hormonal‐to‐hormonal (4/22, 18%), and hormonal‐to‐nonstandard (1/30, 3.3%). Compared to the hormonal‐to‐vigabatrin group (reference), fewer infants had remission in the hormonal‐to‐nonstandard group (OR = .07, 95% confidence interval [CI] = .01–.53), and there was a trend toward fewer infants in the hormonal‐to‐hormonal group (OR = .43, 95% CI = .13–1.4, p = .17). Following initial hormonal treatment, the number needed to treat was three infants for one additional infant to have remission when treated with vigabatrin compared to nonstandard therapy as the second treatment. Significance This updated analysis with an expanded sample size provided power for additional subgroup analysis. Overall response rates were low, and at best only one third had remission after second treatment. Results support a clinical strategy of switching mechanism of action when selecting a second medication for epileptic spasms (i.e., use vigabatrin after hormonal therapy, or hormonal therapy after vigabatrin). Our findings also support the use of standard over nonstandard therapies.

Activation of oncogenes, such as through mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS), triggers profound disruptions in cellular homeostasis that set off a cascade of stress responses. These responses enable cells to cope with the array of challenges encountered during tumorigenesis by activating defense mechanisms that promote adaptation and survival. Key components of this oncogenic stress response include heat shock proteins, the ubiquitin-proteasome system, autophagy, nuclear factor erythroid 2-related factor 2–antioxidant response element signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules. This review concentrates on KRAS-driven oncogenic transformation, as KRAS mutations are among the most common in human cancers, accounting for over 90% of pancreatic ductal adenocarcinoma cases, around 30% of lung cancers, and approximately 50% of colorectal cancers. We examine the intricate molecular interplay between oncogenic stress and the associated cellular defense mechanisms, emphasizing the key molecular events that follow KRAS activation. Importantly, the very pathways that allow cancer cells to adapt to oncogenic stress also offer novel therapeutic opportunities. By selectively targeting pivotal regulators within these stress response pathways, we can potentially disrupt the survival mechanisms of cancer cells. This strategy not only promises to enhance the effectiveness of existing treatments but also paves the way for the development of innovative therapies designed to combat tumor progression. In essence, exploiting oncogenic stress responses represents an original and promising therapeutic approach in the fight against cancer.

AbstractINTRODUCTIONGiven the close interactions between the retina and the brain, retinal amyloid imaging may serve as a diagnostic and prognostic tool for Alzheimer's disease and related dementias. This retrospective study investigated multivariable associations between retinal perivascular amyloid and cognitive domains.METHODSIntegrated analysis of retinal perivascular amyloid imaging, neuropsychological assessment, and brain magnetic resonance imaging in adults with and without cognitive impairment (N = 26; mean age: 65 ± 7 years; 50% female). Correlations between perivascular amyloid plaque burden and cognitive domains were evaluated with linear regression and interactions with hippocampal volumetry were explored.RESULTSHigher perivascular and periarteriolar amyloid plaque count in the secondary small and tertiary branches were associated with poorer verbal and visual memory in this cohort (p = 0.005–0.009). Higher perivascular amyloid burden interacted with hippocampal atrophy to worsen visual memory (p = 0.033).DISCUSSIONRetinal perivascular amyloid may serve as a non‐invasive marker for cognitive impairment and may shed insight into pathological changes in the brain.Highlights In vivo retinal perivascular amyloid plaque counts are associated with poorer memory. Retinal perivascular amyloid interacted with hippocampal atrophy to worsen memory. Retinal amyloid imaging is a potential biomarker for neurodegenerative diseases.

Importance Bilateral vocal cord paralysis is a challenging problem to manage in adults, and a known complication of thyroid surgery which is more common in resource-limited settings. Posterior graft laryngotracheal reconstruction is a management option that has not been studied in this population or setting. Objective To report the surgical outcomes of posterior graft laryngotracheal reconstruction for bilateral vocal cord paralysis in a resource-limited setting, and to evaluate the efficacy of a hybrid system for teaching this technique in Kenya. Design Retrospective cohort study. Setting Tertiary public referral hospital, Eldoret, Kenya Participants Adults >18 years with tracheostomy dependence secondary to bilateral vocal cord paralysis after thyroid surgery or other iatrogenesis. The hybrid training program included Kenyan surgeons and surgical trainees. Intervention or Exposures Posterior graft laryngotracheal reconstruction and hybrid training system included didactic lectures, simulation-based training, case discussion and planning, and live cases. Main Outcomes Measures One-year airway outcomes measured by achievement of tracheostomy decannulation, and self-reported surgeon knowledge and skill acquisition. Results Ten patients met criteria and were included in the analysis, with mean age 42 years (range 30-62 years) and had been tracheostomy dependent for an average of 6 years (range 1-12 years). Seven (70%) had open reconstruction, and 3 (30%) had endoscopic reconstruction. All were decannulated and remained tracheostomy-free at 1 year. Three surgeons and 7 trainees participated in the hybrid teaching methods. All reported increased comfort in laryngotracheal reconstruction, with all 3 surgeons reporting comfort performing the surgeries independently. Conclusion Posterior graft laryngotracheal reconstruction shows promise as a potential method of treating bilateral vocal cord paralysis and achieving decannulation in a resource-limited setting. Relevance The methods reported in this study lend themselves to replication and expansion to other similar settings. The authors plan to replicate this work in other centers in East Africa.

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.

Although innovation in cancer treatment has improved cure rates and survival, the costs have escalated beyond societies' ability to pay. Cancer care costs in the United States are expected to rise to 245 billion by 2030. In this health policy session, we focused on three cost-containment strategies, and their potential impact on cancer care delivery. Site Neutrality: Curbing the Cost of Cancer Care, but at What Risk? , explores legislation that would introduce payment parity across differing sites of care: elimination of facility fees in hospital owned practices and shift of billing for oncology infusions away from hospital owned practices. Unintended consequences could reduce access to care for vulnerable populations, shift costs to patients, and reduce safety. Post-Pandemic Digital Health Reimbursement: Impact on Access to Care , explores how the emergency waivers, licensure flexibilities, and parity reimbursement necessitated by COVID-19 shepherded innovation that outpaced the regulatory framework needed for long-term sustainability. Today, telehealth services, hospital at home, remote patient monitoring, and decentralized clinical trial enrollment face reintroduction of regulatory and payment barriers. Will we live to see efficacy-based pricing for cancer drugs? Learning from international models , explores how lack of drug price negotiation has led to higher prices in the United States compared with Canada and Europe. Comparative clinical effectiveness pricing systems compare the value of each drug to standard treatments. Comparative cost-effectiveness programs look at the incremental cost per additional unit of health gained above the standard of care. The United States could learn from these approaches used in comparable countries.

Prosthetic heart valve (PHV) dysfunction is increasingly seen due to the increase in the number of PHV that are being implanted worldwide. Cardiac CT imaging has emerged as a valuable tool to assess PHVs and determine the cause of dysfunction. This consensus document first summarizes the available techniques for PHV assessment. Then the use of CT in PHV (dys)function assessment is discussed in detail including consensus statements for correct indications and patient selection for CT assessment of PHVs, image acquisition, reconstruction and measurement protocols and how to interpret and report the CT findings for specific types of PHV dysfunction. This article was published in Journal of Cardiovascular Computed Tomography, Budde RPJ et al, Cardiac computed tomography for prosthetic heart valve assessment: An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the European Society of Cardiovascular Radiology (ESCR), the North American Society for Cardiovascular Imaging (NASCI), the Radiological Society of North America (RSNA), the Society for Cardiovascular Angiography & Interventions (SCAI), and the Society of Thoracic Surgeons (STS). The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation may be used when referencing this document. © 2025 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. on behalf of the Society of Cardiovascular Computed Tomography. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Keywords: Computed Tomography, Valve, Cardiac, Imaging, Dysfunction, Prosthetic