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IntroductionPalbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses.Materials and methodsWe conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years).ResultsOf the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]).DiscussionPalbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults.Clinicaltrialsgov:NCT03633331.

Abstract Purpose To evaluate access site adverse events following ClotTriever-mediated large-bore mechanical thrombectomy via small upper extremity deep veins ( 6-mm diameter veins accessed (n = 3) were excluded. Temporary purse-string sutures and manual pressure were used for access site hemostasis in all patients. Vein access site and diameter, technical success (defined as placement of the 13.5-French ClotTriever sheath followed by thrombectomy), and early ( 30-days) access site-related adverse events (according to the Adverse Event Classification by the Society of Interventional Radiology criteria) were recorded. Results Fourteen patients (8 males, 6 females; mean age 51.7 ± 13.6 years) comprising 16 upper extremity venous access sites were included in this study. Access sites included: right brachial (n = 7), left brachial (n = 5), and bilateral brachial (n = 2) veins. The mean access site diameter was 4.3-mm ± 0.67-mm. Technical success was achieved via all access sites. Six (42.9%) patients underwent stent reconstruction following thrombectomy through the same accesses. After the procedure, all purse-string sutures were removed within 24 h. Three (21.4%) patients experienced small access site hematomas that did not require transfusion, intervention, or prolonged hospitalization. Initial follow-up venous duplex ultrasounds were performed at 29.3 ± 21.7 days following intervention. The mean follow-up interval to the second and third venous duplex ultrasounds were 124.3 ± 64-days and 225.1 ± 80.1 days, respectively. One (7.1%) patient developed right arm swelling six days after the procedure and was found to have thrombosis of the previously accessed right brachial vein. No other clinically or sonographically significant access site adverse events were observed. Conclusion ClotTriever-mediated large-bore thrombectomy via small upper extremity veins is safe with minimal access site adverse events.

Advancements in artificial intelligence (AI) have significantly transformed the field of abdominal radiology, leading to an improvement in diagnostic and disease management capabilities. This narrative review seeks to evaluate the current standing of AI in abdominal imaging, with a focus on recent literature contributions. This work explores the diagnosis and characterization of hepatobiliary, pancreatic, gastric, colonic, and other pathologies. In addition, the role of AI has been observed to help differentiate renal, adrenal, and splenic disorders. Furthermore, workflow optimization strategies and quantitative imaging techniques used for the measurement and characterization of tissue properties, including radiomics and deep learning, are highlighted. An assessment of how these advancements enable more precise diagnosis, tumor description, and body composition evaluation is presented, which ultimately advances the clinical effectiveness and productivity of radiology. Despite the advancements of AI in abdominal imaging, technical, ethical, and legal challenges persist, and these challenges, as well as opportunities for future development, are highlighted.

BackgroundThrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding.MethodsSubjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021. Follow-up closed in January 2022. Primary endpoint was dose adjustment for thrombocytopenia. Competing endpoints were discontinuation of drug for other toxicity, disease progression, or for completion of prescribed cycles. The association between Asian ancestry and thrombocytopenia-related dose adjustment was tested at p

Renal cell carcinoma (RCC) is the most common primary renal malignancy. Prevalence of RCC in developed countries has slowly increased. Although partial or total nephrectomy has been the first-line treatment for early-stage RCC, improved or similar safety and treatment outcomes with locoregional therapies have challenged this paradigm. In this review, we explore locoregional techniques for early-stage RCC, including radiofrequency ablation, cryoablation, and microwave ablation with a focus on procedural technique, patient selection, and safety/treatment outcomes. Furthermore, we discuss future advances and novel techniques, including radiomics, combination therapy, high-intensity focused ultrasound, and catheter-directed techniques.

Neuroendocrine tumors (NETs) are a heterogeneous class of cancers, predominately occurring in the gastroenteropancreatic system, which pose a growing health concern with a significant rise in incidence over the past four decades. Emerging from neuroendocrine cells, these tumors often elicit paraneoplastic syndromes such as carcinoid syndrome, which can manifest as a constellation of symptoms significantly impacting patients’ quality of life. The prognosis of NETs is influenced by their tendency for metastasis, especially in cases involving the liver, where the estimated 5-year survival is between 20 and 40%. Although surgical resection remains the preferred curative option, challenges emerge in cases of neuroendocrine tumors with liver metastasis (NELM) with multifocal lobar involvement, and many patients may not meet the criteria for surgery. Thus, minimally invasive and non-surgical treatments, such as locoregional therapies, have surfaced. Overall, these approaches aim to prioritize symptom relief and aid in overall tumor control. This review examines locoregional therapies, encompassing catheter-driven procedures, ablative techniques, and radioembolization therapies. These interventions play a pivotal role in enhancing progression-free survival and managing hormonal symptoms, contributing to the dynamic landscape of evolving NELM treatment. This review meticulously explores each modality, presenting the current state of the literature on their utilization and efficacy in addressing NELM.

This research focusses on the potential application of artificial intelligence (AI) techniques in the analysis of behavioural addictions, specifically addressing problematic Internet use among adolescents. Using tabular data from a representative sample from Serbian high schools, the authors investigated the feasibility of employing eXplainable AI (XAI) techniques, placing special emphasis on feature selection and feature importance methods. The results indicate a successful application to tabular data, with global interpretations that effectively describe predictive models. These findings align with previous research, which confirms both relevance and accuracy. Interpretations of individual predictions reveal the impact of features, especially in cases of misclassified instances, underscoring the significance of XAI techniques in error analysis and resolution. Although AI’s influence on the medical domain is substantial, the current state of XAI techniques, although useful, is not yet advanced enough for the reliable interpretation of predictions. Nevertheless, XAI techniques play a crucial role in problem identification and the validation of AI models.

Abstract Purpose The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long‐term breast cancer survivors 5–15 years after chemotherapy treatment. Methods Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C‐) 5–15 years prior and age‐ and sex‐matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI. Results The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C+ group, 12 participants for the C‐ group, and 13 participants for the HC group. The C+ group had increased gyrification in six local gyral regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in two local gyral regions from TP1 to TP2 (p

Abstract Background Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2‐negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity. Methods In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68). Results We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple‐negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression. Conclusion This retrospective, real‐world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes.

Interventional radiology (IR) is a unique specialty that incorporates a diverse set of skills ranging from imaging, procedures, consultation, and patient management. Understanding how IR generates value to the healthcare system is important to review from various perspectives. IR specialists need to understand how to meet demands from various stakeholders to expand their practice improving patient care. Thus, this review discusses the domains of value contributed to medical systems and outlines the parameters of success. IR benefits five distinct parties: patients, practitioners, payers, employers, and innovators. Value to patients and providers is delivered through a wide set of diagnostic and therapeutic interventions. Payers and hospital systems financially benefit from the reduced cost in medical management secondary to fast patient recovery, outpatient procedures, fewer complications, and the prestige of offering diverse expertise for complex patients. Lastly, IR is a field of rapid innovation implementing new procedural technology and techniques. Overall, IR must actively advocate for further growth and influence in the medical field as their value continues to expand in multiple domains. Despite being a nascent specialty, IR has become indispensable to modern medical practice.

A 50-year-old female developed kidney stones on an eroded embolization coil 16 months after percutaneous nephrolithotomy (PCNL) related bleeding complications. Retrograde ureteroscopy and thulium laser lithotripsy was performed to fragment the exposed portion of the coil into clinically insignificant pieces. Thulium laser coil fragmentation remains a potential strategy to remove eroded coils and their associated kidney stones; however, recurrent stone formation on the coil stump may necessitate repeat intervention if this conservative approach is pursued over radical antegrade coil removal. This case highlights the importance of continued surveillance and multidisciplinary management in preventing and treating coil erosion after PCNL.

The paper deals with the issues of indirect and associative discrimination in the European Union law, with focus on the case law of the European Court of Justice, and the importance of the case law of this court for the sphere of employment. While prohibition of indirect discrimination was introduced in the European Union law a couple of decades ago, associative discrimination at the European Union level is, so far, addressed only by the European Court of Justice. In this regard, the concept of associative discrimination is still, to some extent, vague and subject to debate, while the dilemmas and risks in relation to this concept exponentially grow when reflected upon through lenses of indirect discrimination. The goal of the paper is to point out the importance, but also the risks of recognizing indirect associative discrimination in employment, all in the context of taking one step further in achieving substantive equality in the world of work.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with an average five-year survival rate in the US of 19.6%. With the advent of HBV and HCV treatment and prevention, along with the rising rates of obesity, nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are set to overtake infectious causes as the most common cause of HCC. While surgical resection and transplantation can be curative when amenable, the disease is most commonly unresectable on presentation, and other treatment approaches are the mainstay of therapy. In these patients, locoregional therapies have evolved as a vital tool in both palliation for advanced disease and as a bridge to surgical resection and transplantation. In this review, we will be exploring the primary locoregional therapies for HCC in patients with NAFLD, including transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial radioembolization (TARE), and percutaneous ablation.

PurposeThe objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5–15 years prior.MethodsThis study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C−), and healthy controls (HC). The participants were recruited 5–15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests.ResultsAt TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = −0.585, p = 0.007).ConclusionThe observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

A robust breast cancer prevention strategy requires risk assessment biomarkers for early detection. We show that expression of ELF5, a transcription factor critical for normal mammary development, is downregulated in mammary luminal epithelia with age. DNA methylation of the ELF5 promoter is negatively correlated with expression in an age-dependent manner. Both ELF5 methylation and gene expression were used to build biological clocks to estimate chronological ages of mammary epithelia. ELF5 clock-based estimates of biological age in luminal epithelia from average-risk women were within three years of chronological age. Biological ages of breast epithelia from BRCA1 or BRCA2 mutation carriers, who were high risk for developing breast cancer, suggested they were accelerated by two decades relative to chronological age. The ELF5 DNA methylation clock had better performance at predicting biological age in luminal epithelial cells as compared with two other epigenetic clocks based on whole tissues. We propose that the changes in ELF5 expression or ELF5-proximal DNA methylation in luminal epithelia are emergent properties of at-risk breast tissue and constitute breast-specific biological clocks. PREVENTION RELEVANCE: ELF5 expression or DNA methylation level at the ELF5 promoter region can be used as breast-specific biological clocks to identify women at higher than average risk of breast cancer.

The advent of artificial intelligence (AI) is revolutionizing medicine, particularly radiology. With the development of newer models, AI applications are demonstrating improved performance and versatile utility in the clinical setting. Thoracic imaging is an area of profound interest, given the prevalence of chest imaging and the significant health implications of thoracic diseases. This review aims to highlight the promising applications of AI within thoracic imaging. It examines the role of AI, including its contributions to improving diagnostic evaluation and interpretation, enhancing workflow, and aiding in invasive procedures. Next, it further highlights the current challenges and limitations faced by AI, such as the necessity of ‘big data’, ethical and legal considerations, and bias in representation. Lastly, it explores the potential directions for the application of AI in thoracic radiology.

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).

More than 800,000 people worldwide are diagnosed with HCC (hepatocellular carcinoma) each year, with approximately 700,000 deaths alone occurring in that same year. Treatment of HCC presents complex therapeutic challenges, particularly in intermediate and advanced stages. LRTs such as transarterial chemoembolization (TACE) and ablations have been the mainstay treatment for early to intermediate-stage HCC, and systemic therapies are used to treat intermediate-late-stage HCC. However, novel literature describing combining LRT with systemic therapies has shown promising results. This review explores recent advances in both liver-directed techniques for hepatocellular carcinoma, including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies in conjunction as well as with systemic therapies, with a focus on combination therapies, patient selection, procedural technique, periprocedural management, and outcomes. Our findings suggest that LRT combined with systemic therapies is a viable strategy for improving progression-free survival and time to progression for patients with intermediate-to-late-stage HCC. However, further investigation is required to refine treatment protocols and define patient cohorts that would benefit the most.

Abstract Purpose To assess white matter microstructural changes in older long‐term breast cancer survivors 5–15 years post‐chemotherapy treatment. Methods Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C−) and age‐ and sex‐matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract‐based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. Results There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p

Abstract CRH neurons are found in the paraventricular nucleus(PVN) and central amygdala(CeA) nuclei. This study investigated the effects of sub-chronic CRH administration into the PVN and CeA nuclei on food intake biomarkers in rats divided into five groups: control, two shams, and two CRH-PVN and CRH-CeA groups(receiving CRH in nuclei for seven days). The CRH-PVN group had significantly higher cumulative food intake and food intake trends than the CRH-CeA group. The CRH-CeA and CRH-PVN groups exhibited significant increases in food intake during hours 1 and 2, respectively. Moreover, to be time-dependent, food intake is modulated by different brain nuclei. The CRH signaling pathway appeared to be activated later in the PVN than CeA. Both groups exhibited significantly higher leptin levels, the CRH-PVN group exhibited higher ghrelin levels and lower glucose levels. Repetitive administration of CRH into the PVN and CeA significantly reduced body weight differences. CRH administration into the PVN affected both leptin and ghrelin levels, but ghrelin had a greater impact on glucose variations and cumulative food intake than leptin. Finally, CRH administration into the PVN and CeA likely activated the HPA axis, and the CeA had a greater impact on the stress circuit than on food intake behavior.

Intraoperative tumor thrombus embolization is a potentially lethal complication during inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC). Intraoperative embolization is uncommonly encountered because IVC thrombectomy surgical technique is focused on avoiding this complication. Nonetheless, early recognition of embolization is essential so that emergent management can be instituted. When available, cardiopulmonary bypass (CPB) and embolectomy should be considered the gold standard for the management of intraoperative embolization. Several novel endovascular techniques are also available for selective use. We present the case of a 71-year-old female with a right renal mass and level II (retrohepatic) IVC tumor thrombus. During cytoreductive nephrectomy and IVC thrombectomy, tumor embolization was diagnosed during a period of hypotension based on transesophageal echocardiographic finding of new thrombus within the right atrium. This prompted sternotomy, CPB, and pulmonary artery embolectomy. The patient survived this embolization event and has a complete response to systemic therapy 9 months postoperatively. This case serves as the framework for a discussion on management considerations surrounding intraoperative embolization during IVC thrombectomy.