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Abstract Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients. Median follow up from T-DXd initiation was 13.9 months. The cumulative incidence of symptomatic radiation necrosis at 24 months per lesion was 2.1% and per patient 11%. The 12-month LC was 97%. HER2-low was associated with worse distant intracranial control (DIC) (adjusted HR 2.5, 95% CI 1.1–5.6, p = 0.03) and worse systemic progression free survival (PFS) (HR 4.1, 95% CI 1.6–10.7, p = 0.004). Concurrent SRS and T-DXd has excellent local control, without an increased risk of radiation necrosis. HER2-low disease is associated with worse systemic PFS and DIC with T-DXd compared to HER2+.

Abstract Background Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression‐free survival (PFS) in patients with hormone receptor (HR)‐positive, HER2‐negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real‐world benefit of first‐line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. Methods This study included HR‐positive, HER2‐negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression‐free survival (PFS) was determined using Kaplan–Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil‐to‐lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time‐dependent variable. Results In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93–NR). Median PFS for patients with bone‐only metastases (n = 54) was not reached (95% CI 18.21–NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33–33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71–0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97–1.18, p = 0.203). Conclusion The effectiveness of palbociclib and endocrine therapy in the treatment of HR‐positive, HER2‐negative mBC in the real‐world setting is similar to the efficacy reported in the PALOMA‐2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.

Abstract Background Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). Methods Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. Results Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR−/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15–24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24–30 Gy) in a median of 5 fractions (range: 3–5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. Conclusions In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.

Abstract Background Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. Methods This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. Results One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14–24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. Conclusions We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.

Purpose: We hypothesize treatment with nivolumab and stereotactic radiosurgery (SRS) will be feasible and well tolerated, and may improve intracranial tumor control rates compared with SRS alone. Methods and Materials: The study was designed as a prospective, single-arm, nonrandomized, open-label, phase 1b trial of nivolumab and SRS among patients with metastatic breast cancer brain metastases. Key eligibility criteria included patients with breast cancer brain metastases of all subtypes, age ≥18, Eastern Cooperative Oncology Group Performance Status ≤2 with ≤10 brain metastases. Treatment was initiated with a dose of nivolumab (480 mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1 week later by SRS. This study is closed to accrual and is registered with ClinicalTrials.gov, NCT03807765. Results: Between February 2019 and July 2020, a total of 12 patients were treated to 17 lesions. No dose limiting toxicities were noted in our patient population. The most common neurologic adverse events included grade 1 to 2 headaches and dizziness occurring in 5 (42%) of patients. Median intracranial control was 6.2 months (95% confidence interval, 3-14 months) with 6- and 12-month control rates of 55% and 22%, respectively. A total of 4 patients had systemic progression during the study. Median time to systemic progression free survival has not been reached with 6- and-12 month rates of 63% and 51%, respectively. Conclusions: Nivolumab and SRS is a safe and feasible treatment option in breast cancer brain metastases. Preliminary data reveals activity in certain breast cancer patients to study therapy.

In the past decade, defective DNA repair has been increasingly linked with cancer progression. Human tumors with markers of defective DNA repair and increased replication stress exhibit genomic instability and poor survival rates across tumor types. Seminal studies have demonstrated that genomic instability develops following inactivation of BRCA1, BRCA2, or BRCA-related genes. However, it is recognized that many tumors exhibit genomic instability but lack BRCA inactivation. We sought to identify a pan-cancer mechanism that underpins genomic instability and cancer progression in BRCA-wildtype tumors. Methods: Using multi-omics data from two independent consortia, we analyzed data from dozens of tumor types to identify patient cohorts characterized by poor outcomes, genomic instability, and wildtype BRCA genes. We developed several novel metrics to identify the genetic underpinnings of genomic instability in tumors with wildtype BRCA. Associated clinical data was mined to analyze patient responses to standard of care therapies and potential differences in metastatic dissemination. Results: Systematic analysis of the DNA repair landscape revealed that defective single-strand break repair, translesion synthesis, and non-homologous end-joining effectors drive genomic instability in tumors with wildtype BRCA and BRCA-related genes. Importantly, we find that loss of these effectors promotes replication stress, therapy resistance, and increased primary carcinoma to brain metastasis. Conclusions: Our results have defined a new pan-cancer class of tumors characterized by replicative instability (RIN). RIN is defined by the accumulation of intra-chromosomal, gene-level gain and loss events at replication stress sensitive (RSS) genome sites. We find that RIN accelerates cancer progression by driving copy number alterations and transcriptional program rewiring that promote tumor evolution. Clinically, we find that RIN drives therapy resistance and distant metastases across multiple tumor types.

Abstract Background A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center’s Total Cancer Care (TCC) patients with non-metastatic breast cancer. Methods Affymetrix gene expression profiles were used to interrogate the CS by the principal component method. Breast tumors were classified as high or low score based on median split, and correlations between clinicopathologic variables, PAM50 molecular subtype, and ELN formation were analyzed using the TCC dataset. Differences in overall survival (OS) and recurrence-free survival (RFS) in the larger KM Plot breast cancer public datasets were compared using Kaplan-Meier curves. Results We divided the Total Cancer Care (TCC) breast cancer patients into two groups of high or low CS. Mean CS was 0.24 (range, 2.2–2.1). Patients with higher CS were more likely to be white (172 vs. 159; p = 0.03), had poorly differentiated tumors (112 vs. 59; p

Long-term data establishes the efficacy of radiotherapy in the adjuvant management of breast cancer. New dose and fractionation schemas have evolved and are available, each with unique risks and rewards. Current efforts are ongoing to tailor radiotherapy to the unique biology of breast cancer. In this review, we discuss our efforts to personalize radiotherapy dosing using genomic data and the implications for future clinical trials. We also explore immune mechanisms that may contribute to a tumor’s unique radiation sensitivity or resistance.

Importance: Current chemotherapy regimens for patients with ERBB2 (formerly HER2)-positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies., Objective: To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2-targeted therapies., Design, Setting, and Participants: This phase 1 (lead-in phase of a single-center phase 2 trial) nonrandomized clinical trial was conducted at Moffitt Cancer Center (Tampa, Florida). Patients were enrolled from October 2021 to October 2022. Data were analyzed in 2023 Patients with early-stage ERBB2-positive breast cancer with tumors 1 cm or larger were eligible., Interventions: Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m2, intravenously, 12 times weekly. Trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) were administered intravenously every 3 weeks for 6 cycles starting from day 1 of cDC1 injections. Two dose levels (DLs) of IT cDC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated, including 6 patients in each DL., Main Outcomes and Measures: The primary outcomes were the safety and immune response, and the secondary outcomes were the antitumor efficacy as measured by breast magnetic resonance imaging and residual cancer burden at surgery following neoadjuvant therapy., Results: Twelve ERBB2-positive patients were enrolled and received treatment (DL1 = 6 and DL2 = 6). Nine patients had hormone receptor-positive disease and 3 had hormone receptor-negative disease, with clinical stage I (n = 5), II (n = 4), and III (n = 3). The most frequently observed adverse events with cDC1 were grade 1 to 2 chills (50%), fatigue (41.7%), headache (33%), and injection site reactions (33%). DL2 was associated with a diminished anti-ERBB2 CD4 T-helper 1 blood response with a concomitant increase in innate and adaptive responses within the tumor. Preimmunotherapy and postimmunotherapy breast magnetic resonance imaging results showed 9 objective responses, 6 partial responses, 3 complete responses, and 3 stable diseases. Following surgery, 7 patients had a pathologic complete response., Conclusions and Relevance: In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose., Trial Registration: ClinicalTrials.gov Identifier: NCT05325632.

Background: Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure., Objectives: This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE)., Methods: This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints., Results: Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT., Conclusions: This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66)., Competing Interests: Funding Support and Author Disclosures The study has been supported with an unrestricted grant by AstraZeneca. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Focused cardiac ultrasound (FoCUS) is increasingly applied in many specialities, and adequate education and training of physicians is therefore mandatory. This study aimed to assess the impact of artificial intelligence (AI)-assisted interactive focused cardiac ultrasound (FoCUS) teaching session on undergraduate medical students' confidence level and knowledge in cardiac ultrasound., Methods: The AI-assisted interactive FoCUS teaching session was held during the 9th National Undergraduate Cardiovascular Conference in London in March 2023 and all undergraduate medical students were invited to attend, and 79 students enrolled and attended the training. Two workshops were conducted each over 3-hour period. Each workshop consisted of a theoretical lecture followed by a supervised hands-on session by experts, first workshop trained 39 students and the second workshop trained 40 students. The students' pre- and post-session knowledge and confidence levels were assessed by Likert-type-scale questionnaires filled in by the students before and immediately after the workshop., Results: A total of 61 pre-session and 52 post-session questionnaires were completed. Confidence level in ultrasound skills increased significantly for all six domains after the workshop, with the greatest improvement seen in obtaining basic cardiac views (p < 0.001 for all six domains). Students strongly agreed about the effectiveness of the teaching session and supported the integration of ultrasound training into their medical curriculum., Conclusions: AI-assisted interactive FoCUS training can be an effective and powerful tool to increase ultrasound skills and confidence levels of undergraduate medical students. Integration of such ultrasound courses into the medical curriculum should therefore be considered., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Cardiac arrest is a hyper-acute condition with a high mortality that requires rapid diagnostics and treatment. As such, point-of-care ultrasound (POCUS) has become a valuable tool in the assessment of these patients. While transthoracic echocardiography (TTE) is the more conventional modality used to find reversible causes of cardiac arrest, transoesophageal echocardiography (TOE) has been increasingly utilised due to its superior image quality, continuous imaging, and ability to be operated away from the patient's chest. TOE also has a number of applications in the aftermath of cardiac arrest, such as during the initiation of extracorporeal cardiopulmonary resuscitation (ECPR) and the subsequent monitoring of extracorporeal membranous oxygenation (ECMO). As TOE has evolved, multiple variations have been developed with different utilities. In this article, we will review the evidence supporting the use of TOE in cardiac arrest and where the different forms of TOE can be applied to evaluate the cardiac arrest patient in a timely and accurate manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy, and time efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting., Methods and Results: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiographies with agreement between key imaging parameters assessed using kappa statistics. The immediate clinical impact of hand-held echocardiography in this population was systematically evaluated. Overall, 262 patients (65 ± 12 years, 71% male) participated. Agreement between hand-held and transthoracic echocardiographies was good-to-excellent (kappa 0.60-1.00) with hand-held echocardiography having an overall negative predictive value of 95%. Hand-held echocardiography was performed rapidly (7.7 ± 1.6 min) and completed a median of 5 (interquartile range 3-20) h earlier than transthoracic echocardiography. Systematic hand-held echocardiography in all patients with acute coronary syndrome identified an important cardiac abnormality in 50%, and the clinical management plan was changed by echocardiography in 42%. In 85% of cases, hand-held echocardiography was sufficient for patient decision-making, and transthoracic echocardiography was no longer deemed necessary., Conclusion: In patients with acute coronary syndrome, hand-held echocardiography provides comparable results to transthoracic echocardiography, can be more rapidly applied, and gives sufficient imaging information for decision-making in the vast majority of patients. Systematic echocardiography has clinical impact in half of patients, supporting the clinical utility of echocardiography in this population and providing an evidence base for current guidelines., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Establishing breast MRI imaging patterns associated with neoadjuvant immunotherapy is needed to monitor response. We analyzed serial breast MRIs in patients receiving neoadjuvant chemo-immunotherapy on the I-SPY2 clinical trial., Methods: Patients with stage 2-3 HER2-negative breast cancer were randomized to weekly paclitaxel (control), weekly paclitaxel and pembrolizumab, or weekly paclitaxel, pembrolizumab and intra-tumoral injection of SD-101, a TLR9 agonist. All patients received AC. Regional lymph nodes were retrospectively evaluated on breast MRI at baseline, 3, 12 and 20 weeks by a single blinded radiologist. MRIs were assessed for development of new regional lymphadenopathy, or increase in the longest diameter or cortical thickness of the largest abnormal regional lymph node., Results: Between 12/2015 and 4/2021, a total of 43 patients enrolled in the control (n = 16) and paclitaxel + pembrolizumab ± SD-101 (n = 27) arms. 12 of 27 patients (44.4%) receiving chemo-immunotherapy experienced increased lymphadenopathy within the first 12 weeks compared to 1 of 16 patients (6.3%) in the control group (p = 0.014). Most patients with increased lymphadenopathy were in the SD101/pembro arm (n = 10, p = 0.002). Increased lymphadenopathy was observed despite concomitant decrease in breast tumor size at all time points. 11 of 12 patients with increased lymphadenopathy had pathologically negative nodes at surgery. There was no association between lymphadenopathy and lower residual cancer burden or immune-related toxicity., Conclusions: The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis particularly in the metastatic setting. Treatments with anti-programmed cell death protein-1/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICI) in combination with chemotherapies have demonstrated promising clinical benefit in metastatic TNBC (mTNBC) but there is still an unmet need, particularly for patients with PD-L1 negative tumors. Mechanisms of resistance to ICIs in mTNBC include the presence of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). Eganelisib is a potent and selective, small molecule PI3K-γ inhibitor that was shown in preclinical studies to reshape the TME by reducing myeloid cell recruitment to tumors and reprogramming TAMs from an immune-suppressive to an immune-activating phenotype and enhancing activity of ICIs. These studies provided rationale for the clinical evaluation of eganelisib in combination with the anti-PD-L1 atezolizumab and nab-paclitaxel in firstline mTNBC in the phase 2 clinical trial MAcrophage Reprogramming in Immuno-Oncology-3 (MARIO-3, NCT03961698). We present here for the first time, in-depth translational analyses from the MARIO-3 study and supplemental data from eganelisib monotherapy Ph1/b study in solid tumors (MARIO-1, NCT02637531)., Methods: Paired pre-treatment and post-treatment tumor biopsies were analyzed for immunophenotyping by multiplex immunofluorescence (n=11), spatial transcriptomics using GeoMx digital spatial profiling (n=12), and PD-L1 immunohistochemistry, (n=18). Peripheral blood samples were analyzed using flow cytometry and multiplex cytokine analysis., Results: Results from paired tumor biopsies from MARIO-3 revealed gene signatures of TAM reprogramming, immune activation and extracellular matrix (ECM) reorganization. Analysis of PD-L1 negative tumors revealed elevated ECM gene signatures at baseline that decreased after treatment. Gene signatures of immune activation were observed regardless of baseline PD-L1 status and occurred in patients having longer progression-free survival. Peripheral blood analyses revealed systemic immune activation., Conclusions: This is the first report of translational analyses including paired tumor biopsies from a phase 2 clinical study of the first-in-class PI3K-γ inhibitor eganelisib in combination with atezolizumab and nab-paclitaxel in frontline mTNBC. These results support the mechanism of action of eganelisib as a TAM-reprogramming immunotherapy and support the rationale for combining eganelisib with ICI and chemotherapy in indications with TAM-driven resistance to ICI., Competing Interests: Competing interests: BCO, RI, CH, NZ, JLK and SP were employees, stockholders and consultant advisors for Infinity Pharmaceuticals. DF was an employee and stockholder of Infinity Pharmaceuticals. BCO is an inventor for PCT International, application number 18/265915 filed on June 7, 2023. AE was issued the following grants: NCI LAPS, DOD CTRA, DOD Clinical Extension Grant. MAC received royalties from Exact Science (formerly Genomic Health) for contribution to invention of Oncotype DX assay and participated in a safety monitoring board for Advarra. DJ received grants from Novartis, Genentech, Syros, Eisai, Pfizer, Takeda, Amgen, InventisBio, Arinas, Blueprint, AstraZeneca, and Ribon Therapeutics as well as personal fees from Vibliome, PIC therapeutics, MapKure, and Relay Therapeutics. JV was a consultant advisor for Infinity Pharmaceuticals and received grants, reagents, and tissue material for preclinical work and biomarker studies related to MARIO-1 study NCT02637531 from Infinity Pharmaceuticals. EH is a consultant advisor for Accutar Biotechnology, AstraZeneca, Daiichi Sankyo, Entos, Fosun Pharma, Gilead Sciences, Greenwich LifeSciences, Jazz Pharmaceuticals, Eli Lilly, Medical Pharma Services, Mersana, Novartis, Olema Pharmaceuticals, Orum Therapeutics, Pfizer, Roche Genentech, Stemline Therapeutics, Theratechnologies, Tubulis, Verascity Science and Zentalis Pharmaceuticals and is an investigator on multiple clinical trials including Infinity Pharmaceuticals study NCT03961698. HS is a consultant for Novartis, AstraZeneca, Seattle Genetics, Puma, Eli Lilly, and received payment from Merck for a speaking engagement. MAC, DJ, KHRT, AE, AL, SD, EH, and HS were investigators on Infinity Pharmaceuticals clinical trial NCT 03961698., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study, conducted under the oversight of National Health Service Blood & Transplant, aimed to evaluate the current feasibility and implementation of both comprehensive and focused donor echocardiography in United Kingdom Intensive Care Units through a nationwide survey. Responses from 95 hospitals across all 4 UK nations showed each ICU had median 4 (IQR 2, 6) personal with 3 (IQR 2, 5) consultants and 1 (IQR 0, 2) registrar trained in focused echocardiography. A comprehensive echocardiogram can be acquired in 48% ( n  = 46) of hospitals within 6 h during regular working hours. This percentage drops to 11% ( n  = 10) outside of regular working hours, with 53% ( n  = 50) indicating this would require more than 24 h. In the case of focused echocardiogram acquisition, 60% ( n  = 57) of hospitals can obtain it within 6 h during normal working hours. This figure decreases to 20% ( n  = 19) outside of regular working hours, with 32% ( n  = 30) indicating that this would require more than 24 h to obtain. Overall, 98% of responding units ( n  = 93) have point-of-care ultrasound machines (median 2 (IQR 2, 3) machines per ICU) all equipped with echocardiographic capabilities. However, only 52% ( n  = 49) of respondents indicated have the ability for remote viewing of echocardiogram images., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2024.)

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Pulmonary vein isolation (PVI) with catheter ablation (CA) represents an effective therapy for atrial fibrillation (AF). Unfortunately, it is still not exempt from severe complications. The balance of risks and benefits should be assessed, and a patient-tailored approach is desirable. So far, several clinical and cardiac imaging parameters have been evaluated to investigate pre- and post-procedural features that could help clinicians in the selection of patients at high risk of a poor outcome after CA. This clinical and systematic review analyses the potential role of new LA parameters, such as LA reservoir strain, to predict AF recurrence after CA therapy. Notably, LA reservoir strain gains substantial clinical importance in patients with paroxysmal AF and when a low CHADS2-VASc score is retrieved. LA reservoir strain provides data concerning the risk of AF recurrence after PVI and, thus, in the management of long-term medical therapy in this patient's group.

Aims: To evaluate the diagnosis and imaging of patients with mitral regurgitation (MR) and the management in routine clinical practice across Europe, the European Association of Cardiovascular Imaging Scientific Initiatives Committee performed a survey across European centres. In particular, the routine use of echocardiography, advanced imaging modalities, heart valve clinics, and heart valve teams was explored., Methods and Results: A total of 61 responders, mainly from tertiary centres or university hospitals, from 26 different countries responded to the survey, which consisted of 22 questions. For most questions related to echocardiography and advanced imaging, the answers were relatively homogeneous and demonstrated good adherence to current recommendations. In particular, the centres used a multi-parametric echocardiographic approach and selected the effective regurgitant orifice and vena contracta width as their preferred assessments. 2D measurements are still the most widely used parameters to assess left ventricular structure; however, the majority use 3D trans-oesophageal echocardiography (TOE) to evaluate valve morphology in severe MR. The majority of centres reported the onsite availability and clinical use of ergometric stress echocardiography, cardiac computed tomography (CCT), and cardiac magnetic resonance (CMR) imaging. Heart valve clinics and heart valve teams were also widely prevalent., Conclusion: Consistent with current guidelines, echocardiography (transthoracic echocardiography and TOE) remains the first-line and central imaging modality for the assessment of MR although the complementary use of 3D TOE, CCT, and CMR appears to be growing. Heart valve clinics and heart valve teams are now widely prevalent., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: None declared.

Background: The use of Point-of-Care Ultrasound (POCUS) has become prevalent across a variety of clinical settings. Many healthcare professionals have started getting hands-on training. To evaluate the effectiveness of such training programs, this study aimed to assess a 4 day POCUS training course on healthcare providers' skills and knowledge acquisition. A secondary objective of this study is to gain valuable insights into the degree of perception, attitude, interest levels and perceived barriers of medical providers performing POCUS., Methods: This is a prospective cohort study performed on healthcare providers in an integrated healthcare facility in Abu Dhabi undergoing the POCUS training course in February 2022. Course participants took a pre-course survey to evaluate their baseline knowledge, skills, confidence, perception, and interest in POCUS. The same survey was repeated immediately post-course. In total, seven healthcare professionals responded to the survey with a response rate of 53.8%. All data and information gathered were used to understand the effectiveness of POCUS training and gain insights into the degree of perception, interest and preparedness of POCUS among healthcare professionals in practice., Results: Our results demonstrated that the brief POCUS course was effective in improving POCUS skills, knowledge and confidence amongst in-practice healthcare providers from varying medical specialties. The median skill score increased from 25% pre-course to 50% post-course. There is a notable increase in all skills scores after the POCUS training course with the greatest change in scores seen for adjusting 'gain and depth of image (54.84%), assessing VeXUS score (52.38%) and evaluating lung congestion (50%). The study also provided valuable insights into the perception, attitude, interest and potential barriers of POCUS implementation. Although significant barriers to POCUS are present including the lack of POCUS curriculum, what is challenging is lack of expertise and skills to perform POCUS. Therefore, medical providers must acquire prespecified skills to fully utilize POCUS effectively., Conclusion: The study confirmed the effectiveness of short POCUS training in improving the skills, knowledge and confidence of medical providers in practice. Healthcare professionals can master POCUS skills and techniques and gain confidence through brief training courses., (© 2024. The Author(s).)

Background: Congestion, marked by elevated cardiac filling pressures and their repercussions, is a contributing factor to morbidity and mortality in heart failure and critical illness. Relying on traditional methods for bedside evaluation often leads to inadequate decongestion and increased hospital readmissions. Point-of-care ultrasound (POCUS), particularly multi-organ POCUS, including the Venous Excess Ultrasound (VExUS) score, offers a promising approach in this scenario. VExUS enables the quantification of systemic venous congestion, aiding in fluid overload states by assessing inferior vena cava and venous Doppler waveforms., Summary: This comprehensive review delves into the latest developments in comprehending and evaluating congestion, shedding light on technical intricacies to enhance the effective application of VExUS. Recent studies emphasize the importance of evaluating signs of hemodynamic congestion before administering intravenous fluids, highlighting the concept of "fluid tolerance." Moreover, VExUS-guided decongestion significantly improves decongestion rates in acute decompensated heart failure patients with acute kidney injury. Newer studies also highlight the prognostic implications of VExUS in the general ICU cohorts not confining to cardiac surgery patients. However, performing VExUS without understanding technical pitfalls may lead to clinical errors. Technical considerations in performing VExUS include nuances related to inferior vena cava and internal jugular vein ultrasound and familiarity with Doppler principles, optimal settings, and artifacts. Additionally, local structural alterations such as those seen in liver and kidney disease impact Doppler waveforms, emphasizing the need for careful interpretation., Key Message: Overall, VExUS presents a valuable tool for assessing congestion and guiding management, provided clinicians are familiar with its technical complexities and interpret findings judiciously., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: Conflict of interest: Dr. Gargani: no conflict of interest related to this paper. Outside of this paper, Dr. Gargani has received consultancy honoraria from Philips Helathcare, GE Healthcare, Caption Health, EchoNous. Dr. Girerd: no conflict of interest related to this paper. Outside of this paper, Dr. Girerd has received consultancy honoraria from Astra Zeneca, Bayer, Boehringer-Ingelheim, Novartis, Lilly, Vifor International. Dr. Platz: no conflict of interest related to this paper. Outside of this paper, Dr. Platz’ employer has received support from Novartis for consulting work, and she has consulted for scPharmaceuticals. She has received research support from the NIH (R01HL148439), the American Heart Association and AstraZeneca. Dr. Pellicori: no conflict of interest related to this paper. Outside of this paper, Dr. Pellicori has received consultancy honoraria and/or sponsorship support from Boehringer Ingelheim, Pharmacosmos, Novartis, Vifor, AstraZeneca and Caption Health, and researchsupport from Bristol Myers Squibb. Dr. Stankovic: no conflict of interest related to this paper. Outside of this paper, Dr. Stankovic has received consultancy honoraria from Servier, Boehringer-Ingelheim, Pfizer, Astra Zeneca, Novartis, Merck Sharp & Dohme. Dr. Palazzuoli: no conflict of interest to declare. Dr. Pivetta: no conflict of interest related to this paper. Outside of this paper, Dr. Pivetta has received research support from Butterfly inc. Dr. Miglioranza: no conflict of interest related to this paper. Outside of this paper, Dr. Miglioranza has received consultancy honoraria from Philips, GE Healthcare, Abbott. Dr. Aboumarie: no conflict of interest to declare. Dr. Agricola: no conflict of interest related to this paper. Outside of this paper, Dr. Agricola has received consultancy honoraria from Philips, Edwards Lifesciences. Dr. Volpicelli: no conflict of interest to declare. Dr. Price: no conflict of interest to declare. Dr. Donal: no conflict of interest related to this paper. Outside of this paper, Dr. Donal has received research funding from Abbott. Dr. Cosyns: no conflict of interest related to this paper. Outside of this paper, Dr. Cosyns has received research funding from Abbott. Dr. Neskovic: no conflict of interest related to this paper. Outside of this paper, Dr. Neskovic has received consultancy honoraria from Bayer, AstraZeneca, Pfizer, Boehringer Ingelheim, Servier and Novartis.

Background: The genus Huffmanela Moravec, 1987 (Nematoda, Trichosomoididae, Huffmanelinae), represents a group of nematodes that infect both marine and freshwater fish, and the main gross feature of infection with different species of the genus is the presence of noticeable dark spots or tracks within the parasitized tissues. The purpose of this study was to describe morphologically and morphometrically the eggs of a new marine species of Huffmanela (Huffmanela persica sp. nov.), which was found in the form of black spots in the ovary and the tunica serosa of the stomach of the daggertooth pike conger (Muraenesox cinereus). The new species differs from Huffmanela hamo, another species reported from musculature of this host in Japan, in egg metrics, eggshell features and targeted organ. Molecular identification and pathological examination of the lesions caused by the new species are also reported., Methods: Nematode eggs with varying degrees of development were separated from the infected tissues (ovary and tunica serosa of stomach) and investigated using light and scanning electron microscopy. Different species-specific markers (small subunit ribosomal DNA, 18S; large subunit ribosomal DNA, 28S; internal transcribed spacer, ITS) were used for molecular identification and phylogenetic study of the new species. Infected tissues were fixed in buffered formalin for pathological investigations., Results: The fully developed eggs of H. persica sp. nov. are distinguished from those previously described from this host on the basis of their measurements (size, 54-68 × 31-43 µm; polar plugs, 6.4-9.7 × 8.4-12 µm; shell thickness, 3.5-6.1 µm) and a delicate but ornate uterine layer (UL) covering the entire eggshell including the polar plugs. Histopathological examination revealed a fibro-granulomatous inflammation in the ovary and the serosal layer of the stomach of infected fish. Maximum-likelihood (ML) phylogenetic analysis recovered a sister relationship between the new species of marine origin and Huffmanela species previously collected from freshwater hosts., Conclusions: The present study is the first to report the molecular characterization and phylogenetic position of a teleost-associated marine species of the genus Huffmanela. A comprehensive list of nominal and innominate populations of Huffmanela is also provided., (© 2023. The Author(s).)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

Aims: To assess the level of transesophageal echocardiography (TOE) knowledge and skills of young cardiologists., Methods and Results: A European Association of Cardiovascular Imaging (EACVI) online study using the first fully virtual simulation-based software was conducted in two periods (9-12 December 2021 and 10-13 April 2022). All young cardiologists eligible to participate (<40 years) across the world were invited to participate. After a short survey, each participant completed two tests: a theoretical test to assess TOE knowledge and a practical test using an online TOE simulator to investigate TOE skills. Among 716 young cardiologists from 81 countries, the mean theoretical test score was 56.8 ± 20.9 points, and the mean practical test score was 47.4 ± 7.2 points (/100 points max each), including 18.4 ± 8.7 points for the acquisition test score and 29.0 ± 6.7 points for the anatomy test score (/50 points max each). Acquisition test scores were higher for four-chamber (2.3 ± 1.5 points), two-chamber (2.2 ± 1.4 points) and three-chamber views (2.3 ± 1.4 points) than for other views (all P < 0.001). Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and EACVI certification for TOE were independently associated with a higher global score (all P < 0.001)., Conclusion: Online evaluation of young cardiologists around the world showed a relatively low level of TOE skills and knowledge. Prior participation to a TOE simulation-based training session, a higher number of TOE exams performed per week, and the EACVI certification for TOE were independently associated with a higher global score., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Compared with non-Hispanic White women, Latina women are less likely to receive genetic counseling (GC) and testing (GT) following BC diagnosis. This study used secondary data analysis to explore beliefs about GC among Latina BC survivors in and outside the US mainland. GC/GT-naïve, high-risk, Spanish-preferring Latina BC survivors (n = 52) in FL and PR completed the Behavioral Beliefs about GC scale. Participants reported high positive beliefs about GC (M = 4.19, SD = 0.92); the majority agreed that GC was beneficial to understand cancer risk (90%) and promote discussion (87%) in their family. Participants reported low-to-moderate scores for barriers (Ms = 1.53-3.40; SDs = 0.59-0.90). The most frequently endorsed barriers were desire for additional GC information (M = 3.44; SD = 0.90), and GC logistic concerns (M = 2.71; SD = 0.80). No statistically significant differences for barriers and benefits scales were identified by place of residence (all ps ≥ 0.12). These findings highlight the importance of delivering culturally sensitive GC information to high-risk Latina BC survivors., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)