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Background: Microsatellite instability (MSI) is a well-established predictive biomarker for immune checkpoint inhibitor (ICI) response in metastatic colon cancer. Both high MSI and tumor mutational burden (TMB) are markers of genomic instability. However, the prognostic and predictive value of TMB in patients with microsatellite stable (MSS) tumors remains unclear., Methods: We evaluated the prognostic significance of TMB levels in MSS metastatic colon cancer patients undergoing standard treatments. Tumor responses were assessed using RECIST v1.1 criteria. Comprehensive clinical and molecular profiling was conducted, including next-generation sequencing (NGS) for TMB evaluation with the TruSight Oncology® kit. Overall survival (OS) was the primary endpoint. Multivariate Cox regression analysis was utilized to assess the relationship among potential prognostic factors., Results: Among 102 MSS metastatic colon cancer patients, high TMB (> 10 mut/mb) was associated with a significantly longer median OS compared to low TMB (70.0 vs 45.0 months, respectively; HR: 0.45; 95% CIs 0.21 to 0.96; P = 0.0396). Multivariate analysis, adjusting for age, gender, number of metastatic sites, response to first-line chemotherapy, RAS mutational status, and liver involvement, identified TMB as an independent prognostic factor, along with response to first-line chemotherapy., Conclusions: Our results highlight the prognostic significance of TMB in MSS metastatic colon cancer patients, suggesting its potential role in patient stratification and treatment decision-making., Competing Interests: Declarations. Ethics approval and consent to participate: In accordance with local and national laws, ethics approval and consent to participate were exempted due to the retrospective/observational and non-interventional nature of the work. However, all patients involved in this study provided written informed consent before undergoing treatment administration and molecular assessments. Consent for publication: Not applicable. Competing interests: Roberto Sirica, Giovanni Savarese, and Monica Ianniello are employed by AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Physicians' adherence to guideline-recommended heart failure (HF) treatment remains suboptimal, especially regarding the target doses. In particular, there is evidence that non-cardiologists are less compliant with HF guideline recommendations. This is likely to have a detrimental impact on patients' survival, readmissions and quality of life. Thus, the present document aims to address the reasons underlying low implementation and under-dosing of guideline-directed medical therapy in HF and to update a guidance for the initiation and rapid titration of HF drugs. In particular, aim of this document is to provide practical indications for drug implementation, to be applied not only by cardiologists but also by GPs and internal medicine doctors., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Glioblastoma (GBM) is a highly aggressive brain cancer with poor clinical outcome. Unfortunately, chemotherapy with temozolomide (TMZ) has a limited efficacy due to resistance mainly attributed to O6-methylguanine methyl transferase (MGMT) activity. Recently, miR-603 and miR-221 have been identified to target MGMT, thus improving the efficacy of temozolomide (TMZ) in the treatment of GBM. Previously, self-assembling nanoparticles (SANPs) have been proposed to deliver miRNAs into the brain. Here, SANP co-encapsulating miRNA-603 (miR-603) and miRNA-221 (miR-221) have been developed to enhance the efficacy of TMZ in the treatment of GBM by preventing the occurrence of chemoresistance. Preliminarily, SANPs encapsulating miRNAs were optimized in terms of lipid composition to assure physical stability and no hemolytic activity. Subsequently, SANPs with the lowest cytotoxicity and excellent internalization efficiency of miRNAs were selected through MTT assay and real-time PCR, respectively. To evaluate a potential synergistic effect between TMZ and miRNAs, MTT and clonogenic assays were performed. In our biological model, miRNA delivery via SANPs in combination with TMZ treatment strongly reduced cell viability and tumorigenic potential. Finally, in vivo assays were carried out on orthotopic xenograft mouse models. The treatment with SANPs encapsulating both miRNAs in combination with TMZ greatly decreased tumour growth, and even more significantly increased animal survival. In conclusion, this strategy provides the rationale for the development of new therapeutic approaches based on SANP technology to deliver miRNAs that play a key role in suppressing tumour., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Mineralocorticoid receptor antagonists (MRA) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but are underused. Point prevalent use has been described, but the kinetics of discontinuation and the extent of reinitiation have not been studied., Methods and Results: Patients with HFrEF enrolled in the Swedish Heart Failure Registry between 2006 and 2021 were linked to the Prescribed Drug Register. The rate of discontinuation during the first year of treatment and reinitiation the year after discontinuation were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to assess the predictors of discontinuation. Of 11 474 MRA new users, 71% remained on therapy at 1 year. Baseline characteristics independently associated with discontinuation were: estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m 2 (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.34-2.27), hyperkalaemia (HR 1.73, 95% CI 1.25-2.40), eGFR 30-60 ml/min/1.73 m 2 (HR 1.51, 95% CI 1.37-1.66), age ≥80 years (HR 1.26, 95% CI 1.10-1.43), enrolment as inpatient (HR 1.25, 95% CI 1.14-1.38), a diagnosis of atrial fibrillation (HR 1.24, 95% CI 1.10-1.39), living alone (HR 1.23, 95% CI 1.13-1.34), ischaemic heart disease (HR 1.20, 95% CI 1.09-1.31), anaemia (HR 1.17, 95% CI 1.07-1.29), diabetes mellitus (HR 1.15, 95% CI 1.04-1.27) and New York Heart Association class III-IV (HR 1.13, 95% CI 1.02-1.24). Reinitiation within a year occurred in 46% of cases, mostly within 3 months after discontinuation., Conclusion: Among patients with HFrEF initiated on MRA, 71% remained on therapy at 1 year. Discontinuation occurred early and was more common in patients with advanced kidney disease, hyperkalaemia, lack of follow-up in specialty care, more severe heart failure, comorbidities, and markers of sociodemographic frailty. Among those who discontinued, almost half reinitiated treatment the year following discontinuation., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Long-term outcome of contemporary stress echocardiography has not been systematically assessed., Objective: To evaluate the association between results of stress echocardiography and patients' outcomes with suspected coronary artery disease using randomised controlled trials., Methods: Multiple electronic databases were searched for studies evaluating long-term outcome (>12 months) of stress echocardiography in patients suspected of coronary artery disease since year 2000. A common-effect model was used to derive pooled estimates. The primary outcome was a composite of all-cause mortality or cardiovascular death and non-fatal myocardial infarction, depending on the definition applied in individual trials, termed as major adverse cardiovascular event (MACE). Secondary outcome was all-cause mortality. Positive stress echocardiography result was defined as inducible ischaemia in at least one of the 17 left ventricular segments and negative stress echocardiography with no inducible ischaemia., Results: Among a total of six trials, 16 581 subjects underwent either pharmacological or treadmill stress echocardiography, a median follow-up of 31 months (range 21-101). The annual event rate was 1.76% for the composite MACE and 1.35% for all-cause mortality. Compared with negative stress echocardiography, positive stress echocardiography was associated with an increased risk of the MACE and all-cause mortality with an annual event rate of 1.99% vs 1.54% (OR 2.04, 95% CI 1.79 to 2.33) and 1.68% vs 1.02% (OR 2.06, 95% CI 1.80 to 2.35), respectively., Conclusion: Positive stress echocardiography results were associated with poorer long-term MACE and all-cause mortality. Stress echocardiography results may provide a useful long-term guidance in intensifying preventative treatment in patients with suspected coronary artery disease., Prospero Registration Number: CRD42023416766., Competing Interests: Competing interests: None declared., (© 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.)

Background/objective: Balanced reciprocal translocations are structural chromosomal anomalies that involve a mutual exchange of segments between two non-homologous chromosomes with a consequent 50-80% risk of conceiving fetuses with unbalanced chromosomal anomalies. This study describes a 37-year-old woman, at 13 + 5 weeks of gestation, who is a balanced reciprocal translocation 46,XX,t(9;18)(q34;q11.2) carrier, with a high-risk non-invasive prenatal screening test, NIPT, for chromosome 18 aneuploidy., Methods: The highlighted aneuploidy was characterized with cytogenetic, FISH and SNP-array techniques., Results: Cytogenetic analysis, performed on flask-cultured amniocytes, indicated a 48,XX,+2mar karyotype on 50 metaphases. SNP array analysis showed a 15.3 Mb duplication of chromosome 18p (arr[hg19]18p11.32-p11.21(12,842-15,303,932)x4), consistent with a partial tetrasomy 18p, and a 926 kbp duplication of chromosome 9q (arr[GRCh37]9q34.3(140,118,286-141,044,489)x3), consistent with partial trisomy 9q. FISH analysis with a 9q34.3 probe was performed on flask-cultured amniocytes' metaphases, highlighting the presence of a third signal on one of the two marker chromosomes (18p11.32-p11.21)., Conclusions: The evidence of such partial aneuploidies suggests that different mutational events may be possible at meiotic segregation or probably post-meiotic segregation. The results obtained highlight the high sensitivity of the screening test, NIPT, with massive parallel sequencing, and the usefulness of cytogenetics, cytogenomics and molecular biology techniques, in synergy, to characterize and confirm positive NIPT results.

Aims: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prevalent comorbidities associated with significant morbidity/mortality. We assessed prevalence of, patient profiles and outcomes associated with COPD across the ejection fraction (EF) spectrum., Methods: HF patients enrolled in the Swedish HF registry between 2005 and 2021 were considered. Multivariable logistic regression models were fitted to assess patient characteristics independently associated with COPD and Cox regression models for investigating the associations between COPD and outcomes, that is, morbidity/mortality., Results: Among 97 904 HF patients, COPD prevalence was 13%, highest in HF with preserved EF [HFpEF: 16%, HF with mildly reduced EF (HFmrEF): 12%, HF with reduced EF (HFrEF): 11%]. Key patient characteristics independently associated with a diagnosis of COPD included higher EF, female sex, smoking, obstructive sleep disorder, peripheral artery disease, a lower educational level, more severe HF, more likely mineralocorticoid receptor antagonist and diuretic use but less likely use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin-receptor-neprilysin inhibitors (not in HFrEF), beta-blockers, HF device therapies, and follow-up in HF nurse-led clinics. COPD was independently associated with a 15% higher risk of cardiovascular (CV) death/HF hospitalization [hazard ratio: 1.15 (95% confidence interval: 1.11-1.18)], CV death, non-CV death, all-cause death and HF hospitalizations, regardless of EF., Conclusions: COPD was present in every eight patient with HF, and more common with preserved EF. Patients with COPD had more severe HF, heavier comorbidity burden and worse morbidity/mortality regardless of EF. Our results call for improved diagnostic and management strategies in patients with HF and COPD., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Data from US have shown a reversal in the improvement of heart failure (HF)-related mortality over the last ~10 years. It is unknown whether these trends generalize to European universal healthcare systems. We assessed temporal trends in (i) HF-related mortality in the overall national population; and (ii) all-cause mortality following an incident HF diagnosis, overall and stratified by ejection fraction (EF), in Sweden between 1997 and 2022., Methods and Results: Annual mortality rates with a HF diagnosis as underlying cause were extracted from the Cause of Death Register. All-cause mortality following incident HF was assessed in two HF cohorts derived from the National Patient Register (NPR) and the Swedish HF Registry (SwedeHF). Temporal trends were presented as average annual percentage change (AAPC). Between 1997 and 2022, age-adjusted HF-related mortality in the general population declined from 33.4 to 23.8 per 100 000 individuals (AAPC -2.15%, p < 0.001). In the HF cohort from NPR (n = 423 092), all-cause mortality at 1, 3, and 5 years following a first diagnosis of HF was 25%, 46%, and 58%, respectively, in 2022; 1-year mortality declined (AAPC -1.10%, p < 0.001) over time regardless of age or sex. In SwedeHF (n = 63 753), the decline in 1-year mortality was less steep with increasing EF (AAPC -2.64%, p < 0.001; -2.30%, p = 0.062; and -2.16%, p = 0.032 in EF <40%, 40-49%, and ≥50%, respectively)., Conclusions: Heart failure-related mortality has declined over the last ~25 years in Sweden. All-cause mortality in patients with HF has also declined, more in HF with reduced than preserved EF, mirroring the different availability of life-saving treatments across the EF spectrum., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The HeartLogic algorithm (Boston Scientific, St Paul, MN) integrates data from implantable cardioverter-defibrillator (ICD) sensors to predict heart failure (HF) decompensation: first (S1) and third (S3) heart sounds, intrathoracic impedance, respiration rate, ratio of respiration rate to tidal volume (RSBI), and night heart rate., Objective: This study assessed the relative changes in ICD sensors at the onset of HeartLogic alerts, their association with patient characteristics, and outcomes., Methods: The study included 568 patients with HF carrying ICDs (CRT-D, n = 410) across 26 centers, with a median follow-up of 26 months. HeartLogic alerts triggered patient contact and potential treatment., Results: A total of 1200 HeartLogic alerts were recorded in 370 patients. The sensor with the highest change at the alert's onset was S3 in 27% of alerts, followed by S3/S1 (25%). Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) at implantation had higher prevalence of alerts (AF, 84% vs no AF, 58%; CKD, 72% vs no CKD, 59%; P < .05) and rate (AF, 1.51 per patient-year vs no AF, 0.88 per patient-year; CKD, 1.30 per patient-year vs no CKD, 0.89 per patient-year; P < .05). During follow-up, 247 patients experienced more than 1 alert; in 85%, the sensor with the highest change varied between successive alerts. Of the 88 (7%) alerts associated with HF hospitalization or death, respiration rate or RSBI (11%, P = .007 vs S3/S1) and night heart rate (11%, P = .031 vs S3/S1) were more commonly the sensors showing the highest change. Clinical events were more common with the first alert (12.6%) than subsequent alerts (5.2%, P < .001)., Conclusion: HeartLogic alerts are mostly triggered by changes in heart sounds, but clinical events are more linked to respiration rate, RSBI, and night heart rate. Recurrent alerts often involve different sensors, indicating diverse mechanisms of HF progression., Competing Interests: Disclosures Dr Dello Russo is consultant for Abbott, Biosense Webster, and Boston Scientific. Dr Santini is consultant for Abbott, Boston Scientific, Medtronic, and Biotronik and is a speaker for Medtronic, Boston Scientific, Abbott, Microport, and Biotronik. Dr Bertini is a consultant for Boston Scientific and Microport; speaker and tutor in training courses for Boston Scientific, Microport, Medtronic, Abbott, Biotronik, Pfizer, Bayer, Daiichi-Sankyo, and Boehringer Ingelheim. Dr Casella has received speaker honoraria from Biosense Webster. Dr Averina, Dr Campari, and Dr Valsecchi are employees of Boston Scientific. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: We explored timing, settings and predictors of angiotensin receptor-neprilysin inhibitor (ARNI) initiation in a large, nationwide cohort of patients with heart failure (HF) with reduced ejection fraction (HFrEF)., Methods and Results: Patients with HFrEF (ejection fraction <40%) registered in the Swedish HF Registry in 2017-2021 and naïve to ARNI were evaluated for timing and location of, and their characteristics at ARNI initiation. ARNI use increased from 8.3% in 2017 to 26.7% in 2021. Among 3892 hospitalized patients, 8% initiated ARNI in-hospital or ≤14 days after discharge, 4% between 15 and 90 days, and 88% >90 days after discharge or never initiated. Factors associated with earlier initiation included follow-up in specialized HF care, more severe HF, previous HF treatment use and higher income, whereas older age, higher comorbidity burden and living alone were associated with later/no initiation. Of 16 486 HFrEF patients, 8.1% inpatients and 5.9% outpatients initiated an ARNI at the index date. Factors associated with initiation in outpatients were overall consistent with those linked with an in-hospital/earlier ARNI initiation; 4.9% of 10 209 with HF duration <6 months and 9.1% of 5877 with HF duration ≥6 months initiated ARNI. Predictors of ARNI initiation in HF duration <6 months were inpatient status, lower ejection fraction, hypertension, whereas previous angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use was associated with less likely initiation. Discontinuation at 1 year ranged between 13% and 20% across the above-reported analyses., Conclusions: In-hospital and early initiation of ARNI are limited in real-world care but still slightly more likely than in outpatients. ARNI were more likely initiated in patients with more severe HF, which might suggest its use as a second-line treatment and only following worsening of clinical status. One-year discontinuation rates were consistent regardless of the timing/setting of ARNI initiation., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Real-world data show that guidelines are insufficiently implemented, and particularly guideline-directed medical therapies (GDMT) are underused in patients with heart failure and reduced ejection fraction (HFrEF) in clinical practice. The Council for Cardiology Practice and the Heart Failure Association of the European Society of Cardiology (ESC) developed a survey aiming to (i) evaluate the perspectives of the cardiology community on the 2021 ESC heart failure (HF) guidelines, (ii) pinpoint disparities in disease management, and (iii) propose strategies to enhance adherence to HF guidelines., Methods and Results: A 22-question survey regarding the diagnosis and treatment of HFrEF was delivered between March and June 2022. Of 457 physicians, 54% were general cardiologists, 19.4% were HF specialists, 18.9% other cardiac specialists, and 7.7% non-cardiac specialists. For diagnosis, 52.1% employed echocardiography and natriuretic peptides (NPs), 33.2% primarily used echocardiography, and 14.7% predominantly relied on NPs. The first drug class initiated in HFrEF was angiotensin-converting enzyme inhibitors/angiotensin receptor-neprilysin inhibitor (ACEi/ARNi) (91.2%), beta-blockers (BB) (73.8%), mineralocorticoid receptor antagonists (MRAs) (53.4%), and sodium-glucose cotransporter 2 (SGLT2) inhibitors (48.1%). The combination ACEi/ARNi + MRA+ BB was preferred by 39.3% of physicians, ACEi/ARNi + SGLT2 inhibitors + BB by 33.3%, and ACEi/ARNi + BB by 22.2%. The time required to initiate and optimize GDMT was estimated to be <1 month by 8.3%, 1-3 months by 52%, 3-6 months by 31.8%, and >6 months by 7.9%. Compared to general cardiologists, HF specialists/academic cardiologists reported lower estimated time-to-initiation, and more commonly preferred a parallel initiation of GDMT rather than a sequential approach., Conclusion: Participants generally followed diagnostic and treatment guidelines, but variations in HFrEF management across care settings or HF specialties were noted. The survey may raise awareness and promote standardized HF care., (© 2024 European Society of Cardiology.)

Aims: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry., Methods and Results: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF., Conclusion: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries., (© 2024 European Society of Cardiology.)

Aims: This survey investigates natriuretic peptide (NP) testing in community and hospital settings, assessing awareness, accessibility, and utilization., Methods and Results: This investigator-initiated survey, conceived within the HFA of the European Society of Cardiology, comprised 14 questions. It underwent validation and pilot testing to ensure question readability and online system functionality. The survey was accessible for 87 days, from 5 April 2023 to 1 July 2023 via a web platform. There were 751 healthcare professionals across 99 countries who responded. Of them, 92.5% had access to NPs testing in hospital whereas 34.3% had no access to NTproBNP in community settings. Access to point of care NP testing was uncommon (9.6%). Public insurance fully covered NPs testing in 31.0% of cases, with private insurance providing coverage in 37.9%. The majority (84.0%) of participants believed that the medical evidence supporting NPs testing was strong, and 54.7% considered it cost-effective. Also, 35.8% found access, awareness, and adoption to be in favour of NPs testing both in hospital and community settings. Strategies to optimize NP testing involved regular guideline updates (57.9%), prioritizing NPs testing for dyspnoea assessment (36.4%), and introducing clinician feedback mechanisms (21.2%). Notably, 40% lacked a community-based HF diagnostic pathway for referring high-NP patients for echocardiography and cardiology evaluation., Conclusions: This survey reveals NP awareness, access, and adoption across several countries. Highlighting the importance of community-based early heart failure diagnosis and optimizing HF diagnostic pathways remains a crucial, unmet opportunity to improve patient outcomes., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients., (© The Authors. Published by John Wiley & Sons Limited and Oxford University Press on behalf of the European Society of Cardiology, and Frontiers Media SA on behalf of the European Society for Organ Transplantation.)

Malignancies of the parotid gland are relatively uncommon and in most cases are primary neoplasms; intraparotid metastases are rare. Oral and oropharyngeal squamous cell carcinoma (O- and OP-SCC) can potentially metastasize to the parotid gland or intraparotid lymph nodes. Fine-needle aspiration cytology (FNAC) serves as the initial diagnostic approach for this purpose. HPV status in FNAC specimens is relevant and can guide the diagnostic workup, indicating a potential oropharyngeal origin of the primary tumor. A small series of occult SCC metastases is presented below, in which HPV-DNA testing of FNAC specimens helped identify primary neoplasms located in the oropharynx. US-guided FNAC of parotid nodules was conducted by an experienced interventional cytopathologist in three cases. Each patient underwent assessment of direct smears, cell blocks, and liquid-based samples for HPV testing. The morphological and immunocytochemical features of SCC were documented, and real-time PCR was employed for the detection and genotyping of HPV. The role of HPV testing on FNAC specimens in pinpointing the primary neoplasms in the oropharynx is highlighted. Consequently, FNAC samples emerge as valuable diagnostic and prognostic tools in this context, providing essential insights for patient management., (© 2024 Wiley Periodicals LLC.)

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus., Competing Interests: Conflict of interest: none declared., (© The Authors 2024. Published by John Wiley & Sons Limited and Oxford University Press on behalf of the European Society of Cardiology, and Frontiers Media SA on behalf of the European Society for Organ Transplantation.)

Aims: Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by growing incidence and poor outcomes. A large majority of HFpEF patients are cared by non-cardiologists. The availability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as recommended therapy raises the importance of prompt and accurate identification and treatment of HFpEF across diverse healthcare settings. We evaluated HFpEF management across specialties through a survey targeting cardiologists, HF specialists, and non-cardiologists., Methods and Results: An independent web-based survey was distributed globally between May and July 2023. We performed a post-hoc analysis, comparing cardiologists, HF specialists, and non-cardiologists. A total of 1460 physicians (61% male, median age 41[34-49]) from 95 countries completed the survey; 20% were HF specialists, 65% cardiologists, and 15% non-cardiologists. Compared with HF specialists, non-cardiologists and cardiologists were less likely to use natriuretic peptides (p = 0.003) and HFpEF scores (p = 0.004) for diagnosis, and were also less likely to have access to or consider specific echocardiographic parameters (p < 0.001) for identifying HFpEF. Diastolic stress tests were used in less than 30% of the cases, regardless of the specialty (p = 1.12). Multidrug treatment strategies were similar across different specialties. While SGLT2i and diuretics were the preferred drugs, angiotensin receptor blockers and angiotensin receptor-neprilysin inhibitors were the least frequently prescribed in all three groups. However, when constrained to choose one drug, the proportion of physicians favoring SGLT2i varied significantly among specialties (66% HF specialists, 52% cardiologists, 51% non-cardiologists). Additionally, 10% of non-cardiologists and 8% of cardiologists considered beta blocker the drug of choice for HFpEF., Conclusion: Significant differences among specialty groups were observed in HFpEF management, particularly in the diagnostic work-up. Our results highlight a substantial risk of underdiagnosis and undertreatment of HFpEF patients, especially among non-HF specialists., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Direct oral anticoagulants (DOACs) are increasingly used off-label to treat patients with left ventricular thrombus (LVT). We analysed available meta-data comparing DOACs and vitamin K antagonists (VKAs) for efficacy and safety., Methods: We conducted a systematic search and meta-analysis of observational and randomized data comparing DOACs vs. VKAs in patients with LVT. Endpoints of interest were stroke or systemic embolism, thrombus resolution, all-cause death, and a composite bleeding endpoint. Estimates were pooled using a random-effects model meta-analysis, and their robustness was investigated using sensitivity and influential analyses., Results: We identified 22 articles (18 observational studies, 4 small randomized clinical trials) reporting on a total of 3587 patients (2489 VKA vs. 1098 DOAC therapy). The pooled estimates for stroke or systemic embolism [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.57, 1.15] and thrombus resolution (OR: 1.12; 95% CI: 0.86, 1.46) were comparable, and there was low heterogeneity overall across the included studies. The use of DOACs was associated with lower odds of all-cause death (OR: 0.65; 95% CI: 0.46, 0.92) and a composite bleeding endpoint (OR: 0.67; 95% CI: 0.47, 0.97). A risk of bias was evident particularly for observational reports, with some publication bias suggested in funnel plots., Conclusion: In this comprehensive analysis of mainly observational data, the use of DOACs was not associated with a significant difference in stroke or systemic embolism, or thrombus resolution, compared with VKA therapy. The use of DOACs was associated with a lower rate of all-cause death and fewer bleeding events. Adequately sized randomized clinical trials are needed to confirm these findings, which could allow a wider adoption of DOACs in patients with LVT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Heart failure (HF) and atrial fibrillation (AF) often coexist. We explored AF incidence, prevalence, and treatment strategies in patients with versus without HF across the ejection fraction (EF) spectrum., Methods and Results: We analysed patients with HF from the Swedish HF Registry (1 December 2005-31 December 2021), matched 1:1 by sex, age, and county of residence to patients without HF from Statistics Sweden. Two study cohorts were derived (i) to assess AF prevalence and treatments, and (ii) to evaluate AF incidence and related predictors. Overall, 195 106 patients were considered, 50% of them with HF (of whom 54% with HF with reduced [HFrEF], 23% mildly reduced [HFmrEF], and 23% with preserved EF [HFpEF]). From 2006 to 2021, AF prevalence increased in both patients with (57% to 58%) and without HF (8% to 11%). HF patients, particularly if with HFrEF, were more likely receiving AF treatments than those without HF. Over time, antiarrhythmic use decreased, while rate control drugs and oral anticoagulant use, and AF-related procedures increased, regardless of HF and EF. During a median follow-up of 3.7 years, in 86 210 patients without AF, incident AF risk was two-fold higher in HF versus non-HF (hazard ratio [HR] 2.76, 95% confidence interval [CI] 2.45-3.12), highest in HFpEF (HR 3.12, 95% CI 2.65-3.67) versus HFrEF (HR 2.68, 95% CI 2.34-3.06) and HFmrEF (HR 2.53, 95% CI 2.17-2.94)., Conclusions: Atrial fibrillation prevalence, anticoagulant use, and AF-related procedures increased over time regardless of HF, with HF patients more likely receiving AF treatments. In HF, despite higher AF prevalence and incidence in HFpEF, AF treatment use remained modest, calling for further implementation., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex-specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under-recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex-disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities., (© 2024 European Society of Cardiology.)

Aims: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF., Methods and Results: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P < 0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P = 0.04]., Conclusions: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes., Methods: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events., Conclusion: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The detailed sub-categories of death and hospitalization, and the impact of comorbidities on cause-specific outcomes, remain poorly understood in heart failure (HF) with preserved ejection fraction (HFpEF). We sought to evaluate rates and predictors of cardiovascular (CV) and non-CV outcomes in HFpEF., Methods: The Karolinska-Rennes study was a bi-national prospective observational study designed to characterize HFpEF (ejection fraction ≥45%). Patients were followed for cause-specific death and hospitalization. Baseline characteristics were pre-selected based on clinical relevance and potential eligibility criteria for HFpEF trials. The associations between characteristics and cause-specific outcomes were assessed with univariable and multivariable Cox regressions., Results: Five hundred thirty-nine patients [56% females; median (inter-quartile range) age 79 (72-84) years; NT-proBNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Over 1196 patient-years follow-up [median (min, max) 744 days (13-1959)], there were 159 (29%) deaths (13 per 100 patient-years: CV 5.1 per 100, dominated by HF 3.9 per 100; and non-CV 5.8 per 100, dominated by cancer, 2.3 per 100). There were 723 hospitalizations in 338 patients (63%; 60 per 100 patient-years: CV 33 per 100, dominated by HF 17 per 100; and non-CV 27 per 100, dominated by lung disease 5 per 100). Higher age and natriuretic peptides, lower serum natraemia and NYHA class III-IV were independent predictors of CV death; lower serum natraemia, anaemia and stroke of non-CV death; and anaemia and lower serum natraemia of non-CV death or hospitalizations. There were no apparent predictors of CV death or hospitalization., Conclusions: In a clinical cohort hospitalized and diagnosed with HFpEF, death and hospitalization rates were roughly similar for CV and non-CV causes. CV deaths were predicted primarily by severity of HF; non-CV deaths primarily by anaemia and prior stroke. Lower serum sodium predicted both. Hospitalizations were difficult to predict., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: In recent decades, the topic of gender differences has become central to many areas of study, including medicine. The present study explored gender differences in empathy, gender role ideologies, and gender sensitivity among medical students, highlighting significant variations that can inform medical education and training programs., Materials and Methods: The study involved 155 students (52.1% male; mean age: 22.68±2.48 years) from the Department of Medicine, Surgery, and Dentistry of the University of Salerno in Baronissi, Southern Italy. Participants completed two standardized scales: the Jefferson Scale of Empathy (JSE) to assess empathy, and the Nijmegen Gender Awareness in Medicine Scale (N-GAMS) to evaluate gender awareness. Six open-ended questions were also included in the gender-based violence representations., Results: The ANOVA analysis reveals significant differences in scores between male and female students across the N-GAMS scales, indicating a strong role of gender in these variations. These findings suggest the necessity for further research to understand the contributing factors and inform targeted interventions in medical education. Additionally, there are significant differences in compassionate care (Factor 2) and walking in the patient's shoes (Factor 3), highlighting the substantial impact of gender on these latter aspects of empathy., Conclusions: These gender differences have significant implications for medical education. Training programs should be tailored to address the specific needs and characteristics of both male and female students. For example, encouraging male students to maintain their gender sensitivity while challenging traditional gender role ideologies can promote a more inclusive approach to patient care. For female students, fostering confidence in their compassionate care abilities and providing opportunities to express empathy in diverse ways can help overcome societal constraints., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Independent committee of the Psychological Counseling Center (Centro di Counseling Psicologico) of the University of Salerno issued approval 1/2021. The study was conducted in accordance with the Declaration of Helsinki (1964) and the recommendations of the Association Italian School of Psychology (AIP). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Savarese et al.)

Aims: To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM)., Methods and Results: The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index ≥30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone., Conclusions: In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The growing understanding of cancer biology and the establishment of new treatment modalities has not yielded the expected results in terms of survival for Laryngeal Squamous Cell Cancer (LSCC). Early diagnosis, as well as prompt identification of patients with high risk of relapse would ensure greater chance of therapeutic success. However, this goal remains a challenge due to the absence of specific biomarkers for this neoplasm., Methods: Serum samples from 45 LSCC patients and 23 healthy donors were collected for miRNA expression profiling by TaqMan Array analysis. Additional 20 patients and 42 healthy volunteers were included for the validation set, reaching an equal number of clinical samples for each group. The potential diagnostic ability of the such identified three-miRNA signature was confirmed by ROC analysis. Moreover, each miRNA was analyzed for the possible correlation with HNSCC patients' survival and TNM status by online databases Kaplan-Meier (KM) plotter and OncomiR. In silico analysis of common candidate targets and their network relevance to predict shared biological functions was finally performed by PANTHER and GeneMANIA software., Results: We characterized serum miRNA profile of LSCC patients identifying a novel molecular signature, including miR-223, miR-93 and miR-532, as circulating marker endowed with high selectivity and specificity. The oncogenic effect and the prognostic significance of each miRNA was investigated by bioinformatic analysis, denoting significant correlation with OS. To analyse the molecular basis underlying the pro-tumorigenic role of the signature, we focused on the simultaneously regulated gene targets-IL6ST, GTDC1, MAP1B, CPEB3, PRKACB, NFIB, PURB, ATP2B1, ZNF148, PSD3, TBC1D15, PURA, KLF12-found by prediction tools and deepened for their functional role by pathway enrichment analysis. The results showed the involvement of 7 different biological processes, among which inflammation, proliferation, migration, apoptosis and angiogenesis., Conclusions: In conclusion, we have identified a possible miRNA signature for early LSCC diagnosis and we assumed that miR-93, miR-223 and miR-532 could orchestrate the regulation of multiple cancer-related processes. These findings encourage the possibility to deepen the molecular mechanisms underlying their oncogenic role, for the desirable development of novel therapeutic opportunities based on the use of short single-stranded oligonucleotides acting as non-coding RNA antagonists in cancer., (© 2024. The Author(s).)

Aims: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, regardless of anaemia status. Iron supplementation has been demonstrated to improve exercise capacity and quality of life in patients with HF with an ejection fraction <50% and ID. This survey aimed to provide data on real-world practices related to ID screening and management., Methods and Results: We designed and distributed an online survey (23 questions) regarding ID screening and management in the HF setting. Overall, 256 cardiologists completed the survey (59.8% male, mostly between 30 and 50 years). The majority of physicians defined ID according to the most recent HF recommendations (98.4%) and reported screening for ID in more than half of their patients (68.4%). However, only 54.3% of the respondents performed periodic screening (every 6 months to 1 year). A total of 93.0% of participants prescribed and/or administered iron supplementation, using intravenous iron as the preferred method of administration (86.3%). After iron supplementation, 96.1% of the respondents reassessed ID, most frequently at 3-6 months (67.6%). Most physicians (93.8%) perceived ID as an underestimated comorbidity in HF. Cardiologists' age, training status, subspecialty and work setting (academic vs. non-academic hospitals) were associated with heterogeneity in the answers., Conclusions: The results of this survey highlight the need for more consistent strategies of ID screening and treatment for patients with HF., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The cardiotoxic effects of anthracyclines therapy are well recognized, both in the short and long term. Echocardiography allows monitoring of cancer patients treated with this class of drugs by serial assessment of left ventricle ejection fraction (LVEF) as a surrogate of systolic function. However, changes in myocardial function may occur late in the process when cardiac damage is already established. Novel cardiac magnetic resonance (CMR) parametric techniques, like native T1 mapping and extra-cellular volume (ECV), may detect subclinical myocardial damage in these patients, recognizing early signs of cardiotoxicity before development of overt cancer therapy-related cardiac dysfunction (CTRCD) and prompting tailored therapeutic and follow-up strategies to improve outcome., Methods and Results: We conducted a systematic review and a meta-analysis to investigate the difference in CMR derived native T1 relaxation time and ECV values, respectively, in anthracyclines-treated cancer patients with preserved EF versus healthy controls. PubMed, Embase, Web of Science and Cochrane Central were searched for relevant studies. A total of 6 studies were retrieved from 1057 publications, of which, four studies with 547 patients were included in the systematic review on T1 mapping and five studies with 481 patients were included in the meta-analysis on ECV. Three out of the four included studies in the systematic review showed higher T1 mapping values in anthracyclines treated patients compared to healthy controls. The meta-analysis demonstrated no statistically significant difference in ECV values between the two groups in the main analysis (Hedges´s g =3.20, 95% CI -0.72-7.12, p =0.11, I 2 =99%), while ECV was significantly higher in the anthracyclines-treated group when sensitivity analysis was performed., Conclusions: Higher T1 mapping and ECV values in patients exposed to anthracyclines could represent early biomarkers of CTRCD, able to detect subclinical myocardial changes present before the development of overt myocardial dysfunction. Our results highlight the need for further studies to investigate the correlation between anthracyclines-based chemotherapy and changes in CMR mapping parameters that may guide future tailored follow-up strategies in this group of patients., Competing Interests: Declaration of competing interest CBD is the chief executive officer (part-time) for the Society for Cardiovascular Magnetic Resonance (SCMR), she has received speakers’ fees from Circle Cardiovascular Imaging, Siemens Healthineers, Bayer and GE HealthCare. The other Authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Simonenko, Hansen, Niebauer, Volterrani, Adamopoulos, Amarelli, Ambrosetti, Anker, Bayes-Genis, Ben Gal, Bowen, Cacciatore, Caminiti, Cavarretta, Chioncel, Coats, Cohen-Solal, D’Ascenzi, de Pablo Zarzosa, Gevaert, Gustafsson, Kemps, Hill, Jaarsma, Jankowska, Joyce, Krankel, Lainscak, Lund, Moura, Nytrøen, Osto, Piepoli, Potena, Rakisheva, Rosano, Savarese, Seferovic, Thompson, Thum and Van Craenenbroeck.)

Background: Radiomics, an evolving paradigm in medical imaging, involves the quantitative analysis of tumor features and demonstrates promise in predicting treatment responses and outcomes. This study aims to investigate the predictive capacity of radiomics for genetic alterations in non-small cell lung cancer (NSCLC)., Methods: This exploratory, observational study integrated radiomic perspectives using computed tomography (CT) and genomic perspectives through next-generation sequencing (NGS) applied to liquid biopsies. Associations between radiomic features and genetic mutations were established using the Area Under the Receiver Operating Characteristic curve (AUC-ROC). Machine learning techniques, including Support Vector Machine (SVM) classification, aim to predict genetic mutations based on radiomic features. The prognostic impact of selected gene variants was assessed using Kaplan-Meier curves and Log-rank tests., Results: Sixty-six patients underwent screening, with fifty-seven being comprehensively characterized radiomically and genomically. Predominantly males (68.4%), adenocarcinoma was the prevalent histological type (73.7%). Disease staging is distributed across I/II (38.6%), III (31.6%), and IV (29.8%). Significant correlations were identified with mutations of ROS1 p.Thr145Pro (shape&#95;Sphericity), ROS1 p.Arg167Gln (glszm&#95;ZoneEntropy, firstorder&#95;TotalEnergy), ROS1 p.Asp2213Asn (glszm&#95;GrayLevelVariance, firstorder&#95;RootMeanSquared), and ALK p.Asp1529Glu (glcm&#95;Imc1). Patients with the ROS1 p.Thr145Pro variant demonstrated markedly shorter median survival compared to the wild-type group (9.7 months vs. not reached, p = 0.0143; HR: 5.35; 95% CI: 1.39-20.48)., Conclusions: The exploration of the intersection between radiomics and cancer genetics in NSCLC is not only feasible but also holds the potential to improve genetic predictions and enhance prognostic accuracy.

Right heart failure (RHF) following implantation of a left ventricular assist device (LVAD) is a common and potentially serious condition with a wide spectrum of clinical presentations with an unfavourable effect on patient outcomes. Clinical scores that predict the occurrence of right ventricular (RV) failure have included multiple clinical, biochemical, imaging and haemodynamic parameters. However, unless the right ventricle is overtly dysfunctional with end-organ involvement, prediction of RHF post-LVAD implantation is, in most cases, difficult and inaccurate. For these reasons optimization of RV function in every patient is a reasonable practice aiming at preparing the right ventricle for a new and challenging haemodynamic environment after LVAD implantation. To this end, the institution of diuretics, inotropes and even temporary mechanical circulatory support may improve RV function, thereby preparing it for a better adaptation post-LVAD implantation. Furthermore, meticulous management of patients during the perioperative and immediate postoperative period should facilitate identification of RV failure refractory to medication. When RHF occurs late during chronic LVAD support, this is associated with worse long-term outcomes. Careful monitoring of RV function and characterization of the origination deficit should therefore continue throughout the patient's entire follow-up. Despite the useful information provided by the echocardiogram with respect to RV function, right heart catheterization frequently offers additional support for the assessment and optimization of RV function in LVAD-supported patients. In any patient candidate for LVAD therapy, evaluation and treatment of RV function and failure should be assessed in a multidimensional and multidisciplinary manner., (© 2024 European Society of Cardiology.)

Aims: Recent guidelines recommend four core drug classes (renin-angiotensin system inhibitor/angiotensin receptor-neprilysin inhibitor [RASi/ARNi], beta-blocker, mineralocorticoid receptor antagonist [MRA], and sodium-glucose cotransporter 2 inhibitor [SGLT2i]) for the pharmacological management of heart failure (HF) with reduced ejection fraction (HFrEF). We assessed physicians' perceived (i) comfort with implementing the recent HFrEF guideline recommendations; (ii) status of guideline-directed medical therapy (GDMT) implementation; (iii) use of different GDMT sequencing strategies; and (iv) barriers and strategies for achieving implementation., Methods and Results: A 26-question survey was disseminated via bulletin, e-mail and social channels directed to physicians with an interest in HF. Of 432 respondents representing 91 countries, 36% were female, 52% were aged <50 years, and 90% mainly practiced in cardiology (30% HF). Overall comfort with implementing quadruple therapy was high (87%). Only 12% estimated that >90% of patients with HFrEF without contraindications received quadruple therapy. The time required to initiate quadruple therapy was estimated at 1-2 weeks by 34% of respondents, 1 month by 36%, 3 months by 24%, and ≥6 months by 6%. The average respondent favoured traditional drug sequencing strategies (RASi/ARNi with/followed by beta-blocker, and then MRA with/followed by SGLT2i) over simultaneous initiation or SGLT2i-first sequences. The most frequently perceived clinical barriers to implementation were hypotension (70%), creatinine increase (47%), hyperkalaemia (45%) and patient adherence (42%)., Conclusions: Although comfort with implementing all four core drug classes in patients with HFrEF was high among physicians, a majority estimated implementation of GDMT in HFrEF to be low. We identified several important perceived clinical and non-clinical barriers that can be targeted to improve implementation., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history., Methods and Results: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, p interaction  = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, p interaction  = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, p interaction  = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, p interaction  = 0.69)., Conclusion: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trial´s criteria more likely to impact real-world use (pragmatic scenario)., Methods and Results: We included 31,015 patients with HFrEF lasting ≥3 months and registered in the Swedish HF registry between 2000-2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP≥5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario., Conclusion: Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates., Competing Interests: FL has no conflicts of interest to declare. NØ has no conflicts of interest to declare. MM reports grants and other from Amgen, Abbott Vascular, Edwards Therapeutics, Servier, WindTree Therapeutics, Actelion, Livanova, Vifor Pharma. GR reports no conflicts of interest. UD reports research grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Vifor, Boston Scientific, Roche Diagnostics and honoraria/consultancies from Amgen, Pfizer and AstraZeneca all outside the present manuscript. PM has no conflicts of interest to declare. CH none related to the present work; unrelated to the present work: consulting fees from Novartis, Roche Diagnostics, and AnaCardio; speaker fees from Novartis and Merck Sharp & Dohme. LHL none related to the present work; unrelated to the present work: grants, consulting, honoraria: Abbot, Alleviant, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, FineHeart, MedScape/WebMD, Merck/MSD, Novartis, Novo Nordisk, OrionPharma, Pharmacosmos, Radcliffe Cardiology, Roche, Sanofi, Servier, Translational Medicines Academy, Vifor; Stock ownership: AnaCardio. GS received financial support from Cytokinetics for performing this investigator-initiated study. GS reports grants and personal fees from Vifor, personal fees and grants from Boehringer Ingelheim, grants and personal fees from AstraZeneca, personal fees from Roche, grants and personal fees from Servier, grants and personal fees from Novartis, grants and personal fees from Cytokinetics, personal fees from Medtronic, grants from Boston Scientific, grants and personal fees from Pharmacosmos, grants from Merck, grants from Bayer, personal fees from INTAS, personal fees from Abbott, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Lindberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: To assess the barriers to guideline-directed medical therapy (GDMT) use in heart failure (HF), diagnostic workup and general knowledge about HF among physicians in Sweden., Methods: A survey about the management of HF was sent to 828 Swedish physicians including general practitioners (GPs) and specialists during 2021-2022. Answers were reported as percentages and comparisons were made by specialty (GPs vs. specialists)., Results: One hundred sixty-eight physicians participated in the survey (40% females, median age 43 years; 41% GPs and 59% specialists). Electrocardiography and New York Heart Association class evaluations are mostly performed once a year by GPs (46%) and at every outpatient visit by specialists (40%). Echocardiography is mostly requested if there is clinical deterioration (60%). One-third of participants screen for iron deficiency only if there is anemia. Major obstacles to implementation of different drug classes in HF with reduced ejection fraction are related to side effects, with no significant differences between specialties. Device implantation is deemed appropriate regardless of aetiology (69%) and patient age (86%). Specialists answered correctly to knowledge questions more often than GPs. Eighty-six percent of participants think that GDMT should be implemented as much as possible. Most participants (57%) believe that regular patient assessment in nurse-led HF clinics improve adherence to GDMT., Conclusion: Obstacles to GDMT implementation according to physicians in Sweden mainly relate to potential side effects, lack of specialist knowledge and organizational aspects. Further efforts should be placed in educational activities and structuring of nurse-led clinics., Competing Interests: GF has no conflicts of interest related to this work. Speaker fees from AstraZeneca, Novartis, Vifor and Boehringer Ingelheim. Research grants from the Swedish Heart-Lung foundation. MS reports grants from Swedish Heart- Lung foundation. Consultant fees from Orion Pharma, Werfen and Medtronic. LHL reports grants, consulting, honoraria: Abbot, Alleviant, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, Merck/MSD, Novartis, Novo Nordisk, OrionPharma, Owkin, Pharmacosmos, Vifor Pharma; Stock ownership: AnaCardio. GS reports grants and personal fees from Vifor, grants and personal fees from Boehringer Ingelheim, grants and personal fees from AstraZeneca, grants and personal fees from Servier, grants and personal fees from Novartis, grants and personal fees from Cytokinetics, personal fees from Medtronic, grants from Boston Scientific, grants and personal fees from Pharmacosmos, grants from Merck, grants from Bayer, personal fees from TEVA, personal fees from INTAS, personal fees from Abbott, personal fees from Edwards LifeScience outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Ferrannini, Biber, Abdi, Ståhlberg, Lund and Savarese.)

Prostate cancer, a prevalent malignancy affecting the prostate gland, is a significant global health concern. Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a diverse spectrum of responses exists, and resistance to ADT may emerge over time. This underscores the need to explore innovative treatment strategies for effectively managing prostate cancer progression. Ongoing research endeavors persist in unraveling the complexity of prostate cancer and fostering the development of biologic and innovative approaches, including immunotherapies and targeted therapies. This review aims to provide a valuable synthesis of the dynamic landscape of emerging drug modalities in this context. Interestingly, the complexities posed by prostate cancer not only present a formidable challenge but also serve as a model and an opportunity for translational research and innovative therapies in the field of oncology.

Aims: Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex-based differences in the association between TD achievement and mortality/morbidity in HFrEF., Methods and Results: Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow-up until December 2021) were analysed. Treatments of interest were renin-angiotensin system inhibitors (RASI) or angiotensin receptor-neprilysin inhibitors (ARNI), and beta-blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0-83.0), 29% were female. Over a median follow-up of 1.33 years (IQR 0.29-3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50-99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83-1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p-interaction = 0.030). For beta-blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex., Conclusions: Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex-specific up-titration schemes when testing HFrEF treatments in need of up-titration., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Hospitalization for heart failure (HHF) is associated with poor postdischarge outcomes but the role of time since most recent HHF and potential treatment interactions are unknown. We aimed to assess history of and time since previous HHF, associations with composite of cardiovascular (CV) death and total HHF, first HHF and interactions with randomization to spironolactone, in heart failure with preserved ejection fraction., Methods and Results: We assessed these objectives using uni- and multivariable regressions and spline analyses in TOPCAT-Americas. Among 1,765 patients, 66% had a previous HHF. Over a median of 2.9 years, 1,064 composite events of CV death or total HHFs occurred. Previous HHF was associated with more severe HF, and was independently associated with the composite outcome (HR 1.26, 95%CI 1.05-1.52, P = .014), and all secondary outcomes. A shorter time since most recent HHF appeared to be associated with subsequent first HHF, but not the composite of CV death or total HHF. Spironolactone had a significant interaction with previous HHF (interaction-P .046). Patients without a previous HHF had a larger effect of spironolactone on the composite outcome (HR 0.63, 95%CI 0.46-0.87, P = .005) than patients with a previous HHF (HR 0.91, 95%CI 0.78-1.06, P = .224)., Conclusion: In TOPCAT-Americas, previous HHF was associated with CV death and first and total HHF. Duration since most recent HHF seemed to be associated with time to first HHF only. Spironolactone was associated with better outcomes in patients without a previous HHF. This interaction is hypothesis-generating and requires validation in future trials., Competing Interests: Conflict of interest The authors have no disclosures related to the current research. Unrelated to the present work, the authors disclose: MF: Dr Fudim was supported by the American Heart Association (20IPA35310955), Doris Duke, Bayer, Bodyport, and Verily. He received consulting fees from Abbott, Ajax, Alio Health, Alleviant, Artha, Audicor, AxonTherapies, Bayer, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardioflow, Cardionomics, Coridea, CVRx, Daxor, Deerfield Catalyst, Edwards LifeSciences, EKO, Feldschuh Foundation, Fire1, FutureCardia, Galvani, Gradient, Hatteras, HemodynamicQ, Impulse Dynamics, Intershunt, Medtronic, Merck, NIMedical, NovoNordisk, NucleusRx, NXT Biomedical, Pharmacosmos, PreHealth, ReCor, Rockley, Shifamed, Splendo, Sumacor, SyMap, Verily, Vironix, Viscardia, Zoll. GS reports grants and personal fees from Vifor, grants from Boehringer Ingelheim, personal fees from Societa´ Prodotti Antibiotici, grants and personal fees from AstraZeneca, personal fees from Roche, personal fees from Servier, grants and personal fees from Novartis, personal fees from GENESIS, grants and personal fees from Cytokinetics, personal fees from Medtronic, grants from Boston Scientific, grants and personal fees from PHARMACOSMOS, grants from Merck, grants from Bayer, personal fees from TEVA, outside the submitted work. CH: Grants from Bayer and speaker and honoraria from AstraZeneca and Novartis, consulting fees from Novartis, Roche Diagnostics and AnaCardio, Supported by the Swedish Research Council [grant 20180899]; BP: Dr Pitt has received consulting fees from Lexicon, Bayer, AstraZeneca, Boehringer Ingelheim, Merck, and Phasebio; has received consulting fees and/or stock options from Vifor, KBP Biosciences, Cereno Scientific, Tricida, SCPharmaceuticals, SQinnovation, G-3 Pharmaceuticals, Protonintel, and Brainstorm Medical; and holds U.S. Patent 9931412 on site-specific delivery of eplerenone to the myocardium and U.S. Patent pending 63/045,783 on histone-modulating agents for the protection and treatment of organ damage. LHL: Grants: AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis, MSD; Consulting: Vifor, AstraZeneca, Bayer, Pharmacosmos, MSD, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier, Edwards Life Sciences, Alleviant; Speaker's honoraria: Abbott, OrionPharma, MedScape, Radcliffe, AstraZeneca, Novartis, Boehringer Ingelheim, Bayer; Patent: AnaCardio; Stock ownership: AnaCardio, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF)., Methods and Results: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF., Conclusion: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim : To assess the medium and long-term performance of the Endurant stent graft in a cohort of consecutive patients treated with this device for an abdominal aortic aneurysm (AAA) both inside and outside of the instructions for use (IFU) and to find factors influencing the outcomes. Methods : Our observational, retrospective, single-center study included all patients who consecutively underwent endovascular aneurysm repair with the Endurant stent graft from February 2009 to January 2023. Patients with an AAA to treat according to current guidelines were included. Patients were divided into two groups: Group 1 inside of the IFUs and Group 2 outside of the IFUs for the proximal aortic neck. Patients were followed up after the procedure with computed angiography tomography, ultrasound examination, and interviews. Aneurysm-related mortality, procedure-related reinterventions, and type IA and III endoleaks were considered primary endpoints. Secondary endpoints included aneurysmal sac variations and graft thrombosis. Results : A total of 795 patients were included, 650 in Group 1 and 145 in Group 2; 732 were males, and the mean age was 74 ± 8. Anamnestic baseline did not differ between the two groups. Neck length, width, and angulation were different between the two groups (all p < 0.001). A total of 40 patients had a ruptured AAA, while 56 were symptomatic. At a mean follow-up of 43 ± 39 months, aneurysm-related mortality was less than 1%, and 82 endoleak (10.5%) were observed. Overall endoleak rate and type 1A endoleak, as well as procedure-related reintervention, were significantly more frequent in Group 2. Sac regression of at least 5 mm was observed in 65.9% of cases. AAAs larger than 60.5 mm carried a higher risk of endoleak (HR: 1.025; 95% CI: 1.013-1.37; p < 0.001) and proximal necks shorter than 13.5 mm carried a higher type 1A risk (HR: 0.890; 95% CI: 0.836-0.948; p < 0.001). Patients without chronic obstructive pulmonary disease and taking lipid-lowering drugs had an overall more consistent sac-shrinking rate. Conclusions : The Endurant stent graft proves safe and reliable. Out-of-IFU treatment has poorer medium and long-term outcomes. Some conditions influence medium and long-term reintervention risk and sac behavior. Patients with bigger aneurysms, proximal necks shorter than 13.5 mm, and chronic obstructive pulmonary disease should be more carefully evaluated during follow-up. Consistent follow-up is in keeping low aneurysm-related mortality. Personalized risk profiles and peri and postoperative management strategies are needed.

Obstructive sleep apneas (OSAs) and central sleep apneas (CSAs) are the most common comorbidities in Heart Failure (HF) that are strongly associated with all-cause mortality. Several therapeutic approaches have been used to treat CSA and OSA, but none have been shown to significantly improve HF prognosis. Our study evaluated the effects of a 3-months treatment with sodium-glucose cotransporter type 2 inhibitor (SGLT2i) on polygraphic parameters in patients with sleep apnea (SA) and HF, across the spectrum of ejection fraction, not treated with continuous positive air pressure (CPAP). A group of 514 consecutive elderly outpatients with HF, type 2 diabetes mellitus (T2DM) and SA, eligible for treatment with SGLT2i, were included in the investigation before starting any CPAP therapy. The two groups were compared with the t -test and Mann-Whitney test for unpaired data when appropriate. Then, a simple logistic regression model was built using 50% reduction in AHI as the dependent variable and other variables as covariates. A multivariate stepwise logistic regression model was constructed using the variables that linked with the dependent variable to calculate the odds ratio (OR) for the independent predictors associated with the reduction of 50% in AHI. The treated group experienced significant improvements in polygraphic parameters between baseline values and follow-up with reduction in AHI (28.4 ± 12.9 e/h vs. 15.2 ± 6.5 e/h; p < 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h; p < 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%; p < 0.0001), while mean SpO 2 improved (91. 3 ± 2.3 vs. 93.8 ± 2.5); p < 0.0001. These benefits were not seen in the untreated population. The use of SGLT2i in patients suffering from HF and mixed-type SA not on CPAP therapy significantly contributes to improving polygraphic parameters.

Background: TAS-102 (Lonsurf ® ) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity., Methods: Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m 2 , twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12). Clinical-pathological parameters were described. Activity was evaluated with RECIST criteria (v1.1) and toxicity with NCI-CTC (v5.0). Survival was depicted through the Kaplan-Meyer curves. Genetic features of patients were evaluated with Next Generation Sequencing (NGS) through the Illumina NovaSeq 6000 platform and TruSigt™Oncology 500 kit., Results: Median age of patients was 65 years (range: 46-77). Forty-one patients had 2 or more metastatic sites and 38 patients underwent to more than 2 previous lines of therapies. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) was 2 in 19 patients. The median number of TAS-102 cycles was 4 (range: 2-12). The most frequent toxic event was neutropenia (G3/G4 in 16 patients). There were no severe (> 3) non-haematological toxicities or treatment-related deaths. Twenty-six patients experienced progressive disease (PD), 21 stable disease (SD). Three patients with long-lasting disease control (DC: complete, partial responses or stable disease) shared an FGFR4 (p.Gly388Arg) mutation. Patients experiencing DC had more frequently a low tumour growth rate (P = 0.0306) and an FGFR4 p.G388R variant (P < 0.0001). The FGFR4 Arg388 genotype was associated with better survival (median: 6.4 months) compared to the Gly388 genotype (median: 4 months); the HR was 0.25 (95% CI 0.12- 0.51; P = 0.0001 at Log-Rank test)., Conclusions: This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings., (© 2024. The Author(s).)

Background: A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were investigated., Method: 300 frail adult subjects underwent a full vaccine cycle with recombinant-Shingrix vaccine (RZV vaccine). Hospital Presidia of the Salerno University Hospital Authority, a Hospital Presidium of the Salerno Local Health Authority, and the Public Health Laboratory of the University of Salerno (Campania) participated in the intervention. An ad hoc questionnaire was administered with the following scales: EQ-5D, PSS-10, MSPSS, and representations of HZ and its consequences., Results: Some variables, such as peer support, doctor-patient relationship, level of education, and perception of health, are important in vaccine adherence and information processing. The following factors emerged from the factor analysis: Trust in collective knowledge and collective responsibility (F1); beliefs about virus risk and vaccine function (F2); information about virus and symptomatology (F3); and vaccine distrust (F4). Factor 4 correlates negatively with social support indices (R = -0.363; p < 0.001). There is a significant relationship between factor 3 and satisfaction with national information campaigns (F = 3.376; gdl = 5; p -value = 0.006)., Conclusions: Future vaccination campaigns should be built with the aim of personalizing information and developing contextualized strategies, starting from understanding the stakeholders involved, cultural contexts, and organizational settings.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Liquid biopsy is a minimally invasive diagnostic tool for identification of tumor-related mutations in circulating cell-free DNA (cfDNA). The aim of this study was to investigate feasibility, sensitivity, and specificity of non-invasive prenatal test (NIPT) for identification of chromosomal abnormalities in cfDNA from a total of 77 consecutive patients with non-Hodgkin B-cell lymphomas, Hodgkin lymphoma (HL), or plasma cell dyscrasia. In this case series, half of patients had at least one alteration, more frequently in chromosome 6 (23.1%), chromosome 9 (20.5%), and chromosomes 3 and 18 (16.7%), with losses of chromosome 6 and gains of chromosome 7 negatively impacting on overall survival (OS), with a 5-year OS of 26.9% and a median OS of 14.6 months, respectively (P = 0.0009 and P = 0.0004). Moreover, B-cell lymphomas had the highest NIPT positivity, especially those with aggressive lymphomas, while patients with plasma cell dyscrasia with extramedullary disease had a higher NIPT positivity compared to conventional cytogenetics analysis and a worse outcome. Therefore, we proposed a NIPT-based liquid biopsy a complementary minimally invasive tool for chromosomal abnormality detection in hematological malignancies. However, prospective studies on larger cohorts are needed to validate clinical utility of NIPT-based liquid biopsy in routinely clinical practice., (© 2024. The Author(s).)