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Background: Recently, the PORT-C and LUNG-ART trials, which evaluated the role of postoperative radiation therapy (PORT), have significantly altered the treatment landscape for NSCLC pN2 patients who previously underwent surgery. In response, the Italian Association of Radiotherapy and Oncology Thoracic Oncology study group has initiated an observational multicenter trial to assess both acute and late toxicities of PORT in pN2 NSCLC patients treated with modern techniques., Methods: Data on NSCLC patients submitted to PORT after radical surgery treated between 2015 and 2020 in six Italian Centers were collected. Heart, lung, and esophageal acute and late toxicities have been retrospectively analyzed and related to radiation therapy dosimetric parameters. Furthermore, loco-regional control, distant metastasis and overall survival have been analyzed., Results: A total of 212 patients with a median age of 68 years from six different centers were included in this analysis (142 males and 70 females). Prior to undergoing PORT, 96 patients (45.8%) had a history of heart disease, 110 patients (51.9%) had hypertension, and 51 patients (24%) had COPD. Acute toxicity was observed in 147 patients (69.3%), with lung toxicity occurring in 93 patients (G1 in 70 patients, G2 in 17 patients, and G3 in 4 patients), esophageal toxicity in 114 patients (G1 in 89 patients, G2 in 23 patients, and G3 in 1 patient), and cardiac toxicity in 4 patients (G1 in 2 patients and G3 in 2 patients). Late side effects were found in 60 patients (28.3%), predominantly involving the lungs (51 patients: 32 G1, 11 G2, and 1 G3) and the esophagus (11 patients: 8 G1 and 3 G2), with no reported late cardiac side effects. Various clinical and dosimetric parameters were found to correlate with both acute and chronic toxicities. Over a median follow-up period of 54 months, 48 patients (22.6%) showed locoregional disease relapse, 106 patients (50%) developed distant metastases, and 66 patients (31.1%) died., Conclusions: RAC-TAC retrospective multicentric study showed the low toxicity of PORT when advanced technology is used. At the same time, it's noteworthy to underline that 50% of the patients develop distant recurrences in the follow up., Competing Interests: Declarations Conflict of interest All the authors have no other relevant financial or non-financial interests to disclose. Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Hospital Vanvitelli, Naples, under Protocol Number 0026796/I dated September 21, 2021 and then from all the other participating centers. Consent to participate Informed consent was obtained from all individual participants included in the study. Consent to publish Not applicable., (© 2024. The Author(s).)

The rapid restoration of blood flow in patients with acute myocardial infarction with ST elevation through percutaneous coronary intervention (PCI) is crucial for the survival of this population. Attempts to decrease the time from diagnosis of ST-segment elevation myocardial infarction (STEMI) to arrival at the catheterization laboratory have been extensively investigated. However, strategies during the procedure aiming to reduce the time to reperfusion are lacking. We conducted a meta-analysis to evaluate culprit vessel revascularization prior to complete angiography as a strategy to minimize delays in primary PCI for patients with STEMI. We searched PubMed, Embase, and Cochrane Central. Outcomes: vascular access-to-balloon, door-to-balloon, and first medical contact-to-balloon times; death, reinfarction in 30 days, Bleeding Academic Research Consortium ≥3 type, coronary artery bypass grafting referral, and left ventricular ejection fraction %. Statistical analysis was performed using the R program (version 4.3.2). Heterogeneity was assessed with I2 statistics. We included 2050 patients from six studies, of which two were randomized controlled trials and four were observational studies. Culprit vessel revascularization prior to complete angiography was associated with a statistically significant decrease of times: vascular access-to-balloon time (mean difference -6.79 min; 95% CI: -8.00 to -5.58; P < 0.01; I2 = 82%) and door-to-balloon time (mean difference -9.02 min; 95% CI: -12.83 to -5.22; P < 0.01; I2 = 93%). In this meta-analysis, performing PCI on the culprit lesion prior to complete coronary angiography led to significantly shorter reperfusion times, with no discernible differences in complication rates., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion 1 . In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D) 2 , which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D 3 . In rats with chemically induced or autoimmune diabetes, counter-regulatory glucagon secretion can be restored by SSTR antagonists 4-7 but both the underlying cellular mechanism and whether it can be extended to humans remain unestablished. Here, we show that glucagon secretion is not stimulated by low glucose in isolated human islets from donors with T1D, a defect recapitulated in non-obese diabetic mice with T1D. This occurs because of hypersecretion of somatostatin, leading to aberrant paracrine inhibition of glucagon secretion. Normally, K ATP channel-dependent hyperpolarization of β-cells at low glucose extends into the δ-cells through gap junctions, culminating in suppression of action potential firing and inhibition of somatostatin secretion. This 'electric brake' is lost following autoimmune destruction of the β-cells, resulting in impaired counter-regulation. This scenario accounts for the clinical observation that residual β-cell function correlates with reduced hypoglycaemia risk 8 ., (© 2024. The Author(s).)

A promising superparamagnetic nanomagnetite dipped with Gd was synthesized for possible medical applications. Its size and morphology are independent of Gd content ranging from 1 to 5%. Gadolinium (III) replaced Fe(III) in the lattice. The sizes of Gd-doped nanoparticles ranged from 5 to 50 nm and exhibited a pure magnetite mineralogical phase., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Using green techniques to convert native starches into nanoparticles is an interesting approach to producing stabilizers for Pickering emulsions, aiming at highly stable emulsions in clean label products. Nanoprecipitation was used to prepare the Pickering starch nanoparticles, while ultrasound technique has been used to modulate the size of these nanoparticles at the same time as the emulsion was developed. Thus, the main objective of this study was to evaluate the stabilizing effect of cassava starch nanoparticles (SNP) produced by the nanoprecipitation technique combined with ultrasound treatment carried out in the presence of water and oil (more hydrophobic physicochemical environment), different from previous studies that carry out the mechanical treatment only in the presence of water. The results showed that the increased ultrasound energy input could reduce particle size (117.58 to 55.75 nm) and polydispersity (0.958 to 0.547) in aqueous dispersions. Subsequently, Pickering emulsions stabilized by SNPs showed that increasing emulsification (ultrasonication) time led to smaller droplet sizes and monomodal size distribution. Despite flocculation, long-term ultrasonication (6 and 9 min) caused little variation in the droplet size after 7 days of storage. The cavitation effects favored the interaction between oil droplets through weak attraction forces and particle sharing, favoring the Pickering stabilization against droplet coalescence. Our results show the potential to use only physical modifications to obtain nanoparticles that can produce coalescence-stable emulsions that are environmentally friendly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The benefit of catheter ablation for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain., Objective: We performed a systematic review and meta-analysis to compare catheter ablation and medical therapy (antiarrhythmics for rhythm or rate control) in patients with AF and HFpEF., Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials. Outcomes were the composite end points of death or heart failure (HF) hospitalization, all-cause death, cardiovascular death, all-cause rehospitalization, and HF hospitalization. Statistical analysis was performed using R statistical software, version 4.3.2 (R Foundation for Statistical Computing). Heterogeneity was assessed with I 2 statistics., Results: We included 20,257 patients from 8 studies. Of those, 3 were derived from RCTs, either through post hoc analysis or subgroup analysis, and 5 were observational studies. The median follow-up ranged from 24.6 to 61.2 months. Compared with medical therapy, catheter ablation was associated with a statistically significant lower risk of death or HF hospitalization (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.47-0.83; P = .001; I 2 = 66%), all-cause death (HR 0.68; 95% CI 0.46-0.99; P = .047; I 2 = 61%), cardiovascular death (HR 0.42; 95% CI 0.21-0.84; P = .014; I 2 = 22%), and HF hospitalization (HR 0.43; 95% CI 0.23-0.82; P = .011; I 2 = 87%)., Conclusion: In this meta-analysis, catheter ablation was associated with a lower risk of all-cause death, cardiovascular death, HF hospitalization, and all-cause rehospitalization in comparison to medical therapy in patients with AF and HFpEF., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has shown promise in treating hematologic malignancies, yet its potential cardiotoxic effects require thorough investigation., Objectives: We aim to conduct a systematic review and meta-analysis to examine the cardiotoxic effects of CAR-T therapy in adults with hematologic malignancies., Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies reporting cardiovascular outcomes, such as arrhythmias, heart failure, and reduced left ventricle ejection fraction (LVEF)., Results: Our analysis of 20 studies involving 4789 patients revealed a 19.68% incidence rate of cardiovascular events, with arrhythmias (7.70%), heart failure (5.73%), and reduced LVEF (3.86%) being the most prevalent. Troponin elevation was observed in 23.61% of patients, while NT-Pro-BNP elevation was observed in 9.4. Subgroup analysis showed higher risks in patients with pre-existing conditions, such as atrial arrhythmia (OR 3.12; p < .001), hypertension (OR 1.85; p = .002), previous heart failure (OR 3.38; p = .003), and coronary artery disease (OR 2.80; p = .003)., Conclusion: Vigilant cardiovascular monitoring is crucial for patients undergoing CAR-T therapy to enhance safety and treatment efficacy.Novelty Statements., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Choroid plexus (ChP) is the secretory epithelial structure located in brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of the tumor pathology and limited availability of valid models., Methods: Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/β-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and over-expression of Wnt/β-catenin pathway genes. 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC., Results: We discovered that Wnt/β-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/β-catenin signaling for survival. Constitutive Wnt/β-catenin pathway activation, either through knock-out of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of Wnt/β-catenin pathway in ChP organoids, through treatment with a potent GSK3β inhibitor, reduced the differentiation of mature ChP epithelia cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids., Conclusions: Our research identifies Wnt/β-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The association between atrial fibrillation (AF) and mental health is well-documented, but the relative benefits of catheter ablation versus medical therapy on mental health and quality of life are not clearly understood. This study assesses the impact of these interventions on AF patients' mental health and quality of life., Methods: Through a systematic review of PubMed, Scopus, and Cochrane databases, randomized controlled trials (RCTs) comparing catheter ablation to medical therapy for AF were analyzed. The study focused on a range of outcomes, particularly mental health and quality of life, measured by tools including the SF-36 mental component, HADS, SF-36 physical component, and AFEQT scores, among others. Analyses were stratified by AF type (paroxysmal versus persistent) and synthesized using random or fixed-effects models to calculate mean differences (MDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs)., Results: From 24 RCTs totaling 6,353 patients (51.4% receiving catheter ablation, 71.1% male, average age 59), catheter ablation was found to significantly improve mental health (SMD 0.34; 95% CI 0.05-0.63; p = 0.02) and quality of life as indicated by PCS SF-36 (MD 2.64; 95% CI 1.06-4.26; p < 0.01) and AFEQT scores (MD 6.24; 95% CI 4.43-8.05; p < 0.01), with no significant difference in outcomes between AF subtypes., Conclusion: Catheter ablation offers significant improvements in mental health and quality of life over medical therapy for AF patients, demonstrating its efficacy across different types of AF., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Conduction system pacing (CSP) has emerged as a promising alternative to biventricular pacing (BVP) in patients with heart failure with reduced ejection fraction (HFrEF) and ventricular dyssynchrony, but its benefits are uncertain. In this study, we aimed to evaluate clinical outcomes of CSP vs BVP for cardiac resynchronization in patients with HFrEF. PubMed, Scopus, and Cochrane databases were searched for randomized controlled trials comparing CSP to BVP for resynchronization therapy in patients with HFrEF. Heterogeneity was examined with I 2 statistics. A random-effects model was used for all outcomes. We included 7 randomized controlled trials with 408 patients, of whom 200 (49%) underwent CSP. Compared to BVP, CSP resulted in a significantly greater reduction in QRS duration (MD -13.34 ms; 95% confidence interval [CI] -24.32 to -2.36, P = .02; I 2 = 91%) and New York Heart Association functional class (standardized mean difference [SMD] -0.37; 95% CI -0.69 to -0.05; P = .02; I 2 = 41%), and a significant increase in left ventricular ejection fraction (mean difference [MD] 2.06%; 95% CI 0.16 to 3.97; P = .03; I 2 = 0%). No statistical difference was noted for left ventricular end-systolic volume (SMD -0.51 mL; 95% CI -1.26 to 0.24; P = .18; I 2 = 83%), lead capture threshold (MD -0.08 V; 95% CI -0.42 to 0.27; P = .66; I 2 = 66%), and procedure time (MD 5.99 minutes; 95% CI -15.91 to 27.89; P = .59; I 2 = 79%). These findings suggest that CSP may have electrocardiographic, echocardiographic, and symptomatic benefits over BVP for patients with HFrEF requiring cardiac resynchronization., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background/aim: Overall survival (OS)-predictive models to clinically stratify patients with stage I Non-Small Cell Lung Cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT) are still unavailable. The aim of this work was to build a predictive model of OS in this setting., Patients and Methods: Clinical variables of patients treated in three Institutions with SBRT for stage I NSCLC were retrospectively collected into a reference cohort A (107 patients) and 2 comparative cohorts B1 (32 patients) and B2 (38 patients). A predictive model was built using Cox regression (CR) and artificial neural networks (ANN) on reference cohort A and then tested on comparative cohorts., Results: Cohort B1 patients were older and with worse chronic obstructive pulmonary disease (COPD) than cohort A. Cohort B2 patients were heavier smokers but had lower Charlson Comorbidity Index (CCI). At CR analysis for cohort A, only ECOG Performance Status 0-1 and absence of previous neoplasms correlated with better OS. The model was enhanced combining ANN and CR findings. The reference cohort was divided into prognostic Group 1 (0-2 score) and Group 2 (3-9 score) to assess model's predictions on OS: grouping was close to statistical significance (p=0.081). One and 2-year OS resulted higher for Group 1, lower for Group 2. In comparative cohorts, the model successfully predicted two groups of patients with divergent OS trends: higher for Group 1 and lower for Group 2., Conclusion: The produced model is a relevant tool to clinically stratify SBRT candidates into prognostic groups, even when applied to different cohorts. ANN are a valuable resource, providing useful data to build a prognostic model that deserves to be validated prospectively., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims/hypothesis: Diabetes mellitus is associated with impaired insulin secretion, often aggravated by oversecretion of glucagon. Therapeutic interventions should ideally correct both defects. Glucagon-like peptide 1 (GLP-1) has this capability but exactly how it exerts its glucagonostatic effect remains obscure. Following its release GLP-1 is rapidly degraded from GLP-1(7-36) to GLP-1(9-36). We hypothesised that the metabolite GLP-1(9-36) (previously believed to be biologically inactive) exerts a direct inhibitory effect on glucagon secretion and that this mechanism becomes impaired in diabetes., Methods: We used a combination of glucagon secretion measurements in mouse and human islets (including islets from donors with type 2 diabetes), total internal reflection fluorescence microscopy imaging of secretory granule dynamics, recordings of cytoplasmic Ca 2+ and measurements of protein kinase A activity, immunocytochemistry, in vivo physiology and GTP-binding protein dissociation studies to explore how GLP-1 exerts its inhibitory effect on glucagon secretion and the role of the metabolite GLP-1(9-36)., Results: GLP-1(7-36) inhibited glucagon secretion in isolated islets with an IC 50 of 2.5 pmol/l. The effect was particularly strong at low glucose concentrations. The degradation product GLP-1(9-36) shared this capacity. GLP-1(9-36) retained its glucagonostatic effects after genetic/pharmacological inactivation of the GLP-1 receptor. GLP-1(9-36) also potently inhibited glucagon secretion evoked by β-adrenergic stimulation, amino acids and membrane depolarisation. In islet alpha cells, GLP-1(9-36) led to inhibition of Ca 2+ entry via voltage-gated Ca 2+ channels sensitive to ω-agatoxin, with consequential pertussis-toxin-sensitive depletion of the docked pool of secretory granules, effects that were prevented by the glucagon receptor antagonists REMD2.59 and L-168049. The capacity of GLP-1(9-36) to inhibit glucagon secretion and reduce the number of docked granules was lost in alpha cells from human donors with type 2 diabetes. In vivo, high exogenous concentrations of GLP-1(9-36) (>100 pmol/l) resulted in a small (30%) lowering of circulating glucagon during insulin-induced hypoglycaemia. This effect was abolished by REMD2.59, which promptly increased circulating glucagon by >225% (adjusted for the change in plasma glucose) without affecting pancreatic glucagon content., Conclusions/interpretation: We conclude that the GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of glucagon secretion. We propose that the increase in circulating glucagon observed following genetic/pharmacological inactivation of glucagon signalling in mice and in people with type 2 diabetes reflects the removal of GLP-1(9-36)'s glucagonostatic action., (© 2023. The Author(s).)

Hand osteoarthritis (OA) severity can be assessed visually through radiographs using semi-quantitative grading systems. However, these grading systems are subjective and cannot distinguish minor differences. Joint space width (JSW) compensates for these disadvantages, as it quantifies the severity of OA by accurately measuring the distances between joint bones. Current methods used to assess JSW require users' interaction to identify the joints and delineate initial joint boundary, which is time-consuming. To automate this process and offer a more efficient and robust measurement for JSW, we proposed two novel methods to measure JSW: 1) The segmentation-based (SEG) method, which uses traditional computer vision techniques to calculate JSW; 2) The regression-based (REG) method, which is a deep learning approach employing a modified VGG-19 network to predict JSW. On a dataset with 3,591 hand radiographs, 10,845 DIP joints were cut as regions of interest and served as input to the SEG and REG methods. The bone masks of the ROI images generated by a U-Net model were sent as input in addition to the ROIs. The ground truth of JSW was labeled by a trained research assistant using a semi-automatic tool. Compared with the ground truth, the REG method achieved a correlation coefficient of 0.88 and mean square error (MSE) of 0.02 mm on the testing set; the SEG method achieved a correlation coefficient of 0.42 and MSE of 0.15 mm. Results show the REG method has promising performance in automatic JSW measurement and in general, Deep Learning approaches can facilitate the automatic quantification of distance features in medical images.

The present study investigated the intimate partner femicide (IPF) and intimate partner femicide-suicide (IPFS) perpetrators' individual, relational, and contextual characteristics by analyzing, within the ecological approach, femicide cases that occurred in Italy from 2010 to 2019. On the topic, to date, scant studies examined possible differences between IPF and IPFS risk factors, and no studies have analyzed these factors by adopting an ecological systems model perspective. To this aim, archival research was carried out. Of a total of 1.207 femicides, 409 were IPF, and 227 were IPFS. Perpetrators' age, level of employment, law enforcement membership, mental and/or physical illnesses, use of psychoactive substances, previous crimes, previous violent relationships, presence of children, previous violence in the couple, inability to accept the end of the relationship, quarrels and conflict, jealousy and the psychophysical illnesses of both authors and victims, as well as the use of firearms and victim's request for help were analyzed. The results underlined the existence of different risk factors contributing to the IPF perpetrators' decision to commit suicide such as perpetrators' age, law enforcement membership, and firearm availability. These findings stress the need for specific risk assessment and management strategies for IPFS perpetrators.

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefore, carried out in order to correlate the above-mentioned TA parameters with the frequency of pathological responses in the examined patients' population focusing on the detection of complete pathological response (pCR, with no viable cancer cells: TRG 1) as main statistical endpoint. ROC curves were performed on three different datasets considering that on the 21 patients, only 21% achieved an actual pCR. In our training dataset series, pCR frequency significantly correlated with ADC GLCM-Entropy only, when univariate and binary logistic analysis were performed (AUC for pCR was 0.87). A confirmative binary logistic regression analysis was then repeated in the two remaining validation datasets (AUC for pCR was 0.92 and 0.88, respectively). Overall, these results support the hypothesis that D-TA may have a significant predictive value in detecting the occurrence of pCR in our patient series. If confirmed in prospective and multicenter trials, these results may have a critical role in the selection of patients with locally advanced rectal cancer who may benefit form radical surgery after neoadjuvant chemoradiotherapy.

Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25-40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC.