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Background and Objective: Left bundle branch area pacing (LBBAP) is increasingly used for treating bradycardia and heart failure. However, real-world data are limited. The Conduction-System Pacing Italian Network Group (C-SING) collected prospective data on LBBAP procedures in a nationwide context., Methods: Observational data from 28 Italian sites were analysed for consecutive LBBAP procedures, comparing outcomes based on operator experience levels., Results: From January 2022 to December 2023, 1250 patients (median age 78, 66.2 % male) underwent LBBAP attempt. Most frequent indications were atrioventricular block (40.8 %) and heart failure (25.6 %). Successful lead implantation was achieved in 1207 procedures (96.6 %), with a median fluoroscopy time of 6.2 min. Significant QRS duration reduction was observed in patients with interventricular conduction delay (144 ms to 120 ms, p < 0.001). Compared to low-experience operators (0-10 previous cases), high-experience operators (>50 cases) had significantly better outcomes, with reduced fluoroscopy time (5.9 min versus 9.0 min, p = 0.005) and an 86 % lower risk of lead implantation failure (adjusted odds ratio 0.14, p = 0.002). Periprocedural complications occurred in 6.2 % of patients, unaffected by operator experience. Follow-up data for 794 patients over a median of 93 days showed stable LBBAP pacing parameters and a 1.3 % loss of LBBAP capture., Conclusions: LBBAP is routinely adopted for bradycardia and heart failure indication, with high success and acceptable complication rates, even when performed by less experienced operators. However, procedure outcomes improved significantly as operators gained experience with at least 50 prior cases. Electrical parameters remained stable with a low rate of LBBAP loss during short-term follow-up., Competing Interests: Declaration of competing interest Conflict of interest: Gabriele Dell'Era received fees for lectures and proctorship on conduction system pacing by Abbott, Biotronik and Boston Scientific; Matteo Bertini received small fees for lectures by Abbott, Biotronik, Boston, Microport and proctorship on conduction system pacing by Biotronik and Boston Scientific; Matteo Baroni received fees for lectures and proctorship on conduction system pacing by Abbott, Biotronik and Medtronic; Luca Poggio received fees for lectures and proctorship on conduction system pacing by Biotronik and Boston Scientific; Leonardo Marinaccio received fees for lectures and proctorship on conduction system pacing by Abbott, Biotronik, Boston Scientific and Medtronic; Paola Napoli and Daniele Giacopelli are employees of Biotronik. No other conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Major depression in the older population has a profound impact on patients' quality of life and is associated with an increased risk of developing several medical illnesses. Psychophysiological methods, such as electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and eye-tracking, have provided evidence of physiological changes associated with depression in adult life. However, these aspects have not been thoroughly investigated during late-life (over 60 years of age)., Methods: A systematic review of the scientific literature covering the studies published between 1990 and 2022 was performed to describe the current evidence on easily attainable psychophysiological factors (detected by EEG, fNIRS and eye-tracking) associated with depression in late-life., Results: Twelve studies were included in the systematic review. The included studies showed some consistent physiological patterns associated with late-life depression, such as brain hypoactivation in frontal and temporal areas and attentional biases toward emotional stimuli. No reliable patterns in EEG asymmetry and power spectrum were found, in contrast to studies on early-life depression., Limitations: The small number of available studies, together with the heterogeneity in the techniques and methods used, highlight the need for further research to reliably identify the psychophysiological aspects of depression in late-life., Conclusions: Physiological indices of late-life depression, as assessed by EEG, fNIRS and eye-tracking, may differ from those of early-life. The study of these indices could better clarify the physiological mechanisms underlying late-life depression with possible clinical and research implications. Recommendations for future research are also discussed., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Pancreatic cancer arising in the context of BRCA predisposition may benefit from poly(ADP-ribose) polymerase inhibitors. We analyzed real-world data on the impact of olaparib on survival in metastatic pancreatic cancer patients harboring germline BRCA mutations in Italy, where olaparib is not reimbursed for this indication., Methods: Clinico/pathological data of pancreatic cancer patients with documented BRCA1-2 germline pathogenic variants who had received first-line chemotherapy for metastatic disease were collected from 23 Italian oncology departments and the impact of olaparib exposure on overall survival (OS) was analyzed., Results: Of 114, 53 BRCA-mutant pancreatic cancer patients had received olaparib for metastatic disease. OS was significantly longer in patients who were exposed to olaparib (hazard ratio [HR] 0.568, 95% confidence interval [CI] 0.351-0.918, log-rank p = 0.02) in any setting/line of treatment; similar results were obtained for patients who received olaparib as maintenance treatment (in any line of treatment), patients who had stage IV disease at diagnosis, and patients who did not experience progressive disease as their best response to first-line chemotherapy. Exposure to olaparib in the first-line maintenance setting after platinum-based chemotherapy, however, did not significantly impact survival. At multivariate analysis, CA19.9 levels at diagnosis and response to first-line chemotherapy were independently prognostic; however, when response to chemotherapy was excluded, any exposure to olaparib was a significant independent predictor of longer OS, together with CA19.9 levels., Conclusion: The real-world data presented here support the use of olaparib for metastatic disease in germline BRCA-mutant pancreatic cancer patients, as it may significantly prolong survival., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Literature is lacking strong evidence about comparisons of efficacy and quality of life-related outcomes between laparoscopic total and/or supracervical hysterectomy (LTH/LSCH) with laparoscopic sacrocolpopexy (LSC) and minimally invasive sacrohysteropexy (LSH)., Objective: To summarize and compare available data on this topic providing a useful clinical tool in the treatment decision process., Search Strategy: We performed a systematic research of PubMed (MEDLINE), Web of Science, and Gooogle Scholar., Selection Criteria: We included studies that compared at least one efficacy outcome (objective or subjective outcome) between LTH/LSCH with LSC and LSH. Data on surgery-related morbidities were also extracted where available., Data Collection and Analysis: A random-effect meta-analysis was conducted reporting pooled mean differences and odds ratios (OR) between groups using Review Manager V.7.9.0., Main Results: We included a total of nine observational studies. LTH/LSCH with LSH was associated with a significantly higher objective success (apical compartment OR 7.95; 95% confidence interval [CI] 2.23-28.33; I 2  = 0%; P = 0.001; anterior compartment OR 2.23; 95% CI 1.26-4.30; I 2  = 12%; P = 0.007) and subjective success (OR 3.19; 95% CI 1.42-7.17; I 2  = 39%; P = 0.005). No differences were found regarding intraoperative and postoperative complications, sexual dysfunction, and stress urinary incontinence rate after surgery. Hysteropexy showed shorter operative time and shorter hospital length with a pool mean difference of 27.37 min (95% CI 18.04-32.71; I 2  = 0%; P < 0.001) and 0.7 days (95% CI 0.24-1.17; I 2  = 75%; P = 0.003), respectively. Concurrent hysterectomy was not associated with a higher rate of mesh-related complications (P = 0.53). No major differences were found regarding recurrence and reoperation rate (P = 0.10 and P = 0.93, respectively)., Conclusions: LTH/LSCH with LSC has better objective and subjective outcomes in pelvic organ prolapse surgery than LSH alone, especially for apical and anterior compartments, and is not associated with higher postoperative sexual dysfunction and mesh-related complications. Adequate preoperative counseling is highly recommended in patients who desire uterine preservation., Prospero Registration Number: CRD42024537270., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Actigraphy is increasingly being used to assess sleep in patients with neurodegenerative diseases. However, information on its accuracy relative to polysomnography (PSG) in this clinical population remains scarce. This study investigates the performance of actigraphy compared to PSG in patients with behavioral variant frontotemporal dementia (bvFTD), which is the leading form of early-onset dementia., Methods: Eighteen patients with bvFTD (10 males, mean age 70.50 ± 8.48 years) underwent overnight, in-home PSG while concurrently wearing an actigraph on their non-dominant wrist. Actigraphy performance was assessed through discrepancy analysis, Bland-Altman plots, and epoch-by-epoch analysis (EBE). Analyses were conducted separately for the Cole-Kripke and UCSD scoring algorithms., Results: Discrepancy analysis highlighted that the Cole-Kripke and UCSD algorithms overestimate total sleep time (by 43 and 60 min, respectively) and sleep efficiency (by 7.13 % and 10.33 %, respectively). The Cole-Kripke algorithm also overestimates sleep onset latency (by 7.75 min). Wake after sleep onset (WASO) showed a negative proportional bias for both algorithms, indicating that actigraphy underestimates WASO for subjects with longer PSG-measured WASO. In the EBE analysis, the Cole-Kripke algorithm shows an accuracy of 84 % (sensitivity 93 %, specificity 62 %) and the UCSD algorithm an accuracy of 85 % (sensitivity 96 %, specificity 57 %)., Conclusions: In patients with bvFTD, actigraphy significantly overestimates total sleep time, sleep latency, and sleep efficiency, while underestimating WASO. Clinicians and researchers using actigraphy to study sleep in bvFTD must carefully consider these measurement biases and correct for them based on the results of previous comparison studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For surgeons and clinicians, nonobstetric surgery during pregnancy has certain difficulties and considerations. In order to aid in decision-making in these situations, this manuscript offers a thorough review of the guidelines currently in place from renowned obstetric and surgical societies, such as the American College of Obstetricians and Gynecologists, the Royal College of Obstetricians & Gynecologists, and others. Using AGREE II-S methodology, a comprehensive analysis of guidelines reveals differences in recommendations for anesthetics, surgical procedures, imaging modalities, and thromboembolic prophylaxis. Furthermore, a thorough discussion of strategic surgical planning is provided, covering aspects such as patient positioning, trocar placement, pneumoperitoneum generation, and thromboembolic risk management. The publication highlights that in order to maximize the results for both the mother and the fetus after nonobstetric surgery performed during pregnancy, a multidisciplinary approach and evidence-based decision-making are essential., (© 2024 International Federation of Gynecology and Obstetrics.)

Competing Interests: The authors declare no conflict of interest.

Competing Interests: Conflict of interest: none declared.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to traditional ICDs. The PRAETORIAN score, based on chest radiographs, has been validated to predict the probability of successful S-ICD defibrillation testing by assessing factors like fat thickness between the coil and sternum and generator placement., Objective: This study evaluated the correlation between the PRAETORIAN score and clinical characteristics, as well as implantation variables., Methods: We retrospectively analyzed data from 1253 patients who had undergone implantation of an S-ICD across 33 centers. The intermuscular positioning of the pulse generator was adopted in all patients. Post-implantation posterior-anterior and lateral chest radiographs were analyzed to calculate the PRAETORIAN score., Results: 95.7% of patients had a PRAETORIAN score <90, indicative of a low risk of conversion failure. Body mass index (BMI) was the only independent predictor of a score ≥90, and all patients with BMI <25kg/m2 (normal weight or underweight) had a score <90. The intermuscular positioning technique resulted in optimal posterior placement of the device in all patients and significant sub-generator fat in only 3% of cases. A shock impedance value >88Ohm enabled to detect a PRAETORIAN score ≥90 with 98% (95% CI 97%-99%) negative predictive value., Conclusions: In contemporary practice, the PRAETORIAN score can be simplified. By adopting an intermuscular approach, two of the three steps of the score-evaluating the adequate posterior positioning of the generator and measuring the sub-generator fat-become superfluous, and impedance may serve as a reliable surrogate of sub-coil fat thickness. Furthermore, our data suggest that for non-obese patients, a favorable PRAETORIAN score is assured, making the score evaluation potentially unnecessary., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Despite the advent of the ERAS Program, recovery after urogynecological surgery is still a highly debated topic in clinical practice. The majority of gynecologic surgeons, in fact, continue to advise patients to home rest and to avoid lifting heavy objects after surgery. The aim of the present study was to verify the impact of a moderate-high physical activity and recovery after surgery on anatomical results after LSC, with a 2-year follow-up (FU)., Methods: Two hundred and one consecutive patients with pelvic prolapse were retrospectively selected from our database among women who underwent, from October 2019 to February 2022, a laparoscopic sacral colpopexy. Three-six and 24 months follow-up were studied. At 3 months, patients completed the IPAQ-SF Questionnaire to assess physical activity. According to IPAQ-SF, patients were divided in two arms: Low and Moderate-High activity level., Results: At 3 months follow-up, we obtained a high anatomic success rate in absences of statistical differences between populations, with a significative persistence of these results even at 6 and 24 months. No differences were found in terms of subjective success and vaginal mesh erosions at 3-6 months and 2-years follow-ups between patients despite differences in IPAQ-SF activity levels., Conclusion: Our data highlight the need for urogynecologists, especially after LSC, to invest heavily in patient education and to shift away from the outdated concept of home rest after surgery., Competing Interests: Declarations. Conflicts of interest: None., (© 2025. The Author(s).)

Background: The utilization of poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) as a first-line maintenance therapy for advanced ovarian cancer has increased significantly, with ∼80% of patients potentially eligible. This expansion has led to a rise in the population experiencing platinum-sensitive recurrence, yet data on first recurrence during PARPi are limited. This real-world study from a high-volume referral center aims to elucidate recurrence rates, disease distribution, and treatment modalities at the time of progression in PARPi-treated patients., Materials and Methods: We analyzed our prospectively maintained database to identify patients receiving first-line PARPi maintenance from January 2019 to December 2022 at our institution., Results: A total of 373 cases were identified, 51.5% of which had a BRCA mutation. With a median follow-up of 38 months, 44.8% of patients experienced recurrence, with 90.3% having a platinum-free interval exceeding 6 months. Recurrences were oligometastatic in 44.9% of cases, with BRCA mutations strongly predicting this pattern (hazard ratio 3.014, confidence interval 1.486-6.113, P = 0.002). The median progression-free survival was 39 months, significantly longer for BRCA-mutated and homologous recombination deficiency-positive patients. Over one-third of platinum-sensitive recurrent patients were candidates for local treatments, and PARPi administration was prolonged in 53.7%., Conclusions: Despite the notable survival improvement, a significant proportion of the population will experience a platinum-sensitive recurrence on PARPi, for which local treatments are often a viable option. Our study highlights the need for further research to determine whether the ablation of oligometastatic sites has a significant impact on post-recurrence survival and to identify if there are patient categories that would benefit from personalized follow-up due to their susceptibility to oligometastatic recurrences and local treatments., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In patients with symptomatic, refractory atrial fibrillation the ablate and pace (A&P) strategy (pacemaker implantation followed by atrio-ventricular junction ablation (AVJA)) is superior to medical therapy in improving quality of life and prognosis. Despite its well-proven benefits, this invasive therapeutic option is still underutilized in clinical practice. The choice of pacing modality (right ventricular pacing, biventricular pacing, BVP, or conduction system pacing, CSP) is crucial and can have significant clinical implications. In particular, in recent years CSP is emerging as an alternative to BVP, showing a good effectiveness and safety profile. Other important aspects are the timing of ablation, the approach used for AVJA, and the correct device programming after AVJA., Areas Covered: This article reviews the currently available evidence on this therapeutic strategy with a particular focus on its impact on patient outcome, recognized indications, technical considerations, and future perspectives., Expert Opinion: With the availability of more robust evidence confirming the better effectiveness and safety profile of CSP compared to conventional pacing modalities, in the next few years CSP will become the standard pacing modality in candidates for A&P. The routine adoption of this pacing modality could lead to a wider use of A&P in clinical practice.

» Increased professional, personal, and emotional stress can have compounding negative effects on physicians, which can be detrimental to teamwork dynamics, workplace environment, productivity, and personal well-being. Orthopaedic surgery, in particular, is a medical specialty that demonstrates high workplace demands, elevated rates of burnout, and low workplace diversity.» Professional coaching can help combat these challenges and facilitate professional success by providing an outlet for discussion and planning toward one's career development and goals. Coaches, generally nonphysicians, are trained and certified to advise and guide physicians in their professional career paths.» There has been demonstrated success in the utilization of professional coaching in various medical specialties and groups, including anesthesiology, primary care, general surgery, and female surgeon organizations.» The purpose of this review is to evaluate existing models of professional coaching to inform its use within orthopaedic surgery as a means of promoting well-being, physician success, and workforce diversity., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B188)., (Copyright © 2025 by The Journal of Bone and Joint Surgery, Incorporated.)

Study Objectives: Sleep disorders have been recognized as an integral component of the clinical syndrome in several neurodegenerative diseases, including Alzheimer's disease (AD). However, limited data exist for rarer types of neurodegenerative diseases, such as behavioral variant frontotemporal dementia (bvFTD). This study aims to analyze EEG power spectra and sleep stage transitions in bvFTD patients, hypothesizing that bvFTD may show distinctive sleep stage transitions compared to patients with AD., Methods: Eighteen probable bvFTD patients and 18 age- and sex-matched probable patients with AD underwent overnight polysomnography (PSG) and completed sleep disorders questionnaires. Sleep questionnaires, full-night EEG spectra, and sleep stage transition indexes were compared between groups., Results: bvFTD patients had higher Insomnia Severity Index (ISI) scores (95% confidence intervals [CI]: 0, 5) and reported poorer sleep quality than AD patients (p < .01). Compared to AD, bvFTD patients showed higher N1 percentage (95% CI: 0.1, 6), lower N3 percentage (95% CI: -13.6, -0.6), higher sleep-wake transitions (95% CI: 1.49, 8.86) and N1 sleep-wake transitions (95% CI: 0.32, 6.1). EEG spectral analysis revealed higher spectral power in bvFTD compared to patients with AD in faster rhythms, especially sigma rhythm, across all sleep stages. In bvFTD patients, sleep-wake transitions were positively associated with ISI., Conclusions: Patients with bvFTD present higher rates of transitions between wake and sleep than patients with AD. The increased frequency of sleep transitions indicates a higher degree of sleep instability in bvFTD, which may reflect an imbalance in sleep-wake-promoting systems. Sleep stage transitions analysis may provide novel insights into the sleep alterations of patients with bvFTD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Objective: To provide up-to-date European Society of Urogenital Radiology (ESUR) guidelines for staging and follow-up of patients with ovarian cancer (OC)., Methods: Twenty-one experts, members of the female pelvis imaging ESUR subcommittee from 19 institutions, replied to 2 rounds of questionnaires regarding imaging techniques and structured reporting used for pre-treatment evaluation of OC patients. The results of the survey were presented to the other authors during the group's annual meeting. The lexicon was aligned with the Society of American Radiology (SAR)-ESUR lexicon; a first draft was circulated, and then comments and suggestions from the other authors were incorporated., Results: Evaluation of disease extent at diagnosis should be performed by chest, abdominal, and pelvic CT. The radiological report should map the disease with specific mention of sites that may preclude optimal cytoreductive surgery. For suspected recurrence, CT and [ 18 F]FDG PET-CT are both valid options. MRI can be considered in experienced centres, as an alternative to CT, considering the high costs and the need for higher expertise in reporting., Conclusions: CT is the imaging modality of choice for preoperative evaluation and follow-up in OC patients. A structured radiological report, including specific mention of sites that may preclude optimal debulking, is of value for patient management., Key Points: Question Guidelines were last published for ovarian cancer (OC) imaging in 2010; here, guidance on imaging techniques and reporting, incorporating advances in the field, are provided. Findings Structured reports should map out sites of disease, highlighting sites that limit cytoreduction. For suspected recurrence, CT and 18FDG PET-CT are options, and MRI can be considered. Clinical relevance Imaging evaluation of OC patients at initial diagnosis (mainly based on CT), using a structured report that considers surgical needs is valuable in treatment selection and planning., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Stefania Rizzo. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was not required. Ethical approval: Institutional Review Board approval was not required. Study subjects or cohorts overlap: Not applicable Methodology: Guidelines, (© 2025. The Author(s).)

Background/objectives: The huge concerns associated with biofilm-related infections in surgical procedures, along with the antibiotic resistance demonstrated by an increasing number of bacteria, have highlighted the need for alternative and effective prevention approaches. The aim of this research was to develop novel antimicrobial coatings on surgical sutures for the prevention of surgical site infections through nanotechnology-based methods., Results: The results demonstrated that although very low amounts of silver precursor were adopted for the treatments, the silver coating was effective against Staphylococcus aureus and antibiotic-resistant Pseudomonas aeruginosa in reducing the potential risk of infection., Methods: Nanostructured silver coatings were deposited onto the surface of polyglactin 910 absorbable braided sutures through a technology based on a photo-assisted chemical reaction. The materials were characterized in order to verify the efficacy of the coating in preventing biofilm formation and in reducing the bacterial colonization of the device., Conclusions: As a broad-spectrum antimicrobial agent, silver represents an important option for the prevention and management of surgical site infections. The silver deposition technology adopted in this work provides an interesting strategy for preventing biofilm formation on medical devices such as surgical sutures.

Macroscopic coherence in quantum fluids allows the observation of interference effects in their wavefunctions, and enables applications such as superconducting quantum interference devices based on Josephson tunneling. The Josephson effect manifests in both fermionic and bosonic systems, and has been well studied in superfluid helium and atomic Bose-Einstein condensates. In exciton-polariton condensates-that offer a path to integrated semiconductor platforms-creating weak links in ring geometries has so far remained challenging. In this work, we realize a Josephson junction in a polariton ring condensate. Using optical control of the barrier, we induce net circulation around the ring and demonstrate both superfluid-hydrodynamic and the Josephson regime characterized by a sinusoidal tunneling current. Our theory in terms of the free-energy landscapes explains the appearance of these regimes using experimental values. These results show that weak links in ring condensates can be explored in optical integrated circuits and hold potential for room-temperature applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Heart failure (HF) is strongly associated with inflammation. In pressure overload (PO)-induced HF, cardiac stress triggers adaptive immunity, ablation or inhibition of which blocks disease progression. We hypothesized that PO-HF might fulfill the often-used criteria of autoimmunity: if so, the associated adaptive immune response would be not only necessary but also sufficient to induce HF; it should also be possible to identify self-antigens driving the autoimmune response. Finally, we hypothesized that such an antigen-specific response can be manipulated to preventively reduce the severity of PO-HF in a tolerizing vaccine., Methods: We used the transfer of lymphocytes or serum from PO-HF mice into healthy recipients to assess whether the adaptive response is sufficient to induce disease. We devised a novel pipeline to identify self-antigens driving the response. We immunized healthy mice with novel antigens to assess whether they induce disease. To determine whether these antigens could be present in human patients, we sought to detect existing responses against these antigens in patients with HF. Finally, we used the antigens in an oral tolerance protocol to preventively protect mice from subsequently induced PO-HF, analyzing the results with next-generation sequencing., Results: We found that PO-HF fulfills the criteria of an autoimmune disease, albeit partially, and identified novel cardiac self-antigens, capable of inducing cardiac dysfunction. The novel antigens in a tolerizing vaccine formulation preemptively reduced the severity of disease triggered by subsequent application of PO, via induction of effector regulatory T cells, enabling a potent reduction of PO-driven loss of systolic function, cardiac inflammation, and proinflammatory CD4 + T-cell clonal expansion., Conclusions: We demonstrate that PO-HF is triggered by hemodynamic stress and then sets off an autoimmune-like response against cardiac self-antigens. The antigens can be used to reduce the severity of future-onset disease, via oral tolerization, effectively acting as a protective vaccine., Competing Interests: The authors have no competing interests to disclose. E. Martini, G. Condorelli, and M. Kallikourdis are listed as inventors in pending patent applications stemming from the contents of this work.

•Randomized Clinical Trials (RCTs) are the gold standard for human experimental studies.•RCTs demand equipoise and freedom from treatment preference among investigators.•Neurologic RCTs are costly, time-intensive, and have high participant exclusion rates.•RCTs use randomization to minimize bias/ confounding and test with probability statistical theory the treatment effects.•The CONSORT guidelines enhance the quality of RCT reporting., Competing Interests: None., (© 2025 Published by Elsevier B.V.)

Left ventricular non-compaction (LVNC) is a rare primary cardiomyopathy with genetic etiology, resulting from an abnormality of myocardial development during embryogenesis. It carries an elevated risk of left ventricular dysfunction, thromboembolic events and malignant arrhythmias. We report the case of LVNC associated with paroxysmal atrial fibrillation and ankyrin 2 ( ANK2 ) mutation at the genetic test. An 18-year-old competitive athlete visited our medical center to undergo the diagnostic investigations protocol preparatory to the release of the suitability for competitive practice. The echocardiographic examination shows LVNC without ventricular remodeling (left ventricular ejection fraction (LVEF) 53%, global longitudinal strain (GLS) -18.3%). The echocardiographic diagnosis was confirmed by cardiac magnetic resonance imaging (cMRI), which revealed dense hypertrabeculation in the left ventricular apex and lateral wall. The cardiogenetic investigation showed a c.9145C>T variant (p.Arg3049Trp) identified in the ANK2 gene. This mutation is associated in the literature with rare cases of LVNC. The patient underwent an extended Holter monitoring which excluded ventricular arrhythmic events but showed two brief episodes of paroxysmal atrial fibrillation. Despite the absence of significant ventricular remodeling, considering the presence of paroxysmal atrial fibrillation and the presence of a mutation in the ANK2 gene, which has several variants related to high-risk phenotypes, it has been decided to suspend the competitive practice, and is defined an adequate clinical-diagnostic follow-up., Competing Interests: The authors declare that there is no conflict of interest relevant to this article., (Copyright 2025, De Masi De Luca et al.)

Ketogenic diet has a wide range of beneficial effects but presents practical limitations due to its low compliance, hence dietary supplements have been developed to induce ketosis without nutrient deprivation. The alcohol 1,3-butanediol (BD) is a promising molecule for its ability to induce ketosis, but its effects on brain have been investigated so far only in disease models, but never in physiological conditions. To support BD use to preserve brain health, the analysis of its activity is mandatory. Therefore, we investigated, in healthy rats, the effect of a fourteen-days BD-administration on the hippocampus, an area particularly vulnerable to oxidative and inflammatory damage. Since BD treatment has been reported to reduce energy intake, results were compared with those obtained from rats undergoing a restricted dietary regimen, isoenergetic with BD group (pair fed, PF). Reduced pro-inflammatory signaling pathways and glial activation were revealed in hippocampus of BD treated rats in comparison to control (C) and PF groups. ROS content and the extent of protein oxidative damage were lower in BD and PF groups than in C. Interestingly, higher amounts of nuclear factor erythroid 2-related factor 2 (Nrf2), decreased level of lipid hydroperoxides, lower susceptibility to oxidative insult, higher amounts of superoxide dismutase-2, glutathione reductase and glutathione peroxidase (GPx), and increased GPx activity were observed in BD animals. BD administration, but not dietary restriction, attenuated endoplasmic reticulum stress, reduced autophagic response activation, and was associated with an increase of both the neurotrophin BDNF and pre-synaptic proteins synaptophysin and synaptotagmin. Our results highlight that BD plays a neuroprotective role in healthy conditions, thus emerging as an effective strategy to support brain function without the need of implementing ketogenic nutritional interventions., Competing Interests: Declaration of Competing Interest The authors have no financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: To describe the historical evolution and dissemination of the Oral Medicine and Oral and Maxillofacial Pathology international societies and associations across the globe, and to provide insights into their significant contributions toward oral health promotion., Study Design: This review was conducted in accordance with the JBI Scoping Review Methodology Group guidance. The reporting followed the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR)., Results: Search strategy was applied to 5 databases (MEDLINE/PubMed, Scopus, Embase, Web of Science, Latin American and Caribbean Health Sciences (LILACS)) and grey literature (Google Scholar, Open Grey and ProQuest), as well as additional sources, such as organization websites. Eighty-nine sources were included in this review. Forty-six professional associations/societies were identified, of which 39 represented a country or geopolitical region, 2 represented continents, 2 represented multinational organizations and 3 multinational study groups., Conclusions: Documentation of the historical establishment and development of Oral Medicine and Oral and Maxillofacial Pathology organizations worldwide is limited and describing these processes remains challenging. Analysis of global data reveals heterogeneous development and distribution, resulting in disparities in accessibility and standardization. Further efforts toward oral health promotion should be implemented., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tuberculosis (TB) remains a Global Health challenge, with diagnostic delays contributing significantly to its spread. This study investigates the differences in diagnostic delays between native and migrant TB patients in Italy, examining patient-related diagnostic delay (PDD), health system-related diagnostic delay (HDD), and total diagnostic delay (TDD)., Methods: We conducted a retrospective, multicenter, cross-sectional study of TB cases in 10 Italian hospitals from 2018 to 2023. We compared PDD, HDD, and TDD between native and migrant populations. Socio-demographic data and clinical histories were analyzed to identify factors contributing to diagnostic delays., Results: We included 669 TB patients (390 migrants and 279 natives). Migrants experienced significantly longer PDD (median 90 vs 10 days, P < 0.0001) but shorter HDD (median 5 vs 40 days, P < 0.0001) compared to natives, resulting in a longer TDD (median 96 vs 65 days, P < 0.0001). Furthermore, migrants had higher Timika scores, longer sputum conversion times, and were more frequently lost to follow-up., Conclusion: Migrants face longer PDD, emphasizing substantial barriers to healthcare access. Natives experience longer HDD, reflecting neglect of TB in low-endemic regions. Future research should focus on the impact of social determinants and training for healthcare providers on TB diagnosis and develop strategies to reduce diagnostic delays., Competing Interests: Declarations 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 article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: The Food and Drug Administration approved two disease-modifying treatments (DMTs) for Alzheimer's disease (AD), aducanumab and lecanemab, with limited clinical impact but significant biomarker changes. Identifying suitable candidates for these DMTs outside randomized clinical trials (RCTs) remains uncertain., Methods: This cross-sectional study, conducted in an Italian tertiary centre for cognitive disorders, aimed to evaluate how the RCT eligibility criteria for DMT treatments applies to participants with early AD. The broader Cummings et al. (Journal of Prevention of Alzheimer's Disease, 2021, 2023) criteria and the clinical differences between DMT candidates were also assessed., Results: The study involved 408 participants (mean age 71.1 ± 8.5 years, 48% male) with a clinical diagnosis of mild cognitive impairment (161/408, 39.5%) or mild dementia (247/408, 60.5%). Amongst them, 169 individuals (41%) showed positive AD pathology biomarkers. Eligibility RCT assessment revealed 14 patients eligible for aducanumab (3.43% of 408) and 28 for lecanemab (6.86% of 408). Following Cummings' real-world criteria, aducanumab eligibility increased to 9.56%, whereas lecanemab eligibility rose to 8.33%. Applying selection criteria to only the amyloid positive (169 out of 408), the selection for DMTs was 8.3% for aducanumab and 16.5% for lecanemab., Conclusion: Amongst subjects diagnosed with mild AD and mild cognitive impairment in a tertiary centre for cognitive disorders, only a small percentage of patients using RCT diagnostic criteria are eligible for DMT. The application of Cummings criteria strongly increased the DMT candidates. Nevertheless, the majority of patients with cognitive disorders have been excluded from DMTs approved so far., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Cardiomyopathies, historically regarded as rare, are increasingly recognized due to advances in imaging diagnostics and heightened clinical focus. These conditions, characterized by structural and functional abnormalities of the myocardium, pose significant challenges in both chronic and acute patient management. A thorough understanding of the hemodynamic properties, specifically the pressure-volume relationships, is essential. These relationships provide insights into cardiac function, including ventricular compliance, contractility, and overall cardiovascular performance. Despite their potential utility, pressure-volume curves are underutilized in clinical settings due to the invasive nature of traditional measurement techniques. Recognizing the dynamic nature of cardiomyopathies, with possible transitions between phenotypes, underscores the importance of continuous monitoring and adaptive therapeutic strategies. Enhanced hemodynamic evaluation can facilitate tailored treatment, potentially improving outcomes for patients with these complex cardiac conditions., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Non-motor fluctuations (NMF) in Parkinson's disease (PD) significantly affect patients' well-being. Despite being identified over two decades ago, NMF remain largely under-recognized, under-treated, and poorly understood. While they are often temporally associated with motor fluctuations (MF) and can share common risk factors and pathophysiologic mechanisms, NMF and MF are currently considered distinct entities. The prevalence and severity of NMF, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMF on PD patients' quality of life (QoL) underscores the importance of further investigation via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMF, ultimately enhancing clinicians' diagnostic and treatment options in routine clinical practice.

Objective: To validate the ISGPS complexity grading system for minimally invasive pancreaticoduodenectomy (MIPD)., Background: Although concerns about patient safety persist, MIPD is gaining popularity. The ISGPS recently introduced a difficulty grading system to improve patient selection by aligning procedural complexity with surgeon and center expertise., Methods: Data from MIPD cases reported in the IGOMIPS registry (October 2019-February 2024) were analyzed, with severe postoperative complications as the primary outcome. Logistic regression was used to identify risk factors for complications., Results: Of the 771 MIPD cases, 426 (55.3%) were analyzed. A pancreatic duct size ≤3 mm was the only significant risk factor for severe complications (OR=2.22, P=0.0001). Most cases (n=255; 59.9%) were classified as grade C complexity, whereas 22 (5.1%) were classified as grade A. Severe postoperative complications increased with complexity (grade A, 31.8%; grade B, 36.3%; grade C, 48.6%; P=0.0091). For grade A complexity, the outcomes were consistent across surgeons and centers. Grade B outcomes were similar between grade B and C centers but superior to grade A centers. In grade C cases, outcomes were comparable between grade A and B centers, with improvements at grade C centers. Grade A ISGPS experience correlated strongly with mismatches between planned and performed procedures (grade A, 15.0%; grade B, 3.0%; grade C, 3.1%; P<0.0001), including total pancreatectomy (grade A, 11.5%; grade B, 1.2%; grade C, 3.1%; P=0.0005)., Conclusions: The ISGPS complexity grading system effectively predicted MIPD outcomes, supporting better patient selection and alignment of complexity with surgical expertise., Competing Interests: Conflicts of Interest and Source of Funding: Roberto Salvia is one of the leaders of the ISGPS that developed the complexity score for MIPD that this manuscript aimed to validate. Ugo Boggi and Giovanni Butturini were coauthors in the original study. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We propose an integral model describing an epidemic of an infectious disease. The model is behavioural in the sense that the force of infection includes the information index that describes the opinion-driven human behavioural changes. The information index contains a memory kernel to mimic how the individuals maintain memory of the past values of the infection. We obtain sufficient conditions for the endemic equilibrium to be locally stable. In particular, we show that when the infectivity function is represented by an exponential distribution, stability is guaranteed by the weak Erlang memory kernel. However, through numerical simulations, we show that oscillations, possibly self-sustained, may arise when the memory is more focused in the disease's past history, as exemplified by the strong Erlang kernel. We also show the model solutions in cases of different infectivity functions taken from studies where specific diseases like Influenza and SARS are considered., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Surgical repair is considered the mainstay of genital prolapse management. Several procedures are available both by vaginal and abdominal route, with and without mesh augmentation. The Italian UroGynecology Association (AIUG) promoted this survey with the aim of evaluating current variations in the surgical management of various types of prolapse in different clinical settings and to compare practice amongst practitioners working in high- and medium/low-volume centers., Participants and Methods: The questionnaire examined four contentious areas of contemporary prolapse management. The questionnaire was emailed to the AIUG gynecologist members in Italy in 2023., Results: A total of 104 complete responses were received, resulting in a 6.9% response rate. Native-tissue repair represents the preferred option in most scenarios and was proposed by 76%, 68.3%, 94.2%, and 52.9% of practitioners in the case of primary anterior, uterovaginal, posterior, and vault prolapse respectively. The use of vaginal mesh in these scenarios is very limited. Native tissue repairs in case of recurrent anterior, posterior, or apical recurrent prolapse would be performed only by 37.5%, 47.1%, and 28% of surgeons respectively. In these cases, the use of mesh - by vaginal and abdominal route - increased significantly., Conclusion: This survey showed that in Italy surgical management of genital prolapse is very heterogeneous. Native-tissue repair remains the preferred option, but practitioners tend to lose confidence in mesh-free procedures in case of prolapse recurrence. Despite mesh kits recalls and recommendations, the use of transvaginal implants is still considered an option for prolapse repair., Competing Interests: The author(s) report no conflicts of interest in this work., (© 2024 Frigerio et al.)

Background: Non-meningothelial intracranial mesenchymal tumors are a heterogeneous group of central nervous system neoplasms endowed with great variability clinically and histologically. For this precise reason, significant difficulties exist in specifically cataloguing tumor entities with such distant characteristics and such uncertain clinical course., Case Description: In an attempt to increase the knowledge inherent in this type of central nervous system lesions we report a case of a rare and unusual myxoid mesenchymal tumor of difficult anatomopathological classification characterized by rapid progression and optimal therapeutic response after combined surgical and radiotherapy treatment, with histo-molecular definition and DNA methylation profile. In this case, multidisciplinary management led to timely surgical intervention based on the rapid clinical deterioration and radiological progression; after adjuvant therapy with hadron therapy, the patient has no signs of recurrence two years after the surgical procedure. No FET-CREB fusion was detected, and the DNA methylation profile suggested the presence of multiple chromosomal gains and losses., Conclusions: The molecular definition as well the optimal therapeutic regimen of these tumors is not clearly defined yet and analysis of larger series is strongly warranted., Competing Interests: Declarations. Informed consent: Informed consent was obtained from the subjects, and the clinical investigation was conducted in accordance with the guidelines of the Declaration of Helsinki. Institutional review board statement: Ethical review and approval were waived for this study since a sigle patient is involved and informed consent was acquired. Informed consent statement: Informed consent was obtained from all subjects involved in the study. Conflict of interest: The authors declare no conflicts of interest associated with this manuscript., (© 2024. Fondazione Società Italiana di Neurologia.)

Background Context: Spondylodiscitis management presents significant clinical challenges, particularly in critically ill patients, where the risks and benefits of surgical intervention must be carefully balanced. The optimal timing of surgery in this context remains a subject of debate., Purpose: This study aims to evaluate the effectiveness of early surgery versus delayed surgery or conservative management in critically ill patients with de novo pyogenic spondylodiscitis., Study Design/setting: This is an international, multicenter retrospective cohort study involving 24 centers, primarily in Europe., Patient Sample: The study included 192 critically ill patients (65.63% male) with a median age of 69 years, all severely affected by pyogenic spondylodiscitis characterized by an initial CRP level >200 mg/l or the presence of two out of four Systemic Inflammatory Response Syndrome criteria upon admission., Outcome Measures: The primary outcome was 30-day mortality. Secondary outcomes included length of ICU stay, length of hospital stay, and relapse rates of spondylodiscitis., Methods: Patients were divided into three groups: early surgery (within three days of admission), delayed surgery (after three days of admission), and conservative therapy. Propensity score matching and multivariate regression analyses were performed to adjust for baseline differences and assess the impact of treatment modalities on mortality and other clinical outcomes., Results: Delayed surgery was associated with significantly lower 30-day mortality (4.05%) compared to early surgery (27.85%) and conservative therapy (27.78%) (p<.001). Delayed surgery also resulted in shorter hospital stays (42.76 days) compared to conservative therapy (55.53 days) and early surgery (26.33 days) (p<.001), and shorter ICU stays (4.52 days) compared to conservative therapy (16.48 days) and early surgery (7.92 days) (p<.001). The optimal window for surgery, minimizing mortality, was identified as ten to fourteen days post-admission (p=.02). Risk factors for increased mortality included age (p<.05), multiple organ failure (p<.05), and vertebral body destruction (p<.05), whereas delayed surgery (p<.05) and the presence of an epidural abscess were associated with reduced mortality (p<.05)., Conclusions: Delayed surgery, optimally between 10 to 14 days post-admission, was associated with lower mortality in critically ill spondylodiscitis patients. These findings highlight the potential benefits of considering surgical timing to improve patient outcomes., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Observational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian randomisation (MR) approach., Methods: Analyses have been conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (more than 20 000 individuals), a case-cohort study of T2D nested in the EPIC cohort. Education was measured as Years of Education and Relative Index of Inequality. Prentice-weighted Cox models were performed to estimate the association between education and T2D. One-sample MR analyses investigated whether genetic predisposition towards longer education was associated with risk of T2D and investigated potential mediators of the association., Results: MR estimates indicated a risk reduction of about 15% for each year of longer education on the risk of developing T2D, confirming the protective role estimated by observational models (HR 0.96, 95% CI 0.95 to 0.96). MR analyses on putative mediators showed a significant role of education on body mass index, alcohol consumption, adherence to the Mediterranean diet and smoking habits., Conclusion: The results supported the hypothesis that higher education is a protective factor for the risk of developing T2D. Based on its position in the causal chain, education may be antecedent of other known risk factors for T2D including unhealthy behaviours. These findings reinforce evidence obtained through observational study designs and bridge the gap between correlation and causation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Pulsed field ablation (PFA) is an innovative technology recently adopted for the treatment of atrial fibrillation (AF). Preclinical and clinical studies have reported a remarkable safety profile, as a result of its tissue-specific effect targeting cardiomyocytes and sparing adjacent tissues. Single-shot pentaspline system was the first PFA device to receive regulatory approval. We performed a meta-analysis to compare the efficacy and safety of PFA with the single-shot pentaspline system vs. currently available second-/third-/fourth-generation cryoballoon ablation (CRYO) technologies., Methods and Results: We systematically searched electronic databases for studies focusing on AF ablation employing the PFA single-shot pentaspline system or second-/third-/fourth-generation CRYO technologies. The primary endpoints were acute procedural success assessed on a vein and patient basis. Safety endpoints included overall periprocedural complications and major periprocedural complications. We also compared procedural, fluoroscopy times, and freedom from atrial tachyarrhythmias (ATs) at follow-up (secondary endpoints). Twenty and 70 studies were included for PFA and CRYO, respectively. Pulsed field ablation demonstrated greater acute procedural success on a vein basis (99.9% vs. 99.1%; P < 0.001), as well as per patient (99.5% vs. 98.4%; P < 0.001). Pulsed field ablation yielded lower overall periprocedural complications (3.1% vs. 5.6%; P < 0.001), shorter procedural time (75.9 min vs. 105.6 min; P < 0.001), and fluoroscopy time (14.2 min vs. 18.9 min; P < 0.001) compared with CRYO. No differences were found for major periprocedural complications (1.2% vs. 1.0%; P = 0.46) and freedom from ATs at 1 year (82.3% vs. 80.3%; log-rank P = 0.61)., Conclusion: Pulsed field ablation contributed to higher acute procedural success and safety compared with CRYO. No statistically significant differences in AT recurrence at 1-year follow-up were observed., Competing Interests: Conflict of interest: The authors of this manuscript have the following competing interests. A.N. received speaker honoraria from Boston Scientific, Biosense Webster, Abbott, Biotronik, and Medtronic and is a consultant for Biosense Webster, Abbott, and Janssen. G.-B.C. received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. C.d.A. receives research grants on behalf of the centre from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus. The other authors have declared that no competing interests exist., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To compare the efficacy and safety of three different treatment options (vaginal estriol, vaginal dehydroepiandrosterone (DHEA), and ospemifene) for treating genitourinary syndrome of menopause (GSM) in breast cancer and gynecologic cancer survivors., Methods: A retrospective comparative analysis was performed among 185 cancer survivors (including breast, endometrial, ovarian, cervical, and vulvar cancer) affected by GSM. Women were divided into three groups according to the prescribed therapy (vaginal estriol, vaginal DHEA, and ospemifene). Safety and efficacy of therapies were assessed over a 6-month follow-up. Improvement in symptoms was compared using the following questionnaires: Female Sexual Function Index, Female Sexual Distress Scale, Visual Analogue Scale (VAS)-dyspareunia, VAS-vulvar pain, Short Form (36) Health Survey, and Patients' Impression of Global Improvement. Cancer recurrence was evaluated according to oncological protocol., Results: After the 6-month follow-up, no significant endometrial thickening or cancer recurrence was observed in any group. The rate of sexually active women significantly increased in all groups, as well as the frequency of sexual intercourse. Scores on questionnaires assessing women's sexual function significantly improved in all patients. Women also complained of less vulvar pain and dyspareunia. Safety and efficacy of treatment were comparable between the three groups for all items except for dyspareunia. Patients taking ospemifene complained of less dyspareunia than those receiving local hormone treatment., Conclusions: Vaginal estriol, vaginal DHEA, and ospemifene were effective in improving symptoms of GSM in cancer survivors and were not associated with cancer recurrence over the 6-month follow-up. Ospemifene was more effective than local hormones in treating dyspareunia., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © by The Korean Society of Menopause.)

Background: Cognitive screening tools are widely used in clinical practice to screen for age-related cognitive impairment and dementia. These tools' test scores are known to be influenced by age and education, leading to routine correction of raw scores for these factors. Despite these corrections being common practice, there is evidence suggesting that corrected scores may perform worse in terms of discrimination than raw scores., Objective: To address the ongoing debate in the field of dementia research, we assessed the impact of the corrections on discrimination, specificity, and sensitivity of the Montreal Cognitive Assessment test in Italy, both for the overall population and across age and education strata., Methodology: We created a realistic model of the resident population in Italy in terms of age, education, cognitive impairment and test scores, and performed a simulation study., Results: We confirmed that the discrimination performance was higher for raw scores than for corrected scores in discriminating patients with cognitive impairment from individuals without (areas under the curve of 0.947 and 0.923 respectively). With thresholds determined on the overall population, raw scores showed higher sensitivities for higher-risk age-education groups and higher specificities for lower-risk groups. Conversely, corrected scores showed uniform sensitivity and specificity across demographic strata, and thus better performance for certain age-education groups., Conclusion: Raw and corrected scores show different performances due to the underlying causal relationships between the variables. Each approach has advantages and disadvantages, the optimal choice between raw and corrected scores depends on the aims and preferences of practitioners and policymakers., Competing Interests: Declarations Competing interests Hans-Aloys Wischmann worked for Philips in various healthcare research and innovation management roles, up to April 2021. Outside of the submitted work, Giancarlo Logroscino reports having received speaking honoraria from Lilly, GE Healthcare, Lundbeck and being an associate editor of Neuroepidemiology/Karger. Outside of the submitted work, Tobias Kurth reports receiving research grants from the Gemeinsamer Bundesausschuss (G-BA Federal Joint Committee, Germany) and the Bundesministerium für Gesundheit (BMG—Federal Ministry of Health, Germany). He further reports having received personal compensation from Eli Lilly and Company, Novartis, the BMJ, and Frontiers. Marco Piccininni reports having received partial funding from Novartis Pharma and being awarded a research grant from the Center for Stroke Research Berlin (private donations), both outside of the submitted work. Ethical approval and Informed consent Ethical approval was not required for this research as all analyzed data were simulated based on publicly available statistics, and no human participants were involved., (© 2024. The Author(s).)

Lymphoma and plasma cell disorders are the most common indications for autologous hematopoietic stem cell (HSC) transplantation. We conducted a prospective multicenter study with the aim of testing the feasibility of plerixafor (PLX) in combination with R-DHAP and G-CSF in 37 patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) in order to collect a large number of HSC with a goal of transplantation. After R-DHAP, daily monitoring of peripheral blood CD34 + cells by flow cytometry was performed starting on day + 13. If, on day + 14, peripheral blood CD34 + cells were > 20 × 10e6/L apheresis was started, if they were < 20 × 10e6/L and WBC > 4.0 × 10e9/L, PLX was administered. Results: The median CD34 + cell count collected was 10.5 × 10e6/kg (range 0-51). 81% of patients achieved the minimum CD34 + target cell count of 6 × 10e6/kg. 66% of patients required only one apheresis to achieve collection goals. The rate of engraftment was 10 days for neutrophils > 0.5 × 10e9/L and 13 days for platelets > 20 × 10e9/L. In conclusion, the addition of PLX to salvage therapy in patients with R/R DLBCL is effective and may be routinely used in the future to increase the number of CD34 + cells collected and minimize the risk of poor mobilization., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Author contributions: FG, AO and VP conceived and designed the study. AMaggi, NDR, GM and EP acquired the data. FG, AM, FEL and VP analysed and interpreted the data. AM, FEL and FG drafted the manuscript. All authors revised the manuscript. All authors read and approved the final manuscript. Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki. Ethical review and approval were waived for this study: since the study data were collected during routine clinical activity and fully anonymized, a formal institutional review board approval was exempted. Informed consent statement: Each patient enrolled in this study was informed about the procedures and signed consent to allow data collection and analysis for research purposes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The emotional and cognitive cerebellum has been explored by several studies in the past years. Recent evidence suggested the possible contribution of the cerebellum in processing emotional prosody, namely the ability to comprehend the emotional content of a given vocal utterance, likely mediated by anatomical and functional cerebello-prefrontal connections. In the present study, the involvement of a functional cerebello-prefrontal network in recognising emotional prosody was assessed by combining non-invasive anodal transcranial direct current stimulation (tDCS) over the right or the left cerebellum and functional Near Infrared Spectroscopy of the prefrontal cortex, in a double-blind within-subject experimental design on healthy participants. The results showed that right and, to a less extent, left cerebellar tDCS (as compared to sham stimulation) reduced neural activation in the prefrontal cortex while accuracy and reaction times at the vocal recognition task remained unchanged. These findings highlight functional properties of the cerebello-frontal connections and the psychophysiological effects of cerebellar brain stimulation, with possible clinical applications in psychiatric and neurological conditions., Competing Interests: Declarations. Ethics approval: The study was approved by the Institutional Ethic Committee and were in accordance with the 1964 Helsinki Declaration and its later amendments. Consent to participate: All participants gave their written informed consent to participate. Consent for publication: All authors consent to publication; all participants gave their written informed consent to publication. Conflicts of interest: The authors declare no competing interests. Open practice statement: Data or materials for the experiments are available upon request, and none of the experiments was preregistered., (© 2024. The Author(s).)

Background: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of nonresectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model)., Objective: The aim was to demonstrate the noninferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI)/MRI) in predicting nonresectable tumor (defined as residual disease >1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated., Study Design: This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of nonresectability at ultrasound, CT, WB-DWI/MRI, and surgical exploration. Ultrasound and CT were mandatory index tests, while WB-DWI/MRI was an optional test (non-available in all centers). The predictors of nonresectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV >8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in 6 predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease >1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting nonresectability was reported. Concordance between index tests at the detection of disease at 6 predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa., Results: The study was between 2018 and 2022 in 5 European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1 cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was>1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out, and 50/80 underwent laparoscopy only, because cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of 3 imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and nonresectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI, and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) than CT and WB-DWI/MRI to assess all parameters included in the updated PIV model., Conclusion: Ultrasound showed noninferiority to CT and to WB-DWI/MRI in discriminating between resectable and nonresectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict nonresectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In the worldwide, real-life setting, some candidates for right colectomy still receive no bowel preparation, some receive oral antibiotics alone, some receive mechanical bowel preparation alone, and some receive mechanical bowel preparation with oral antibiotics, with varying degrees of compliance to preoperative intravenous antibiotic prophylaxis. Previous studies mainly focused on left-sided colorectal anastomoses while less attention has been devoted to right-sided ileocolic anastomoses. When high-level evidence from randomized clinical trials is lacking, multiple-treatment propensity score weighting analysis of prospective data on the basis of generalized boosted model is superior to a simple propensity score-matching analysis and to an inverse probability weighting in terms of external validity and bias reduction., Methods: This is an analysis on the basis of machine-learning procedures of 2,617 patients who underwent elective right colectomies., Results: The risk of surgical-site infections (5.0% after no bowel preparation) was significantly lower after mechanical bowel preparation with oral antibiotics (4.0%, P = .017), significantly greater after mechanical bowel preparation alone (8.6%, P = .019), and comparable after oral antibiotics alone (3.9%). The risk of anastomotic leakage (3.2% after no bowel preparation) was significantly greater after oral antibiotics alone (4.8%, P = .013). Concerning secondary outcomes, no significant differences were recorded for the risk of overall morbidity and reoperation. The risk of readmission (3.0% after no bowel preparation) was significantly reduced after mechanical bowel preparation with oral antibiotics (1.5%, P = .046), and the risk of major morbidity (5.1% after no bowel preparation) was significantly greater after oral antibiotics alone (6.7%, P = .007)., Conclusion: This multitreatment machine-learning analysis, despite some limitations, showed that mechanical bowel preparation with oral antibiotics is associated with a decrease in surgical-site infections after elective right colectomy compared with no bowel preparation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available., Materials and Methods: The CAPRI 2-GOIM trial investigates efficacy and safety of ctDNA-driven, cetuximab-based sequence of three treatment lines in patients with RAS/BRAF V600E wild-type (WT) mCRC, as determined by the local laboratory. Before first-line therapy, CGP is carried out with FoundationOne (F1) CDx and F1 Liquid (F1L) CDx (324 genes) on tumor tissue DNA and plasma ctDNA, respectively., Results: For 2/207 (0.96%) patients, no ctDNA was detected by F1L CDx. No patient displayed tumor fraction (TF) below 1%, whereas elevated ctDNA (TF ≥ 10%) was detected among 140/205 (68.3%) patients. One thousand and thirteen genomic variants were identified. F1L CDx found KRAS, NRAS, or BRAF V600E alterations in 19 patients, whose tumors were classified as RAS/BRAF V600E WT by the local laboratory. Both F1 CDx and F1L CDx were available for 164/205 (80%) patients. A concordance of 61.4% between the two tests was observed. The concordance increased to 72.7% for F1L CDx with TF ≥ 10%. Concordance for genes potentially involved in anti-epidermal growth factor receptor resistance was found in 137/164 (83%) patients, increasing to 91.5% for F1L CDx with TF ≥ 10%. A higher number of genomic alterations was detected by F1L CDx compared with F1 CDx, including six cases with KRAS and NRAS alterations. Overall, 109/205 (53.2%) patients displayed at least one actionable genomic alteration (I to IIIB), according to the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT)., Conclusion: Baseline liquid biopsy-based CGP is feasible, has high concordance with tumor tissue-based CGP, could better recapitulate tumor heterogeneity, and is clinically informative by identifying additional actionable genomic alterations in approximately half of RAS/BRAF V600E WT mCRC patients., (Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: The aim was to evaluate the performance of the Peritoneal Cancer Index (PCI) using imaging (ultrasound, contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) in assessing peritoneal carcinomatosis and predicting non-resectability in tubo-ovarian carcinoma patients., Methods: This was a prospective multicenter observational study. We considered all patients with suspected primary ovarian/tubal/peritoneal cancer who underwent preoperative ultrasound, CT, and WB-DWI/MRI (if available). The optimal cut off value for assessing the performance of the methods in predicting non-resectability was identified at the point at which the sensitivity and specificity were most similar. The reference standard to predict non-resectability was surgical outcome in terms of residual disease >1 cm or surgery not feasible. Agreement between imaging methods and surgical exploration in assessing sites included in the PCI score was evaluated using the Intraclass Correlation Coefficient (ICC)., Results: 242 patients were included from January 2020 until November 2022. The optimal PCI cut-off for predicting non-resectability for surgical exploration was >12, which achieved the best AUC of 0.87, followed by ultrasound with a cut-off of >10 and AUC of 0.81, WB-DWI/MRI with a cut-off of >12 and AUC of 0.81, and CT with a cut-off of >11 and AUC of 0.74. Using ICC, ultrasound had very high agreement (0.94) with surgical PCI, while CT and WB-DWI/MRI had high agreement (0.86 and 0.87, respectively)., Conclusion: Ultrasound performed by an expert operator had the best agreement with surgical findings compared to WB-DWI/MRI and CT in assessing radiological PCI. In predicting non-resectability, ultrasound was non-inferior to CT, while its non-inferiority to WB-DWI/MRI was not demonstrated., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pharmacovigilance agencies did not collect data regarding menstrual changes after COVID-19 vaccination even if many women experienced it. Our aim was to evaluate whether COVID-19 vaccination is associated with secondary changes in menstrual cycle and to assess both quality of life (QoL) and sexual function (SF)., Methods: This study is a retrospective analysis referred to our Department from January 2021 to December 2021. The study cohort responded to same questionnaires before the second dose of vaccination (referring to previous 3 months) and 3 months after that (referring to three menstrual cycles after full-dose vaccination). The surveys administered were FSFI, FSDS, SF-36, MEDI-Q and the VAS-scale for dysmenorrhea., Results: Four-hundred-nineteen vaccinated women were included in the study. The survey did not show a significant change in menstrual cycle length before and after COVID-19 vaccine (5.88±3.67 vs. 4.97±2.89, P=0.21); the interval between periods was significantly higher after a full-cycle vaccination (28.32±7.34 vs. 32.38±7.45, P<0.02); 32 patients (7.6%) developed amenorrhea after the second dose; VAS Scale did not change significantly (median range 3 (3-5) vs. 4 (3-6), P=0.20). MEDI-Q did not show significant variations before and after the vaccination (43.21±11.65 vs. 40.28±9.88, P=0.35). QoL and SF did not change significantly (FSFI median 27 [24-29] vs. 28 [25-30], P=0.12, FSDS median 9 [5-11] vs. 8 [4-12], P=0.22), SF-36 median 81 [70-85] vs. 82 [72-86], P=0.43)., Conclusions: COVID-19 vaccination is associated with a significant change in intervals between menstrual cycles without other alterations in menstrual characteristics, in QoL or SF.

Ovarian masses encompass various conditions, from benign to highly malignant, and imaging plays a vital role in their diagnosis and management. Ultrasound, particularly transvaginal ultrasound, is the foremost diagnostic method for adnexal masses. Magnetic Resonance Imaging (MRI) is advised for more precise characterisation if ultrasound results are inconclusive. The ovarian-adnexal reporting and data system (O-RADS) MRI lexicon and scoring system provides a standardised method for describing, assessing, and categorising the risk of each ovarian mass. Determining a histological differential diagnosis of the mass may influence treatment decision-making and treatment planning. When ultrasound or MRI suggests the possibility of cancer, computed tomography (CT) is the preferred imaging technique for staging. It is essential to outline the extent of the malignancy, guide treatment decisions, and evaluate the feasibility of cytoreductive surgery. This article provides a comprehensive overview of the key imaging processes in evaluating and managing ovarian masses, from initial diagnosis to initial treatment. It also includes pertinent recommendations for properly performing and interpreting various imaging modalities. KEY POINTS: MRI is the modality of choice for indeterminate ovarian masses at ultrasound, and the O-RADS MRI lexicon and score enable unequivocal communication with clinicians. CT is the recommended modality for suspected ovarian masses to tailor treatment and surgery. Multidisciplinary meetings integrate information and help decide the most appropriate treatment for each patient., Competing Interests: Compliance with ethical standards Guarantor The scientific guarantor of this publication is Evis Sala. Conflict of interest The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. Statistics and biometry No complex statistical methods were necessary for this paper. Informed consent Written informed consent was not required. Ethical approval Institutional Review Board approval was not required. Study subjects or cohorts overlap Not applicable. Methodology Practice recommendations, (© 2024. The Author(s).)

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Some studies indicate that brown adipose tissue (BAT) represents a promising target in the fight against dysmetabolic diseases, with indications suggesting it as a potential target for the effects of ketone bodies. We investigate whether the elevation of plasma levels of the ketone body β-hydroxybutyrate, achieved through the in vivo administration of its precursor 1,3-butanediol (BD) to rats, could impact interscapular BAT (iBAT) mitochondrial biochemistry and functionality. We examined the effects induced by BD within 3 h and after 2 weeks of treatment. A large-scale quantitative proteomics approach, coupling liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, and Western blot associated with functional studies by respirometry allowed us to evaluate the changes in iBAT mitochondrial protein expression and bioenergetics induced by BD. BD administration increased β-hydroxybutyrate plasma levels, which correlated with an enhancement in iBAT mitochondrial respiration rate, likely due to the activation of the respiratory chain and uncoupling protein-1. The proteomic analysis demonstrated that BD influenced the mitochondrial levels of specific subunits belonging to the five respiratory complexes, uncoupling protein-1, and proteins involved in propanoate metabolism. BD administration also induced lysine β-hydroxybutyrylation of mitochondrial proteins, including specific subunits of the respiratory chain complexes and uncoupling protein-1. Most of the BD-induced effects were observed within 3 h of its administration and persisted/increased after 2 weeks of treatment. In conclusion, by using BD to increase β-hydroxybutyrate levels, we provide evidence supporting the role of β-hydroxybutyrate as a signaling molecule capable of rapidly modulating BAT physiology by acting at the mitochondrial level., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Not available.

Optimizing high-productivity farming techniques trough mechanization and lower workforce input in terraced olive groves is helpful to preserve local olive oil production, reducing costs and preserving ecosystem functionality. However, efficient work organisation should be provided. Moreover, mechanization can affect environmental sustainability. In this paper operative, economic and environmental performances of four olive harvesting techniques are reported; experimentations were performed in an olive grove in the Sorrento Peninsula (NA) during 2022-2023 productive seasons. Mechanized techniques (Harvesting technique 1 and Harvesting technique 4) performed highest working capacities (159.01 kg h -1 and 200.51 kg h -1 ) and the lowest unitary costs (630.00 € ha -1 for Harvesting technique 2 and 840.00 € ha -1 for harvesting technique 4), whereas environmental performances were the worst (266.30 kg CO 2 eq and 252.59 kg CO 2 eq) due to diesel intakes. Thus, their applications are helpful, but morphological or agronomic boundaries may affect their effectiveness in other areas. Among aided methods, Harvesting technique 1 overcame Harvesting technique 3 in any aspect (91.01 kg h -1 vs 76.13 kg h -1 : 1822.09 € ha -1 vs 2793.80 € ha -1 ; 33.01 kg CO 2 eq vs 127.21 kg CO 2 eq); the absence of diesel inputs in harvesting technique 1 and its superior work capacity explain the environmental impact differences. Thus, the former may be adopted in farms where slope and irregular shape hinder mechanized harvest. Life Cycle Assessment dataset may be helpful to perform similar analysis in other Italian olive oil supply chains., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Background: Alterations in gut microbiota are observed in Parkinson's disease (PD). Previous studies on microbiota-derived metabolites in PD were small-scale and post-diagnosis, raising concerns about reverse causality., Objectives: Our goal was to prospectively investigate the association between plasma microbial metabolites and PD risk within a metabolomics framework., Methods: A nested case-control study within the prospective EPIC4PD cohort, measured pre-diagnostic plasma microbial metabolites using untargeted metabolomics., Results: Thirteen microbial metabolites were identified nominally associated with PD risk (P-value < 0.05), including amino acids, bile acid, indoles, and hydroxy acid, although none remained significant after multiple testing correction. Three pathways were implicated in PD risk: valine, leucine, and isoleucine degradation, butanoate metabolism, and propanoate metabolism. PD-associated microbial pathways were more pronounced in men, smokers, and overweight/obese individuals., Conclusion: Changes in microbial metabolites may represent a pre-diagnostic feature of PD. We observed biologically plausible associations between microbial pathways and PD, potentially influenced by individual characteristics. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Metabolic distress is often associated with heart failure with preserved ejection fraction (HFpEF) and represents a therapeutic challenge. Metabolism-induced systemic inflammation links comorbidities with HFpEF. How metabolic changes affect myocardial inflammation in the context of HFpEF is not known., Methods: We found that ApoE knockout mice fed a Western diet recapitulate many features of HFpEF. Single-cell RNA sequencing was used for expression analysis of CD45 + cardiac cells to evaluate the involvement of inflammation in diastolic dysfunction. We focused bioinformatics analysis on macrophages, obtaining high-resolution identification of subsets of these cells in the heart, enabling us to study the outcomes of metabolic distress on the cardiac macrophage infiltrate and to identify a macrophage-to-cardiomyocyte regulatory axis. To test whether a clinically relevant sodium glucose cotransporter-2 inhibitor could ameliorate the cardiac immune infiltrate profile in our model, mice were randomized to receive the sodium glucose cotransporter-2 inhibitor dapagliflozin or vehicle for 8 weeks., Results: ApoE knockout mice fed a Western diet presented with reduced diastolic function, reduced exercise tolerance, and increased pulmonary congestion associated with cardiac lipid overload and reduced polyunsaturated fatty acids. The main immune cell types infiltrating the heart included 4 subpopulations of resident and monocyte-derived macrophages, determining a proinflammatory profile exclusively in ApoE knockout-Western diet mice. Lipid overload had a direct effect on inflammatory gene activation in macrophages, mediated through endoplasmic reticulum stress pathways. Investigation of the macrophage-to-cardiomyocyte regulatory axis revealed the potential effects on cardiomyocytes of multiple inflammatory cytokines secreted by macrophages, affecting pathways such as hypertrophy, fibrosis, and autophagy. Finally, we describe an anti-inflammatory effect of sodium glucose cotransporter-2 inhibition in this model., Conclusions: Using single-cell RNA sequencing in a model of diastolic dysfunction driven by hyperlipidemia, we have determined the effects of metabolic distress on cardiac inflammatory cells, in particular on macrophages, and suggest sodium glucose cotransporter-2 inhibitors as potential therapeutic agents for the targeting of a specific phenotype of HFpEF., Competing Interests: None.