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Roberto Lipsi,1 Paola Rogliani,1 Luigino Calzetta,2 Andrea Segreti,1 Mario Cazzola1 1Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 2Department of Pulmonary Rehabilitation, San Raffaele Pisana Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Rome, Italy Abstract: Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. Keywords: chronic obstructive pulmonary disease, stem cells, regenerative therapy, all-trans retinoic acid, photobiostimulation

Previous studies have demonstrated an increasing trend of the number of authors across various fields over the years. This trend has been attributed to the necessity for larger collaborations and, at times, to ethical issues regarding authorship attribution. Our study focuses on the evolution of authorship trends in the field of Neuroscience. We conducted our analysis based on a dataset containing 580,782 neuroscience publications produced from 2000 to 2022, focusing on the publications within the Group of ten (G10) countries. Using a matrix-based methodology, we extracted and analyzed the average number of authors per country. Our findings reveal a consistent rise in authorship across all G10 countries over the past two decades. Italy emerged with the highest average number of authors, while France stood out for experiencing the most significant increase, particularly in the last decade. The countries with the lowest number of authors per publication were the USA, UK and Canada. Differences between countries could result from variations in the size of collaboration between researchers in different countries. Additionally, these differences may depend on utilitarian considerations aimed at receiving higher scores in the individual evaluation of their own work. We propose that a normalization procedure for the number of authors should be implemented to ensure a fair evaluation of researchers.

Mario Cazzola,1 Andrea Segreti,1 Maria Gabriella Matera2 1Department of System Medicine, University of Rome 'Tor Vergata', Rome, Italy; 2Department of Experimental Medicine, Second University, Naples, Italy Abstract: An increasing body of evidence suggests that the long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination appears to play an important role in maximizing bronchodilation, with studies to date indicating that combining different classes of bronchodilators may result in significantly greater improvements in lung function compared to the use of a single drug, and that these combinations are well tolerated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). An inhaled, fixed-dose combination of two 24-hour bronchodilators, the LAMA umeclidinium and the LABA vilanterol, is under development as a once-daily treatment for COPD. The efficacy of both mono-components has already been demonstrated. The information currently available suggests that umeclidinium/vilanterol is an effective once-daily dual bronchodilator fixed-dose combination in the treatment of COPD. However, it remains to be seen if it compares favorably with current therapies. Moreover, the question remains whether umeclidinium/vilanterol fixed-dose combination, which significantly improves FEV1, is also associated with improvements in other outcome measures that are important to COPD patients. Keywords: muscarinic antagonist, dual bronchodilation, COPD

Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115 mg/dl, high-density lipoprotein (HDL) <40 mg/dl for males, or HDL <50 mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150 mg/dl. At the follow-up, a variation of ±40 mg/dl for LDL, ±6 mg/dl for HDL, and ±50 mg/dl for triglycerides was considered relevant. Athletes with follow-up <10 months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6 months. Mean age was 27.2 ± 4.8 years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Background: Indiscriminate urine culturing of patients with indwelling urinary catheters may lead to overdiagnosis of urinary tract infections, resulting in unnecessary antibiotic treatment and inaccurate reporting of catheter-associated urinary tract infections (CAUTIs) as a hospital quality metric. We evaluated the impact of a computerized diagnostic stewardship intervention to improve urine culture testing among patients with indwelling urinary catheters. Methods: We performed a single-center retrospective observational study at Rush University Medical Center from April 2018 – July 2023. In February 2021, we implemented a computerized clinical decision support tool to promote adherence to our internal urine culture guidelines for patients with indwelling urinary catheters. Providers were required to select one guideline criteria: 1) neutropenia, 2) kidney transplant, 3) recent urologic procedure, 4) urinary tract obstruction; or if none of the criteria were met, then an infectious diseases consultation was required for approval. We compared facility-wide CAUTI rate per 10,000 catheter days and standardized infection ratio (SIR) during baseline and intervention periods using ecologic models, controlling for time and for monthly Covid-19 hospitalizations. In the intervention period, we evaluated how providers responded to the intervention. Potential harm was defined as collection of a urine culture within 7 days of the intervention that resulted in a change in clinical management. Results: In unadjusted models, CAUTI rate decreased from 12.5 to 7.6 per 10,000 catheter days (p=0.04) and SIR decreased from 0.77 to 0.49 (p=0.09) during baseline vs intervention periods. In adjusted models, the CAUTI rate decreased from 6.9 to 5.5 per 10,000 catheter days (p=0.60) (Figure 1) and SIR decreased from 0.41 to 0.35 (p=0.65) during baseline vs intervention periods. Urine catheter standard utilization ratio (SUR) did not change (p=0.36). There were 598 patient encounters with ≥1 intervention. Selecting the first intervention for each encounter, 284 (47.5%) urine cultures met our guidelines for testing and 314 (52.5%) were averted (Figure 2). Of these, only 3 ( < 1 %) had a urine culture collected in the subsequent 7 days that resulted in change in clinical management. Conclusion: We observed a trend of decreased CAUTIs over time, but effect of our diagnostic stewardship intervention was difficult to assess due to healthcare disruption caused by Covid-19. Adverse outcomes were rare among patients who had a urine culture averted. A computerized clinical decision support tool may be safe and effective as part of a multimodal program to reduce unnecessary urine cultures in patients with indwelling urinary catheters.

The number of vascular centers performing endovascular repair of ascending aortic disease is constantly increasing. Accordingly to the guidelines, open surgical repair remains the gold standard for these pathologies. However, approximately one quarter of patients are deemed unfit for open surgery. In this study, we describe three cases of ascending thoracic endovascular aortic repair (TEVAR) performed at our center. All the patients were deemed unfit for open surgery by the aortic team. Two patients had an ascending aortic pseudoaneurysm, and the third had a focal type A aortic dissection. In two cases, we used two abdominal aortic cuffs deployed from zone 0B to zone 0C, with no need for supra-aortic trunk debranching. In one case, we performed a “reverse” extrathoracic debranching, and we deployed a thoracic endograft from zone 0B to zone 2. Complications included one minor stroke and one inguinal hematoma. In one patient with an infected pseudoaneurysm, we performed ascending TEVAR as a bridge strategy for open repair. This patient developed a type Ia endoleak; however, clinical stabilization and infection control were obtained, and he was able to undergo heart surgery successfully. He underwent a second reintervention to treat superior mesenteric embolic occlusion. At 2 years of follow-up, all three patients were alive. Our preliminary experience demonstrates the technical feasibility and clinical appropriateness of ascending TEVAR using standard, commercially available endografts. However, no consensus has been reached regarding some critical aspects, such as the development of a standardized technique or the efficacy of the currently available devices. The improvements in graft design and the adoption of the “aortic team” approach could help in the near future to standardize the procedure, establish appropriate indications, and ensure good clinical outcomes.

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

Abstract Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SI n = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22–42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80–1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management.

Background: A knee injury in an athlete leads to periods of forced exercise interruption. Myocardial work (MW) assessed by echocardiographic and cardiopulmonary exercise testing (CPET) are two essential methods for evaluating athletes during the period following injury. However, compared to pre-surgery evaluations, the variations in cardiovascular parameters and functional capacity assessed by these methods after surgery remain unclear. Methods: We evaluated 22 non-professional athletes aged 18–52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, who were affected by a knee pathology requiring surgical treatment. The evaluation was performed at rest using transthoracic echocardiography, including MW assessment, and during exercise using CPET. Each athlete underwent the following two evaluations: the first before surgery and the second after surgery (specifically at the end of the deconditioning period). Results: Resting heart rate (HR) increased significantly (from 63.3 ± 10.85 to 71.2 ± 12.52 beats per minute, p = 0.041), while resting diastolic and systolic blood pressure, forced vital capacity, and forced expiratory volume in the first second did not show significant changes. Regarding the echocardiographic data, global longitudinal strain decreased from −18.9 ± 1.8 to −19.3 ± 1.75; however, this reduction was not statistically significant (p = 0.161). However, the global work efficiency (GWE) increased significantly (from 93.0% ± 2.9 to 94.8% ± 2.6, p = 0.006) and global wasted work (GWW) reduced significantly (from 141.4 ± 74.07 to 98.0 ± 50.9, p = 0.007). Additionally, the patients were able to perform maximal CPET at both pre- and post-surgery evaluations, as demonstrated by the peak respiratory exchange ratio and HR. However, the improved myocardial contractility (increased GWE and decreased GWW) observed at rest did not translate into significant changes in exercise parameters, such as peak oxygen consumption and the mean ventilation/carbon dioxide slope. Conclusions: After surgery, the athletes were more deconditioned (as indicated by a higher resting HR) but exhibited better resting myocardial contractility (increased GWE and reduced GWW). Interestingly, no significant changes in exercise capacity parameters, as evaluated by CPET, were found after surgery, suggesting that the improved myocardial contractility was offset by a greater degree of muscular deconditioning.

Although it is known that exercise improves cardiovascular health and extends life expectancy, a significant number of people may also experience an elevation in cardiac troponin levels as a result of exercise. For many years, researchers have argued whether exercise-induced cardiac troponin rises are a consequence of a physiological or pathological reaction and whether they are clinically significant. Differences in cardiac troponin elevation and cardiac remodeling can be seen between athletes participating in different types of sports. When forecasting the exercise-induced cardiac troponin rise, there are many additional parameters to consider, as there is a large amount of interindividual heterogeneity in the degree of cardiac troponin elevation. Although it was previously believed that cardiac troponin increases in athletes represented a benign phenomenon, numerous recent studies disproved this notion by demonstrating that, in specific individuals, cardiac troponin increases may have clinical and prognostic repercussions. This review aims to examine the role of cardiac troponin in athletes and its role in various sporting contexts. This review also discusses potential prognostic and clinical implications, as well as future research methods, and provides a straightforward step-by-step algorithm to help clinicians interpret cardiac troponin rise in athletes in both ischemic and non-ischemic circumstances.

Background: Existing data on the impact of sex differences on transvenous lead extraction (TLE) outcomes in cardiac device patients are limited. Objective: The purpose of this study was to evaluate the safety and efficacy of mechanical TLE in female patients. Methods: A retrospective evaluation was performed on 3051 TLE patients (group 1: female; group 2: male) from a single tertiary referral center. All individuals received treatment using single sheath mechanical dilation and various venous approaches as required. Results: Our analysis included 3051 patients (group 1: 750; group 2: 2301), with a total of 5515 leads handled with removal. Female patients were younger, had a higher left ventricular ejection fraction, and lower prevalences of coronary artery disease and diabetes mellitus. Infection was more common in male patients, whereas lead malfunction or abandonment were more frequent in female patients. Radiologic success was lower in female patients (95.8% vs 97.5%; P = .003), but there was no significant difference in clinical success between groups (97.2% vs 97.5%; P = .872). However, major complications (1.33% vs 0.60%; P

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.

BackgroundHighly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have the potential to act as a reliable predictor of the durability of the lesions created.ObjectiveWe aimed to collect data on the procedural parameters affecting LI-guided ablation in a large multicenter registry.MethodsA total of 212 consecutive patients enrolled in the CHARISMA registry and undergoing their first pulmonary vein (PV) isolation for paroxysmal and persistent AF were included.ResultsIn all, 13,891 radiofrequency (RF) applications of ≥3 s duration were assessed. The first-pass PV isolation rate was 93.3%. A total of 80 PV gaps were detected. At successful ablation spots, baseline LI and absolute LI drop were larger than at PV gap spots (161.4 ± 19 Ω vs. 153.0 ± 13 Ω, p 21 Ω at anterior sites and >18 Ω at posterior sites. There was a non-linear association between the magnitude of LI drop and contact-force (CF) (r = 0.14, 95% CI: 0.13–0.16, p 21 Ω at anterior sites and >18 Ω at posterior sites predicts successful ablation. A higher CF was associated with an increased likelihood of ideal LI drop. The combination of good CF and adequate LI drop allows a significant reduction in RF DT.Clinical trial registrationhttp://clinicaltrials.gov/, identifier: NCT03793998.