Search

Abstract Defining the molecular mechanisms underlying cardiac resilience is crucial to find effective approaches to protect the heart. A physiologic level of ROS is produced in the heart by fatty acid oxidation, but stressful events can boost ROS and cause mitochondrial dysfunction and cardiac functional impairment. Melusin is a muscle specific chaperone required for myocardial compensatory remodeling during stress. Here we report that Melusin localizes in mitochondria where it binds the mitochondrial trifunctional protein, a key enzyme in fatty acid oxidation, and decreases it activity. Studying both mice and human induced pluripotent stem cell-derived cardiomyocytes, we found that Melusin reduces lipid oxidation in the myocardium and limits ROS generation in steady state and during pressure overload and doxorubicin treatment, preventing mitochondrial dysfunction. Accordingly, the treatment with the lipid oxidation inhibitor Trimetazidine concomitantly with stressful stimuli limits ROS accumulation and prevents long-term heart dysfunction. These findings disclose a physiologic mechanism of metabolic regulation in the heart and demonstrate that a timely restriction of lipid metabolism represents a potential therapeutic strategy to improve cardiac resilience to stress.

In this Correspondence, F. Mari and colleagues report a second two-generation family with distal arthrogryposis caused by a mutation in MET tyrosine kinase.

Background: The benefit of immune checkpoint inhibitors (ICIs) for poor performance status patients with advanced urothelial carcinoma (UC) remains unknown. Objective: In the present sub-analysis of the ARON-2 study, we investigated the role of pembrolizumab for advanced UC patients with ECOG (Eastern Cooperative Oncology Group) performance status (ECOG-PS) 2. Patients and Methods: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of advanced UC progressing or recurring after platinum-based therapy and treated with pembrolizumab between 1 January 2016 to 1 April 2024 were included. In this sub-analysis we focused on patients with ECOG-PS 2. Results: We included 1,040 patients from the ARON-2 dataset; of these, 167 patients (16%) presented an ECOG-PS 2. The median overall survival (OS) was 14.8 months (95% confidence interval (CI) 12.5–16.1) in the overall study population, 18.2 months (95% CI 15.8–22.2) in patients with ECOG-PS 0–1, and 3.7 months (95% CI 3.2–5.2) in subjects with ECOG-PS 2 (p < 0.001). The median progression-free survival (PFS) in the overall study population was 5.3 months (95% CI 4.3–97.1), 6.2 months (95% CI 5.5–97.1) in patients with ECOG-PS 0–1, and 2.8 months (95% CI 2.1–3.4) in patients with ECOG-PS 2. Among the latter, liver metastases and progressive disease during first-line therapy were significant predictors of OS at both univariate and multivariate analyses. For PFS, univariate and multivariate analyses showed a prognostic role for lung metastases, liver metastases, and progressive disease during first-line therapy. Conclusions: This large real–world evidence study suggests the effectiveness of second-line pembrolizumab for mUC patients with poor performance status. The presence of liver metastases and progressive disease during first-line therapy is associated with worse clinical outcomes and, thus, should be taken into account when making treatment decisions in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to provide an updated European narrative review spanning the last decade, focusing on the cost-effectiveness of cochlear implants (CIs) for adults with severe to profound post-lingual hearing loss. Methods: This review encompasses both prospective and retrospective approaches, as well as cross-sectional and longitudinal trials conducted on CIs in adults. All studies related to European countries (Austria, Germany, Switzerland, the Netherlands, Sweden, the UK and Poland) were conducted in English and were published between 2012 and June 2023. Results: Nine studies were included in the analysis. The patients' ages ranged from 18 years to over 67 years, with sample sizes ranging from 20 to 100 patients; two of these studies were focused on single-sided deafness in adults. The Markov model was identified as the most commonly utilized analysis method. Conclusions: This review identified a general consensus on CI cost-effectiveness, despite substantial variability among countries in factors such as observation time horizons, cost-effectiveness thresholds, methods of cost collection, discount rates, CI eligibility criteria and country-specific health systems. Generally, CIs yield positive societal benefits for working-age individuals, potentially less for seniors. Early unilateral CI enhances cost-effectiveness, highlighting the importance of prompt candidate identification. A consistent undersupply of CIs relative to the percentage of potential recipients emerged across countries. Therefore, further investigation into subcategories such as single-sided deafness is warranted, along with country-specific cost analyses. Emphasizing the significance of detailed information on health systems and associated costs and benefits is crucial for facilitating comparisons across different settings. [ABSTRACT FROM AUTHOR]

Male infertility is a complex issue influenced by multiple environmental and pathological factors. In this context, the impact of Human papillomavirus (HPV) infection on male fertility remains controversial. The introduction of new WHO 2021 evaluation criteria, included in the 6th ed. of Laboratory Manual for the examination and processing of human semen, i.e. DNA fragmentation index (DFI), slow and rapid progressive motility, could provide additional information about this correlation. 121 semen samples of male partners of HPV-positive women attending In Vitro Fertilization (IVF) were evaluated following WHO 2021 and HPV-DNA test. Comparing HPV-negative and positive samples for rapid and slow progressive motility showed significantly different results (p = 0.0018, p = 0.0004), contrary to what was observed for total progressive motility. Regarding sperm DFI, only high-risk HPV infections affected DNA integrity. In addition, the correlation between the different semen parameters revealed a significant correlation between midpiece morphological defects and rapid progressive motility in the HPV-positive group (rho = 0.43, p = 0.0006). In conclusion, WHO 2021 provides additional information regarding HPV's impact on seminal parameters. The correlation between HPV positivity, midpiece defects and a higher rapid progressive motility opens new research perspectives that may help unravel the issues surrounding the role of HPV in compromising sperm quality. [ABSTRACT FROM AUTHOR]

Sperm motility is a crucial factor in male fertility. Photobiomodulation (PBM) has been reported to increase sperm motility, but a consistent approach suitable for identifying standardizable protocols is lacking. We collected asthenozoospermic (n = 70) and normozoospermic (n = 20) semen. The asthenozoospermic samples were irradiated with an 810 nm diode laser, in continuous wave mode, at 0.25 W, 0.5 W, 1 W and 2 W for 60 s on a circular area of 1 cm2 through a novel handpiece with an innovative flat-top profile. Sperm motility was assessed immediately, after 30 and 60 min. A sample size calculator, unpaired t-test and one-way ANOVA with post-hoc Tukey HSD tests were used for statistics. One and 2 W were the most effective outputs in increasing progressive motility compared to control (p < 0.001). The maximum effect was immediately after 1 W-PBM (p < 0.001) and decreased after 60 min (p < 0.001). Time physiologically decreased vitality (p < 0.001), but less in the 1 W-PBM samples (p < 0.05). 1 W-PBM did not affect chromatin condensation. Asthenozoospermic samples displayed an impairment of 80% in oxygen consumption and ATP production and a slight inefficiency of oxidative phosphorylation compared to normozoospermic samples (p < 0.001). 1 W-PBM partially restored the functionality of aerobic metabolism (p < 0.001) by recovery of oxidative phosphorylation efficiency. PBM did not affect lactate dehydrogenase (glycolysis pathway). No irradiated samples increased accumulated malondialdehyde, a marker of lipidic peroxidation. In conclusion, PBM improves progressive motility in asthenozoospermia through increased mitochondrial energetic metabolism without harmful oxidative stress. [ABSTRACT FROM AUTHOR]

The automatic analysis of histology images is an open research field where machine learning techniques and neural networks, especially deep architectures, are considered successful tools due to their abilities in image classification. This paper proposes a granular computing methodology for histopathological image classification. It is based on embedding tiles of histopathology images using deep metric learning, where a self-organizing map is adopted to generate the granular structure in this learned embedding space. The SOM enables the implementation of an explainable mechanism by visualizing a knowledge space that the experts can use to analyze and classify the new images. Additionally, it provides confidence in the classification results while highlighting each important image fragment, with the benefit of reducing the number of false negatives. An exemplary case is when an image detail is indicated, with small confidence, as malignant in an image globally classified as benign. Another implemented feature is the proposal of additional labelled image tiles sharing the same characteristics to specify the context of the output decision. The proposed system was tested using three histopathology image datasets, obtaining the accuracy of the state-of-the-art black-box methods based on deep learning neural networks. Differently from the methodologies proposed so far for the same purpose, this paper introduces a novel explainable method for medical image analysis where the advantages of the deep learning neural networks used to build the embedding space for the image tiles are combined with the intrinsic explainability of the granular process obtained using the clustering property of a self-organizing map. [ABSTRACT FROM AUTHOR]

Background: Malignant Distal Biliary Obstruction (MBDO) is a common event occurring along the natural history of both pancreatic cancer and cholangiocarcinoma. Epidemiological and biological features make MBDO one of the key elements of the clinical management of patients suffering for of pancreatic cancer or cholangiocarcinoma. The development of dedicated biliary lumen-apposing metal stents (LAMS) is changing the clinical work up of patients with MBDO. i-EUS is an Italian network of clinicians and scientists with a special interest in biliopancreatic endoscopy, EUS in particular. Methods: The scientific methodology was chosen in line with international guidance and in a fashion similar to those applied by broader scientific associations. PICO questions were elaborated and subsequently voted by a broad panel of experts within a simplified Delphi process. Results and conclusions: The manuscripts describes the results of a consensus conference organized by i-EUS with the aim of providing an evidence based-guidance for the appropriate use of the techniques in patients with MBDO. [ABSTRACT FROM AUTHOR]

Background: The widespread diffusion of Artificial Intelligence (AI) platforms is revolutionizing how health-related information is disseminated, thereby highlighting the need for tools to evaluate the quality of such information. This study aimed to propose and validate the Quality Assessment of Medical Artificial Intelligence (QAMAI), a tool specifically designed to assess the quality of health information provided by AI platforms. Methods: The QAMAI tool has been developed by a panel of experts following guidelines for the development of new questionnaires. A total of 30 responses from ChatGPT4, addressing patient queries, theoretical questions, and clinical head and neck surgery scenarios were assessed by 27 reviewers from 25 academic centers worldwide. Construct validity, internal consistency, inter-rater and test–retest reliability were assessed to validate the tool. Results: The validation was conducted on the basis of 792 assessments for the 30 responses given by ChatGPT4. The results of the exploratory factor analysis revealed a unidimensional structure of the QAMAI with a single factor comprising all the items that explained 51.1% of the variance with factor loadings ranging from 0.449 to 0.856. Overall internal consistency was high (Cronbach's alpha = 0.837). The Interclass Correlation Coefficient was 0.983 (95% CI 0.973–0.991; F (29,542) = 68.3; p < 0.001), indicating excellent reliability. Test–retest reliability analysis revealed a moderate-to-strong correlation with a Pearson's coefficient of 0.876 (95% CI 0.859–0.891; p < 0.001). Conclusions: The QAMAI tool demonstrated significant reliability and validity in assessing the quality of health information provided by AI platforms. Such a tool might become particularly important/useful for physicians as patients increasingly seek medical information on AI platforms. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced neutropenia poses a significant risk to cancer patients, with pegfilgrastim being commonly used for its prevention. While pegfilgrastim can be administered via prefilled syringe or pen device, patient preferences and experiences with these delivery methods remain unclear. Methods: We conducted a prospective, open-label, randomized, observational trial (NCT05910164) at the Rafael Institute, France, comparing patient preferences for pegfilgrastim administration using a prefilled syringe versus a prefilled pen device. Patients undergoing chemotherapy and requiring pegfilgrastim were enrolled and randomized 1:1 to receive either syringe or pen first, with crossover administration. Questionnaires assessed patient preferences, learning experiences, autonomy, pain levels, emotional responses, satisfaction with nursing care, and empowerment. Results: Among 150 randomized patients (mean age 58 years; 69% female), both groups showed a preference for the pen device, with significantly higher mean scores favoring pen administration (4.94 ± 1.70 vs. 4.27 ± 1.84; p = 0.00106). Patients reported significantly lower perceived pain with pen administration and stronger positive emotions compared to syringe use. Satisfaction with nursing care was higher with syringe use. Empowerment levels were similar across groups but significantly stronger when using the pen in complete autonomy. Conclusion: A preference for pegfilgrastim administration via the pen device was observed, though this may have been influenced by the administration sequence and the absence of syringe self-administration. The insights gained can help inform clinical decision-making and improve patient-centered care in managing chemotherapy-induced neutropenia. Trial registration: NCT05910164 on June 15, 2023. [ABSTRACT FROM AUTHOR]

Introduction: Stroke negatively impacts both patients and their families, who must face multiple changes after the onset of the disease. Family caregivers must face new problems with a possible sense of inadequacy, stress and burden. Our retrospective study aimed to assess the burden of caregivers during the rehabilitation process of patients with Stroke. Material and method: This study included patients with a diagnosis of stroke and their caregiver, who attended the Day Hospital of the IRCCS Neurolesi Center "Bonino-Pulejo", Messina, Italy, between January 2018 and October 2019, using electronic recovery system data. The final sample consisted of 30 patients and their caregivers. Results: Significant improvements were observed in patients' cognitive and mood scores, reflecting the efficacy of rehabilitation therapies. Additionally, a correlation emerged between patients' reported anxiety levels and caregivers' reported depression levels, highlighting a dynamic interaction between the emotional states of the two groups. Conclusion: The study highlights the intricate interplay between caregiver characteristics, patient outcomes, and family dynamics in the context of caregiving. Targeted interventions aimed at improving family resilience and coping mechanisms are crucial to optimizing the well-being of both caregivers and patients. [ABSTRACT FROM AUTHOR]

Cardiac toxicity is an adverse event of several classes of anti-cancer drugs. Herein, we present the case of a 52-year-old woman with metastatic renal cell carcinoma (RCC), previously treated with debulking surgery, pembrolizumab (immune checkpoint inhibitor) in combination with axitinib (tyrosine kinase inhibitor (TKI)), followed by lenvatinib (TKI) and belzutifan (HIF-2α inhibitor), who developed myocarditis proven by cardiac magnetic resonance and endomyocardial biopsy. The case was notable for reporting a not-yet described adverse event during treatment with belzutifan plus lenvatinib, the etiology of which was of unobvious determination given the pre-exposure to pembrolizumab, a known cause of drug-related myocarditis. We surmise that myocarditis was a delayed adverse event related to pembrolizumab (8 months after treatment interruption), although we emphasize that only attentive monitoring of cardiac adverse events of patients exposed to belzutifan and lenvatinib in the context of large clinical trials may rule out any causal implication of these drugs. [ABSTRACT FROM AUTHOR]

Background: To assess the reliability and comprehensibility of breast radiology reports simplified by artificial intelligence using the large language model (LLM) ChatGPT-4o. Methods: A radiologist with 20 years' experience selected 21 anonymized breast radiology reports, 7 mammography, 7 breast ultrasound, and 7 breast magnetic resonance imaging (MRI), categorized according to breast imaging reporting and data system (BI-RADS). These reports underwent simplification by prompting ChatGPT-4o with "Explain this medical report to a patient using simple language". Five breast radiologists assessed the quality of these simplified reports for factual accuracy, completeness, and potential harm with a 5-point Likert scale from 1 (strongly agree) to 5 (strongly disagree). Another breast radiologist evaluated the text comprehension of five non-healthcare personnel readers using a 5-point Likert scale from 1 (excellent) to 5 (poor). Descriptive statistics, Cronbach's α, and the Kruskal–Wallis test were used. Results: Mammography, ultrasound, and MRI showed high factual accuracy (median 2) and completeness (median 2) across radiologists, with low potential harm scores (median 5); no significant group differences (p ≥ 0.780), and high internal consistency (α > 0.80) were observed. Non-healthcare readers showed high comprehension (median 2 for mammography and MRI and 1 for ultrasound); no significant group differences across modalities (p = 0.368), and high internal consistency (α > 0.85) were observed. BI-RADS 0, 1, and 2 reports were accurately explained, while BI-RADS 3–6 reports were challenging. Conclusion: The model demonstrated reliability and clarity, offering promise for patients with diverse backgrounds. LLMs like ChatGPT-4o could simplify breast radiology reports, aid in communication, and enhance patient care. Relevance statement: Simplified breast radiology reports generated by ChatGPT-4o show potential in enhancing communication with patients, improving comprehension across varying educational backgrounds, and contributing to patient-centered care in radiology practice. Key Points: AI simplifies complex breast imaging reports, enhancing patient understanding. Simplified reports from AI maintain accuracy, improving patient comprehension significantly. Implementing AI reports enhances patient engagement and communication in breast imaging. [ABSTRACT FROM AUTHOR]

Background: This pilot prospective study aimed to evaluate ultrasound-guided cryoablation of breast cancer (BC) by assessing: (i) technical efficacy as the presence of necrosis in surgical specimens and rate of complete tumor ablation; (ii) safety as incidence and severity of complications; and (iii) patients' satisfaction using a dedicated questionnaire. In addition, (iv) we tested the capability of magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM) to predict cryoablation efficacy. Methods: From 07/2022 to 01/2023, we enrolled 20 patients with early-stage BC scheduled for breast surgery. Ten of them, with a cryo-feasible cancer location, were sent to cryoablation (cryo-group) and ten to routine surgical practice (control group). Both groups underwent surgery and were asked to answer a satisfaction questionnaire. Results: Of eleven patients screened for cryoablation, only one refused to be treated at another hospital (acceptance rate 10/11, 91%). Surgery was quadrantectomy in 19 cases and mastectomy in 1. In the cryo-group, the procedure was completed and steatonecrosis was observed in 10/10 cases, with complete tumor ablation in nine of them. The post-procedural status was evaluated with MRI in five patients, with CEM in four patients, and with ultrasound in one patient who refused MRI and CEM. MRI or CEM correctly predicted complete cryoablation in eight patients and incomplete cryoablation in one patient. Patients in both groups did not have serious complications and responded positively to satisfaction questionnaires. Conclusion: Ultrasound-guided cryoablation of early-stage BC is well accepted by patients, effective, and safe. MRI and CEM were able to predict the procedure's technical efficacy. Trial registration: https://clinicaltrials.gov/study/NCT05727813 updated February 14, 2023. Relevance statement: Our pilot study showed that ultrasound-guided cryoablation is a promising nonsurgical alternative for treating early-stage BC. Key Points: Ultrasound-guided cryoablation was effective and safe in early BC patients. The procedure was well-tolerated, with low morbidity and high patient satisfaction. MRI and CEM predicted cryoablation efficacy, in accordance with histopathologic findings. Cryoablation can be considered a potential alternative to surgery in selected patients. [ABSTRACT FROM AUTHOR]

Purpose: Disk battery (DB) ingestion in children can lead to severe complications and mortality. This study details our experience in managing DB ingestion and its complications. Methods: We analyzed data from all patients treated for DB ingestion at our hospital from June 2010 to January 2024. A protocol established in 2010 requires angio-CT scans for esophageal DB cases and a multidisciplinary approach involving gastroenterologists, otolaryngologists, pediatric and airway surgeons, and cardiac surgeons. Results: We treated 22 patients. In June 2010, following the tragic death of a patient from an undiagnosed DB ingestion that led to an aortoesophageal fistula, our protocol was established. All DBs were removed endoscopically. Four patients needed additional surgery: two had tracheal resection/anastomosis and esophageal repair for large tracheoesophageal fistulas; one required aortic wall reinforcement with a patch; one underwent endoscopic removal with a sternal split to explore the aortic arch. All 22 patients survived and recovered clinically. One developed bilateral vocal cord palsy as a complication. Conclusion: Effective management of DB ingestion complications necessitates a collaborative, multidisciplinary approach. Our protocol has improved management strategies and patient outcomes. [ABSTRACT FROM AUTHOR]

Functional nanocomposite materials are hybrid systems combining nanoscale fillers with a matrix, resulting in enhanced properties such as mechanical strength, thermal stability, and electrical conductivity. These materials are highly versatile, finding applications across a broad range of fields, including aerospace for lightweight, strong components, electronics for flexible and high-performance devices, healthcare for targeted drug delivery and tissue engineering, and environmental sectors for water purification and pollutant sensing. Their tunable properties make them ideal for addressing emerging challenges in various industries. This special issue entitled as "Functional Nanocomposite Materials" of Journal of Materials Science is a remarkable collection of invited and contributed papers on this topic, showcasing outstanding recent research results in this field. [ABSTRACT FROM AUTHOR]

A molecular tool has been developed for the molecular identification of Ips sexdentatus (Börner 1776) (Coleoptera Curculionidae Scolytidae), the well-known six thooted bark beetle, widely distributed in Eurasia, where it infests several species of the genus Pinus and occasionally a few conifer species of the genera Abies, Larix and Picea. The developed test can be useful both in countries where I. sexdentatus is handled as a quarantine species and, to greater reason, in Europe to discriminate biological traces of this commonly found beetle from those produced by regulated pests. The protocol is based on real-time PCR with TaqMan probe technology and has been developed on whole insect bodies (adults) as well as on artificial frass contaminated by DNA of the beetle. The molecular test developed here for both direct and indirect identification of I. sexdentatus has proven effective in terms of analytical specificity, analytical sensitivity, reliability and reproducibility. The recommended protocol is a practical diagnostic tool allowing a rapid identification of the six toothed bark beetle in the presence of any biological trace of other xylophagous pests collected at points of entry during phytosanitary surveys. [ABSTRACT FROM AUTHOR]

Purpose: Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior diagnostic accuracy over traditional methods and enabling theragnostic applications. However, a significant diagnostic challenge has emerged with identifying unspecific bone uptakes (UBUs), which could lead to over-staging and inappropriate treatment decisions if misinterpreted. This systematic review explores the phenomenon of UBUs in PCa patients undergoing PSMA-PET imaging. Methods: Studies assessing the prevalence, topographical distribution, and potential clinical implications of UBUs were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Results: The percentage of PCa patients with UBUs on PSMA-PET scans ranged from 0 to 71.7%, depending on the radiopharmaceutical used, with [18F]PSMA-1007 showing the highest incidence. The ribs are the primary site of UBUs across all PSMA-targeted radiopharmaceuticals. The spine is the second most frequent UBU site for [68Ga]Ga-PSMA-11, [18F]DCFPyL, [18F]rhPSMA-7, while the pelvic girdle represents the second most frequent site for [18F]PSMA-1007. The average maximum Standardized Uptake Value (SUVmax) of UBUs varied from 3.4 to 7.7 and was generally lower than that of bone metastases. Conclusions: Our findings underscore the need for heightened awareness and precise interpretation of UBUs to avoid potential over-staging and subsequent inappropriate treatment decisions. Considering the radiopharmaceutical used, PET-derived semiquantitative parameters, the topographical distribution of UBUs, and accurately evaluating the pre-test probability based on clinical and laboratory parameters may aid nuclear medicine physicians in interpreting PSMA-PET findings. [ABSTRACT FROM AUTHOR]

We prove the existence of weak solutions for a class of second-order traffic models with relaxation, without requiring the sub-characteristic stability condition to hold. With the help of numerical simulations, we show how, in this unstable setting, large but bounded oscillations may arise from small perturbations of equilibria, thus reproducing the formation of stop-and-go waves commonly observed in traffic dynamics. An analysis of the corresponding traveling waves completes the study. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) accounts for the 5–10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 235 patients were included in our analysis. Median OS was 8.6 months (95% CI 6.6–12.1), the 1 year OS rate was 43% while the 2 years OS rate 29%. The median PFS was 5.1 months (95% CI 3.9–6.9); 46% of patients were alive at 6 months, 34% at 12 months and 25% at 24 months. According to RECIST 1.1, 18 patients (8%) experienced complete response (CR), 57 (24%) partial response (PR), 44 (19%) stable disease (SD), and 116 (49%) progressive disease (PD), with an ORR of 32%. Our study confirms the effectiveness of pembrolizumab in patients pretreated with a platinum-based combination, irrespective of their sensitivity to the first-line treatment and of their histology. In addition, we emphasized the limited benefit of the treatment with pembrolizumab in patients with hepatic metastases and poor ECOG performance status. [ABSTRACT FROM AUTHOR]

Purpose: This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis. Methods: Narrative review of the literature published until May 2024. Results: The early onset age of EMAP (50–55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication. Conclusion: EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management. Key messages: What is known • Extensive Macular Atrophy with Pseudodrusen (EMAP) is a rapidly-progressive macular atrophy developing in the fifth-decade and leading to legal blindness. • Typical characteristics at multimodal imaging are reticular pseudodrusen-like lesions starting at the superior perifovea and vertically-oriented macular atrophy. What is new • Dysregulated complement cascade and pesticide-related toxicity have been proposed as possible etiologies. • In the late stages of the disease 50% of EMAP patients were legally blind by US standards and, after 7 years on average, atrophy reaches the mid-periphery. [ABSTRACT FROM AUTHOR]

In the 2nd century AD, Galen argued that the failure to remove any single 'root' of a malignant tumor could result in a local relapse. After nearly 2 millennia, this problem appears to be even more challenging due to our increased understanding of the complexity of tumor formation and spread. Pathological analysis of tumor margins under a microscope remains the primary and only accepted method for confirming the complete tumor removal. However, this method is not an all-or-nothing test, and it can be compromised by various intrinsic and extrinsic limitations. Among the intrinsic limitations of pathological analysis we recall the pathologist handling, tissue shrinkage, the detection of minimal residual disease and the persistence of a precancerous field. Extrinsic limitations relate to surgical tools and their thermal damage, the different kinds of surgical resections and frozen sections collection. Surgeons, as well as oncologists and radiotherapists, should be well aware of and deeply understand these limitations to avoid misinterpretation of margin status, which can have serious consequences. Meanwhile, new technologies such as Narrow band imaging have shown promising results in assisting with the achievement of clear superficial resection margins. More recently, emerging techniques like Raman spectroscopy and near-infrared fluorescence have shown potential as real-time guides for surgical resection. The aim of this narrative review is to provide valuable insights into the complex process of margin analysis and underscore the importance of interdisciplinary collaboration between pathologists, surgeons, oncologists, and radiotherapists to optimize patient outcomes in oral cancer surgery. [ABSTRACT FROM AUTHOR]

Purpose: Functional hypothalamic amenorrhea (FHA) is characterized by an estrogen deficiency which in turn can cause vascular dysfunction. The aim of this study is to evaluate any changes in the chorio-retinal circulation in patients affected by FHA. 24 patients with FHA and 24 age-matched controls underwent a gynecological evaluation and an OCT angiography (OCTA) to study chorio-retinal vascularization. Results: OCTA in FHA patients showed an increase in vessel density in the choriocapillaris (CC) layer (both in the fovea area, at 5% p value = 0.037 and in the whole area, at 5% p value = 0.028) and an increase in vascular density in the deep fovea (DVP) (at 10% p value = 0.096) in the whole district compared to controls. Simple linear regressions show a significant negative association between CC vessel density and insulin (p = 0.0002) and glucose values (p = 0.0335) for the fovea district and a negative association between DVP vessel density and endometrial thickness (at 10%, p value: 0.095) in the whole district. Conclusion: Our study shows that CC vessel density is increased in women affected by FHA. This could represent a compensation effort to supply the vascular dysfunction caused by estrogen deficiency. We also found an increasing trend in vascular density in DVP associated with the decrease of endometrial thickness, an indirect sign of estrogenization. Considering that these changes occur in absence of visual defects, they could be used as a biomarker to estimate hypoestrogenism-induced microcirculation changes before clinical appearance. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the changes of pro-inflammatory interleukins in 10 horses subjected to road transport practices (distance of 150 km) from the training site (Messina, Sicily) to the competition centre in Syracuse (Sicily). Blood sampling and interleukins analysis were performed during a round trip transportation (transport 1 and transport 2). In particular, blood samples were collected before the transport took place (Pre), five minutes later (Post) and one hour later (Post 1 h), for each transport, in order to assess the serum concentration of IL-1α, IL-1β, IL-2 and IL-6. The results showed that the serum concentration of IL-1α decreased at Post and Post 1 h compared to the values obtained at rest condition (P < 0.05). The other interleukins analysed (i.e. IL-1β, IL-2 and IL-6) showed increased levels at Post than Rest and Post 1 h in transport 1 (P < 0.05). In transport 2 the analysed parameters showed no change throughout the analysed time points (P > 0.05); however, higher levels of IL-1α at Pre and higher IL-1β, IL-2 and IL-6 values at Post were found in transport 1 than transport 2 (P < 0.05). The increase in pro-inflammatory cytokines after transport 1 suggests the triggering of the inflammatory event and this may show that, although horses are animals accustomed to transport, this is a stressful event that could activate the well-orchestrated inflammation cascade, albeit physiological and temporary, as highlighted by the lower serum concentrations of the investigated interleukins found in transport 1 than transport 2 and by the lack of significant differences in the serum concentrations of the investigated interleukins among the time points of transport 2. It must be taken into account that enrolled animals are well-trained and healthy athletic horses participating to a jumper competition, thus, such inflammation did not occur thanks to a good balance between pro-inflammatory and anti-inflammatory cytokines which allowed a prompt restoration of homeostasis eventually impaired by the stressful event. [ABSTRACT FROM AUTHOR]

Introduction: Despite the technological advancements in catheter ablation strategies, the recurrence of atrial fibrillation (AF) post-ablation remains a concern that requires further investigation. Glucagon-like peptide 1 (GLP-1) receptor agonists have shown a significant effect on weight reduction, which in turn is associated with freedom from AF recurrence in both patients who are obese and not obese undergoing ablation. Therefore, we aimed to summarize the available evidence on the efficacy of GLP-1 receptor agonists in maintaining sinus rhythm post-ablation. Methods: Medline, Cochrane Library, and Scopus were searched until June 9, 2024. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled using DerSimonian-Laird random effects meta-analysis. Results: Three propensity score-matched studies (n = 6031 participants) were analyzed. Over a 12-months follow-up, the use of GLP-1 receptor agonists was associated with a significant reduction in AF recurrence compared to controls, hazard ratio (HR) = 0.549, 95% confidence interval (CI) = [0.315, 0.956], P = 0.034; I2 = 57%. No significant heterogeneity was observed (Q statistic = 4.6, heterogeneity P = 0.1). Conclusion: The use of GLP-1 receptor agonists is associated with a lower risk of AF recurrence in patients receiving AF ablation therapy. Further large-scale randomized trials are necessary to explore the efficacy of GLP-1 receptor agonists in maintaining ablation outcomes over the long term. [ABSTRACT FROM AUTHOR]

Objectives: Persistent idiopathic dentoalveolar pain (PIDP) is a challenging clinical entity associated with both physical and emotional consequences. Currently, the management is symptom-based and includes both topical and/or systemic treatments. More recently, botulinum neurotoxin-A (BONT-A) has been suggested as a treatment option. Materials and methods: We present a case series of 9 patients (5 female) with mean age 56 ± 15 diagnosed with PIDP. All patients reported prior experience with systemic drugs without a sufficient pain-relieving effect. BONT-A (BOTOX, Allergan) 100 U diluted with saline solution was used and the dose ranged from 20U to 50U distributed in 3 sites (intraoral and/or extraoral) per session. Patients underwent further injections (50U) monthly if pain severity measured using a Numerical Rating Scale (NRS 0–10) was still > 3 for 3 months. Pain severity and characteristics were recorded at baseline (T0), after 1 month (T1), 2 months (T2) and 3 months (T3). Results: Mean pain intensity at baseline was NRS 6 (4–10). Latency before analgesic effect was at least 5–10 days after injection. Minor adverse effects were sickness and muscular hypotonia. Pain significantly reduced to NRS 4 (0–8) at T1, to NRS 2 (0–8) at T2 and to NRS 2 (NRS 0–8) at T3. Patients’ functional variables (discomfort while chewing, talking, swallowing) were also recorded. Conclusions: BONT-A is widely used and although the exact mechanism of action remains unclear, it can be used effectively in reducing pain for a variety of conditions including PIDP. Clinical relevance: Our results suggest that BONT-A seems to be an alternative therapeutic approach for patients with PIDP. [ABSTRACT FROM AUTHOR]

The extended depth-of-focus AcrySof IQ Vivity intraocular lens technology offers promising features for presbyopia management, evaluated in this research in a 6 months real-world setting. Prospective interventional mono-centric study including 40 patients who underwent elective bilateral phacoemulsification. We performed one pre-operative visit (V0) and one evaluation six months post-operatively (V1), evaluating uncorrected and corrected visual acuity for near (UNVA/CNVA), intermediate (UIVA/CIVA) and far (UDVA/UCVA), slit-lamp evaluation, tomography with static pupillometry, endothelial cell count and contrast sensitivity chart. In order to assess post-operative Quality of Life, we administered the patients McAlinden's Quality of Vision test and Morlock's Patient-Reported Spectacle Independence Questionnaire. We divided eyes in with Toric-IOL and with non-Toric IOL. A total of 36 eyes received non-tonic IOL implantation, whereas 44 eyes received toric IOL implantation. There were no statistically significant disparities observed in visual outcome measures and contrast sensitivity between the toric group and the non-toric group. Furthermore, we assessed the predictive preoperative refractive astigmatism (PPRA) and residual refractive astigmatism (RRA) in both cohorts, and no statistical significance was found between the two cohorts (p = 0.08). Twenty-one (53%) patients reported total independence from their glasses at all distances. The mean difference between the predicted and measured refractive error, as calculated by spherical equivalent, was 0.09 D. AcrySof IQ Vivity is a well-tolerated and effective IOL with optimal refractive target for both distant and intermediate vision, needing slight spherical addition for the best near vision. Great questionnaire-based satisfaction was reported by the patients. [ABSTRACT FROM AUTHOR]

Background: Detailed information about the epidemiological and phenomenological differences among the aetiological subtypes of oromandibular dystonia (OMD) is lacking. Moreover, the OMD tendency to spread to other body sites has never been investigated. Aim: To compare the main demographic and clinical features of OMD in different aetiological groups and assess the risk of spread. Materials and methods: We retrospectively analysed data from patients contained in the Italian Dystonia Registry. The risk of spread was assessed by Kaplan Meyer curves and Cox regression analysis. Results: The study included 273 patients (175 women) aged 55.7 years (SD 12.7) at OMD onset. Female predominance was observed. Idiopathic dystonia was diagnosed in 241 patients, acquired dystonia in 22. In 50/273 patients, dystonia started in the oromandibular region (focal OMD onset); in 96/273 patients the onset involved the oromandibular region and a neighbouring body site (segmental/multifocal OMD onset); and in 127/273 patients OMD was a site of spread from another body region. Sensory trick (ST) and positive family history predominated in the idiopathic group. No dystonia spread was detected in the acquired group, whereas spread mostly occurred within the first five years of history in 34% of the focal OMD onset idiopathic patients. Cox regression analysis revealed ST as a significant predictor of spread (HR, 12.1; 95% CI, 2.5 – 18.8; P = 0.002). Conclusion: This large study provides novel information about the clinical phenomenology of idiopathic and acquired OMD. We pointed out a possible role of oestrogens in favouring dystonia development. Moreover, we described for the first time the association between ST and dystonia spread, revealing possible common pathophysiological mechanisms. Our findings may be suggested as a referral point for future pathophysiological and therapeutic studies on OMD. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the efficacy of two advanced Large Language Models (LLMs), OpenAI's ChatGPT 4 and Google's Gemini Advanced, in providing treatment recommendations for head and neck oncology cases. The aim is to assess their utility in supporting multidisciplinary oncological evaluations and decision-making processes. Methods: This comparative analysis examined the responses of ChatGPT 4 and Gemini Advanced to five hypothetical cases of head and neck cancer, each representing a different anatomical subsite. The responses were evaluated against the latest National Comprehensive Cancer Network (NCCN) guidelines by two blinded panels using the total disagreement score (TDS) and the artificial intelligence performance instrument (AIPI). Statistical assessments were performed using the Wilcoxon signed-rank test and the Friedman test. Results: Both LLMs produced relevant treatment recommendations with ChatGPT 4 generally outperforming Gemini Advanced regarding adherence to guidelines and comprehensive treatment planning. ChatGPT 4 showed higher AIPI scores (median 3 [2–4]) compared to Gemini Advanced (median 2 [2–3]), indicating better overall performance. Notably, inconsistencies were observed in the management of induction chemotherapy and surgical decisions, such as neck dissection. Conclusions: While both LLMs demonstrated the potential to aid in the multidisciplinary management of head and neck oncology, discrepancies in certain critical areas highlight the need for further refinement. The study supports the growing role of AI in enhancing clinical decision-making but also emphasizes the necessity for continuous updates and validation against current clinical standards to integrate AI into healthcare practices fully. [ABSTRACT FROM AUTHOR]

The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in β-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum. [ABSTRACT FROM AUTHOR]

The chemical characterisation of archaeological finds necessitates a continuous focus on the development of nano/micro-invasive methodologies. These methodologies yield insights into the historical background, production processes, and conservation state of the items, often revealing astonishing properties of materials that have been unexpectedly preserved over the centuries. This work aims to characterise the molecular composition of a putative historical resin recovered during an archaeological excavation in Campese Bay off the island of Giglio in the 1980s. The resin was sampled from a trade amphora used for wine transport; it was likely employed as a coating to ensure better waterproofing of the containers. The characterisation was performed by detecting specific molecular markers using a GC–MS direct injection approach. In addition, we investigated the volatile fraction of the same sample through solid-phase microextraction (SPME) coupled with GC–MS to address the need for a fast, solvent-free, and field-compatible sample preparation method. [ABSTRACT FROM AUTHOR]

Purpose: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI). Methods: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels. Results: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (pFWE = 0.02) and WM (pFWE = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03). Conclusions: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, defined as the loss of skeletal muscle mass, has been associated with a worse functional outcome after stroke. Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients with sarcopenia. Our study aims to investigate the correlation between pre-stroke sarcopenia, measured by TMT assessment, and functional outcome in patients treated with revascularization procedures for acute ischemic stroke. Methods: We included consecutive adult patients who underwent thrombolysis, endovascular thrombectomy or both for acute ischemic stroke at our Centre from January 2020 to June 2022. Besides collecting baseline clinical and neuroradiological features, TMT was measured on brain computed tomography scans according to a standardized protocol. Modified Rankin Scale (mRS) scores at 3 months represented the main endpoint of functional outcome. Results: A total of 261 patients were available for the analysis. In univariate models, patients with excellent outcomes (mRS = 0–1) were younger, had higher TMT values and lower pre-event disability and stroke severity. In multivariate models higher TMT values resulted independently associated with reduced mortality (Odds Ratio 0.708, 95% Confidence Interval 0.538–0.930, p = 0.013). Age, diabetes, brain bleeding events and stroke severity were found to be predictors of mortality, too. Conclusions: Our retrospective analysis shows that in patients who underwent revascularization treatments for ischemic stroke TMT is as an independent predictor of survival easily obtainable from the baseline CT scan. Further investigation is required to confirm the role of sarcopenia assessment and TMT measurement in the prognostication toolkit of this disease. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to define the capability of ChatGPT-4 and Google Gemini in analyzing detailed glaucoma case descriptions and suggesting an accurate surgical plan. Methods: Retrospective analysis of 60 medical records of surgical glaucoma was divided into "ordinary" (n = 40) and "challenging" (n = 20) scenarios. Case descriptions were entered into ChatGPT and Bard's interfaces with the question "What kind of surgery would you perform?" and repeated three times to analyze the answers' consistency. After collecting the answers, we assessed the level of agreement with the unified opinion of three glaucoma surgeons. Moreover, we graded the quality of the responses with scores from 1 (poor quality) to 5 (excellent quality), according to the Global Quality Score (GQS) and compared the results. Results: ChatGPT surgical choice was consistent with those of glaucoma specialists in 35/60 cases (58%), compared to 19/60 (32%) of Gemini (p = 0.0001). Gemini was not able to complete the task in 16 cases (27%). Trabeculectomy was the most frequent choice for both chatbots (53% and 50% for ChatGPT and Gemini, respectively). In "challenging" cases, ChatGPT agreed with specialists in 9/20 choices (45%), outperforming Google Gemini performances (4/20, 20%). Overall, GQS scores were 3.5 ± 1.2 and 2.1 ± 1.5 for ChatGPT and Gemini (p = 0.002). This difference was even more marked if focusing only on "challenging" cases (1.5 ± 1.4 vs. 3.0 ± 1.5, p = 0.001). Conclusion: ChatGPT-4 showed a good analysis performance for glaucoma surgical cases, either ordinary or challenging. On the other side, Google Gemini showed strong limitations in this setting, presenting high rates of unprecise or missed answers. [ABSTRACT FROM AUTHOR]

Abstract The telomeric repeat‐binding factor 2 (TRF2) is a telomere‐capping protein that plays a key role in the maintenance of telomere structure and function. It is highly expressed in different cancer types, and it contributes to cancer progression. To date, anti‐cancer strategies to target TRF2 remain a challenge. Here, we developed a miRNA‐based approach to reduce TRF2 expression. By performing a high‐throughput luciferase screening of 54 candidate miRNAs, we identified miR‐182‐3p as a specific and efficient post‐transcriptional regulator of TRF2. Ectopic expression of miR‐182‐3p drastically reduced TRF2 protein levels in a panel of telomerase‐ or alternative lengthening of telomeres (ALT)‐positive cancer cell lines. Moreover, miR‐182‐3p induced DNA damage at telomeric and pericentromeric sites, eventually leading to strong apoptosis activation. We also observed that treatment with lipid nanoparticles (LNPs) containing miR‐182‐3p impaired tumor growth in triple‐negative breast cancer (TNBC) models, including patient‐derived tumor xenografts (PDTXs), without affecting mouse survival or tissue function. Finally, LNPs‐miR‐182‐3p were able to cross the blood–brain barrier and reduce intracranial tumors representing a possible therapeutic option for metastatic brain lesions.

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival. [ABSTRACT FROM AUTHOR]

Cyberbullying is characterized by asymmetry of power, reiteration of conduct, and desire to victimize. During the COVID-19 pandemic, young people were overexposed to social media and to instances of cyberbullying. The aim of this study was to determine whether the anonymity afforded by fake profiles and the longer hours spent online led to an increase in cyberbullying. The survey involved a sample of 4338 students (52.4% girls; age range, 11–19 years, M 14.1 SD 1.6) attending lower and upper secondary schools. Multiple regression analysis with mediation revealed an association between having a fake profile and cyberbullying in the context of longer non-school time spent online. Our findings suggest that having a fake profile can become a risk for cyberbullying. Our study also underscores the relevance of digital technologies for blocking fake profiles. Such measures could benefit both cybervictims and cyberattackers alike, who often act out of ignorance without realizing the possible consequences of their actions. [ABSTRACT FROM AUTHOR]

Purpose: Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child’s pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement. Methods: This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected. Results: Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p < 0.05). A statistically significant association between child’s pain intensity (β = 0.953, P < 0.05) and the difference between child self-reported and parent-proxy reported PROMIS functional interference scores was found. Conclusion: Parents underestimated pain-related functional disability relative to children’s self-reports. The difference between the paired child self-report and parent-proxy report of functional disability was significantly associated with greater child self-reported pain intensity. Although parent-proxy reports in pediatric chronic pain is often used in research and practice, findings underscore the importance of incorporating child and adolescent self-report, when possible, to comprehensively capture the child’s pain experience and best inform clinical interventions. [ABSTRACT FROM AUTHOR]

This article discusses a case of a 33-year-old male who presented with progressive ascending hypoesthesia and other neurological symptoms. Initially, the symptoms mimicked Neuromyelitis Optica spectrum disorder (NMOSD), but further investigation revealed a longitudinally extensive spinal cord lesion caused by nitrous oxide (N2O) toxicity. The article highlights the importance of considering N2O toxicity as a potential cause of subacute myelopathy, especially in young individuals. It emphasizes the need for a comprehensive medical history, including inquiry about N2O use, and prompt treatment with vitamin B12 supplementation. The article also mentions the increasing trend of N2O-induced subacute combined degeneration of the cord among young adults and the need for guidelines on managing these cases. [Extracted from the article]

Key summary points: Aim: Mexican American older adults with Metabolic Syndrome (MetS) are at greater risk of arthritis. Findings: Stratifying by sex showed no difference in the risk of arthritis. Pain on weight-bearing was associated with arthritis in both males and females. Message: MetS screening may prevent arthritis and symptomatic arthritis. Purpose: To examine the sex differences in the relationship of metabolic syndrome (MetS) criteria with arthritis and symptomatic arthritis among Mexican American older adults aged ≥ 65 without self-reported arthritis at baseline over 23-years of follow-up. Methods: Participants (N = 1447) were from the Hispanic Established Population for the Epidemiologic Study of the Elderly (1993/94–2016). Measures included MetS criteria, arthritis defined as self-reported physician-diagnosed arthritis, socio-demographics, morbidities, depressive symptoms, pain on weight-bearing, cognitive and physical function, handgrip strength, mobility, and activities of daily living (ADLs) limitations. Symptomatic arthritis was defined as self-reported arthritis and having ≥ 1 of the following: pain, mobility limitation, or limited ADLs. Results: At baseline, the mean age was 72.6 years and 730 (50.5%) of our participants were females. Female participants with 2 and 3 MetS criteria had greater odds of arthritis [odds ratio (OR) = 1.77, 95% Confidence Interval (Cl) = 1.28–2.45 and OR = 2.68, 95% CI = 1.69–4.27, respectively) and symptomatic arthritis (OR = 1.74, 95% Cl = 1.24–2.44 and OR = 3.27, 95% CI = 2.04–5.26, respectively) after controlling for covariates. Male participants with 2 and 3 MetS criteria had greater odds of arthritis (OR = 1.65, 95% Cl = 1.14–2.39 and OR = 2.52, 95% CI = 1.51–4.19, respectively) and symptomatic arthritis (OR = 1.93, 95% Cl = 1.30–2.86 and OR = 2.98, 95% CI = 1.62–5.47, respectively) after controlling for covariates. Both females and males with pain on weight-bearing had greater odds of arthritis than those without pain. Conclusions: At 23-years of follow-up, Mexican American older adults with MetS have an increased risk of arthritis and symptomatic arthritis. Early MetS screening and management may reduce arthritis in this population at high risk of disability. [ABSTRACT FROM AUTHOR]

Background: Dietary habits significantly influence the risks of type 2 diabetes and cardiovascular disease. Through metabolomics, we've previously measured plasma metabolites to gauge dietary quality, introducing a healthy dietary metabolic signature (HDMS) linked to a decreased risk of future type 2 diabetes and coronary artery disease. Objectives: To assess the impact of a 6-day dietary intervention on plasma metabolites and the HDMS. Methods: Fifty-nine Swedish participants (71% women, mean age 69 years) underwent a 6-day Mediterranean diet (MD) intervention in Italy's Cilento region. All meals, crafted from local recipes and ingredients, were provided. Metabolite profiling pre- and post-intervention was conducted with a UHPLC-QTOF. Alterations in metabolite levels and the HDMS were examined using paired T-test. Results: The MD intervention notably enhanced the HDMS across participants (mean increase: 1.3 standard deviations (SD), 95% CI 1.1–1.4, p = 6E-25). Out of 109 metabolites, 66 exhibited significant alterations (fdr adjusted p < 0.05). Among the 10 most significant changes, increases were observed in several diet related metabolites such as pipecolate, hippurate, caffeine, homostachydrine, acylcarnitine C11:0, acetylornithine, beta-carotene and 7-methylguanine. The most significant decreases manifested in piperine and 3-methylhistidine. Conclusions: The HDMS, which is linked to a healthy diet and inversely associated with cardiometabolic disease, was significantly improved by the 6-day Mediterranean diet intervention. Notably, metabolite markers previously shown to be indicative of the intake of vegetables, fruits, grains, and legumes increased, while markers previously associated with red meat consumption decreased. These findings highlight the potential of short-term dietary interventions to induce significant changes in plasma metabolite profiles. [ABSTRACT FROM AUTHOR]

Two new neotypes designations are proposed for the species Siboglinum besnardi and Siboglinum nonatoi, based on specimens collected from the Southwestern Atlantic deep waters, type locality of both species. This designation is necessary due to the loss of the original type series for both species. Species identities were validated through morphological analyses, and comprehensive redescriptions are conducted for both species, which not only expand upon the original descriptions but also introduce additional diagnostic characters, including stereomicroscope and SEM images. In addition, genetic material from a specimen of Siboglinum besnardi was obtained, enabling a molecular phylogenetic analysis utilizing COI, 16S and 28S molecular markers. This analysis confirmed not only the species placement within the family Siboglinidae but also provided substantial support for the monophyly of the Frenulata, Vestimentifera, Monilifera and Osedax groups within the annelid family Siboglinidae. [ABSTRACT FROM AUTHOR]

Purpose: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance. Case presentation: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain. Conclusion: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Purpose: The choice of surgical approach for floor of the mouth (FOM) cancer, particularly for intermediate-stage tumors (cT2–cT3), remains controversial. This study aims to evaluate a method considering mylohyoid muscle (MM) invasion as a determinant for surgical approach selection, utilizing magnetic resonance imaging (MRI) preoperatively and frozen section (FS) analysis intraoperatively. Methods: This observational retrospective cohort study analyzed patients undergoing surgical resection of cT2 and cT3 FOM squamous cell carcinoma (SCC) between January 2013 and June 2023. MM infiltration assessed by preoperative MRI determined the surgical approach: clear infiltration led to compartmental surgery (CS), while doubtful or absent infiltration led to transoral surgery (TOS). Conversion from TOS to CS occurred intraoperatively based on macroscopic evidence or positive FS. Data collected included demographic, clinical, surgical, and pathological variables. Survival analysis was conducted using Kaplan–Meier method. Results: Among 44 patients included, majority had cT2 tumors (59.1%). MM resection was necessary in 22.7% of cases. Overall survival (OS) and progression-free survival (PFS) did not significantly differ between TOS and CS groups. Radiological depth of invasion (rDOI) < 10 mm is correlated with MM preservation in 89% of cases, while rDOI > 10 mm is correlated with MM resection only in 23.8% of cases. Pathological depth of invasion (pDOI) discrepancies were observed in the two groups: in CS group is shown a higher pDOI (> 10 mm) confirmation (90%). Surgical complications and functional outcomes differed between TOS and CS groups. Conclusion: Considering MM invasion for surgical approach selection in cT2–cT3 FOM tumors appears oncologically safe, with better functional outcomes in muscle preservation. Preoperative MRI for MM assessment combined with intraoperative FS analysis provides reliable guidance for surgical decision-making. [ABSTRACT FROM AUTHOR]

Progressive ataxia and palatal tremor (PAPT) and anti-IgLON5 disease share possible clinical presentations. Furthermore, both have been associated to a tauopathy mainly affecting the brainstem. Nonetheless, anti-IgLON5 antibodies have never been tested in PAPT. We report on two PAPT cases without evidence of anti-IgLON5 antibodies in both CSF and serum. Despite common clinical and pathological characteristics, PAPT and IgLON5 disease are two distinct entities. [ABSTRACT FROM AUTHOR]