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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.

Abstract More than 500 kinases are implicated in the control of most cellular process in mammals, and deregulation of their activity is linked to cancer and inflammatory disorders. 80 clinical kinase inhibitors (CKIs) have been approved for clinical use and hundreds are in various stages of development. However, CKIs inhibit other kinases in addition to the intended target(s), causing both enhanced clinical effects and undesired side effects that are only partially predictable based on in vitro selectivity profiling. Here, we report an integrative approach grounded on the use of chromatin modifications as unbiased, information-rich readouts of the functional effects of CKIs on macrophage activation. This approach exceeded the performance of transcriptome-based approaches and allowed us to identify similarities and differences among CKIs with identical intended targets, to recognize novel CKI specificities and to pinpoint CKIs that may be repurposed to control inflammation, thus supporting the utility of this strategy to improve selection and use of CKIs in clinical settings.

Abstract Polycystic kidney disease (PKD) is a genetic disorder characterized by bilateral cyst formation. We showed that PKD cells and kidneys display metabolic alterations, including the Warburg effect and glutaminolysis, sustained in vitro by the enzyme asparagine synthetase (ASNS). Here, we used antisense oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD murine models and show that treatment leads to a drastic reduction of total kidney volume (measured by MRI) and a prominent rescue of renal function in the mouse. Mechanistically, the upregulation of an ATF4–ASNS axis in PKD is driven by the amino acid response (AAR) branch of the integrated stress response (ISR). Metabolic profiling of PKD or control kidneys treated with Asns-ASO or Scr-ASO revealed major changes in the mutants, several of which are rescued by Asns silencing in vivo. Indeed, ASNS drives glutamine-dependent de novo pyrimidine synthesis and proliferation in cystic epithelia. Notably, while several metabolic pathways were completely corrected by Asns-ASO, glycolysis was only partially restored. Accordingly, combining the glycolytic inhibitor 2DG with Asns-ASO further improved efficacy. Our studies identify a new therapeutic target and novel metabolic vulnerabilities in PKD.

Abstract Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, metabolic dysfunction-associated steatotic liver disease (MASLD) is gaining importance as the disease can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in MASLD development, but molecular mechanisms responsible for disease progression remained unresolved. Here, we uncover in primary hepatocytes from a preclinical model fed with a Western diet (WD) an increased basal MET phosphorylation and a strong downregulation of the PI3K-AKT pathway. Dynamic pathway modeling of hepatocyte growth factor (HGF) signal transduction combined with global proteomics identifies that an elevated basal MET phosphorylation rate is the main driver of altered signaling leading to increased proliferation of WD-hepatocytes. Model-adaptation to patient-derived hepatocytes reveal patient-specific variability in basal MET phosphorylation, which correlates with patient outcome after liver surgery. Thus, dysregulated basal MET phosphorylation could be an indicator for the health status of the liver and thereby inform on the risk of a patient to suffer from liver failure after surgery.

Abstract In the age of Machine Learning Algorithms, Artificial Intelligence and Natural Language Processing, digital technologies have become interwoven in various aspects of society, including in our practices for ethical deliberation and decision-making. In this study, we present a systematic mapping and taxonomy of digital tools designed explicitly for this purpose and published between 2010 and 2023. By providing a comprehensive overview of the landscape, we identify the key features and mechanisms employed to facilitate ethical deliberation. This research enhances our understanding of the potential role that digital tools can play in supporting ethical decision-making processes, offering valuable insights for ethicists, educators, government organizations, and private institutions seeking to develop, deploy, or utilize such tools.

Abstract Cell signaling is central to neuronal activity and its dysregulation may lead to neurodegeneration and cognitive decline. Here, we show that selective genetic potentiation of neuronal ERK signaling prevents cell death in vitro and in vivo in the mouse brain, while attenuation of ERK signaling does the opposite. This neuroprotective effect mediated by an enhanced nuclear ERK activity can also be induced by the novel cell penetrating peptide RB5. In vitro administration of RB5 disrupts the preferential interaction of ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates ERK1/2 nuclear translocation, and enhances global ERK activity. Importantly, RB5 treatment in vivo promotes neuroprotection in mouse models of Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) disease, and enhances ERK signaling in a human cellular model of HD. Additionally, RB5‐mediated potentiation of ERK nuclear signaling facilitates synaptic plasticity, enhances cognition in healthy rodents, and rescues cognitive impairments in AD and HD models. The reported molecular mechanism shared across multiple neurodegenerative disorders reveals a potential new therapeutic target approach based on the modulation of KPNA2‐ERK1/2 interactions.

Abstract This study seeks to understand the impact of extra-curricular entrepreneurship support within a University Based Entrepreneurial Ecosystem (UBEE) on the entrepreneurial self-efficacy and entrepreneurial intentions of engineering students in India. A UBEE can directly affect the likelihood that students identify and exploit entrepreneurial opportunities, which, affects their entrepreneurial intentions. However, there is a dearth of research investigating the impact of university entrepreneurial support initiatives on engineering students’ entrepreneurial intentions and entrepreneurial self-efficacy. This is especially true in the Indian context despite its start-up friendly policies. This study aims to address this gap and contribute to advance knowledge in the area of UBEE research. Grounded in Social Cognitive Theory, this study takes an ecosystem approach that considers the interactions and inter-dependencies among different elements of UBEE, such as entrepreneurial support initiatives and students’ beliefs and intentions to start up. This study adopts a quantitative research design. Survey data was collected from 314 undergraduate engineering students from five engineering colleges in South India and data was analysed using structural equation modelling. Results suggest that the extracurricular support programs within a UBEE significantly influences beliefs of entrepreneurial self-efficacy in students, which in turn predicts the intentions of students to startup new ventures. This study found that entrepreneurial self-efficacy has a mediating effect between the extracurricular support programs and entrepreneurial intentions of engineering students. Findings of this study have several practical and policy implications for government, university management and entrepreneurship educators. This study contributes to the emerging literature on engineering entrepreneurship education.

Abstract MYC is a key oncogenic driver in multiple tumor types, but concomitantly endows cancer cells with a series of vulnerabilities that provide opportunities for targeted pharmacological intervention. For example, drugs that suppress mitochondrial respiration selectively kill MYC‐overexpressing cells. Here, we unravel the mechanistic basis for this synthetic lethal interaction and exploit it to improve the anticancer effects of the respiratory complex I inhibitor IACS‐010759. In a B‐lymphoid cell line, ectopic MYC activity and treatment with IACS‐010759 added up to induce oxidative stress, with consequent depletion of reduced glutathione and lethal disruption of redox homeostasis. This effect could be enhanced either with inhibitors of NADPH production through the pentose phosphate pathway, or with ascorbate (vitamin C), known to act as a pro‐oxidant at high doses. In these conditions, ascorbate synergized with IACS‐010759 to kill MYC‐overexpressing cells in vitro and reinforced its therapeutic action against human B‐cell lymphoma xenografts. Hence, complex I inhibition and high‐dose ascorbate might improve the outcome of patients affected by high‐grade lymphomas and potentially other MYC‐driven cancers.

Abstract Extracting meaningful information from short texts like tweets has proved to be a challenging task. Literature on topic detection focuses mostly on methods that try to guess the plausible words that describe topics whose number has been decided in advance. Topics change according to the initial setup of the algorithms and show a consistent instability with words moving from one topic to another one. In this paper we propose an iterative procedure for topic detection that searches for the most stable solutions in terms of words describing a topic. We use an iterative procedure based on clustering on the consensus matrix, and traditional topic detection, to find both a stable set of words and an optimal number of topics. We observe however that in several cases the procedure does not converge to a unique value but oscillates. We further enhance the methodology using semantic enrichment via Word Embedding with the aim of reducing noise and improving topic separation. We foresee the application of this set of techniques in an automatic topic discovery in noisy channels such as Twitter or social media.

Abstract Early‐life stress can result in life‐long effects that impact adult health and disease risk, but little is known about how such programming is established and maintained. Here, we show that such epigenetic memories can be initiated in the Drosophila embryo before the major wave of zygotic transcription, and higher‐order chromatin structures are established. An early short heat shock results in elevated levels of maternal miRNA and reduced levels of a subgroup of zygotic genes in stage 5 embryos. Using a Dicer‐1 mutant, we show that the stress‐induced decrease in one of these genes, the insulator‐binding factor Elba1, is dependent on functional miRNA biogenesis. Reduction in Elba1 correlates with the upregulation of early developmental genes and promotes a sustained weakening of heterochromatin in the adult fly as indicated by an increased expression of the PEV wm4h reporter. We propose that maternal miRNAs, retained in response to an early embryonic heat shock, shape the subsequent de novo heterochromatin establishment that occurs during early development via direct or indirect regulation of some of the earliest expressed genes, including Elba1.

Backgrounds: The use of drains in pancreatic surgery remains controversial. The present study investigated postoperative outcomes in patients undergoing minimally invasive distal pancreatectomy (MIDP) without intraperitoneal drain placement. Methods: Data of consecutive patients undergoing MIDP between 2013 and 2023 were prospectively collected. Patients were divided in drain group (DG), including patients with prophylactic abdominal drain placed, and no-drain group (NDG) including those without drain. The groups were compared in terms of postoperative outcomes, using a propensity score-matched analysis. Results: 116 patients were selected. After matching, DG and NDG consisted of 29 patients each. The rates of POPF and abdominal collection were lower in NDG in comparison to DG (3.4% vs. 27.6%, p 0.025 and 3.4% vs. 31.0%, p 0.011, respectively). The length of stay was significantly shorter in the NDG (5 vs. 9 days, p < 0.001). No difference between the groups was found for other outcomes. Conclusion: Drain omission was associated with lower rates of POPF and abdominal collections, as well as shorter hospital stays, not affecting the rate of severe complication, reoperation and readmission. [ABSTRACT FROM AUTHOR]

Purpose: This retropective multicentric study aims to investigate the clinical applicability of the NSE score in the elderly, to verify the role of this tool as an easy help for decision making also for this class of patients. Methods: All elderly patients (> 65 years) suffering from spinal metastases undergoing surgical or non-surgical treatment at the authors' Institutions between 2015 and 2022 were recruited. An agreement group (AG) and non-agreement group (NAG) were identified accordingly to the agreement between the NSE score indication and the performed treatment. Neurological status and axial pain were evaluated for both groups at follow-up (3 and 6 months). The same analysis was conducted specifically grouping patients older than 75 years. Results: A strong association with improvement or preservation of clinical status (p < 0.001) at follow-up was obtained in AG. The association was not statistically significant in NAG at the 3-month follow-up (p 1.00 and 0.07 respectively) and at 6 months (p 0.293 and 0.09 respectively). The group of patients over 75 years old showed similar results in terms of statistical association between the agreement group and better outcomes. Conclusion: Far from the need or the aim to build dogmatic algorithms, the goal of preserving a proper performance status plays a key role in a modern oncological management: functional outcomes of the multicentric study group showed that the NSE score represents a reliable tool to establish the need for surgery also for elderly patients. [ABSTRACT FROM AUTHOR]

This paper addresses the prediction of spontaneous self-sustained transverse combustion instabilities in multi-injector engines using a multi-dimensional non-linear low-order Eulerian model. The approach utilizes a physically aware response function that directly links pressure oscillations to fuel mass flow rate, independent of external data. This enables accurate capture of the behavior of shear coaxial injectors that have been proven to show a peculiar dynamics of cyclic fuel accumulation and release in response to acoustic waves. A NASA test case is employed as a reference, and a comprehensive analysis is conducted to investigate the behavior of the model. Firstly, a preliminary analysis is performed within a quasi-one-dimensional framework for a reduced single-injector configuration. This analysis provides insights into the influence of key parameters on the instability onset. Subsequently, the full-scale geometry is considered in a multi-dimensional framework, and the low-order solver is employed to analyze the thermo-acoustic behavior of the engine. The model successfully captures the instability dynamics, including temporal evolution, dominant frequency, and mode shapes. Sensitivity analyses are conducted to examine the impact of the model free parameters on the unstable modes. Additionally, the effect of introducing baffles as damping devices within the combustion chamber is investigated. The results highlight the model predictive capabilities and its potential for guiding the design and optimization of liquid rocket engines. [ABSTRACT FROM AUTHOR]

Naturally Occurring Asbestos (NOA) has drawn the attention worldwide when investigation revealed an increased incidence of malignant mesothelioma in population living near NOA sites. In Basilicata region (South Italy), population living in the villages of Castelluccio Superiore and Inferiore, Lauria, Latronico, Episcopia, San Severino Lucano, and Francavilla in Sinni may be considered at high risk of asbestos exposure because these villages are either surrounded by or built on NOA-rich ophiolitic outcrops. In this work we investigated an asbestos tremolite sample coming from the ophiolitic rocks outcropping in the quarry of Iacolinei, widely used in the past to extract aggregates for various applications. A detailed mineralogical characterization has been attained by using a multi-analytical approach (EMPA, SEM-EDS, TEM-EDS, Mössbauer, µ-Raman, X-ray powder diffraction, and thermal analysis). Morphological investigation highlighted that the sample is composed of long fibers (> 5 µm) with a significant fraction (ca. 55%) having width below 0.25 µm, considered the most biologically active fibers. Moreover, the crystal chemical characterization showed that Fe occurs at the octahedral sites of the tremolite structure. It should be noted that Fe plays a primary role in the toxicity of asbestos. Based on these results, the investigated asbestos tremolite may be considered a potent mesothelial carcinogen, requiring therefore special attention for public health protection purposes. Investigations using sentinel animals to assess the diffusion of the tremolite fibers into the environment from the serpentinite rocks and soils of Iacolinei quarry are in progress. [ABSTRACT FROM AUTHOR]

This viewpoint summarizes findings from analyses of large personal patient databases of myeloproliferative neoplasms (MPNs) to assess the impact of thrombosis on mortality, disease progression, and second cancers (SC). Despite advances, the current incidence of arterial and venous thrombosis remains a challenge. These events appear to signal a more aggressive disease course, as evidenced by their association with myelofibrosis progression and mortality using multistate models and time-dependent multivariable analysis. Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with the aggressiveness of polycythemia vera (PV) and essential thrombocythemia (ET), linking thrombosis to SC risk. This suggests a common inflammatory pathway likely influencing cardiovascular disease and cancer incidence. Notably, this is observed more frequently in younger patients, likely due to prolonged exposure to MPN and environmental inflammatory triggers. These data underscore the need for new studies to validate these associations, delineate the sequence of events, and identify therapeutic targets to mitigate thrombotic events and potentially improve overall patient outcomes in MPN. [ABSTRACT FROM AUTHOR]

Interpersonal Distance (IPD) is defined as the physical distance that individuals maintain between themselves and others during social interactions. While literature has extensively focused on this everyday social behavior, how IPD changes throughout the lifespan remains an open question. In this study, 864 participants, aged 3–89 years, performed the Stop Distance Paradigm in their real-life environments, and we measured the distance they kept from both familiar and unfamiliar others during social interactions. We found that IPD not only differs based on the identity of the other person (familiar versus unfamiliar) but critically declines as a function of age, following two distinct non-linear trends for familiar and unfamiliar others. Moreover, behavioral variability also undergoes a lifetime development, with IPD becoming more stable as age increases. Overall, the present study suggests that IPD is a complex and acquired behavior that changes throughout the lifespan and varies according to individual and situational variables. [ABSTRACT FROM AUTHOR]

Background: Although neuroimaging investigations have consistently demonstrated that "hyperresponsive" and "hyperconnected" visual cortices may represent the functional substrate of cortical spreading depolarization in patients with migraine with aura, the mechanisms which underpin the brain "tendency" to ignite the cortical spreading depolarization and, consequently, aura phenomenon are still matter of debate. Considering that triggers able to induce aura phenomenon constrain brain to increase global (such as physical activity, stressors and sleep abnormalities) or local (such as bright light visual stimulations) energy demand, a vascular supply unable to satisfy the increased energy requirement could be hypothesized in these patients. Methods: Twenty-three patients with migraine with aura, 25 patients with migraine without aura and 20 healthy controls underwent a 3-Tesla MRI study. Cerebral blood flow and local functional connectivity (regional homogeneity) maps were obtained and registered to the MNI space where 100 cortical regions were derived using a functional local-global normative parcellation. A surrogate estimate of the regional neurovascular coupling for each subject was obtained at each parcel from the correlation coefficient between the z-scored ReHo map and the z-scored cerebral blood flow maps. Results: A significantly higher regional cerebral blood flow across the visual cortex of both hemispheres (i.e. fusiform and lingual gyri) was detected in migraine with aura patients when compared to patients with migraine without aura (p < 0.05, corrected for multiple comparisons). Concomitantly, a significantly reduced neurovascular coupling (p < 0.05, false discovery rate corrected) in the primary visual cortex parcel (VIS-4) of the large-scale visual network was observed in the left hemisphere of patients with migraine with aura (0.23±0.03), compared to both patients with migraine without aura (0.32±0.05) and healthy controls (0.29±0.05). Conclusions: Visual cortex neurovascular "decoupling" might represent the "link" between the exposure to trigger factors and aura phenomenon ignition. While physiological vascular oversupply may compensate neurovascular demand-supply at rest, it becomes inadequate in case of increased energy demand (e.g. when patients face with trigger factors) paving the way to the aura phenomenon ignition in patients with migraine with aura. Whether preventive treatments may exert their therapeutic activity on migraine with aura restoring the energy demands and cerebral blood flow trade-off within the visual network should be further investigated. [ABSTRACT FROM AUTHOR]

The 'shark-fin' ECG-sign is a rare electrocardiographic pattern seen in ACS, typically associated with poor prognosis. However, its manifestation in acute aortic syndromes remains largely unexplored. Here, we present a case of a patient diagnosed with Ascending Aortic Dissection, who presented to ED with acute chest pain and shark-fin ECG-pattern. [ABSTRACT FROM AUTHOR]

Achieving an anatomical reduction in acetabular fracture is essential but may also be challenging. Most of complex fractures are treated with anterior approaches without direct visualization of the acetabular surface. In this paper, we present the surgical technique for arthroscopic assistance during open reduction and fixation for complex acetabular fractures. To our knowledge, this technique has not been described in the literature yet. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). Methods: Consecutive patients submitted to LDP or RDP from 2010 to 2020 in four high-volume Italian centers were included, with a minimum of 12 months of postoperative follow-up were included. QoL was evaluated using the EORTC QLQ-C30 and EQ-5D questionnaires, self-reported by patients. After a propensity score matching, which included BMI, gender, operation time, multiorgan and vascular resections, splenic preservation, and pancreatic stump management, the mean differential cost and Quality-Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. Results: The study population consisted of 564 patients. Among these, 271 (49%) patients were submitted to LDP, while 293 (51%) patients to RDP. After propensity score matching, the study population was composed of 159 patients in each group, with a median follow-up of 59 months. As regards the QoL analysis, global health and emotional functioning domains showed better results in the RDP group (p = 0.037 and p = 0.026, respectively), whereas the other did not differ. As expected, the median crude costs analysis confirmed that RDP was more expensive than LDP (16,041 Euros vs. 10,335 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay more than 5697 Euros/QALY was accepted. Conclusion: RDP was associated with better QoL as explored by specific domains. Crude costs were higher for RDP, and the cost-effectiveness threshold was set at 5697 euros/QALY. [ABSTRACT FROM AUTHOR]

Background: Nowadays, video-assisted thoracic surgery (VATS) lobectomy represents the treatment of choice for early-stage lung cancer. Over the years, different methods for VATS training have evolved. The aim of this study is to present an innovative beating-heart filled-vessel cadaveric model to simulate VATS lobectomies. Methods: Via selective cannulation of the cadaver heart, the pulmonary vessels were filled with a gel to improve their haptic feedback. An endotracheal tube with a balloon on its tip then allowed movement of the heart chambers, transmitting a minimum of flow to the pulmonary vessels. A simulated OR was created, using all instrumentation normally available during surgery on living patients, with trainees constantly mentored by experienced surgeons. At the end of each simulation, the participants were asked 5 questions on a scale of 1 to 10 to evaluate the effectiveness of the training method ("1" being ineffective and "10" being highly effective). Results: Eight models were set up, each with a median time of 108 min and a cost of €1500. Overall, 50 surgeons were involved, of which 39 (78%) were consultants and 11 (22%) were residents (PGY 3–5). The median scores for the 5 questions were 8.5 (Q1; IQR1–3 8-9), 8 (Q2; IQR1–3 7–9), 9 (Q3; IQR1–3 8–10), 9 (Q4; IQR1–3 8–10), and 9 (Q5; IQR1–3 8–10). Overall, the model was most appreciated by young trainees even though positive responses were also provided by senior surgeons. Conclusions: We introduce a new beating-heart filled-vessel cadaveric model to simulate VATS lobectomies. From this initial experience, the model is cost effective, smooth to develop, and realistic for VATS simulation. [ABSTRACT FROM AUTHOR]

Intraosseous arteriovenous malformations (AVM) are uncommon high-flow vascular malformation that can affect the maxilla or mandible. AVM may present with aspecific and misleading signs and symptoms. The diagnosis is often accidental and bleeding may represent the first symptom. Radiographically, there are few characteristic features and misdiagnosis is easy. Here we report the case of a young male affected by arteriovenous fistula on the right side of the mandible initially misdiagnosed as a cystic lesion. The patient underwent transarterial embolization of the vascular malformation and subsequently the lesion was surgically removed. 1-year follow-up showed complete healing of the mandibular bone and absence of recurrence. Intraosseous arteriovenous malformations are rare entities. However, due to their harmfulness, both clinicians and radiologists must be aware of this type of lesion and should always consider them in the differential diagnosis of osteolytic lesions. [ABSTRACT FROM AUTHOR]

Appropriate regeneration of jawbone after dental or surgical procedures relies on the recruitment of osteoprogenitor cells able to differentiate into matrix-producing osteoblasts. In this context, photobiomodulation (PBM) has emerged as promising therapy to improve tissue regeneration and to facilitate wound healing processes. The aim of this study was to determine the effect of PBM on human osteoprogenitor cells isolated from mandibular trabecular bone. Bone marrow stromal cell cultures were established from 4 donors and induced toward osteogenic differentiation for 14 days in a standard osteogenic assay. Cells were irradiated with a combined red/near-infrared (NIR) laser following different schedules and expression of osteogenic, matrix-related, osteoclastogenic and inflammatory genes was analyzed by quantitative PCR. Gene expression analysis revealed no overall effects of PBM on osteogenic differentiation. However, a statistically significant reduction was observed in the transcripts of COL1A1 and MMP13, two important genes involved in the bone matrix homeostasis. Most important, PBM significantly downregulated the expression of RANKL, IL6 and IL1B, three genes that are involved in both osteoclastogenesis and inflammation. In conclusion, PBM with a red/NIR laser did not modulate the osteogenic phenotype of mandibular osteoprogenitors but markedly reduced their expression of matrix-related genes and their pro-osteoclastogenic and pro-inflammatory profile. [ABSTRACT FROM AUTHOR]

Background: There is a dearth of artificial intelligence (AI) development and research dedicated to pediatric radiology. The newest iterations of large language models (LLMs) like ChatGPT can process image and video input in addition to text. They are thus theoretically capable of providing impressions of input radiological images. Objective: To assess the ability of multimodal LLMs to interpret pediatric radiological images. Materials and methods: Thirty medically significant cases were collected and submitted to GPT-4 (OpenAI, San Francisco, CA), Gemini 1.5 Pro (Google, Mountain View, CA), and Claude 3 Opus (Anthropic, San Francisco, CA) with a short history for a total of 90 images. AI responses were recorded and independently assessed for accuracy by a resident and attending physician. 95% confidence intervals were determined using the adjusted Wald method. Results: Overall, the models correctly diagnosed 27.8% (25/90) of images (95% CI=19.5–37.8%), were partially correct for 13.3% (12/90) of images (95% CI=2.7–26.4%), and were incorrect for 58.9% (53/90) of images (95% CI=48.6–68.5%). Conclusion: Multimodal LLMs are not yet capable of interpreting pediatric radiological images. [ABSTRACT FROM AUTHOR]

Segmentation of multiple sclerosis (MS) lesions on brain MRI scans is crucial for diagnosis, disease and treatment monitoring but is a time-consuming task. Despite several automated algorithms have been proposed, there is still no consensus on the most effective method. Here, we applied a consensus-based framework to improve lesion segmentation on T1-weighted and FLAIR scans. The framework is designed to combine publicly available state-of-the-art deep learning models, by running multiple segmentation tasks before merging the outputs of each algorithm. To assess the effectiveness of the approach, we applied it to MRI datasets from two different centers, including a private and a public dataset, with 131 and 30 MS patients respectively, with manually segmented lesion masks available. No further training was performed for any of the included algorithms. Overlap and detection scores were improved, with Dice increasing by 4-8% and precision by 3-4% respectively for the private and public dataset. High agreement was obtained between estimated and true lesion load (ρ = 0.92 and ρ = 0.97) and count (ρ = 0.83 and ρ = 0.94). Overall, this framework ensures accurate and reliable results, exploiting complementary features and overcoming some of the limitations of individual algorithms. [ABSTRACT FROM AUTHOR]

Acute diverticulitis (AD) is associated with relevant morbidity/mortality and is increasing worldwide, thus becoming a major issue for national health systems. AD may be challenging, as clinical relevance varies widely, ranging from asymptomatic picture to life-threatening conditions, with continuously evolving diagnostic tools, classifications, and management. A 33-item-questionnaire was administered to residents and surgeons to analyze the actual clinical practice and to verify the real spread of recent recommendations, also by stratifying surgeons by experience. CT-scan remains the mainstay of AD assessment, including cases presenting with recurrent mild episodes or women of child-bearing age. Outpatient management of mild AD is slowly gaining acceptance. A conservative management is preferred in non-severe cases with extradigestive air or small/non-radiologically drainable abscesses. In severe cases, a laparoscopic approach is preferred, with a non-negligible number of surgeons confident in performing emergency complex procedures. Surgeons are seemingly aware of several options during emergency surgery for AD, since the rate of Hartmann procedures does not exceed 50% in most environments and damage control surgery is spreading in life-threatening cases. Quality of life and history of complicated AD are the main indications for delayed colectomy, which is mostly performed avoiding the proximal vessel ligation, mobilizing the splenic flexure and performing a colorectal anastomosis. ICG is spreading to check anastomotic stumps' vascularization. Differences between the two experience groups were found about the type of investigation to exclude colon cancer (considering the experience only in terms of number of colectomies performed), the size of the peritoneal abscess to be drained, practice of damage control surgery and the attitude towards colovesical fistula. [ABSTRACT FROM AUTHOR]

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry (https://rediscover.unipi.it/) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC. [ABSTRACT FROM AUTHOR]

Introduction: Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) has a cardinal role in the diagnosis and staging of non-small cell lung cancer (NSCLC), providing an accurate nodal staging in a less invasive way than surgical biopsy. The aim of this study was to assess the diagnostic accuracy of EBUS-TBNA in the pre-operative NSCLC mediastinal staging, as well as to evaluate EBUS-TBNA specificity and sensibility in our cohort. Methods: We retrospectively analyzed data of NSCLC patients who underwent EBUS-TBNA followed by major pulmonary resection between January 2020 and December 2022. EBUS-TBNA was performed in patients with NSCLC (central T ≤ 3 cm, peripheral/central T > 3 cm), following the ESTS guidelines. The target nodes were selected on the basis of their radiologic/metabolic characteristics. Each procedure was conducted together with rapid on-site cytological evaluation (ROSE). Results: Twenty-five patients were included (M/F = 17/8). At least three needle passages on each target lymph node were performed. No complications during or after the procedures occurred. We found a 100% correspondence between ROSE on the sampled nodes and postoperative pathologic findings. An upstaging occurred in three cases (12%) because of the involvement of stations 5 and 6 (not accessible via EBUS), while the only case of downstaging (N2 → N0, 4%) was probably due to intercurrent neoadjuvant chemotherapy. In all cases, EBUS-TBNA has proved to achieve a diagnostic procedure on the target nodes. Conclusions: EBUS-TBNA is a safe and effective procedure that offers high sensitivity and specificity when performed together with ROSE, which improves the accuracy of sampling. Doubt on nodal stations 5 and 6 involvement should be settled by other techniques. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a clinical syndrome characterized by well-defined signs and symptoms due to structural and/or myocardial functional impairment, resulting in raised intracardiac pressures and/or inadequate cardiac stroke volume at rest or during exercise. This could derive from direct ischemic myocardial injury or other chronic pathological conditions, including valvular heart disease (VHD) and primary myocardial disease. Early identification of HF etiology is essential for accurate diagnosis and initiation of early and appropriate treatment. Thus, the presence of accurate means for early diagnosis of HF symptoms or subclinical phases is fundamental, among which echocardiography being the first line diagnostic investigation. Echocardiography could be performed at rest, to identify overt structural and functional abnormalities or during physical or pharmacological stress, in order to elicit subclinical myocardial function impairment e.g. wall motion abnormalities and raised ventricular filling pressures. Beyond diagnosis of ischemic heart disease, stress echocardiography (SE) has recently shown its unique value for the evaluation of diastolic heart failure, VHD, non-ischemic cardiomyopathies and pulmonary hypertension, with recommendations from international societies in several clinical settings. All these features make SE an important additional tool, not only for diagnostic assessment, but also for prognostic stratification and therapeutic management of patients with HF. In this review, the unique value of SE in the evaluation of HF patients will be described, with the objective to provide an overview of the validated methods for each setting, particularly for HF management. [ABSTRACT FROM AUTHOR]

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative. [ABSTRACT FROM AUTHOR]

Abstract The genetic changes sustaining the development of cancers of unknown primary (CUP) remain elusive. The whole‐exome genomic profiling of 14 rigorously selected CUP samples did not reveal specific recurring mutation in known driver genes. However, by comparing the mutational landscape of CUPs with that of most other human tumor types, it emerged a consistent enrichment of changes in genes belonging to the axon guidance KEGG pathway. In particular, G842C mutation of PlexinB2 (PlxnB2) was predicted to be activating. Indeed, knocking down the mutated, but not the wild‐type, PlxnB2 in CUP stem cells resulted in the impairment of self‐renewal and proliferation in culture, as well as tumorigenic capacity in mice. Conversely, the genetic transfer of G842C‐PlxnB2 was sufficient to promote CUP stem cell proliferation and tumorigenesis in mice. Notably, G842C‐PlxnB2 expression in CUP cells was associated with basal EGFR phosphorylation, and EGFR blockade impaired the viability of CUP cells reliant on the mutated receptor. Moreover, the mutated PlxnB2 elicited CUP cell invasiveness, blocked by EGFR inhibitor treatment. In sum, we found that a novel activating mutation of the axon guidance gene PLXNB2 sustains proliferative autonomy and confers invasive properties to stem cells isolated from cancers of unknown primary, in EGFR‐dependent manner.

Background: Immune checkpoint inhibitors (ICIs) are standard treatments for advanced solid cancers. Resistance to ICIs, both primary and secondary, poses challenges, with early mortality (EM) within 30–90 days indicating a lack of benefit. Prognostic factors for EM, including the lung immune prognostic index (LIPI), remain underexplored. Methods: We performed a retrospective, observational study including patients affected by advanced solid tumors, treated with ICI as single agent or combined with other agents. Logistic regression models identified factors associated with EM and 90-day progression risks. A nomogram for predicting 90-day mortality was built and validated within an external cohort. Results: In total, 637 patients received ICIs (single agent or in combination with other drugs) for advanced solid tumors. Most patients were male (61.9%), with NSCLC as the prevalent tumor (61.8%). Within the cohort, 21.3% died within 90 days, 8.4% died within 30 days, and 34.5% experienced early progression. Factors independently associated with 90-day mortality included ECOG PS 2 and a high/intermediate LIPI score. For 30-day mortality, lung metastasis and a high/intermediate LIPI score were independent risk factors. Regarding early progression, high/intermediate LIPI score was independently associated. A predictive nomogram for 90-day mortality combining LIPI and ECOG PS achieved an AUC of 0.76 (95% CI 0.71–0.81). The discrimination ability of the nomogram was confirmed in the external validation cohort (n = 255) (AUC 0.72, 95% CI 0.64–0.80). Conclusion: LIPI and ECOG PS independently were able to estimate 90-day mortality, with LIPI also demonstrating prognostic validity for 30-day mortality and early progression. [ABSTRACT FROM AUTHOR]

Introduction: Dislocations of the elbow are the second most frequent upper-body injury after shoulder dislocations, comprising 11–28% of all elbow injuries. Complex elbow dislocations pose challenging management due to the involvement of critical stabilizing structures. This study aimed to investigate functional and subjective outcomes (MEPS, DASH, Oxford score) in 44 patients with complex elbow dislocations who underwent surgery between 2018 and 2020, with subgroup analysis focusing on gender and age differences. Material and methods: A retrospective analysis was conducted on patients treated at C.T.O. Hospital, Turin, for complex elbow dislocations between January 2018 and December 2020. Surgical approaches included radial head synthesis, coronoid fixation, ligamentous repair, and ulnar nerve management. Postoperatively, patients followed a standardized or individualized program. Data analysis involved t-tests to assess score differences between subgroups. Results: Among the 44 analyzed patients, the mean age was 48 years, and the mean follow-up time was 29 months. Various types of complex dislocations were identified, with radial head and coronoid fractures classified accordingly. Surgical approaches included multiple methods of reduction and synthesis. While most patients adhered to postoperative programs, subsequent reoperations were conducted in 11% of cases. Scores did not significantly differ between genders, although a trend toward better DASH scores in males was observed. Younger patients showed better, though not statistically significant, outcomes in mobility and functional measures. Conclusion: This study underscores the importance of pre-operative assessment for positive surgical outcomes in complex elbow dislocations. Additionally, findings suggest that younger age may correlate with slightly better functional outcomes. Despite limitations such as retrospective design and sample size, the study enhances our understanding of complex dislocation outcomes and provides valuable insights for future interventions. [ABSTRACT FROM AUTHOR]

We consider a gas of bosons interacting through a hard-sphere potential with radius a in the thermodynamic limit. We derive an upper bound for the ground state energy per particle at low density. Our bound captures the leading term 4 π ρ a and shows that corrections are smaller than C ρ a (ρ a 3) 1 / 2 , for a sufficiently large constant C > 0 . In combination with a known lower bound, our result implies that the first sub-leading term to the ground state energy of a dilute gas of hard spheres is, in fact, of the order ρ a (ρ a 3) 1 / 2 , in agreement with the Lee–Huang–Yang prediction. [ABSTRACT FROM AUTHOR]

Background: Vestibular schwannomas (VS) are slowly growing tumor, deriving from the vestibular component of cranial nerve VIII. Primary treatment modalities include microsurgery, radiosurgery, a combination of microsurgery and radiosurgery, and conservative treatment. The management of VS is a matter of debate, particularly in case of small tumors (less than 2 cm in diameter size). Methods: We performed an institutional retrospective review of a consecutive series of 28 surgically treated patients suffering from VS, operated in our institution. Patients were assigned on the ground of the preoperative imaging in two groups: tumors with major diameter of extra-meatal portion measuring ≥ 3 cm (Group I, 16 patients) and tumors with major diameter < to 3 cm (Group II, 12 patients). Results: The total amount of 18/28 patients were females; the average age was 60.1 years. The average duration of the preoperative symptoms was 25.2 months, while the average interval between the diagnosis and surgical treatment was 8.68 months. The average preoperative volume was, respectively, for Group I and II tumors of 14.35 cm3 and 3.73 cm3. Age was associated to the duration of the preoperative symptoms (r = − 364; p = 0.044), with the probability to develop a complication (p = 0.031) and preoperative low HB score (r = − 324; p = 0.040). The presence of hypoacusis as preoperative symptom was strongly associated to a lesser postoperative maximum diameter and smaller residual disease (p = 0.014). Group I had a significantly longer hospitalization period in respect to Group II (p = 0.001) that impacted negatively to postoperative performance status (r = 0.368, p = 0.042). Conclusions: We confirmed the strong association between age and size of the lesion and the clinical results, where larger lesions in older patients are more prone to complications than smaller in young patients. We found that the patients presenting hypoacusis at onset were associate to lesser preoperative FN impairment outlining a possible differential involvement of the CN related to the internal meatus. We also introduce the strong association of Koos grade with postoperative performance status, hospitalization and facial nerve functionality. [ABSTRACT FROM AUTHOR]

Improving the quality of lung cancer care at a cost that can be sustained is a hotly debated issue. High-risk, low-volume procedures (such as lung resections) are believed to improve significantly when centralised in high-volume centres. However, limited evidence exists to support volume requirements in lung cancer surgery. On the other hand, there was no evidence that the number of lung resections affected either the short-term perioperative results or the long-term cost. Using data from an extensive nationwide registry, this study investigated the correlations between surgical volumes and selected perioperative outcomes. A retrospective analysis of a prospectively filled national registry that follows stringent quality assurance and security procedures was conducted to ensure data accuracy and security. Patients who underwent VATS lobectomy from 2014 to 2019 at the participating centres were included. Selected perioperative outcomes were reported. Total direct hospital cost is measured at discharge for hospitalisations with a primary diagnosis of lung cancer, hospital stay costs, and postoperative length of hospital stay after lobectomy. After the propensity score matched, centres were divided into three groups according to the surgical volume of the unit where VATS lobectomies were performed (high-volume centre: > 500 lobectomies; medium-volume centre: 200–500 lobectomies; low-volume centre: < 200 lobectomies). 11,347 patients were included and matched (low-volume center = 2890; medium-volume center = 3147; high-volume center = 2907). The mean operative time density plot (Fig. 1A) showed no statistically significant difference (p = 0.67). In contrast, the density plot of the harvested lymph nodes (Fig. 1B) showed significantly higher values in the high-volume centres (p = 0.045), albeit without being clinically significant. The adjusted rates of any and significant complications were higher in the low-volume centre (p = 0.034) without significantly affecting the length of hospital stay (p = 0.57). VATS lobectomies for lung cancer in higher-volume centres seem associated with a statistically significantly higher number of harvested lymph nodes and lower perioperative complications, yet without any significant impact in terms of costs and resource consumption. These findings may advise the investigation of the learning curve effect in a complete economic evaluation of VATS lobectomy in lung cancer. [ABSTRACT FROM AUTHOR]

We aimed to develop and validate a COVID-19 specific scoring system, also including some ECG features, to predict all-cause in-hospital mortality at admission. Patients were retrieved from the ELCOVID study (ClinicalTrials.gov identifier: NCT04367129), a prospective, multicenter Italian study enrolling COVID-19 patients between May to September 2020. For the model validation, we randomly selected two-thirds of participants to create a derivation dataset and we used the remaining one-third of participants as the validation set. Over the study period, 1014 hospitalized COVID-19 patients (mean age 74 years, 61% males) met the inclusion criteria and were included in this analysis. During a median follow-up of 12 (IQR 7–22) days, 359 (35%) patients died. Age (HR 2.25 [95%CI 1.72–2.94], p < 0.001), delirium (HR 2.03 [2.14–3.61], p = 0.012), platelets (HR 0.91 [0.83–0.98], p = 0.018), D-dimer level (HR 1.18 [1.01–1.31], p = 0.002), signs of right ventricular strain (RVS) (HR 1.47 [1.02–2.13], p = 0.039) and ECG signs of previous myocardial necrosis (HR 2.28 [1.23–4.21], p = 0.009) were independently associated to in-hospital all-cause mortality. The derived risk-scoring system, namely EL COVID score, showed a moderate discriminatory capacity and good calibration. A cut-off score of ≥ 4 had a sensitivity of 78.4% and 65.2% specificity in predicting all-cause in-hospital mortality. ELCOVID score represents a valid, reliable, sensitive, and inexpensive scoring system that can be used for the prognostication of COVID-19 patients at admission and may allow the earlier identification of patients having a higher mortality risk who may be benefit from more aggressive treatments and closer monitoring. [ABSTRACT FROM AUTHOR]

Purpose: Informative image selection in laryngoscopy has the potential for improving automatic data extraction alone, for selective data storage and a faster review process, or in combination with other artificial intelligence (AI) detection or diagnosis models. This paper aims to demonstrate the feasibility of AI in providing automatic informative laryngoscopy frame selection also capable of working in real-time providing visual feedback to guide the otolaryngologist during the examination. Methods: Several deep learning models were trained and tested on an internal dataset (n = 5147 images) and then tested on an external test set (n = 646 images) composed of both white light and narrow band images. Four videos were used to assess the real-time performance of the best-performing model. Results: ResNet-50, pre-trained with the pretext strategy, reached a precision = 95% vs. 97%, recall = 97% vs, 89%, and the F1-score = 96% vs. 93% on the internal and external test set respectively (p = 0.062). The four testing videos are provided in the supplemental materials. Conclusion: The deep learning model demonstrated excellent performance in identifying diagnostically relevant frames within laryngoscopic videos. With its solid accuracy and real-time capabilities, the system is promising for its development in a clinical setting, either autonomously for objective quality control or in conjunction with other algorithms within a comprehensive AI toolset aimed at enhancing tumor detection and diagnosis. [ABSTRACT FROM AUTHOR]

The Iron Age was a period of change, with many innovations in the glass-making technology. The chemical composition of the set of objects considered in the present study demonstrates the diversity of the raw materials used and the depth of knowledge about the manipulation of glass appearance in the eighth-sixth centuries BCE. The study was carried out using fibre optics reflection spectroscopy and portable X-ray fluorescence spectrometry at the museums’ premises to examine a large number of glass beads and preliminarily group them on the basis of their composition and spectral characteristics. In addition, a smaller set of selected samples was analysed by laser ablation inductively coupled plasma mass spectrometry to provide a comprehensive chemical characterisation of the material. The compositional data indicated that the samples belonged to the high magnesium and low magnesium glass compositional types. Only one sample was recognised as low magnesium medium potassium glass. Glasses within each group were made from different sands, suggesting different provenances. Some of the samples were suggested to be of local origin, while the others were interpreted as imported glass. Evidence of glass colouring, decolouring and recycling are also discussed. [ABSTRACT FROM AUTHOR]

Purpose: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression. Methods: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses. Results: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16–61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97–17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12–2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2. Conclusions: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment. [ABSTRACT FROM AUTHOR]

The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature. A survey addressing the treatments options and management of meningioma in elderly was designed on behalf of SINch® (Società Italiana di Neurochirurgia) and sent via email to all Chiefs of Neurosurgical Departments. The survey remained open for responses from May 5th, 2022, until November 21st, 2022. A search of the literature published between January 2000 and March 2023, in accordance to PRISMA guidelines, was included. A total of 51 Neurosurgical centers participated in the survey. The caseload profile of each center influences the choice of treatment selection (Stereotactic Radiosurgery versus open surgery) (p = 0.01) and the consolidated practice of discussing cases within a multidisciplinary group (p = 0.02). The pooled meta-analysis demonstrated a significant increased risk in the elderly group for permanent deficits (p < 0.00001), postoperative infections (p = 0.0004) and hemorrhage (p = 0.0001), perioperative mortality (p < 0.00001), and medical complications (p < 0.00001) as compared to the young population. This study presents the initial comprehensive analysis of the existing trends in the surgical management of MEP in Italy. The significant variation in practices primarily stems from the absence of standardized guidelines. While most centers have adopted an integrated approach, there is a need to promote a multidisciplinary care model. Prospective studies are needed to gather robust evidence in this clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the incidence of postoperative complications after cytoreductive nephrectomy (CN) following first-line treatment for metastatic renal cell carcinoma (mRCC), and to compare it with postoperative complications of upfront CN. Methods: For this population-based retrospective study, the PearlDiver Mariner database (PearlDiver Technologies, Colorado Springs, CO), a database of insurance billing records was analyzed. Using relevant ICD-9/10 and CPT codes, patients diagnosed with mRCC between 2011 and 2021, who received first-line systemic molecular therapy (SMT), either tyrosine kinase inhibitors (TKI) or immune-checkpoint inhibitors (ICI), were identified. The selected population was stratified into two cohorts according to the timing of CN (deferred: after SMT vs. upfront: before SMT). Propensity-score matching (PSM) was performed as per baseline patients' characteristics to control for potential confounders between the two cohorts. The primary outcome was to compare 30-day postoperative complications rate between patients undergoing upfront vs. deferred CN. Results: After PSM, 162 patients who received upfront CN were compared with 162 patients who underwent deferred CN. The overall rate of 30-day postoperative complications was statistically significantly higher in patients undergoing deferred CN (33.9%), compared to patients treated with upfront CN (21%, p < 0.01). In addition, the rate of both medical (26.5% vs. 14.2%, p < 0.01) and surgical (14.8 vs. 7.4%, p = 0.03) complication rate was statistically significantly higher in deferred vs. upfront CN. Multivariable logistic regression analysis revealed that none of the treatment regimens significantly predicted the occurrence of postoperative complications. Conclusion: Patients undergoing deferred CN experience a higher rates of overall, medical, and surgical 30-day postoperative complications compared to those receiving upfront surgery. Findings from this study should be interpreted within the limitations of this type of analysis. [ABSTRACT FROM AUTHOR]

The use of microelectrode recording (MER) during deep brain stimulation (DBS) for Parkinson Disease is controversial. Furthermore, in asleep DBS anesthesia can impair the ability to record single-cell electric activity. The purpose of this study was to describe our surgical and anesthesiologic protocol for MER assessment during asleep subthalamic nucleus (STN) DBS and to put our findings in the context of a systematic review of the literature. Sixty-three STN electrodes were implanted in 32 patients under general anesthesia. A frameless technique using O-Arm scanning was adopted in all cases. Total intravenous anesthesia, monitored with bispectral index, was administered using a target controlled infusion of both propofol and remifentanil. A systematic review of the literature with metanalysis on MER in asleep vs awake STN DBS for Parkinson Disease was performed. In our series, MER could be reliably recorded in all cases, impacting profoundly on electrode positioning: the final position was located within 2 mm from the planned target only in 42.9% cases. Depth modification > 2 mm was necessary in 21 cases (33.3%), while in 15 cases (23.8%) a different track was used. At 1-year follow-up we observed a significant reduction in LEDD, UPDRS Part III score off-medications, and UPDRS Part III score on medications, as compared to baseline. The systematic review of the literature yielded 23 papers; adding the cases here reported, overall 1258 asleep DBS cases using MER are described. This technique was safe and effective: metanalysis showed similar, if not better, outcome of asleep vs awake patients operated using MER. MER are a useful and reliable tool during asleep STN DBS, leading to a fine tuning of electrode position in the majority of cases. Collaboration between neurosurgeon, neurophysiologist and neuroanesthesiologist is crucial, since slight modifications of sedation level can impact profoundly on MER reliability. [ABSTRACT FROM AUTHOR]

Purpose: Patients undergoing laparoscopic sleeve gastrectomy (LSG) commonly experience moderate to severe postoperative pain. We conducted a randomized, prospective double-blind placebo-controlled study to evaluate the analgesic effect of laparoscopic-guided TAP (LG-TAP) block after LSG in a high-volume bariatric center, applying an enhanced recovery after bariatric surgery (ERABS) pathway. Material and Methods: One hundred ten patients were randomly allocated to receive LG-TAP block with local anesthetic (LA) or saline solution (placebo), both combined with port-site infiltration with LA (LA-PSI). Primary outcome was pain score measured in post-anesthesia care unit (PACU) and at 6, 12, and 24 h after surgery. Secondary outcomes included postoperative nausea and/or vomiting (PONV), analgesic requirement, time to walking, time to flatus, length of hospital stay (LOS), and surgical complications. Results: No significant differences were observed between LG-TAP and placebo groups in postoperative analgesia, with a median (IQR) NRS of 2 (4.75–0) vs. 2 (5.25–0) in PACU, 5.5 (7–3) vs. 6 (7–4) at 6 h, 2 (6–0) vs. 3 (5.25–1.75) at 12 h, and 2 (3.75–0) vs. 1 (2–0) at 24 h; all p > 0.05. A significant difference was found in PONV in PACU (LG-TAP, 46%; placebo, 25%, p-value, 0.019) and at 6 h postoperatively (LG-TAP, 69%, placebo, 41%, p-value, 0.003). No differences were observed as regards other secondary outcomes. Conclusion: Our results suggest that LG-TAP block is not related to more effective postoperative analgesia compared to placebo when LA-PSI is performed. [ABSTRACT FROM AUTHOR]

At the end of the last century, European Union (EU) energy policies encouraged the use of dedicated short rotation forestry (SRF) plantations in member countries in which fast-growing woody species are grown for energy purposes. Recently, in Italy some SRF plantations developed in the 90s have been abandoned or managed more extensively for economic and environmental reasons. However, these abandoned plantations can play a key role in biodiversity conservation and carbon storage. The present study is aimed to estimate carbon stock (C-stock) in living biomass and deadwood in three abandoned SRF plantations in Central Italy. The C-stock was estimated in three different 20-years SRF plantations (hybrid poplar, willow, black locust) located on the same site and unmanaged for 15 years. The results show a C-stock considering three of five C pools equal to: 47.30 MgC ha−1 for hybrid poplar (65.3% in biomass and 34.7% in deadwood respectively), 23.02 MgC ha−1 for willow (77.6% and 22.4% respectively), and 80.41 MgC ha−1 for black locust (95.9% and 4.1% respectively). Outcomes of this research offer support for the forest restoration practices of similar abandoned SRF plantations. The application of extensive management techniques and the development of the naturalization process will ensure the role of biodiversity reservoir of these plantations, helping their evolution toward semi-natural systems mainly oriented to biodiversity conservation and climate change mitigation. [ABSTRACT FROM AUTHOR]

Background: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. Methods: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010–2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. Results: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). Conclusion: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology. Methods: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up. Results: LID prevalence (according to MDS UPDRS score 4.1 ≥ 1) was 16% (42/251); these patients were more likely women (p = 0.01), had higher motor (p < 0.001) and depression scores (p = 0.01) and lower putaminal DAT binding ratio (p = 0.01). LID were associated with the exposure time to L-DOPA (2.2 ± 1.07 vs 2.6 ± 0.9, p = 0.02) and to the exposure to ADMs, in particular to SNRI (4.8% vs 21.4%, p < 0.001). The latter persisted after correcting for significant covariates (e.g., disease duration, cognitive status, motor impairment, depression, dopaminergic denervation). A similar difference in LID prevalence in PD patients exposed vs non-exposed to SNRI was observed on matched data by the real-world TriNetX repository (22% vs 13%, p < 0.001). Discussion: This study supports the presence of an effect of SNRI on LID priming in patients with early PD. Independent prospective cohort studies are warranted to further verify such association. [ABSTRACT FROM AUTHOR]

Italian guidelines recommend HIV pre-exposure prophylaxis (PrEP) only upon satisfying strict eligibility criteria. The objective of this study is to evaluate if PrEP candidates attending a community-based service comply with these criteria and whether these prescribing conditions affect retention in care and sexually transmitted infections (STIs) acquisition. A retrospective analysis was performed on PrEP candidates evaluated from January 2019 to June 2022. Data were collected from self-administered questionnaires and clinical files. The population was divided in subjects with 0/1 (0/1 C) and ≥ 2 (≥ 2 C) criteria. Descriptive statistics and non-parametric tests were employed to describe study population. Incidence of PrEP discontinuation and of STIs was estimated per 100 persons-year of follow up (PYFU), and incidence rate ratio (IRR) was calculated. Univariate and multivariable Cox regression analyses were used to evaluate the association strength between PrEP drop out and other variables. The analyses enrolled 659 individuals: 422 individuals were included in 0/1 C, 237 in ≥ 2 C group, respectively. Inconsistent condom use was the most reported prescribing criteria (399 individuals, 60.6%), followed by a previous STI (186 individuals, 28.2%). 0/1 C exhibited lower STIs incidence. PrEP discontinuation was 29% in 0/1 C and 38% in ≥ 2 C (p = 0.031). Cox model revealed that inconsistent condom use was the only prescribing criteria associated to PrEP persistence. The majority of PrEP candidate did not comply with prescribing conditions. Eligibility criteria failed to identify individuals with better retention in care. Our results suggest that Italian guidelines should be updated removing barriers to prescription. [ABSTRACT FROM AUTHOR]

Background: Burnout is a maladaptive response to chronic stress, particularly prevalent among clinicians. Anesthesiologists are at risk of burnout, but the role of maladaptive traits in their vulnerability to burnout remains understudied. Methods: A secondary analysis was performed on data from the Italian Association of Hospital Anesthesiologists, Pain Medicine Specialists, Critical Care, and Emergency (AAROI-EMAC) physicians. The survey included demographic data, burnout assessment using the Maslach Burnout Inventory (MBI) and subscales (emotional exhaustion, MBI-EE; depersonalization, MBI-DP; personal accomplishment, MBI-PA), and evaluation of personality disorders (PDs) based on DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) criteria using the assessment of DSM-IV PDs (ADP-IV). We investigated the aggregated scores of maladaptive personality traits as predictor variables of burnout. Subsequently, the components of personality traits were individually assessed. Results: Out of 310 respondents, 300 (96.77%) provided complete information. The maladaptive personality traits global score was associated with the MBI-EE and MBI-DP components. There was a significant negative correlation with the MBI-PA component. Significant positive correlations were found between the MBI-EE subscale and the paranoid (r = 0.42), borderline (r = 0.39), and dependent (r = 0.39) maladaptive personality traits. MBI-DP was significantly associated with the passive-aggressive (r = 0.35), borderline (r = 0.33), and avoidant (r = 0.32) traits. Moreover, MBI-PA was negatively associated with dependent (r = − 0.26) and avoidant (r = − 0.25) maladaptive personality features. Conclusions: There is a significant association between different maladaptive personality traits and the risk of experiencing burnout among anesthesiologists. This underscores the importance of understanding and addressing personality traits in healthcare professionals to promote their well-being and prevent this serious emotional, mental, and physical exhaustion state. [ABSTRACT FROM AUTHOR]