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PROs Assessment in Dual (Either Oral or Injectable) Antiretroviral Regimen in People with HIV: A Narrative Review
No full textBackground: With modern antiretroviral regimens, durable viral suppression is now achieved in most people with HIV (PWH), whose life expectancy approaches that of the general population. Consequently, recent guidelines emphasise, beyond virological and immunological control, health-related quality of life and patient-reported outcomes (PROs) as targets of HIV care, including for dual regimens. Methods: We conducted a narrative review of clinical trials and observational studies evaluating PROs in adults treated with dual antiretroviral therapies, either oral or long-acting injectable. We also examined guideline documents and implementation studies addressing the role, feasibility, and interpretation of PROs in routine HIV care. Results: Trials of dual regimens reported high treatment satisfaction, convenience, and stable or improved quality of life, with some concerns related to injection-site reactions and visit burden for long-acting formulations. Emerging real-world data broadly confirm these findings but remain heterogeneous, with variability in instruments, assessment timing, and analytic approaches, limiting comparability and clinical use. Conclusions: PROs may support shared decision-making and optimise the use of dual therapies in PWH, but their uptake in clinical practice is still limited. Standardised tools, clearer interpretative frameworks, and pragmatic implementation strategies are needed to better integrate PROs into everyday HIV care
Characterization of tumor-associated macrophages in canine soft tissue sarcomas reveals histotype-dependent immune microenvironments and correlations with mitotic count and histological grade
No full textThe tumor-immune microenvironment (TIME) plays a pivotal role in cancer progression, yet its characterization in veterinary oncology remains limited. Eighty-five soft tissue sarcomas (STSs), comprising fibrosarcomas, leiomyosarcomas, liposarcomas, myxosarcomas, and perivascular wall tumors (PWTs), were immunohistochemically assessed for IBA-1 (total tumor-associated macrophages) and CD204 (M2-like macrophages) expression, scored by image analysis, and correlated with histological parameters. IBA-1 was higher in grade 3 STSs compared with grade 1 (W = 3.40, P = .043) and in PWTs compared with myxosarcomas (W = 6.037, P < .001). CD204 was lower in PWTs compared with fibrosarcomas (W = 5.152, P = .003), leiomyosarcomas (W = 4.394, P = .016), and myxosarcomas (W = 4.812, P = .006). Stratifying by STS type, IBA-1 was higher in grade 2 myxosarcomas compared with grade 1 (Mann U = 4, P = .018). IBA-1 and CD204 were higher in myxosarcomas with necrosis compared with those without (Mann U = 5, P = .026, and Mann U = 0, P = .001, respectively). In PWTs, the mitotic count was higher in cases with higher IBA-1 (Spearman's rho = 0.438, P = .041) and cases with lower CD204 (Spearman's rho = -0.459, P = .035). Considering all STSs, IBA-1 correlated with total tumor-infiltrating lymphocytes (TILs), T-cells, and regulatory T-cells (Tregs). In fibrosarcomas, IBA-1 and CD204 directly correlated with total TILs, T-cells, and Tregs. In myxosarcomas, CD204 correlated with Tregs. In leiomyosarcomas, IBA-1 scores correlated with Tregs and CD204 with T-cells and Tregs. In PWTs, B-cells correlated with IBA-1 and inversely correlated with CD204. These findings suggest the presence of a TIME favoring anti-tumor immunity in PWTs and a pro-tumoral TIME in myxosarcomas, reinforcing the concept that canine STS histotypes elicit distinct immune responses
Exploring the Role of Skull Base Anatomy in Surgical Approach Selection and Endocrinological Outcomes in Craniopharyngiomas
No full textBackground/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m2; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework
Suction mini-percutaneous nephrolithotomy versus standard percutaneous nephrolithotomy for the management of 2–4 cm kidney stones: study protocol for an international, multicenter, parallel-group, noninferiority, randomized controlled trial
No full textPurpose: Percutaneous nephrolithotomy (PCNL) is recommended as the first-line treatment choice for the management of kidney stones larger than 2 cm. However, tract-related complications have always been a concern, especially in standard PCNL where a larger tract > 24Fr is established. The mini-PCNL technique with smaller tract (≤ 18 Fr) has been introduced to decrease tract related complications. Yet, with a smaller mini-PCNL tract, fragments must be fragmented into smaller pieces before extraction, potentially prolonging the operative time. Moreover, if the outflow of irrigation fluid is insufficient via the smaller tract, the intrarenal pressure (IRP) can build up, leading to pyelovenous backflow and infectious complications - an issue theoretically mitigated by the addition of suction techniques. However, high-level evidence comparing suction mini-PCNL outcomes to standard PCNL is still lacking. Methods: The present multicenter, international, randomized controlled noninferiority trial compares suction mini-PCNL to standard PCNL in the management of 2-4 cm kidney stones. The primary outcomes are the immediate postoperative stone-free rate (SFR) and operative time, while secondary outcomes include the final SFR at 1 month, postoperative pain score, length of hospital stay, postoperative complications, and quality of life. Results: A total of 960 patients from 20 urological centers will be randomized to receive either suction mini-PCNL or standard PCNL. Intention-to-treat analysis will be performed. For SFR, non-inferiority will be concluded if the lower bound of the 95% confidence interval for the absolute risk difference exceeds - 10%. For operative time, non-inferiority will be concluded if the lower bound of the 95% confidence interval for the mean difference exceeds - 10 min. For all other analyses, a two-sided p-value of < 0.05 will be regarded as statistically significant. Subgroup analyses will be performed to explore potential effect modification by stone location and stone density. Conclusion: The aim of this trial is to generate high-level evidence regarding the noninferiority of suction mini-PCNL compared to standard PCNL for 2-4 cm renal stones. The trial is registered on ClinicalTrials.gov as NCT05088213
Multipolarity in the Post-War Film Industries: An Introduction
No full textIn this article, based on the evidence brought by a research project we were involved in the last few years and focused on the Italian case, we advance a set of methodological and operational hypotheses for the study of international relations in post-war cinema, developed in dialogue with the contributions collected in this issue. Our central claim is that a multipolar model of productive, distributive, and cultural relations was in place, in the years surrounding the Second World War, with timelines and durations that varied across geographical contexts and in relation to the specific challenges faced by different film industries. This model places under strain a fixed conception of centre-periphery relations, already questioned in transnational approaches to European cinema , as well as a monolithic understanding of the cultural and industrial dominance of American cinema, which nevertheless remained the key reference point in the global system.
After having summarized the scientific discussion on transnational cinemas to determine which elements can be retained and what new tools are needed to outline and study what we consider a multipolar system, in the following section we delve into the Italian case, focusing particularly on the trade association ANICA. During the post-war period, ANICA was structured as an interface between different systems, managing current practices such as export and co-production instructions and film credit guarantees, as well as strategic actions such as defining agreements and conducting periodic revisions. Two specific examples relating to the definition of exchange and co-production agreements with the film industries of Mexico and Yugoslavia illustrate ANICA’s concrete functioning in relation to other national and foreign entities, including public and private stakeholders. Finally, we reflect on the concept of borders as a key element in the relationship between film systems and infrastructures
A discrete Kumaraswamy distribution for modeling rating and ranking data
No full textWe propose a discrete probability distribution supported on the first k positive integers ( k ≥ 3 , defined in terms of the cumulative distribution function of the continuous two-parameter Kumaraswamy distribution supported on the interval (0,1). This distribution offers an alternative to existing models, such as the discrete Beta, the Beta-Binomial, and the CUB distributions, for modeling ordinal data, which are ubiquitous in applied disciplines. The key properties of the distribution are explored, with a particular focus on the possible shapes of its probability mass function, moments, pseudo-random simulation, and inferential procedures. Regression models where the response variable follows the proposed discrete Kumaraswamy distribution are also discussed. Analyses of different real data sets, regarding individuals’ perspectives on environmental matters, are provided to practically illustrate the model introduced in this work and assess its ability to fit rating or ranking data.
Patient-level CAD-RADS scoring from coronary radiomic features
No full textSynthesizing coronary radiomic data to obtain a single patient-wise Coronary Artery Disease-Reporting and Data System (CAD-RADS) score remains challenging. This work proposes four strategies for summarizing radiomic features extracted from 2779 multiplanar reconstruction images derived from coronary computed tomography angiography of 238 patients. A cascade pipeline was developed to train gradient boosting classifiers for CAD-RADS scoring through consecutive tasks, considering 80%-20% training/test split with five-fold cross-validation on the training set. Two statistical-based and two majority voting approaches were implemented to obtain patient-level classification. The former consisted in computing features average, minimum, maximum and standard deviation, across the coronary images, leading to intermediate coronary classification, followed by patient classification according to the worst coronary class. The latter consisted in single image predictions and the application of majority voting either to all the images, to obtain patient classification (MV_P), or to the images of single coronary arteries, followed by patient classification according to the worst coronary class (MV_C). Majority-voting approaches outperformed statistical-based ones, with MV_P achieving an AUC of CAD-RADS_0 = 0.94, CAD-RADS_1 = 0.92, CAD-RADS_2 = 0.97, CAD-RADS_3 = 0.77, CAD-RADS_4 = 0.88, CAD-RADS_5 = 0.85, and MV_C of CAD-RADS_0 = 0.82, CAD-RADS_1 = 0.78, CAD-RADS_2 = 0.84, CAD-RADS_3 = 0.96, CAD-RADS_4 = 0.98 and CAD-RADS_5 = 0.85. This study represents a significant advancement toward robust and reproducible coronary radiomics tools for automated CAD-RADS scoring
Sleeping in supine position may increase angina frequency-a perspective from 'gravity-opposition physiology', the oculo-cardiac reflex, and astronauts with papilledema
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Artificial intelligence-generated marathon training programs: reliable tools in exercise prescription for athletic performance?
No full textBackground: Marathon running has evolved into a global phenomenon, with rising participation across age and experience groups. Training for a marathon requires adherence to well-established principles involving pacing, training volume, and periodization. With the increasing integration of artificial intelligence (AI) into healthcare and fitness, it remains unclear whether AI can reliably prescribe evidence-based training programs for such demanding endurance events. Sources of data: We conducted a descriptive study using outputs from leading AI models: Claude 3.5 Sonnet, Claude 3.5 Haiku (Free), ChatGPT 4.0 (o-model), ChatGPT 0.1, ChatGPT 4 (free), Gemini 2.0 Flash, Gemini 2.0 Flash Thinking, and DeepSeek R1. Each was prompted to generate a 6-month marathon training plan tailored to three athlete levels: Beginner, Intermediate, and Advanced. Outputs were compared with peer-reviewed literature on the determinants of marathon training. Areas of agreement: Most AI systems identified key training components: weekly mileage progression, tapering, and intensity distribution (>80% at low intensity), which aligns with current endurance training theory. Areas of controversy: AI responses varied in accuracy and completeness. Some engines omitted key details (e.g. weekly mileage), failed to differentiate clearly between athlete levels (intermediate and advanced have been merged as if they were the same level), or offered inconsistent pacing data, especially for advanced runners. This descriptive analysis evaluated qualitative adherence to evidence-based training principles rather than quantitative outcomes requiring statistical inference. Growing points: AI demonstrates strong potential in accessible, structured training content. When properly prompted, outputs often align with contemporary training principles, though significant limitations regarding personalization and professional oversight necessitate further validation before clinical implementation. Areas timely for developing research: Future studies should evaluate the real-world outcomes of AI-generated programs in randomized trials including the integration of personal physiological data. Inizio moduloFine modulo