Medicine and Pharmacology

Abstract: We present ChestPathCT5-S100, an open dataset of 87 real-world chest CT examinations spanning five common thoracic pathologies: rib fracture, pleural effusion, lung mass, pulmonary embolism, and pneumothorax. The dataset was assembled from a retrospective single-centre cohort over a ten-year period, intentionally preserving acquisition heterogeneity and concomitant findings representative of routine clinical practice. Cases include both contrast-enhanced (arterial and venous phase) and non-contrast examinations, drawn from emergency, oncologic, and trauma settings. All imaging volumes are provided in NIfTI format. Technical validation by two radiologists confirmed correct pathology category assignment, image integrity, and unambiguous visibility of the dominant pathology for each case. A binary co-occurrence matrix of concomitant findings is provided to support multi-label research designs. ChestPathCT5-S100 is publicly available on Zenodo under a CC0 1.0 license, permitting unrestricted use and redistribution. The dataset supports classification, detection, weakly supervised learning, and multi-task learning paradigms.

Abstract: Major depressive disorder (MDD) is clinically heterogeneous, and peripheral inflammatory biomarkers may help clarify early biological mechanisms before illness chronicity or pharmacologic treatment confound interpretation. This systematic review synthesized evidence on peripheral inflammatory biomarkers in first-episode, drug-naïve major depressive disorder (FEDN-MDD) compared with healthy controls and examined associations with clinical severity. Following PRISMA 2020, searches of PubMed/MEDLINE, Embase, PsycINFO, and Scopus from inception to March 19, 2026 identified 313 records; after screening, 16 publications were included in qualitative synthesis. Studies varied in age group, biological matrix, assay platform, and statistical reporting, precluding meta-analysis. The most frequently assessed biomarkers were IL-1β, TNF-α, IL-6, and CRP/hs-CRP. IL-6 showed the clearest recurrent tendency toward elevation in FEDN-MDD, whereas CRP/hs-CRP findings were partially positive but methodologically limited. TNF-α and IL-1β findings were mixed, and clinical correlations with depressive severity were sparse and inconsistent. Overall, the evidence supports heterogeneous early immune dysregulation in a subset of patients with FEDN-MDD rather than a single reproducible inflammatory signature. Peripheral inflammatory biomarkers should currently be considered research tools for biological stratification and mechanistic hypothesis generation, pending larger standardized longitudinal studies.

Abstract: Background: Staphylococcus argenteus is a recently recognized member of the Staphylococcus aureus complex that is almost identical to S. aureus phenotypically and by 16S rRNA gene sequences. Although genomic analyses demonstrate that S. argenteus is phylogenetically distinct from S. aureus, the two species exhibit more than 90% nucleotide identity and routine identification methods—including routine biochemical assays and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)—cannot reliably distinguish between the two. Objectives: We develop and validate a MALDI-TOF MS–based model for accurate identification of S. argenteus. Methods: A multiplex PCR assay targeting crtM and NRPS genes served as the reference standard. MALDI-TOF MS spectra from 25 S. argenteus and 25 methicillin-susceptible S. aureus (MSSA) isolates were analyzed using ClinProTools to identify characteristic peaks and develop the identification model. The model was validated using 40 S. argenteus and 80 MSSA isolates, then applied to 130 randomly selected clinical isolates. Results: Five characteristic peaks—m/z values 5005, 5285, 5323, 6440, and 6526—were identified. Isolates exhibiting at least 4 of these 5 peaks were classified as S. argenteus; those exhibiting fewer than 4 were classified as S. aureus. The model achieved 100% specificity and 100% sensitivity in both the development and validation phases. In the clinical application phase, the model correctly classified all isolates, whereas conventional MALDI-TOF MS yielded several misidentifications. Conclusions: The identification model, and the simple peak-based rule it is based on, can accurately distinguish S. argenteus from MSSA, offering a practical diagnostic tool for clinical microbiology laboratories.

Abstract: Background/Objective: Vitamin K (VK) comprises a family of quinone compounds with potential involvement in cell death-related pathways through their redox properties. However, consistent findings have not been obtained regarding the clinical significance of VK in breast cancer (BC). Thus, we used the FDA Adverse Event Reporting System (FAERS) to examine the co-reporting patterns of BC-related adverse-event terms among VK-related reports. Methods: Reporting disproportionality analysis was conducted using FAERS data spanning the first quarter of 2004 to the third quarter of 2024. BC-related reports were defined using all valid Preferred Terms included in the relevant narrow-scope Standardized MedDRA Query (SMQ). Reporting odds ratios (RORs) and proportional reporting ratios were calculated for all VK types and each homolog, followed by exploratory comparisons with other compounds containing quinone structures. Results: In total, 32,156 VK-related reports were identified, including 136 BC-related reports. VK-related reports showed significantly lower reporting disproportionality for breast cancer-related reports (ROR = 0.486, 95% confidence interval = 0.411–0.575). In homolog-specific analyses, similar trends were observed for the quinone-type homologs phytomenadione, menatetrenone, and menadione, whereas no significant reporting disproportionality was detected for the hydroquinone-type homolog menadiol. Conclusions: The differences in reporting patterns among quinone-type VK homologs, hydroquinone-type VK, and other quinone-containing compounds suggest that differences in redox properties may be partially related to the structure of reporting disproportionality. Although this study did not demonstrate causality or clinical efficacy, it provides a hypothesis-generating basis for linking basic, epidemiological, and clinical research using FAERS data. Future validation through mechanistic research and analytical epidemiological studies with stricter control of confounding is warranted.

Abstract: Background: This study evaluated the use of circulation time (Tcirc) calculated from polysomnogram (PSG) with pulse oximetry to identify poor cardiac function with low left ventricular ejection fraction (EF). Methods: Subjects over 18 years with sleep apnea (apnea-hypopnea index (AHI) >5/hr) diagnosed by PSG who had transthoracic echocardiography (TTE) within 1 year of PSG were included in this retrospective study. Tcirc of each sleep stage (N2, N3, and REM) were measured and averaged and EF was recorded. Statistical analysis was done using Wilcoxon rank sum test, logistic regression and Youden index. Results: There were 89 sub-jects who met inclusion criteria, 14 with EF ≤45% (Group A) and 75 with EF ≥ 50% (Group B). All 14 Group A subjects had prolonged overall Tcirc with a median time of 27.8 seconds (range 14.1 - 39.6 sec), compared to Group B subjects with median Tcirc of 23.5 seconds (range 14.3 – 37.6 sec), p = 0.311. The op-timal cut-point for overall sleep Tcirc with moderate discrimination (AUC = 0.6) was 28.6 sec. Those with to-tal sleep Tcirc > 28.6 sec were 2.5 x more likely to have low EF with OR =2.56 (95% CI, 0.55-11.16). Con-clusions: In sleep apnea patients, total sleep Tcirc > 28.6 seconds is associated with low ejection fraction with specificity = 0.78.

Abstract: Melasma is a chronic hyperpigmentation disorder that significantly impacts quality of life. Given the persistent challenges in melasma management, there is a need to evaluate therapies that may offer long-term treatment. This review analyzes placebo- and hydroquinone (HQ)-controlled interventional studies of melasma published between January 1, 2014, and December 31, 2024. Screening, data extraction, and discussion synthesis were performed with artificial intelligence assistance under human oversight. Treatments were grouped into five categories: HQ-based Standard Treatments, Isolated Molecules as Depigmenting Therapies, Botanical and Antioxidant-Based Therapies, Regenerative and Microenvironment-Modulating Therapies, and Procedure-Assisted and Combination Treatments. HQ remained a key benchmark, although recurrence and tolerability limitations were frequently observed. Several non-HQ or adjunctive approaches demonstrated benefit when administered orally, topically, intradermally, or via iontophoresis. Botanical antioxidants, synbiotics, epidermal growth factor, and platelet-rich plasma also showed promising efficacy. Nevertheless, the evidence base was constrained by small sample sizes, heterogeneous comparators, inconsistent endpoints, mixed objective and subjective assessments, and variable follow-up durations, which prevented meta-analysis. Research on melasma treatment is growing worldwide, with several promising non-HQ and adjunctive strategies emerging. However, standardization of outcomes, comparator selection, and longer follow-up periods is needed to clarify efficacy, tolerability, and relapse prevention throughout diverse skin tones.

Abstract: Neurolymphomatosis (NL), a rare manifestation of non-Hodgkin’s lymphoma affecting the peripheral nervous system, remains a diagnostic challenge. This study aimed to define an optimal diagnostic approach for timely and effective identification of NL. We analyzed 559 NL cases from 231 articles published from 1951 to 2022, examining how patient outcomes correlated with various diagnostic modalities, including magnetic resonance imaging (MRI), computed tomography (CT), [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), electromyography-nerve conduction studies (EMG-NCS), ultrasound, and tissue biopsy when used individually or in combination. Separate analyses were performed in a mutually exclusive fashion to minimize confounding effects from multiple modalities. The results of this investigation revealed that patients with biopsies had a longer time interval from treatment 1 to progression (Kruskal-Wallis p< 0.0001), survival from diagnosis (overall survival) (p< 0.0001), and survival from symptom onset (p< 0.0001), but not symptom onset to diagnosis (p=0.2134). Pairwise comparisons of biopsy plus 2, 3, or 4 diagnostic modalities revealed a positive trend for the combination of biopsy + PET + MRI + EMG-NCS. A majority of patients without biopsy had secondary NL. In this non-biopsied population, no diagnostic modality had a significant correlation with outcome. The collective data indicate that histological confirmation of NL from biopsy was associated with a positive patient outcome. Management of NL patients requires timely testing using PET, MRI, and EMG-NCS to quickly identify a site for image-guided nerve biopsy.

Abstract: Background: Thoracic surgery is associated with severe post-operative pain caused by chest wall manipulation and intercostal nerve injury. Multimodal analgesia with non-opioid agents such as lidocaine, ketamine and magnesium might be beneficial for pain control and reduce opioid consumption. Methods: In this prospective cohort study, we recruited 118 consecutive patients who underwent lung resection via thoracotomy from January 2019 to January 2021 at Hospital Universitari de Girona Doctor Josep Trueta. The primary outcome was total intravenous morphine consumption within the first 24 h post-operatively. Multi-variable linear regression modelling was used to determine the adjusted association between lidocaine, ketamine and magnesium administration and morphine consumption in the first 24 h after surgery. Statistical analysis was performed using Wilcoxon’s rank-sum and Fisher’s exact tests. Results: In total, 71 patients received lidocaine, ketamine and magnesium intraoperatively (LKM) and 47 patients did not receive this regimen (non-LKM group). The LKM group had a higher prevalence of hypertension and higher proportions of patients undergoing lobectomy and pneumonectomy. Morphine consumption within 24 h post-operatively was lower in the LKM group than in the non-LKM group (median [interquartile range], 2 [2–6] mg vs. 5 [3–8] mg; p = 0.001). No drug-related adverse events were observed. After multi-variable risk adjustment, lidocaine, ketamine and magnesium use was associated with significantly decreased total intravenous morphine consumption within 24 h post-operatively (−1.76, 95% confidence interval = −3.40 to −0.12, p = 0.03). Conclusions: Lidocaine, ketamine and magnesium use was associated with lower 24-h morphine consumption in our prospective cohort.

Abstract: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by substantial clinical and immunological heterogeneity. Traditionally considered a disorder of epidermal barrier dysfunction primarily, AD is now increasingly recognized as a complex systemic inflammatory condition involving dysregulated immune responses, epithelial-derived signaling, neuroimmune interactions, and diverse molecular endotypes. Advances in molecular immunology have significantly expanded current understanding of the cytokine networks underlying disease pathogenesis and have accelerated the transition toward precision medicine approaches in AD. This narrative review summarizes current evidence regarding the immunopathogenesis of AD, with particular emphasis on the interplay between classical and emerging cytokines, biomarker development, and recent therapeutic innovations. Classical type 2 cytokines, including interleukin (IL)-4 and IL-13, remain central drivers of allergic inflammation and epidermal barrier impairment, whereas emerging mediators such as IL-31, IL-33, IL-22, thymic stromal lymphopoietin (TSLP), and OX40/OX40L signaling pathways contribute significantly to chronic inflammation, neuroimmune activation, epidermal remodeling, and pruritus. Comparative analysis of these cytokine pathways highlights the molecular heterogeneity of AD and supports the identification of distinct immunological endotypes. The review additionally discusses current and emerging biomarkers associated with disease severity, therapeutic responsiveness, and inflammatory profiling, including cytokine signatures, serum biomarkers, and transcriptomic approaches. Furthermore, major therapeutic advances involving biologic agents and Janus kinase (JAK) inhibitors are examined within the context of mechanism-based and biomarker-guided therapeutic strategies. Importantly, this review proposes a conceptual precision medicine framework integrating immunopathogenesis, cytokine profiling, molecular endotyping, and targeted therapeutic innovation in AD. Continued advances in biomarker discovery, multi-omics technologies, and individualized therapeutic algorithms may further refine disease stratification and improve personalized management strategies for patients with AD.

Abstract: Activation-loop mutations in receptor tyrosine kinases alter catalytic-state equilibria by changing the balance between local flexibility, global allostery, and inhibitor-induced conformational selection. Here we analyze the c-Kit D816V substitution as a model for how mutation-induced entropy loss can convert a regulated kinase into a rigidified active-like enzyme that resists type II inhibition. Using vibrational-entropy mapping, normal-mode analysis, molecular dynamics simulations, docking, dimer-interface energetics, and in silico saturation mutagenesis, we identify a conformational rigidification mechanism centered on Val816. The substitution replaces the wild-type Asp816-centered hydrogen-bond network with a Val816-Asn819 hydrophobic seam that propagates rigidity through the juxtamembrane latch, N-lobe wedges, and activation loop. This architecture is predicted to pre-organize the catalytic spine and restrict access to the inactive DFG-out state. Although imatinib and dasatinib retain favorable calculated binding energies, D816V imposes a larger predicted energetic penalty on imatinib than on dasatinib, and the rigidified pocket is predicted to impair the conformational collapse required for productive type II inhibition, thereby uncoupling binding from functional shutdown. Saturation mutagenesis separates hydrophobic D816 substitutions into a rigid/stabilizing thermodynamic regime and N819 substitutions into a flexible/destabilizing regime, indicating that activation-loop variants can be classified by the conformational states they impose rather than by position alone. Residual local disorder near residue 816 and energetically permissive mutant-wild-type heterodimerization suggest additional mechanisms for signaling adaptability. These results support a testable biophysical model in which conformational entropy loss, rather than increased flexibility, drives D816-centered c-Kit activation and type II inhibitor resistance.

Abstract: Accurate, complete-arch digital implant impressions remain challenging because cumulative image stitching distortion may increase across geometrically complex edentulous arches. This in vitro study evaluated the influence of implant spatial configuration on the trueness of complete-arch digital implant impressions obtained using current-generation intraoral scanners. Three edentulous mandibular models representing different implant spatial configurations were fabricated: closely spaced parallel implants, widely distributed parallel implants, and angulated implants. Seven intraoral scanners (Trios 3, Trios 4, Trios 5, Medit i500, Primescan 1, Primescan 2, and Aoralscan 3) were evaluated. Ten scans were acquired per model and scanner, generating 210 STL datasets. A CAD replacement workflow based on scan body library geometries was performed prior to deviation analysis. Trueness was evaluated using root-mean-square (RMS) deviation values following iterative closest point alignment with reference datasets obtained using a laboratory scanner. Statistical analysis was performed using two-way ANOVA and post hoc comparisons (α=.05). Significant differences were observed among scanners (p< .001), implant configurations (p< .001), and their interaction (p< .001). Lower RMS deviation values were generally observed in the closely spaced implant configuration, whereas widely distributed implants demonstrated the highest deviations across most scanners. Primescan 1 and Primescan 2 exhibited lower RMS deviation values and smaller increases in distortion across geometrically complex configurations. The spatial configuration of implants significantly influenced the trueness of complete-arch digital implant impressions. Increased implant spatial complexity was associated with greater cumulative stitching distortion during intraoral scanning procedures. Scanner performance varied with implant configuration, suggesting differing resistance to cumulative distortion among current-generation intraoral scanners.

Abstract: Summary. Rehabilitation for older people has a history that mirrors changing understandings of ageing, disability, work and citizenship. This article offers a longue durée analysis of rehabilitative practices directed at older adults, from Greco-Roman antiquity and non-European medical traditions to contemporary geriatric rehabilitation. It asks how societies constructed old age in ways that affected eligibility for rehabilitative care, which institutions provided such care, and how older patients shaped rehabilitative regimes. The article argues that the social value accorded to older adults consistently determined who qualified for intervention, what such intervention sought to achieve, and under what economic, religious and political conditions it became available. Tracing these developments into the nineteenth and twentieth centuries, it shows how geriatric rehabilitation emerged at the intersection of welfare-state formation, demographic transition and disability rights activism, bringing the histories of ageing and rehabilitation into sustained dialogue within modern historiography today across regions and periods globally alike.The article argues that the social value accorded to older adults has consistently determined who qualifies for rehabilitative intervention, what such intervention aims to achieve and under what economic, religious and political conditions it becomes available. Practices recognisable as rehabilitative, including therapeutic exercise, training in activities of daily living, prosthetic adaptation and social reintegration, appear across many pre-modern traditions, from Ayurvedic Jara Chikitsa and Chinese tonification regimens to the Islamic bimaristan and the medieval European almshouse. In each setting access was stratified by status, gender and institutional priority, with productive utility and civic or spiritual standing frequently determining whether older bodies were deemed worth rehabilitating.Tracing these genealogies into the nineteenth and twentieth centuries, the article shows how geriatric rehabilitation emerged from the intersection of welfare-state formation, demographic transition and disability rights activism. It concludes that contemporary practice requires a rights-based framework capable of addressing the enduring ageism that continues to structure access to rehabilitative care globally.

Abstract: Background: Adnexal torsion is an uncommon cause of abdominal pain, and its clinical presentation in children is nonspecific. In some studies, serum D-dimer showed promise as a biochemical marker. The aim of this multicenter prospective observational study was to evaluate the sensitivity and specificity of preoperative serum D-dimer levels for diagnosing adnexal torsion in children and adolescents. Methods: Female patients aged <18 years presenting to the emergency departments of participating centers with symptoms suggestive of adnexal torsion between January 2022 and December 2024 were invited to participate in the study. Preoperative serum D-dimer levels were measured in all patients undergoing surgical exploration. Patients’ characteristics were examined using descriptive and inferential statistics, and the accuracy of preoperative serum D-dimer levels for diagnosing adnexal torsion was assessed using univariate logistic regression and a receiver operating characteristic curve. Results: Twenty-eight patients aged 4–17 years were enrolled. Adnexal torsion was found in 17 patients, on the left side in 4 (23.53%) and on the right side in 13 (76.47%). Almost all patients were treated laparoscopically, and no postoperative complications occurred. Preoperative serum D-dimer levels were higher among patients with adnexal torsion than among those without. The univariate model of serum D-dimer levels had an odds ratio of 1, a sensitivity of 0.77, and a specificity of 0.82 (p = 0.27). Conclusions: No direct association was observed between preoperative serum D-dimer levels and adnexal torsion. Nonetheless, the sensitivity and specificity suggest the possible utility of including serum D-dimer levels in multi-marker diagnostic models to complement rather than replace existing tools.

Abstract: Bioidentical hormone replacement therapy (BHRT) traditionally operates within a triad consisting of sex hormones, thyroid hormones, and adrenal glucocorticoids. Despite widespread adoption, a substantial proportion of patients experience persistent dysglycemia, adrenal instability, fluctuations in symptom control, and inconsistent responses to therapy even when laboratory values appear biochemically normalized. These clinical patterns suggest that an essential regulatory element is missing from the current BHRT conceptual model. This narrative review proposes the Insulin–Cortisol–Vitamin C (ICV) Axis as a previously unrecognized hormonal network central to metabolic and endocrine homeostasis. Insulin profoundly influences sex-hormone binding globulin (SHBG), estradiol and testosterone bioavailability, progesterone responsiveness, thyroid hormone conversion, mitochondrial ATP production, and cortisol reactivity—yet insulin is rarely evaluated in BHRT. Cortisol, in turn, directly modulates insulin sensitivity and metabolic function, while vitamin C is required for cortisol synthesis, adrenal recovery, endothelial nitric oxide signaling, mitochondrial redox regulation, and antioxidant defense. Together, disturbances in these three components can generate characteristic clinical presentations frequently encountered in BHRT practice. In parallel, emerging evidence—including metabolic insights from GLP-1 receptor agonist therapy—indicates that vitamin C status and oxidative stress modulation play broader roles in insulin sensitivity and hormonal signaling than previously recognized. Integrating these findings, the ICV Axis provides a systems-level framework capable of explaining BHRT treatment failures, variable patient responses, and persistent symptomatology despite standard hormone optimization. The purpose of this review is to synthesize biochemical, endocrine, and nutritional evidence supporting this new axis, and to outline a clinically actionable update to BHRT incorporating insulin dynamics and vitamin C sufficiency. Recognition of the ICV Axis represents a conceptual advancement that can improve therapeutic outcomes across metabolic, endocrine, and integrative medical practice.

Abstract: Background: Cancer pain remains highly prevalent and undertreated despite established guidelines. In Italy, Law 38/2010 mandates systematic pain assessment, yet only 26% of clinicians routinely evaluate pain at each clinical visit, and fewer than one-quarter have received formal training in pain medicine or palliative care. A national multidisciplinary roundtable, convened in Rome in March 2025, formally identified four systemic gaps – insufficient education, fragmented care pathways, unclear professional roles, and challenges in implementing shared diagnostic and therapeutic pathways – and planned the development of a structured Delphi consensus. Methods: A Delphi study was conducted in accordance with CREDES guidelines. The Steering Committee, comprising representatives of six Italian scientific societies (AIRO, AIOM, AISD, Federdolore-SICD, SICP, ACD-SIAARTI) and a patient advocacy group (Fondazione Nora e Alberto Gentili), developed 15 clinical statements addressing pain assessment, management, referral criteria, monitoring, and documentation. Sixty-six Italian clinicians from various specialties were invited to participate. Consensus was defined as ≥75% agreement (scoring 4 or 5 on a 5-point Likert scale). Results: Fifty-six clinicians completed the voting rounds (response rate: 84.8%), representing medical oncology, radiation oncology, pain therapy, and palliative care specialties. All statements reached consensus in the first round (78–100%), precluding the need for a second voting round. Panelists’ qualitative comments informed minor wording refinements; substantial content was unchanged. Conclusions: The Delphi process produced a validated, multidisciplinary clinical pathway for cancer pain management in the Italian NHS - National Health System. The pathway establishes structured roles for the clinical reference physician and specialist consultants, objective decision thresholds for analgesic titration and referral, and minimum requirements for standardized pain documentation. These consensus-based statements provide actionable clinical guidance that may help address analgesic undertreatment and support the implementation of Law 38/2010 across Italian oncology centers.

Abstract: Background and Objectives: GLP-1 receptor agonists (GLP-1 RAs) are effective weight-loss therapies, but data on body composition changes in pediatric obesity remain scarce. The primary objective was to evaluate the effects of GLP-1 RAs on body composition in children with obesity. Materials and Methods: We conducted a retrospective study of children with obesity evaluated at the National Institute for Mother and Child Health “Alessandrescu-Rusescu”, Bucharest, Romania, who initiated weekly injectable GLP-1 RA therapy (semaglutide) between January and December 2025. Patients were assessed at baseline and after a median follow-up of 5 months. Eight of ten participants with complete paired data were included in the final analysis; two were excluded because one was non-responder with weight gain and suspected non-compliance, while one responder could not maintain the standing position for bioimpedance measurement. Bioimpedance analysis and anthropometry were performed at both visits. Paired data were analyzed using Wilcoxon signed-rank tests. Results: Eight children (4 boys, 4 girls; mean age 14.9±1.8 years) completed the study. Significant Body Mass Index (BMI) Z-score improvements were observed (CDC: -0.14, p=0.012; WHO: -0.37, p=0.012), with median weight reduction of 4.75 kg (p=0.036). While absolute muscle mass showed non-significant change (-1.3 kg, p=0.362), predicted muscle mass percentage increased significantly (+1.9%, p=0.012), suggesting selective fat loss. Fat-free mass percentage increased (+2.0%, p=0.012) with reciprocal fat mass reduction (absolute: -3.85 kg, p=0.017; percentage: -2.0%, p=0.012). Fat-free mass index remained stable (-0.67 kg/m², p=0.161). No serious adverse events occurred. Sensitivity analysis (n=10) confirmed the robustness of the results, with BMI Z-score improvements remaining significant. Conclusions: GLP-1 RA therapy in children with obesity leads to notable improvements in BMI Z-scores and beneficial body composition changes, suggesting muscle mass preservation along with weight loss, even at submaximal doses. These findings support conducting a larger prospective study with body composition as the primary endpoint.

Abstract: Background: Subcutaneous edema is a common condition seen on ultrasonography, characterized by thickening of the subcutaneous tissue with anechoic or hypoechoic fluid-containing spaces interspersed among fat lobules. The current descriptive term “cobblestone appearance” is used to describe this finding, but the metaphor lacks the vividness of the irregular, reticular pattern we have observed. Observation: We propose the “Cracked Earth Sign” as a novel sonographic sign to describe subcutaneous edema. The sign is defined by thickening of the subcutaneous tissue with irregular, reticular, or branching anechoic or hypoechoic clefts interspersed among fat lobules, resembling cracks in dry, sun-baked earth. Unlike the cobblestone sign, which focuses attention on individual fat lobules, the term “cracked earth sign” emphasizes the reticular network of clefts as a whole, offering a more intuitive visualization of edema distribution. Conclusion: The “Cracked Earth Sign” provides a simple, intuitive sonographic sign for recognizing subcutaneous edema. It may serve as a useful teaching tool for trainees.

Abstract: We present AortaSeg-60, an open dataset of 60 real-world thoraco-abdominal CT-angiography scans of the aorta encompassing normal anatomy and pathological variations, designed for AI research, benchmarking, and educational purposes. The dataset is organized into six balanced categories: young normal, elderly normal, aortic aneurysms, aortic dissections, venous acquisition, and non-contrast acquisition, capturing realistic anatomical and pathological diversity. All scans are provided in NIfTI format with fully automated aortic segmentation masks generated using TotalSegmentator, without manual correction, enabling evaluation of typical algorithmic errors and testing of refinement strategies. Two radiologists performed a technical validation to ensure dataset curation and correct category assignment. AortaSeg-60 is publicly available on Zenodo under a CC0 license. By providing paired imaging and automated labels, the dataset facilitates reproducible research, algorithm development, and method comparison for vascular segmentation, while noting limitations of sample size, single-centre acquisition, and reliance on automated annotations.

Abstract: Introduction: Obesity is a chronic, multifactorial disease associated with significant metabolic and cardiovascular complications. Glucagon-like peptide-1 receptor ago-nists (GLP-1RAs) have emerged as effective pharmacological options for weight man-agement, demonstrating clinically relevant weight loss in controlled trials. However, real-world evidence is essential to assess their effectiveness and safety under routine clinical conditions and to verify if trial results are reproducible in diverse populations. Objective: To evaluate the effectiveness and safety of GLP-1RAs in terms of weight loss in real-world clinical practice and to compare outcomes among different available agents, focusing on their impact on obesity management. Method: A cross-sectional, observational pilot study was conducted in Spain. Adult patients receiving GLP-1RAs for at least four weeks were included. Data collected included sociodemographic vari-ables, treatment characteristics, anthropometric measurements, and adverse effects. Weight loss outcomes were analyzed using descriptive statistics, ANOVA for in-ter-drug comparisons, and multivariate ANCOVA to adjust for confounders. This pilot study also validated the protocol for a subsequent nationwide multicenter study. Re-sults: A total of 32 patients (62.5% women; mean age 58.2 years) were analyzed. Mean weight loss was 2.97 kg (3.17%). Significant differences between drugs were observed (p = 0.005), with semaglutide 2.4 mg (Wegovy) showing the greatest reduction (11.0 kg). Patients without diabetes achieved significantly greater weight loss than those with diabetes (5.0 vs. 0.8 kg; p = 0.021). Treatments were well tolerated, with 53.1% re-porting no adverse effects; most side effects were mild gastrointestinal symptoms. Conclusions: GLP-1RAs are effective and well-tolerated for obesity treatment in re-al-world clinical practice, although weight loss is more modest than in pivotal clinical trials. Differences between agents persist after adjustment, with specific formulations like semaglutide 2.4 mg showing superior effectiveness. These findings support the need for individualized treatment strategies in obesity care. This pilot study success-fully validated the methodology for an ongoing nationwide investigation

Abstract: Hard flaccid syndrome (HFS) is an emerging condition of male sexual dysfunction characterized by a persistent semi-rigid penis in the flaccid state, altered penile sensation, erectile dysfunction, and pelvic or perineal pain. Single-modality treatments have shown limited success, and multimodal protocols have been reported only in single-patient case studies. Our objective was to conduct a retrospective analysis of clinical outcomes from an integrative multimodal rehabilitation protocol in men with HFS. Thirty-two men with HFS completed a comprehensive protocol combining class IV laser therapy, dry needling, radial pressure wave shockwave therapy, therapeutic ultrasound, biofeedback training, manual therapy, therapeutic exercise, behavioral coaching, and oral tadalafil. Patient-reported outcomes were collected at treatment initiation and completion. The main outcome measures were Erection Hardness Scale (EHS), penile satisfaction, PROMIS Sexual Interest, and PROMIS Global Health Physical and Mental Component scores. In this case series, median EHS increased from 2 to 4 and median penile satisfaction increased from 2 to 5 (both P<0.01). All 32 patients achieved EHS ≥3 by treatment end, compared with 8 of 32 (25%) at baseline. PROMIS Sexual Interest, Physical Component, and Mental Component scores all improved significantly (P<0.01). Common comorbid features included low back pain (53%), hip or groin pain (38%), pelvic floor pain (31%), and urinary symptoms (28%). In this retrospective case series, multimodal treatment produced substantial improvements in erectile function and sexual quality of life in men with HFS, supporting an integrative model in which musculoskeletal and end organ pathologies initiate the syndrome and are amplified by central and peripheral nervous system contributions.