Medicine and Pharmacology

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.

Abstract: Non–small cell lung cancer (NSCLC) exhibits genomic heterogeneity that affects tumor immunogenicity and PD-L1 expression. Patient clustering based on shared mutational profiles using social network analysis (SNA) has been narrowly explored. The study aimed to identify subgroups of NSCLC patients with similar somatic mutation profiles using network-based modularity clustering, and to compare these groups with respect to PD-L1 expression, Tumor mutation burden (TMB), and clinical variables. Data of NSCLC patients who underwent surgery between 2022 and 2024 was analyzed. This retrospective study included NSCLC patients harboring actionable driver mutations in genes such as EGFR, KRAS, ALK, BRAF, MET. A social network of 129 patients was constructed. Two distinct genomic clusters were identified. Cluster 2 (n=55) showed a higher prevalence of KRAS, TP53, BRAF, STK11 and additional mutations, while cluster 1 (n=74) displayed a limited number of driver mutations. Cluster 2 had significantly higher PD-L1 expression (29.8% vs. 13.7%, p=0.001) and higher TMB (7.8 vs. 5.8, p=0.021). In multivariate logistic regression, both PD-L1 and TMB independently predicted cluster assignment (p&lt;0.05). Mutation-based SNA clustering successfully delineated biologically distinct subgroups of NSCLC patients. The highly mutated cluster displayed increased immunogenicity, reflected in elevated PD-L1 and TMB levels. This method offers a novel integrative approach that requires prospective validation before clinical implementation.

Abstract: Plant-derived compounds exhibit well-documented osteogenic and anti-resorptive activities; however, their translation into consistent skeletal benefits remains limited. This review proposes a transformation-state–dependent framework in which the efficacy of plant-based interventions is interpreted through the exposure architectures they generate rather than solely through intrinsic molecular activity. By integrating plant matrix organization, gastrointestinal processing, microbial biotransformation, and formulation-driven pharmacokinetics with the temporal dynamics of bone remodeling, the review addresses a critical gap in current literature, which largely evaluates phytochemicals independent of their delivery context. Across a continuum ranging from intact plant matrices to isolated compounds and advanced delivery systems, distinct pharmacokinetic regimes emerge, characterized by differences in release kinetics, metabolic transformation, systemic persistence, and target-site exposure. Evidence indicates that sustained, metabolite-mediated exposure profiles are more compatible with the prolonged, cumulative nature of bone remodeling, whereas transient exposure often limits efficacy despite mechanistic activity. Formulation strategies, including phospholipid complexes, bioenhancers, and nano- or vesicle-based systems, can partially overcome these limitations by modulating exposure behavior. By reframing plant-based interventions as dynamic exposure systems, this framework provides a unifying basis for interpreting variability across studies and offers a rational foundation for designing strategies that align pharmacokinetic behavior with skeletal biology, thereby improving translational potential.

Abstract: Mitral valve regurgitation is the second most common valvular heart disease in Europe, and an estimated 10% of individuals older than 75 years have severe mitral regurgitation. Mitral valve repair is the preferred strategy to treat mitral regurgitation and is associated with better outcomes than mitral valve replacement. Despite the proven efficacy of surgical repair, available data in functional aetiologies reported a not negligible rate of echocardiographically detected severe mitral regurgitation within ten years of the index procedure, in some cases resulting in redo interventions. Data on the optimal management of patients with failed mitral repair remain limited. The aim of this review is to present the available approaches for treating failed mitral valve repair and to describe criteria for selecting the most appropriate strategy on the basis of the underlying mechanism of repair failure, with respect to possible surgical re-repair and novel transcatheter edge-to-edge repair techniques in presence of favourable mitral valve anatomies.

Abstract: Isavuconazole is increasingly being used for the treatment of invasive fungal disease (IFD), although real-world pediatric data remain limited. We retrospectively reviewed patients aged ≤18 years who received isavuconazole for fungal infection at two tertiary centers in Chile between 2021 and 2025. Twenty patients were included, with a median age of 13.7 years (IQR, 9.4–15.5); 14 (70%) had an underlying malignancy, and 6 (30%) were allogeneic hematopoietic cell transplant recipients. Isavuconazole was used for treatment in 16 patients and for prophylaxis in 4, predominantly as second-line therapy due to prior antifungal intolerance, inadequate response, drug–drug interactions, or QT prolongation. Fifteen patients had IFD, with Mucorales (n=3) being the most frequently identified pathogens in proven cases and pulmonary involvement predominating in probable IFD. A succesful response at 90 days was achieved in 60% (6/10) of evaluable cases. No breakthrough fungal infections occurred during treatment or prophylaxis. Hepatic enzyme elevations were observed in four patients. Isavuconazole was associated with favorable outcomes and an acceptable safety profile, supporting its use as an alternative antifungal in pediatric patients.

Abstract: Background: Empathy, compassion, self-compassion, and resilience are essential to medical practice and education. While some evidence shows that these traits may decline during medical school, few studies have examined all these capacities in the same cohorts or trends within an academic year. This study examines first-year longitudinal findings on cohort and within-year changes in these constructs among medical students. Methods: 98 students (58.2% female; MS1 25.5%, MS2 25.5%, MS3 20.4%, MS4 26.5%) from a large West Coast school participated in at least one wave of an online survey distributed 4 times during the 2023-2024 academic year. Validated measures assessed empathy (IRI), compassion (SCBCS), self-compassion (Neff SCS), and resilience (CD-RISC-10). Linear Mixed Models analyzed between-cohort differences over time with gender and race/ethnicity as covariates. Results: Compared to MS4 students, MS2 and MS3 students had significantly lower cognitive empathy and self-compassion, with marginally lower compassion and higher resilience (p = 0.06). Women reported higher compassion toward others but lower self-compassion and resilience than men. Conclusions: Lower empathy and compassion were observed as early as the second year of medical school, suggesting erosion factors, such as academic pressure and standardized testing, may impact trainees earlier than previously reported.

Abstract: Background: Lung cancer is a highly heterogeneous disease in which molecular characte-rization has become essential for guiding personalized therapies. The implementation of next-generation sequencing (NGS) allows the simultaneous detection of multiple genomic alterations, improving tumor profiling and therapeutic decision-making. This study aimed to characterize the molecular landscape of lung cancer using NGS and to evaluate its as-sociation with histological subtypes and programmed death-ligand 1 (PD-L1) expression. Methods: A retrospective observational study was conducted on 96 patients diagnosed with lung cancer between 2023 and 2025. Molecular profiling was performed using the Action OncoKitDx panel. Associations between genetic alterations, histological subtypes, and PD-L1 expression were analyzed using Fisher’s exact test, with p < 0.05 considered statistically significant. Results: Adenocarcinoma was the most common histological subtype (67.7%), followed by squamous cell carcinoma (26%). The most common mutations were KRAS (34.4%), TP53 (29.2%), and EGFR (11.5%). KRAS mutations were significantly associated with adenocar-cinoma (p = 0.001), while the absence of detectable mutations was associated with squa-mous cell carcinoma (p = 0.002). Co-mutations were identified in 22.9% of cases, with KRAS–TP53 being the most common combination. Tumors harboring EGFR mutations showed a significantly lower frequency of co-mutations (p = 0.012). No significant asso-ciations were found between PD-L1 expression and either histological subtypes or the analyzed genetic alterations. Conclusions: Lung cancer exhibits marked molecular heterogeneity, with a predominance of KRAS mutations in adenocarcinoma. The low frequency of co-mutations in EGFR-mutated tumors supports their role as dominant driver alterations. The lack of asso-ciation between PD-L1 expression and genomic alterations highlights the complexity of its regulation and suggests the involvement of multiple biological factors. These findings reinforce the clinical value of NGS in comprehensive tumor profiling and in the develop-ment of precision medicine strategies.

Abstract: Background: Drug-coated balloons (DCBs) have emerged as a "leave-nothing-behind" strategy in percutaneous coronary intervention (PCI), with potential advantages over drug-eluting stents (DES) in selected patients with acute coronary syndrome (ACS).Methods: We performed a narrative review of randomized controlled trials, registries, and meta-analyses evaluating DCB therapy in ACS, including PEPCAD NSTEMI, REVELATION, BASKET-SMALL 2, AGENT IDE, REC-CAGEFREE I/II, and the ongoing TRANSFORM II trial. Articles were identified through searches of PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL covering January 2005 to February 2026.Results: Across published studies, DCBs have shown outcomes that are non-inferior to those of DES in selected ACS subsets, together with a lower risk of major bleeding attributable to shorter dual antiplatelet therapy (DAPT) requirements. Advances in intravascular imaging and lesion preparation, alongside emerging applications of artificial intelligence (AI) and robotic-assisted PCI, may further improve DCB performance, although evidence specific to DCB use in ACS remains limited for these adjunctive technologies. Conclusions: DCBs are a reasonable alternative to DES in selected patients with ACS, particularly those at high bleeding risk or with lesion subsets in which DES perform less well (small vessels, in-stent restenosis, bifurcations, diffuse disease). Adequately powered randomized trials with long-term follow-up are required before broader recommendations can be made.