Observational studies have linked psychotic disorders to impaired lung function and respiratory diseases, but the potential association between mood swings-a potential predisposing factor for psychotic disorders-and lung health remains poorly understood. Using summary-level data from large-scale genome-wide association studies, we investigated the shared genetic basis and putative causal links between mood swings and lung function, asthma, and chronic obstructive pulmonary disease (COPD). Evident genetic correlations in our study were observed between mood swings and FEV1 ( = -0.09), FVC ( = -0.09), PEF ( = -0.09), asthma ( = 0.33), and COPD ( = 0.28). Local genetic correlation analysis identified 10 significant local genomic regions, including chr17p12-p11.2 and chr16q23.1. Furthermore, cross-trait meta-analysis revealed 55 SNPs shared between mood swings and lung function, 2 SNPs with asthma, and 1 SNP with COPD. A transcriptome-wide association study identified 43 shared genes that largely overlapped with those revealed in the cross-trait meta-analysis, implicating tissues in the nervous, respiratory, digestive, and cardiovascular systems. Mendelian randomization analysis provided evidence that mood swings are significantly linked to reduced FEV1 (OR = 0.85, 95% CI = 0.77-0.93), reduced FVC (OR = 0.86, 95% CI = 0.77-0.96), reduced PEF (OR = 0.82, 95% CI = 0.74-0.91), and an elevated risk of asthma (OR = 2.22, 95% CI = 1.60-3.06) and COPD (OR = 2.02, 95% CI = 1.37-2.98). This study highlights a shared genetic basis and putative causal relationship between mood swings and impaired lung function and respiratory diseases, providing genetic evidence that underscores the importance of investigating mood instability in the context of respiratory health.

: Dravet syndrome, a severe early-onset epileptic encephalopathy, is treated with multiple antiepileptic drugs such as clobazam (CLB) and stiripentol (STP), increasing the risk of drug-drug interactions (DDIs). Given the limited pediatric pharmacokinetic data, this study developed physiologically based pharmacokinetic (PBPK) models for CLB and STP to optimize dosing and assess DDI risk across pediatric age groups. : We developed PBPK models for CLB, its active metabolite, -desmethylclobazam (N-CLB), and STP in healthy adults and pediatric patients with Dravet syndrome aged two years and older. We evaluated the inhibitory effect of STP on CLB and N-CLB metabolism, accounting for CYP2C19 phenotypes. The model was extrapolated to predict drug exposure in pediatric patients under two years of age. : PBPK models for CLB, , and STP successfully recapitulated observed pharmacokinetics in healthy adults and pediatric patients older than two years. Model verification against clinical DDI data showed that co-administration of STP with CLB resulted in a clinically insignificant increase in CLB exposure (C ratio = 1.77). In contrast, N-CLB exposure increased approximately 7-fold in CYP2C19 extensive metabolizers (C ratio ≈ 7) and slightly decreased in poor metabolizers (C ratio = 0.9), consistent with the CYP2C19-dependent metabolism of N-CLB. Extrapolation to pediatric patients under two years of age predicted CLB, N-CLB, and STP exposures that were comparable to older children and remained within their reported efficacy and safety margins, suggesting no major ontogeny-related effect on exposure. : The PBPK model supports the safe extrapolation of CLB and STP co-administration to pediatric Dravet syndrome patients as young as six months.

The incidence of early-onset colorectal cancer (EOCRC) is rising worldwide, although its biological and clinical features remain incompletely understood. Emerging evidence implicates gut microbial dysbiosis as a key driver of EOCRC pathogenesis, acting through complex interactions with host genetics, mucosal immunity, and early-life exposures. This review synthesizes current evidence on EOCRC-specific microbial signatures, delineates host-microbiome interactions, and evaluates how these insights may inform precision prevention, early detection, and therapeutic strategies. A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025, using combinations of "early-onset colorectal cancer," "gut microbiome," "dysbiosis," and "host-microbiome interactions." Both clinical and preclinical studies were included. Extracted data encompassed microbial composition, mechanistic insights, host-related factors, and microbiome-targeted interventions. Evidence was synthesized narratively to highlight consistent patterns, methodological limitations, and translational implications. EOCRC is consistently associated with enrichment of pro-inflammatory and genotoxic taxa (e.g., , colibactin-producing , enterotoxigenic ) and depletion of short-chain fatty acid-producing commensals. Multi-omics analyses reveal distinct host-microbiome signatures influenced by germline predisposition, mucosal immunity, sex, and early-life exposures. However, substantial methodological heterogeneity persists. Collectively, these data point to candidate microbial biomarkers for early detection and support the rationale for microbiome-targeted preventive and adjunctive therapeutic approaches. EOCRC harbors unique microbial and host-environmental features that distinguish it from late-onset disease. Integrating host determinants with microbiome signatures provides a framework for precision prevention and tailored therapeutic strategies. Future priorities include harmonizing methodologies, validating microbial biomarkers in asymptomatic young adults, and rigorously testing microbiome-targeted interventions in clinical trials.

: Melanoma is a malignant tumour of melanocytes. Cutaneous melanoma accounts for the vast majority of cases and has benefitted from advances in targeted and immune checkpoint inhibitor therapies, leading to substantial improvements in survival. In contrast, mucosal and vulvovaginal melanomas are rare, aggressive subtypes with distinct molecular and immune profiles and poor prognoses. This review synthesises evidence comparing cutaneous, mucosal, and vulvovaginal melanoma, with emphasis on biology, treatment, and outcomes : A narrative comparative review was undertaken, examining the published literature on the epidemiology, molecular and immune characteristics, and treatment outcomes of cutaneous, mucosal, and vulvovaginal melanoma, including systemic therapies and surgical approaches. : Cutaneous melanoma demonstrates high tumour mutational burden and frequent BRAF and mutations, underpinning the success of targeted therapy and immunotherapy. Mucosal and vulvovaginal melanomas exhibit lower mutational burden, distinct mutation patterns, and reduced immunogenicity, correlating with poorer treatment responses. Surgery remains the mainstay of management, though optimal margins in vulvovaginal melanoma are unclear. Recurrence rates are high, and five-year survival remains poor. Evidence for systemic therapy is limited to small retrospective cohorts and subgroup analyses, showing lower response and survival rates compared with cutaneous melanoma. Chemotherapy has minimal benefit. : Mucosal and vulvovaginal melanomas are biologically and clinically distinct from cutaneous melanoma and continue to have poor survival outcomes. Their rarity restricts high-quality evidence, highlighting the need for collaborative, innovative research to inform effective treatment strategies.

Colonic lipomas (CLs) are benign neoplasms originating from adipose tissue within the gastrointestinal tract. They are often asymptomatic, but in certain cases, patients may present with gastrointestinal bleeding or symptoms related to intestinal obstruction. We report the cases of 18 patients undergoing both surgical and endoscopic resection of colonic lipomas. Given the variability in symptoms, lesion size, and patient demographics, the management of CLs represents a clinical scenario where treatment must be tailored to the individual, aligning with the principles of personalized medicine. This study aims to clarify the clinical and morphological factors guiding treatment selection for colonic lipomas, emphasizing a personalized approach to management. We retrospectively reviewed a prospectively collected database of 18 patients with histological diagnosis of colon lipoma after both endoscopic and surgical resection at the Campus Bio-Medico University Hospital, Rome, from 2016 to the first months of 2025. The average patient age was 66 years, and the average maximum size of lipoma was 2.87 cm. The anatomical location of lipomas is very varied, ranging from the ileocecal valve to the distal sigma, and most procedures were endoscopic. Despite the fact that no established guidelines about the management of the CLs are reported in literature, the different approaches are related to symptomatology. Our findings try to clarify and demonstrate how the therapeutic decision, whether endoscopic or surgical, is personalized based on the patients and their clinical condition, illustrating how CL management reflects the broader framework of personalized medicine. Our work confirms that the patients most prone to intussusception phenomena are young women with large colonic lipomas.

: Major depressive disorder (MDD) and metabolic syndrome (MetS) are highly prevalent, bidirectionally linked conditions. Individuals with MetS are at increased risk of developing depression, while depression predisposes to metabolic dysfunction. Evidence suggests that comorbid MDD and MetS present a distinct psychopathological profile, with neurovegetative symptoms such as fatigue, sleep disturbances, and appetite dysregulation being more prominent. This study aimed to determine whether depressive symptom structures differ between MDD patients with and without MetS, applying Bayesian network methods to uncover probabilistic dependencies that may inform precision psychiatry. : Data were drawn from 1779 adults with ICD-10-diagnosed MDD in the 2013-2020 National Health and Nutrition Examination Survey (NHANES). Using standard metabolic criteria, participants were categorized as MetS ( = 315) or non-MetS ( = 1464). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ-9). Directed Acyclic Graphs (DAGs) were estimated via a hill-climbing algorithm with 5000 bootstrap replications to ensure network stability. : MetS patients displayed a denser and more interconnected symptom network. Fatigue (PHQ4) emerged as a central hub linking sleep, appetite, cognition, and functional impairment. In contrast, non-MetS patients showed a more fragmented network dominated by affective symptoms (low mood, anhedonia) and negative self-cognitions. : Depressive symptoms propagate differently depending on metabolic status. These results highlight the value of personalized medicine approaches, advocating for treatment strategies that address neurovegetative dysfunctions in MDD with MetS and affective-cognitive symptoms in non-MetS. Aligning interventions with individual symptom architectures and metabolic profiles may enhance therapeutic precision and improve clinical outcomes.

Facial clefts are rare congenital malformations, occurring in approximately 1 in 700 live births for cleft lip and palate and fewer than 1 in 100,000 for atypical Tessier clefts. They pose significant diagnostic and surgical challenges. While genetic, vascular, and environmental factors are well documented, growing embryological evidence suggests that the trigeminal nerve may also contribute to craniofacial development. This narrative review explores the association between trigeminal nerve development and facial clefts, aiming to provide a neurodevelopmental perspective with clinical implications, particularly in the context of personalized medicine, where patient-specific neuroanatomical and developmental factors can guide tailored care. A narrative review of embryological, anatomical, and clinical data was conducted. Histological analyses of malformed fetuses and normal human embryos were integrated with published studies. Clinical findings were compared with Paul Tessier's facial cleft classification and mapped against trigeminal innervation territories. Two groups of facial clefts emerged according to the timing of trigeminal disruption. Early embryonic damage (before 10 weeks of gestation) produces superficial epidermal continuity with fibrotic tissue replacing normal deep structures. Later fetal damage results in complete clefts with full tissue discontinuity. The distribution of these clefts corresponds to trigeminal nerve terminal branch territories, supporting the hypothesis that trigeminal innervation exerts trophic effects on craniofacial morphogenesis through neurohormonal signaling. Early impairment of trigeminal development may play a pivotal role in the pathogenesis of certain clefts. The spatial and temporal relationship between nerve development and morphogenesis should be considered in classification and surgical planning. However, limitations of this narrative approach include selective literature coverage and lack of quantitative synthesis. Future directions include single-cell transcriptomics, organoid models, and fetal MRI tractography to clarify trigeminal-mesenchyme interactions and inform therapeutic strategies. These advances may foster a personalized medicine approach, enabling more precise prenatal diagnosis, individualized surgical planning, and optimized long-term outcomes.

This study evaluates the real-world application of anifrolumab in managing articular involvement in systemic lupus erythematosus (SLE), providing insights into its efficacy and safety in routine clinical practice. Additionally, a systematic review examines anifrolumab's role specifically in joint manifestations of SLE, consolidating existing real-world data on its therapeutic impact in articular disease. This monocentric case series presents data from four patients with SLE-related arthritis treated with anifrolumab. Clinical outcomes, including joint symptoms, clinimetric indices (DAS28, SLEDAI-2K, and SLICC), and treatment tolerability, were assessed. Ultrasound evaluation did not represent an outcome since it was not performed regularly. A systematic review was conducted to explore anifrolumab's real-world application in articular disease manifestations, offering a comparative perspective. All patients achieved complete remission of arthritis and lupus disease activity within four months, with no serious adverse reactions and without treatment discontinuation. Additionally, two patients completely discontinued corticosteroid (GC) therapy within two months, while the remaining two significantly reduced their GC doses. Only three promising relevant articles emerged from the systematic review, underlining the need for further studies to better support the role of anifrolumab in the treatment of arthritis in SLE. These findings highlight anifrolumab's practical utility in real-world settings, particularly for articular involvement, while the systematic review contextualizes its impact within SLE management. The results underscore anifrolumab's potential as a valuable treatment option for joint manifestations of SLE, addressing an unmet clinical need in routine practice. This evidence may assist clinicians in selecting the most suitable therapeutic approach based on predominant clinical features, thus enhancing personalized treatment strategies in SLE.

Over the past two decades, the αGal (Galα1-3Galβ1-4GlcNAc-R) epitope, a carbohydrate found in many non-primate mammals, has gained significant relevance in medicine due to its association with an increasing number of allergic reactions to animal-derived foods, drugs, and medical devices. Due to a mutated gene coding for α1,3-galactosyltransferase (α1-3GT), humans lack αGal and, therefore, naturally produce anti-α-Gal antibodies (IgM, IgA, and IgG), especially in the context of a xenotransplantation, which can lead to extreme immunological reactivity, including hyperacute rejection of the transplant. Recently, these uncontrollable immune reactions have driven demand for more accurate procedures to better detect αGal in animal-derived foods or bioprosthetics. The currently most widely used α-Gal-specific monoclonal antibody is an IgM antibody (clone M86), developed in KO mice and isolated from hybridoma tissue culture. As the IgM isotype has limited purification properties, specificity, and sensitivity, we aimed to produce a novel IgG antibody with high affinity and extensive applicability. An experimental murine IgG1 anti-αGal antibody (IgG-αGalomab) was developed by immunization of knockout (KO) mice, and its affinity was evaluated using ELISA, Western blot, flow cytometry, and immunohistochemistry/immunofluorescence. Compared to IgM-M86, IgG-αGalomab demonstrated ~1200-fold higher binding potency and lower cross-reactivity with competitive molecules, i.e., bovine serum albumin, galactobiose, and lactose. Unlike IgM-M86, IgG-αGalomab showed an increasing affinity over time in the binding tests performed on xenogeneic tissues. Notably, high-affinity for αGal was detected by Western blot at high dilution [1:200,000] of IgG-αGalomab compared to IgM-M86 [1:1000]. By flow cytometry, specificity and dose-dependent response were confirmed using in vitro cultures of porcine and human fibroblasts. Finally, in immunofluorescence and immunohistochemistry analysis, αGal was demonstrated to be detectable by IgG-αGalomab at a dilution of [1:1000], while IgM-M86 was demonstrated to be detectable at [1:100]. Altogether, our newly developed antibody showed high sensitivity and specificity for α-Gal in various applications. Based on its potential binding capacity, IgG-αGalomab could have important applications in precision medicine for predicting, treating, and preventing immune-mediated phenomena of patients in different medical areas.

Neurodevelopmental disorders (NDs), including autism spectrum disorder and related conditions, are increasingly recognized among women of reproductive age, yet their unique needs during pregnancy and childbirth remain poorly studied. Communication differences, sensory sensitivities, and co-occurring psychiatric conditions may complicate maternity care, leading to higher risks of adverse outcomes and ethical challenges in clinical practice. This study aimed to examine pregnancy complications, delivery outcomes, and postpartum characteristics in women with NDs, compared with a control group, and to identify specific barriers in perinatal care. A retrospective observational study was conducted at the National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, including 18 pregnant women with confirmed NDs and 21 matched controls with uncomplicated pregnancies. Data were extracted from medical records and included demographic parameters, pregnancy course, complications, labor management, neonatal outcomes, and documented communication or ethical issues. Comparative analyses were performed using chi-square or Fisher's exact tests for categorical variables and Student's -test or Mann-Whitney U test for continuous variables. Pregnant women with NDs had significantly higher rates of pelvic girdle pain (66.7% vs. 23.8%, = 0.01), vaginal bleeding (44.4% vs. 14.3%, = 0.04), anxiety (61.1% vs. 19.0%, = 0.007), and depression (50.0% vs. 14.3%, = 0.02) compared with controls. Persistent daily nausea was also more common (50.0% vs. 14.3%, = 0.03). Attendance of prenatal physician visits was lower in the ND group (66.7% vs. 95.2%, = 0.02). Cesarean delivery occurred in 83.3% of ND women versus 23.8% of controls ( < 0.001), with psychiatric recommendations often cited as the indication. Breastfeeding was declined in 94.4% of ND cases versus 4.8% of controls. Labor duration was prolonged, and neonatal anthropometrics were lower in the ND group. Communication difficulties were documented in 83.3% of ND participants, and postpartum depressive symptoms were identified in 77.8%. Pregnant women with NDs face a multidimensional vulnerability in maternity care, including higher frequencies of pain, bleeding, nausea, anxiety, and depression, prolonged labor, markedly increased cesarean rates, reduced breastfeeding initiation, and smaller neonatal anthropometrics. Frequent communication barriers, guardian decision-making, and postpartum separation further complicate care. These findings underscore the necessity of neurodiversity-informed, individualized perinatal strategies, integrating sensory accommodations, trauma-informed communication, and proactive mental health support to improve both clinical outcomes and patient experiences.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of hospitalization and mortality in older adults. Sudden cardiac arrest (SCA) is a leading cause of death in this population, yet national trends in incidence, outcomes, and disparities remain poorly defined. We performed a retrospective cohort study using the National Inpatient Sample from 2016 to 2020. Hospitalizations for patients aged ≥65 years with HFpEF and in-hospital cardiac arrest (CA) were identified using ICD-10-CM codes. Demographics, comorbidities, hospital outcomes, and temporal trends were examined. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, hospital charges, and discharge disposition. Among 7,738,108 HFpEF admissions, 93,440 (1.2%) involved CA. Incidence rose from 1.1% in 2016 to 1.5% in 2020 (36% relative increase). The median age was 81 years; 54% were female, 70% White, 19% Black, and 8% Hispanic. CA incidence increased across all groups, with the largest relative rises among Native American (1.0% to 1.9%), Black (1.7% to 2.3%), and Hispanic patients (1.4% to 2.0%). In-hospital mortality was high, increasing from 58.2% to 61.7% over the study period ( < 0.001). Mortality rose most steeply among Black and low-income patients. Comorbidity patterns shifted toward greater metabolic complexity, including higher rates of complicated diabetes, hypertension, hyperlipidemia, and obesity. Elderly patients hospitalized with HFpEF are experiencing rising rates of in-hospital CA and persistently high mortality, with marked racial and socioeconomic disparities. These findings highlight the need for better risk stratification, targeted metabolic and inflammatory therapies, and more equitable care delivery.

Despite recent progress in lymphoma immunotherapy, outcomes for patients with peripheral T cell lymphomas (PTCLs) remain poor. The challenge of PTCLs reflects the profound biological heterogeneity and relative rarity of this disease group and its resistance to conventional chemotherapy, as well as the formidable challenge of generating definitive clinical evidence. However, deepening insight into the immunogenomic and microenvironmental basis of PTCL has revealed diverse mechanisms of immune escape, spanning defects in antigen presentation, apoptotic signaling, adhesion, and extensive tumor microenvironmental remodeling. These vulnerabilities provide a sound rationale for novel immunotherapeutic strategies-checkpoint inhibitors, CAR-T and NK cell platforms, bispecific antibodies, oncolytic viruses, and immunomodulatory agents. Early studies show encouraging but inconsistent activity, and the variability in response highlights the urgent need for biomarker-driven stratification to deliver personalized approaches and clinically meaningful efficacy. This review synthesizes the current literature on the immune dysregulation of PTCLs, as well as advances in PTCL immunotherapy, outlining the biological rationale underpinning these approaches. We discuss approaches to molecular, transcriptomic, and microenvironmental profiling with circulating biomarkers that could enable adaptive trial designs and personalized treatment strategies. Together, these developments chart a path away from empiricism and toward precision therapy in PTCLs.

We aimed to study the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) in the treatment of unresectable hepatocellular carcinoma (HCC) with extrahepatic spread (EHS). A total of 323 patients with unresectable HCC received HAIC plus lipiodol microvascular embolization. HAIC was performed via puncture of the left subclavian artery with a temporary 4-French angio-catheter placed in the common/proper hepatic artery. The HAIC regimen consisted of a daily infusion of cisplatin (10 mg/m), mitomycin-C (2 mg/m), and leucovorin (15 mg/m), administered over a period of 20-30 min, and then a 5-fluorouracil (5-FU, 100 mg/m) infusion for the remaining of 22 h of each day, for five consecutive days. Before the temporary catheter was removed, 10 mL of ethiodized oil (Lipiodol, Guerbet, France) was injected to obtain a synergistic effect of chemoinfusion and lipiodol microvascular embolization. Treatment responses were evaluated based on mRECIST criteria. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients with EHS were compared to those without. Subgroup analyses of patients with and without major portal vein tumor thrombosis (PVTT) were performed both before and after propensity score matching (PSM). The survival analyses were conducted with the Kaplan-Meier method and compared using the log-rank test. All the statistical analyses were performed by SPSS (version 26.0). The overall ORR was 59.1%. The median OS of the initial cohort and patients positive and negative for EHS were 16.3, 12.0, and 18.0 months, respectively ( = 0.002). In the subgroup analysis, there was no statistical difference in survival in patients with major PVTT between the with-EHS and without-EHS groups (13.0 vs. 15.0 months, = 0.407). However, the median OS in patients with EHS was significantly shorter than those without EHS (11.4 vs. 19.4 months, < 0.001) in the subgroup of non-major PVTT patients. After PSM, there were no significant survival differences between the EHS and non-EHS groups in any patient cohort or sub-cohort analysis. For unresectable HCC, controlling intrahepatic tumor progression through HAIC is more important than controlling extrahepatic tumor growth, especially in patients with major PVTT. Personalized locoregional HAIC can be performed in patients with EHS.

: Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous neoplasms. and mutations are associated with the activated B-cell-like (ABC) subtype of DLBCL and often co-occur and lead to constitutive activation of the NF-κB pathway. Several different genetic classifications to date have recognized - and -mutated DLBCLs as a unique subtype with poor response to therapy and unfavorable survival. However, little is known about gene expression in DLBCLs with mutated (and ) in comparison to their wild type counterparts. The objective of this study was to compare the gene expression in DLBCLs according to their mutational status. : A total of 48 primary, treatment-naïve DLBCLs (-mutated: 35%/n = 17, -wild type: 65%/n = 31) were investigated using RNA expression profiling (770 genes), followed by immunohistochemical analysis of the up-regulated genes and survival analysis. : The gene expression analysis revealed that downstream of CD79B and the NF-κB targets , , , and were up-regulated in -mutated DLBCLs. The strongest up-regulation was detected for and . Other up-regulated genes included the apoptosis-related and , as well as genes of cell cycle regulation such as , and . Up-regulation was also found for , , , and the subunit. mutation showed an association with poorer overall survival in a secondary analysis, consistent with prior reports, while survival by / mutation status and the differentially expressed genes showed no significant differences in this cohort. : In conclusion, the current study identified novel up-regulated genes in -mutated DLBCLs beyond NF-κB pathway signaling, which may contribute to a better definition of potential therapeutic targets and further improves the characterization of this distinct and aggressive DLBCL subgroup.

: Evaluate outcomes and treatment patterns with 2 mg intravitreal aflibercept injection among patients who completed the phase 3 PANORAMA trial and enrolled in the VOYAGE (ClinicalTrials.gov identifier, NCT04708145; 12 January 2021) long-term extension study. : During VOYAGE, patients were evaluated every 16 weeks and treated with 2 mg intravitreal aflibercept injection as needed depending on ophthalmoscopic examination findings. Those with no history of panretinal photocoagulation (PRP) received aflibercept if their clinician-determined diabetic retinopathy severity scale (DRSS) level was ≥47, corresponding to moderately severe non-proliferative diabetic retinopathy (NPDR). Patients with a history of PRP received aflibercept if active neovascularization was present. New or worsening diabetic retinopathy (DR) severity prompted more frequent treatment. : 320 patients (1 eye per patient) from 87 sites completed the PANORAMA trial. Of these, 41 patients (13% of PANORAMA completers) from 14 sites (16%) enrolled in VOYAGE after a mean interim period of 33.7 months, and 35 patients (85%) completed study visits through 1 year. At year 1 in VOYAGE, the mean number of anti-vascular endothelial growth factor (VEGF) injections increased from 1.1 per year during the interim period to 3.4 per year and was associated with stabilization or improvement in DRSS level in 81% (26/32) of patients. Mean best-corrected visual acuity (BCVA) remained relatively stable, and mean central subfield thickness (CST) improved by 24.4 µm to 269.5 μm through year 1 of VOYAGE. There were no unexpected safety events. : Following a mean of 3 years of routine clinical care with associated declines in DRSS level, CST, and BCVA, stabilization of DRSS level and BCVA with reductions in CST was achieved through year 1 of the VOYAGE extension study, with a concurrent increase in aflibercept dosing frequency.

Mucins, particularly MUC1, are involved in the pathogenesis of chronic respiratory diseases. In chronic rhinosinusitis with nasal polyposis (CRSwNP), altered mucin expression may contribute to chronic inflammation and tissue remodeling. However, the specific role of MUC1 in CRSwNP and its correlation with clinical severity and inflammatory pathway remains unclear. We aimed to evaluate the MUC-1 expression in nasal polyps of patients with CRSwNP and to assess the correlation of MUC-1 expression and disease severity, according to Clinical-Cytological Grading (CCG). Eighteen consecutive patients with CRSwNP who underwent endoscopic sinus surgery (ESS) were enrolled. A double-label immunofluorescence was performed to evaluate the expression of MUC-1, CD15 and Tryptase and their eventual co-localization on histological samples. Double-positive MUC-1+CD15+ and MUC-1+Tryptase+ inflammatory cells were counted by confocal microscopy. MUC1 was expressed in all samples, with a significantly increasing expression in relation to CCG ( < 0.001). A significant co-localization between MUC1 and CD15+ eosinophils was observed, with a progressive increase in the number of double-positive cells from low to high CCG ( < 0.001). On the contrary, the co-localization between MUC1 and Tryptase+ mast cells was not significant, although both markers showed a higher expression in cases with high CCG ( < 0.001). A strong correlation between CRSwNP severity and MUC-1 expression, mainly colocalized with infiltrating eosinophils, was shown. This offers a promising perspective for the use of MUC-1 as a biomarker of CRSwNP.

: Many patients with breast cancer are treated with chemotherapy, including taxanes. These regimens bear a significant risk of potentially burdensome peripheral neuropathy. A scoring system supported by a neuropathy tracker, which can be self-administered by the patients, likely facilitates and speeds up the diagnosis of chemotherapy-induced peripheral neuropathy (CIPN). Before such a scoring system can be used, determination of the optimal cut-off score to discriminate between CIPN and no CIPN is necessary. The prospective NEURO-BREAC trial (NCT07148336) aims to identify the optimal cut-off score in patients treated with chemotherapy and adjuvant irradiation for breast cancer. : The main goal of the NEURO-BREAC trial is to provide the optimal cut-off of a scoring system to discriminate between moderate to severe CIPN and no CIPN in breast cancer survivors previously treated with paclitaxel- or docetaxel-based chemotherapy and irradiation. The scores (0 to 44 points) are obtained by using a neuropathy tracker. This tracker is based on self-evaluation of symptoms and signs of CIPN by study participants. In addition, satisfaction of the patients with the scoring system is assessed. Twenty-four patients (sixteen patients with moderate to severe CIPN and eight patients without CIPN) are required for the Full Analysis Set. Assuming that about 5% of patients will not qualify for this set, 26 patients should be recruited for the NEURO-BREAC trial. The results of this trial are considered an important step for the development of a scoring system contributing to the identification of CIPN in breast cancer patients.

Critically ill patients receiving continuous renal replacement therapy (CRRT) face distinct nutritional challenges requiring specialized parenteral nutrition (PN) strategies. This review synthesizes current evidence with clinical expertise to provide a comprehensive nutritional framework for this population. Key findings reveal that CRRT significantly impacts nutrient homeostasis through daily losses of amino acids (14-22 g), water-soluble vitamins, and trace elements via the extracorporeal circuit. Results from observational studies demonstrate that higher protein targets (1.8-2.5 g/kg/day) are necessary to achieve positive nitrogen balance, while energy prescriptions must subtract "hidden" calories from citrate anticoagulation (3-4 kcal/mmol) and propofol (1.1 kcal/mL). Clinical outcome data, though primarily observational, indicate that achieving nutritional adequacy correlates with reduced ICU stays (average reduction 2.1-3.4 days), shorter mechanical ventilation duration, and improved functional recovery. Evidence supports that early PN prescription when indicated, coupled with systematic consideration of therapy modality, extracorporeal losses, oral intake capacity, and mobilization status, optimizes nutritional support. We conclude that successful implementation requires: (1) dynamic adjustment based on CRRT parameters, (2) integration with enteral nutrition when feasible, (3) regular metabolic monitoring, (4) multidisciplinary collaboration, and (5) structured protocols. Future research using point-of-care analysis and AI-driven support systems is needed to establish evidence-based guidelines in this specialized population.

In recent years, the concept of personalized medicine has moved beyond a theoretical framework to become a tangible clinical imperative [...].

: Pharmacogenetics (PGx), which examines how genetic variations influence drug metabolism and response, offers promise in hospice care where patients commonly experience polypharmacy, complex symptoms, and limited life expectancy. This study assessed the utility of PGx results in guiding medication adjustments to improve symptom management at the end of life. : A retrospective chart review was conducted on ten patients enrolled in a Precision Hospice Program who had PGx results for six key metabolic genes. A PGx-trained pharmacist reviewed Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline-based recommendations, which were discussed during interdisciplinary hospice team meetings. : Patients had a mean age of 85.7 years and were prescribed an average of 17.9 medications. Among the 27 prescriptions reviewed, actionable gene-drug interactions were identified, primarily involving antidepressants and analgesics. Three patients underwent medication changes based on PGx guidance, including switching from citalopram to bupropion and adding morphine to tramadol therapy, which improved symptom control. : While not yet routinely implemented in hospice settings, this pilot study suggests PGx-guided prescribing can support personalized medication decisions and enhance emotional and physical comfort in end-of-life care when test results are available.

: Artificial intelligence (AI) is transforming surgical practice by enhancing training, intraoperative guidance, decision-making, and postoperative assessment. However, its specific role in laparoscopic and robotic general surgery remains to be clearly defined. The objective is to systematically review the current applications of AI in laparoscopic and robotic general surgery and categorize them by function and surgical context. : A systematic search of PubMed and Web of Science was conducted up to 22 June 2025, using predefined search terms. Eligible studies focused on AI applications in laparoscopic or robotic general surgery, excluding urological, gynecological, and obstetric fields. Original articles in English or Spanish were included. Data extraction was performed independently by two reviewers and synthesized descriptively by thematic categories. : A total of 152 original studies were included. Most were conducted in laparoscopic settings ( = 125), while 19 focused on robotic surgery and 8 involved both. The majority were technical evaluations or retrospective observational studies. Seven thematic categories were identified: surgical decision support and outcome prediction; skill assessment and training; workflow recognition and intraoperative guidance; object or structure detection; augmented reality and navigation; image enhancement; technical assistance; and surgeon perception and preparedness. Most studies applied deep learning, for classification, prediction, recognition, and real-time guidance in laparoscopic cholecystectomies, colorectal and gastric surgeries. : AI has been widely adopted in various domains of laparoscopic and robotic general surgery. While most studies remain in early developmental stages, the evidence suggests increasing maturity and integration into clinical workflows. Standardization of evaluation and reporting frameworks will be essential to translate these innovations into widespread practice.