Istituto di Cura e Cura a Carattere Scientifico Basilicata

Objective Children with refractory focal epilepsy differ from adults, although many centers will offer invasive electroencephalography (iEEG) to both. Outcomes in terms of likelihood of resection and subsequent seizure outcome after either subdural grid electrode implantation (SDE) or stereoelectroencephalography (SEEG) have, however, not been directly compared between age groups. Methods We retrospectively included adults and children undergoing iEEG monitoring at four European centers. We compared the two age groups and techniques regarding complication rate, chance of proceeding to resection, and seizure freedom. Results In total, 857 individuals were included (447 SEEG, 410 SDE; 572 adults, 285 children). Adults more often had a history of focal to bilateral tonic–clonic seizures (FBTCS) and prior epilepsy surgery and were more often magnetic resonance imaging‐negative. Children had a higher seizure frequency and rate of preexisting neurologic deficits. In SEEG, likelihood of resection was 64% in adults and 76% in children (p < .05), but chance of seizure freedom did not differ. Adults and children had similar chances of resection and seizure freedom rates after SDE. In children, postoperative seizure freedom was less likely after SDE than SEEG. In adults, history of FBTCS was associated with lower chance of seizure freedom. Overall complication rate was higher in children (22% vs. adults 15%) and in SDE (29% vs. SEEG 7%). Significance Either iEEG technique provides an equally valid but very different road to success, with no difference in seizure outcome between the two age groups, but with higher risk of complications in SDE. We found similar surgical results for dissimilar techniques and a higher threshold for children. In case of an assumed lower chance of focality of epilepsy or chance of seizure freedom after resection, adults were more often explored with iEEG, whereas children were more severely affected when considered for iEEG.

Twin reversed arterial perfusion (TRAP) sequence is a rare and severe complication of monochorionic twins, occurring in approximately 1 in 35 000 pregnancies. It is characterized by the presence of a severely abnormal, nonviable acardiac twin and a structurally normal pump twin, which sustains the circulation of both fetuses through abnormal vascular placental anastomoses. This pictorial essay aims to illustrate the sonographic and Doppler findings associated with TRAP sequence, emphasizing the diagnostic prenatal features. Typical findings include the absence of cardiac activity in the acardiac twin, structural anomalies such as acardia, acrania, underdeveloped upper body, and paradoxical reversed flow patterns in the umbilical artery. Early diagnosis and close ultrasound monitoring are crucial for selecting antenatal treatment, including expectant management and fetal intervention. By presenting illustrative cases, this article provides a comprehensive overview to bolster the understanding of the different associated phenotypes and recognition of TRAP sequence amongst clinicians and sonographers.

Objective The field of rheumatoid arthritis (RA) is moving towards identification of and intervention in people at risk of RA, but a validated risk stratification method is lacking. This work was undertaken to develop a risk stratification method for persons presenting with arthralgia considered to be at risk of RA. Methods A joint EULAR/American College of Rheumatology (ACR) expert committee was established. Risk factor and outcome data from 10 arthralgia cohorts (including clinically suspect arthralgia and autoantibody‐positive arthralgia) were studied. The work focused on differentiating the risk of progression to clinically apparent inflammatory arthritis (IA) within 1 year, using clinical and serologic variables, without and with subclinical joint inflammation detected by ultrasound (US) or magnetic resonance imaging (MRI). Developing RA according to the 2010 EULAR/ACR criteria within 1 year was a secondary outcome. A set of validated risk stratification criteria was developed. Results Using data from 2,293 symptomatic at‐risk individuals, a stratification method was derived consisting of 6 clinical and serologic variables (morning stiffness, patient‐reported joint swelling, difficulty making a fist, C‐reactive protein, rheumatoid factor, and anti‐citrullinated peptide antibody) yielding an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.77–0.83) for IA development. The inclusion of US variables did not increase the discriminative ability. When MRI‐detected subclinical inflammation variables were included, the AUC was 0.87 (95% CI 0.82–0.90). In the presence of clinical, serologic, and MRI variables, a sensitivity and specificity of >75% was achieved. For RA development, the AUC of the criteria with MRI was 0.93 (95% CI 0.90–0.97). Conclusions EULAR/ACR risk stratification criteria have been developed for people with arthralgia in secondary care who are considered at risk for RA. The criteria can be applied in the absence or presence of imaging data and have been developed to define homogeneous risk groups for future prevention trials.

Introduction: Comorbidities affect diagnosis and treatments in cancer patients. This study explores the prevalence and patterns of comorbidities in non-small cell lung cancer (NSCLC) patients and their association with survival. Materials and Methods: This retrospective population-based cohort study included 1674 incident NSCLC patients. Comorbidities were classified based on the ICD-9-CM system, with 13 disease categories analyzed. Patients with more than two comorbidities were classified into three mutually exclusive and exhaustive latent classes (Latent Class Analysis [LCA]). The optimal number of latent classes was determined by applying the Akaike Information Criterion. Cox regression models were run to assess overall and cancer-specific mortality, adjusting for the comorbidity groups, sex, age, and stage at diagnosis. Results: In 1674 NSCLC patients, the most prevalent medical conditions were respiratory (35.8%) and cardiovascular (33.5%). The Cox regression showed that even one comorbidity is associated with an increased hazard of overall mortality (HR = 1.33, 95%CI: 1.11–1.59, p = 0.002). LCA-derived Class-1 (cardiovascular-respiratory and endocrine) reported HR = 1.74 (95%CI: 1.39–2.17, p < 0.001), Class-2 (multi-organ) HR = 1.44 (95%CI: 1.18–1.77, p < 0.001), and Class-3 (socio-multifactorial-neuro) HR = 1.62 (95%CI: 1.36–1.93, p < 0.001). Instead, in patients with one comorbidity, NSCLC-specific mortality showed no significant trend towards increased risk (HR = 1.17, 95%CI: 1.00–1.43, p = 0.114). Significant associations emerged between NSCLC-specific mortality and LCA-classes: Class-1: HR = 1.49 (95%CI: 1.20–1.91, p = 0.001); Class-2 HR = 1.25 (95%CI: 1.0–1.57 p = 0.048); and Class-3: HR = 1.23 (95%CI: 1.00–1.48, p = 0.035). Conclusions: The adverse impact of comorbidities on NSCLC-specific mortality requires their inclusion as risk factors in cancer treatment and prognosis.

Recent findings suggest that preschoolers are capable of adapting cognitive control (CC) through bottom–up associative learning. However, it is not clear how motivational contextual triggers may influence this ability. This study investigated adaptive CC in a “hot” experimental context administering a modified version of the Balloon Analogue Risk Task to 170 children (83 F; 4–7 years). Specifically, a proportion manipulation induced different risky attitudes based on item-specific features (i.e., the balloon color). Overall, children were capable of inferring environmental regularities embedded in the context to optimize their performance. Regarding their ability to exploit and update these regularities for flexible CC adaptation, results suggest that reversal learning is ambiguous at the block level—overshadowed by a general increase in risk-taking—but tentatively present at the sub-block level, with asymmetric effects. Indeed, children seem to successfully adapt CC when going from a low to a high advantageous context but not vice versa. Moreover, different adaptive CC profiles were predictive of daily behavioral difficulties revealed by parental questionnaires.

Background: Though cortical changes in frontotemporal dementia (FTD) are well-documented, the cerebellum’s role, closely linked to these areas, remains unclear. Objectives: To provide evidence on cerebellar involvement in FTD across clinical, genetic, imaging, neuropathological, and neurophysiological perspectives. Additionally, we sought evidence supporting the application of cerebellar non-invasive brain stimulation (NIBS) in FTD for both diagnostic and therapeutic purposes. Methods: We performed a literature review using MEDLINE (via PubMed), Scopus, and Web of Science databases. Results: We emphasized the involvement of specific cerebellar regions which differentiate each FTD subtypes and may account for some of the characteristic symptoms. Furthermore, we highlighted peculiarities in FTD genetic alterations. Finally, we outlined neurophysiological evidence supporting a role for the cerebellum in FTD pathogenesis. Conclusion: The cerebellum is critically involved in the FTD spectrum. Moreover, it can be speculated that cerebellar modulation, as already shown in other neurodegenerative disorders, could restore the interneuronal intracortical circuits typically impaired in FTD patients, providing clinical improvements and fundamental outcome measures in clinical trials.

Background Emerging evidence implicates early dysfunction of dopaminergic neurons in the Ventral Tegmental Area (VTA) as a key contributor to Alzheimer’s Disease (AD) pathophysiology. Specifically, the VTA dopaminergic neurodegeneration and the consequent reduction of dopamine (DA) in mesocorticolimbic targets are associated with the onset of cognitive impairments and neuropsychiatric-like manifestations in AD animal models. Moreover, decreased midbrain volume and functional VTA disconnection are identified as predictors of accelerated progression from Mild Cognitive Impairment to AD-dementia in clinical populations. Given these findings, interventions capable of directly modulating VTA activity and augmenting DA release, despite the ongoing neurodegeneration, may hold therapeutic potential for mitigating DA-related deficits in AD. This study aims at evaluating the therapeutic potential of prefrontal transcranial Direct Current Stimulation (tDCS) in the Tg2576 mouse model of AD, exhibiting early VTA dopaminergic neurodegeneration. Methods Repeated tDCS was applied to assess its ability to activate VTA DA neurons. We also evaluated tDCS effects on synaptic plasticity, cognitive and non-cognitive behaviours and AD-related pathology. Hippocampal DA release and Nucleus Accumbens (NAc) DA transporter (DAT) expression were measured. With immunohistochemistry we examined microglial density and morphological complexity at different disease stages. Additionally, intracellular amyloid-β (Aβ) levels and plaque burden were evaluated to determine the impact of tDCS on AD pathology. Results Prefrontal tDCS enhanced the activity of VTA dopaminergic neurons, leading to increased hippocampal DA release and higher DAT levels in the NAc. The enhanced DA outflow is associated with restored CA3-CA1 synaptic plasticity and improvements in recognition memory and motivational behaviours. tDCS reduced microglial numbers and morphological complexity in Tg2576 mice at both pre-plaque stage (7-months) and at an advanced stage characterized by plaque accumulation (12-months). Notably, tDCS also decreased Aβ plaque burden, although no changes in intracellular Aβ levels were observed in younger Tg2576 mice. Conclusions These findings highlight the multifaceted therapeutic potential of prefrontal tDCS in targeting key AD pathophysiological hallmarks, including dopaminergic dysfunction, synaptic impairments, neuroinflammation and plaque deposition. As a non-invasive neuromodulatory approach, prefrontal tDCS emerges as a promising early intervention strategy to complement existing AD treatments, with the potential to improve patient outcomes and quality of life.

Background Early detection of vital sign changes is key to recognizing patient deterioration promptly, enabling timely interventions and potentially preventing adverse outcomes. Objective In this study, vital parameters (heart rate, respiratory rate, oxygen saturation, and blood pressure) will be measured using the Comestai app to confirm the accuracy of photoplethysmography methods compared to standard clinical practice devices, analyzing a large and diverse population. In addition, the app will facilitate big data collection to enhance the algorithm’s performance in measuring hemoglobin, glycated hemoglobin, and total cholesterol. Methods A total of 3000 participants will be consecutively enrolled to achieve the objectives of this study. In all patients, personal data, medical condition, and treatment overview will be recorded. The “by face” method for remote photoplethysmography vital sign data collection involves recording participants’ faces using the front camera of a mobile device (iOS or Android) for approximately 1.5 minutes. Simultaneously, vital signs will be continuously collected for about 1.5 minutes using the reference devices alongside data collected via the Comestai app; biochemical results will also be recorded. The accuracy of the app measurements compared to the reference devices and standard tests will be assessed for all parameters. CIs will be calculated using the bootstrap method. The proposed approach’s effectiveness will be evaluated using various quality criteria, including the mean error, SD, mean absolute error, root mean square error, and mean absolute percentage error. The correlation between measurements obtained using the app and reference devices and standard tests will be evaluated using the Pearson correlation coefficient. Agreement between pairs of measurements (app vs reference devices and standard tests) will be represented using Bland-Altman plots. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and likelihood ratios will be calculated to determine the ability of the new app to accurately measure vital signs. Results Data collection began in June 2024. As of March 25, 2025, we have recruited 1200 participants. The outcomes of the study are expected at the end of 2025. The analysis plan involves verifying and validating the parameters collected from mobile devices via the app, reference devices, and prescheduled blood tests, along with patient demographic data. Conclusions Our study will enhance and support the accuracy of data on vital sign detection through PPG, also introducing measurements of biochemical risk indicators. The evaluation of a large population will allow for continuous improvement in the performance and accuracy of artificial intelligence algorithms, reducing errors. Expanding research on mobile health solutions like Comestai can support preventive care by validating their effectiveness as screening tools and guiding future health care technology developments. Trial Registration ClinicalTrials.gov NCT06427564; https://clinicaltrials.gov/study/NCT06427564

Classic Hodgkin lymphoma (cHL) in patients with immune deficiency/dysregulation represents a critical unmet need in hematology, demanding the appropriate revision of classification and therapeutic paradigms. Epstein–Barr virus (EBV) is a pivotal driver of lymphomagenesis in this high-risk subset, where viral oncoproteins (e.g., LMP1/2A) exploit immune vulnerabilities to activate NF-κB, rewire tumor microenvironments (TME), and evade immune surveillance. EBV-positive cHL, prevalent in immunosuppressed populations, exhibits distinct molecular hallmarks, including reduced somatic mutations, unique HLA associations, and profound PD-L1-mediated immune suppression, that diverge from EBV-negative cases reliant on genetic aberrations. Despite advances in combined antiretroviral therapy, HIV co-infection exacerbates pathogenesis, M2 macrophage dominance, and T-cell exhaustion, while links to other viruses remain ambiguous. Current therapies fail to adequately target these viral and immune complexities, leaving patients with poorer outcomes. This review synthesizes insights into EBV’s etiological role, immune contexture disparities, and the genetic–environmental interplay shaping cHL heterogeneity. The WHO classification highlights the need to reclassify EBV-associated cHL as a distinct subset, integrating viral status and immune biomarkers into diagnostic frameworks. Urgent priorities include global epidemiological studies to clarify causal mechanisms, development of virus-targeted therapies (e.g., EBV-specific T-cell strategies, PD-1/CTLA-4 blockade), and personalized regimens for immune-dysregulated cohorts.

Background Invasive lobular carcinoma (ILC), the second most common histologic subtype of breast cancer, has a higher risk of positive surgical margins than invasive ductal carcinoma (IDC). Whether this risk persists for patients undergoing breast-conserving surgery (BCS) with oncoplastic approaches remains unclear. We conducted a systematic review and meta-analysis to assess positive margins following oncoplastic BCS by histologic subtype and evaluate the impact of oncoplastic surgery on positive margins in ILC. Methods We systematically searched the literature for articles reporting positive margin rates after oncoplastic BCS in ILC patients. Relative risks (RR) were log transformed and displayed with forest plots. Results Eight studies, encompassing 754 ILC patients undergoing BCS (338 with oncoplastic surgery), were included. The pooled positive margin rate for ILC patients undergoing oncoplastic surgery was 31% (95% confidence interval [CI] 21–40%). Patients with ILC had a significantly higher RR for positive margins after oncoplastic BCS compared with IDC (RR 3.4, 95% CI 1.5–7.4). However, for ILC patients with larger tumors, oncoplastic BCS was associated with a significantly lower RR for positive margins compared with standard BCS (RR 0.5, 95% CI 0.3–0.9). Conclusions Invasive lobular carcinoma patients undergoing oncoplastic BCS have higher positive margin risks than IDC patients, underscoring the need for improved preoperative imaging and systemic therapies. However, the addition of oncoplastic surgery to BCS reduces positive margin rates compared with standard BCS in ILC patients, particularly for larger tumors. These findings highlight the role of oncoplastic surgery as an important technique to optimize outcomes for those at high risk of positive margins.

Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia associated with stroke, heart failure, and increased mortality. Due to its efficacy and safety, cryoballoon ablation (CBA) is widely accepted for rhythm control; however, long-term AF recurrence remains a challenge. Continuous monitoring with implantable loop recorders (ILRs) enhanced by artificial intelligence (AI) can detect both symptomatic and asymptomatic episodes, potentially optimizing patient management. This analysis assessed the long-term effectiveness of CBA in maintaining sinus rhythm and investigated the role of ILR-guided monitoring in enhancing therapeutic decisions. Methods: Data from 91 patients with paroxysmal or persistent atrial fibrillation (AF) who underwent pulmonary vein isolation using cryoballoon ablation at four Italian centers between April 2022 and April 2024 were analyzed. All patients received an insertable loop recorder (ILR) before or during hospitalization for ablation, allowing for the continuous remote monitoring of arrhythmias. Baseline demographics, procedural details, AF occurrence, AF burden (calculated as the total duration of all AF episodes occurring within a day and categorized by episode duration), therapeutic adjustments, and the effect of artificial intelligence (AI) on data processing were evaluated. Results: The cohort’s average age was 62.4 years, with 24.2% of participants being female. Physician-confirmed AF recurrence was noted in 26.7% of patients at 12 months and 49.5% at 24 months. The device data indicated a daily AF burden of ≥6 min in 47.2% at 12 months, with 25.9% surpassing 1 h. AI algorithms decreased false-positive alerts by 21%, resulting in an estimated saving of 19 clinician hours. In patients with pre-ablation ILR data, the median AF burden significantly decreased from 7% to 0.2% (p = 0.017). ILR-guided monitoring affected treatment adjustments, leading to the discontinuation of antiarrhythmic therapy in 36 patients and redo ablations in 8. Conclusions: Continuous ILR monitoring, combined with AI-driven analysis, enables the detection of AF recurrences and burden, thereby facilitating timely therapeutic adjustments.

Chronic inflammatory skin disorders are characterized by keratinocyte hyperproliferation and hyperactivation as well as immune cell infiltration. We investigated whether immune cell–derived acetylcholine (ACh) is a modulator of skin inflammation in mice. Here, we identify skin epithelial B cells as a key source of ACh that damps down inflammation. We used imiquimod (IMQ) to induce inflammatory skin disease (ISD) in mice lacking ACh production specifically in B cells (ChAT fl/fl;Mb1-Cre mice). Increased keratinocyte proliferation, epidermal thickening, and elevated levels of proinflammatory cytokines resulted. ACh binding to α9 nicotinic ACh receptor (encoded by Chrna9 ) expressed on wild-type mouse keratinocytes reduced their proliferation. Chrna9 -deficient mice exhibited the same exacerbated ISD phenotype as ChAT fl/fl;Mb1-Cre mice following IMQ induction. Our data suggest that B cell–derived ACh maintains skin homeostasis by modulating keratinocyte turnover and controlling immune-related inflammation. Therapeutic manipulation of this cholinergic pathway might mitigate both keratinocyte dysfunction and immune dysregulation in human patients, potentially pointing to treatments for ISDs such as psoriasis and related disorders.

Background In the letermovir-primary-prophylaxis (LET-PP) era the epidemiology of human-cytomegalovirus-infections (HCMV-i) in allogeneic hematopoietic-stem-cell-transplant (allo-HSCT) has changed Methods We prospectively evaluated incidence and risk factors for clinically significant (CS) HCMV-i at 180 days from transplant and 1-year overall-survival in 1,310 allo-HSCTs performed from January 2021 to March 2022 according to LET-PP use. Results The cumulative incidence of CS-HCMV-i at 100 and 180 days from transplant were 3.8% and 16% in patients who received LET-PP, and 14% and 17% in patients who did not. Variables associated with increased risk of CS-HCMV-i in patients who received LET-PP included transplant from a HCMV seronegative donor, transplant from a donor other than matched related, >20 days to engraftment and acute-GVHD. Transplant in HCMV seropositive recipient was associated with increased risk of CS-HCMV-i in patients who did not receive LET-PP. One-year overall survival after transplant was 81.1%. Acute leukemia, disease not in remission at transplant, ECOG-performance-status >1, > 20 days to engraftment, acute GVHD, CS EBV DNAemia, Gram-negative bacteremia, and invasive fungal disease were associated with increased mortality in patients who received LET-PP. HCMV recipients seropositivity, HCT comorbidity-index score >=3 and Gram-negative bacteremia were associated with increased mortality in patients who did not receive LET-PP. Conclusions In patients who received LET-PP recipient/donor serology no longer correlates with early CS-HCMV-i while it still predicts late CD-HCVM-I as well as risk of CS-HCMV-i in patients who did not receive LET-PP. Donor serology, CS-HCMV-i and diseases no longer impact survival in allo-HSCT recipients who receive LET-PP. Clinical trial registration NCT04412811

This study aimed to evaluate the role of adjuvant HPV vaccination in women undergoing conization for cervical intraepithelial neoplasia. This prospective study assessed factors influencing recurrence in patients undergoing conization for high-grade cervical dysplasia. After conization, patients were counseled on the potential benefits of vaccination. We compared outcomes between two groups: women who underwent conization with adjuvant human papillomavirus (HPV) vaccination and observation versus conization with observation only. Data from 281 patients were analyzed, comprising 168 (59.8%) patients in the conization-only group and 113 (40.2%) patients in the conization-plus vaccination group. Vaccinated patients were younger than nonvaccinated patients (38 vs. 45 years, P < 0.001). Positive surgical margins were more frequently observed in the vaccinated group compared with the nonvaccinated group (9.7 vs. 3.6%; P = 0.038). Median follow-up was shorter in the vaccinated group, although this difference was not statistically significant (24.9 vs. 27.8 months; P = 0.395). The risk of developing HPV-related lesions was similar between the vaccinated and nonvaccinated groups ( P = 0.594, log-rank test). Likewise, the need for reconization did not differ significantly between the groups ( P = 0.593, log-rank test). Multivariate analysis showed no significant impact of HPV vaccination on postoperative outcomes [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.15–1.68) for any lesion; HR: 0.90, 95% CI: 0.47–1.73 for reconization]. This study indicates that adjuvant HPV vaccination does not significantly affect short-term outcomes in women undergoing conization for cervical dysplasia. Ongoing randomized trials will provide more robust evidence to clarify the role of adjuvant vaccination in this setting.

Cortical stimulation with single pulses is a common technique in clinical practice and research. However, we still do not understand the extent to which it engages subcortical circuits that may contribute to the associated evoked potentials (EPs). Here we show that cortical stimulation generates remarkably similar EPs in humans and mice, with a late component similarly modulated by the state of the targeted cortico-thalamic network. We then optogenetically dissect the underlying circuit in mice, demonstrating that the EPs late component is caused by a thalamic hyperpolarization and rebound. The magnitude of this late component correlates with bursting frequency and synchronicity of thalamic neurons, modulated by the subject's behavioral state. A simulation of the thalamo-cortical circuit highlights that both intrinsic thalamic currents as well as cortical and thalamic GABAergic neurons contribute to this response profile. We conclude that single pulse cortical stimulation engages cortico-thalamo-cortical circuits largely preserved across different species and stimulation modalities.

Background Cardiopulmonary exercise testing (CPET) is essential for assessing patients with hypertrophic cardiomyopathy (HCM), but the role of pulmonary function testing (PFT) in refining patient stratification remains underexplored. This study investigates the relationship between PFT and CPET parameters in patients with HCM. Methods In this prospective two-centre study, 102 clinically stable patients with HCM underwent PFT and CPET. Spearman’s correlation and multiple linear regression were used to assess relationships between PFT (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV ₁ )) and CPET variables, adjusting for confounders. Results Patients exhibited preserved lung function (mean FVC: 90.7%; FEV 1 : 92.5%). Strong correlations were observed between PFT and CPET metrics, including peak VO ₂ (FVC: r=0.649, p<0.001; FEV ₁ : r=0.691, p<0.001) and peak ventilation (FVC: r=0.682, p<0.001; FEV ₁ : r=0.688, p<0.001). Regression analysis confirmed independent associations between PFT and CPET performance (all p<0.001). Conclusion PFT metrics strongly correlate with CPET parameters in HCM, suggesting that PFT could complement CPET for a more comprehensive assessment of exercise capacity and patient stratification.

TNF receptor-associated factor 2 (TRAF2) plays a crucial role in both physiological and pathological processes. It takes part in the regulation of cell survival and death, tissue regeneration, development, endoplasmic reticulum stress response, autophagy, homeostasis of the epithelial barrier and regulation of adaptive and innate immunity. Initially identified for its interaction with TNF receptor 2 (TNFR2), TRAF2 contains a TRAF domain that enables homo- and hetero-oligomerization, allowing it to interact with multiple receptors and signaling molecules. While best known for mediating TNFR1 and TNFR2 signaling, TRAF2 also modulates other receptor pathways, including MAPK, NF-κB, and Wnt/β-catenin cascades. By regulating NF-κB-inducing kinase (NIK), TRAF2 is a key activator of the alternative NF-κB pathway, linking it to inflammatory diseases, immune dysfunction, and tumorigenesis. In the innate immune system, TRAF2 influences macrophage differentiation, activation, and survival and stimulates natural killer cell cytotoxicity. In the adaptive immune system, it represses effector B- and T-cell activity while sustaining regulatory T-cell function, thus promoting immune suppression. The lack of fine-tuning of TRAF2 activity leads to excessive NF-kB activation, driving chronic inflammation and autoimmunity. Although TRAF2 can act as a tumor suppressor, it is predominantly described as a tumor promoter, as its expression has been correlated with increased metastatic potential and poorer prognosis in several types of cancer. Targeting TRAF2 or TRAF2-dependent signaling pathways might represent a promising anti-cancer therapeutic strategy.

Arterial hypertension is one of the most common and preventable risk factors for cardiovascular disease and its related mortality. Currently, the prevalence of hypertension in different European countries appears to be around 30–45% of the general population, with a steep increase with ageing. Recent European guidelines have introduced novel recommendations for the management and treatment of hypertensive patients, with direct implications in daily clinical practice. Therefore, in this focused review, we will provide answers to the most common questions regarding the diagnosis, management and treatment of arterial hypertension according to the latest available European guidelines.