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Sepsis remains one of the most complex and lethal syndromes in pediatric critical care, driven by dysregulated and heterogeneous host responses to infection. Despite decades of biomarker research, few biomarkers have been translated into routine clinical use for diagnosis or prognostication. This is largely because single marker approaches cannot capture the systemic complexity of sepsis pathobiology with high sensitivity and specificity. This review explores how the convergence of multi-omic technologies and computational biology is transforming biomarker discovery, from isolated molecular signals into integrated, systems-level understanding of disease, with an emphasis on pediatric sepsis. Recent omic studies reveal dysregulation across immune, endothelial, metabolic, and microbial networks in sepsis. Advances in bioinformatics and artificial intelligence now enable characterization of complex biological patterns that link molecular profiles into interpretable clinical phenotypes and outcomes. Multi-omic integration represents a paradigm shift in pediatric sepsis research, uniting biomarker discovery with clinical application through biologically coherent, computationally derived signatures. As these approaches mature, they promise to transform pediatric sepsis care from empiric treatment to precision medicine guided by the molecular pathways that define each patient’s pathobiology.
Cluster headache (CH) is a primary headache disorder characterized by circadian rhythmicity and autonomic symptoms. While the posterior hypothalamus has been historically implicated, converging evidence now supports a distributed, network-level dysfunction involving cortical and subcortical regions. This study aimed to: (1) assess whole-brain cortical thickness alterations in episodic CH (eCH) during the bout period, (2) examine their associations with clinical burden, and (3) investigate resting-state functional connectivity patterns of cortical regions showing structural alterations. We investigated whole-brain cortical thickness and subcortical volumes in 26 patients with episodic CH scanned during the bout period but outside of attacks and 20 matched healthy controls (HC) using surface-based morphometry (FreeSurfer). Associations between cortical thickness and clinical variables (attack frequency, duration, disease history, and pain intensity) were assessed using general linear models corrected for multiple comparisons. Resting-state functional connectivity (FC) was further analyzed using seed-to-voxel correlations in the CONN toolbox, with seeds placed in cortical regions showing significant thinning. Compared with HC, eCH patients showed cortical thinning in the right inferior frontal gyrus (pars triangularis, BA45) and left superior frontal gyrus (BA9/10) (p < 0.05, Bonferroni correction). No significant subcortical volumetric differences were observed. Cortical thickness showed significant positive associations with clinical burden in associative parietal and occipital regions (p < 0.01, Bonferroni correction). Seed-based FC analyses revealed decreased coupling between the left superior frontal gyrus and right supramarginal cortex, but increased connectivity with the left precentral gyrus. Conversely, the right inferior frontal gyrus showed widespread hyperconnectivity with bilateral insulae, supramarginal, and sensorimotor cortices, and decreased connectivity with the right superior frontal region. These findings identify coexisting structural and functional alterations within frontal cortices and their distributed targets, suggesting a differential reorganization of frontal attentional and sensorimotor networks in eCH. The pattern of fronto-parietal disconnection and fronto-insular hyperconnectivity extends the network model of cluster headache beyond the well-established hypothalamic–thalamic dysregulation. Together, these results strengthen the concept of cluster headache as a network-level disorder involving both executive and sensorimotor control systems.
Since the initial description of HDV, in the last four decades Italy has witnessed a profound decline of the infection driven by HBV vaccination, contrasted however by the reconstitution of a viral reservoir through migratory flows from endemic HDV areas; in parallel, the medical scenario has changed, resulting in different clinical outcomes. The epidemiological and clinical changes were documented by national surveys performed up to 2025, which provided an ongoing perspective on the long-term evolution of HDV, highlighting the temporal trends in prevalence, risk factors, and clinical features. This review summarises the changes over time of HDV in Italy and the contemporary epidemiologic features of an infection that is vanishing among natives but increasing among migrants, outlining the medical challenge of a new heterogeneous clinical spectrum, including indolent phenotypes.
Abstract Background and aims Mechanical thrombectomy (MT) is effective for acute Basilar artery occlusion(BAO), but the optimal technique for quick recanalization and improved outcomes remains unclear. We compared Stent retriever (SR), Contact aspiration (CA) and combined SR plus CA technique as first-line approach during mechanical thrombectomy for BAO. Methods We emulated a hypothetical trial comparing CA, SR and combined technique as first-line in patients with BAO, using data from the Italian Registry of Endovascular Treatment. The primary outcome was first-pass effect (FPE), defined as mTICI 2b-3 with 1 pass of MT. We used inverse probability weighting (IPW) adjusted for prespecified covariates to weight each individual’s contribution to the outcome. Results We included 960 patients with BAO treated with MT: 570 with CA, 268 with SR, and 122 with combined technique as first approach. After applying IPW, SR was associated with lower odds of FPE as compared to CA (aOR 0.48[95%CI 0.33-0.70]), no differences were found comparing SR versus combined technique neither CA versus combined technique. First-pass mTICI 3 was less frequent with SR as compared to CA (0.62[95%CI 0.43-0.90]). 90-day mRS 0-3 after FPE was more frequent with CA as compared to both SR (aOR 0.57[95%CI 0.38-0.85]) and combined technique (aOR 0.50[95%CI 0.28-0.89]). The results were consistent across all the subgroups (p for interaction>0.05). Conclusions In patients with BAO, CA was more effective than SR and was associated with better oucome compared to other techniques. Therefore, less traumatic approaches might be preferred as first-line in BAO. Conflict of interest E.N. is member of the medical and scientific advisory board of Cercare Medical and declares speaker's honoraria from Boehringer Ingelheim; A.C. has nothing to disclose; V.S. has nothing to disclose; G.P. has nothing to disclose; P.N. has nothing to disclose; M.D. has nothing to disclose; M.R. has nothing to disclose; D.T. declares consulting or advisory board fees or speaker’s honoraria from Alexion, ASTRA Zeneca, Boehringer, Medtronic and Pfizer. Figure 1 - belongs to Methods Figure 2 - belongs to Results
Although the clinical differences between hemodialysis (HD) and peritoneal dialysis (PD) are well established, the specific biological mechanisms underlying these differences remain incompletely understood. We performed untargeted proteomic and transcriptomic analyses of peripheral blood mononuclear cells (PBMCs) from healthy controls (CTRs) and patients with chronic kidney disease undergoing HD or PD. Key findings were validated in an independent cohort using standardized biomolecular techniques. Bioinformatic analysis identified 36 differentially expressed proteins and 19 transcripts between HD and PD according to the predefined FDR-adjusted significance threshold. Functional enrichment analysis revealed that these factors were primarily involved in cellular senescence, aging, and stress-response pathways. Among the identified molecules, interferon regulatory factor 8 (IRF8) was the only factor consistently upregulated in HD compared with PD in both omics analyses. This finding was confirmed by ELISA in an independent cohort (p < 0.0001). Kinase enrichment analysis prioritized Checkpoint Kinase 2 (CHEK2), which was also identified by proteomics, as a predicted upstream regulator and warrants further investigation. Overall, these findings identify distinct molecular signatures in PBMCs from HD and PD patients and suggest a potential association between HD and increased PBMC IRF8 abundance and a senescence-related signature, which requires validation in larger and longitudinal cohorts.
