Ospedale D. Cotugno

To compare two sodium hyaluronate formulations (HYMOVIS® ONE and MONOVISC®) for single intra-articular (IA) injection in patients with knee osteoarthritis pain. This randomized, controlled study included 347 subjects allocated to two treatment arms: HYMOVIS® ONE (n = 175) and MONOVISC® (n = 172). The primary endpoint assessed non-inferiority of HYMOVIS® ONE versus MONOVISC® based on change from baseline in the WOMAC LK3.1 A1 Pain subscale. Secondary outcomes evaluated patient response using OMERACT-OARSI criteria, changes in WOMAC stiffness and function scores, health-related quality of life (SF-12), global assessments by patients and clinicians, and rescue medication use. The mean WOMAC LK3.1 A1 walking pain subscale score decreased significantly from baseline at week 12 in both groups, with reductions of 65 % for HYMOVIS® ONE and 66 % for MONOVISC®. At week 26, reductions were 73 % for HYMOVIS® ONE and 69 % for MONOVISC®. The non-inferiority test yielded a p-value of 0.0003. Clinically significant change from baseline was observed for all secondary endpoints. For the WOMAC LK3.1 Function subscale, the comparison between groups at week 26 showed a statistically significant difference (p = 0.0367) favoring HYMOVIS® ONE. Both treatments were well tolerated. A single injection of HYMOVIS® ONE was well tolerated and non-inferior to MONOVISC®, with improvements across all study endpoints maintained through 26 weeks, indicating sustained symptomatic relief of knee OA. NCT06528600 (www.clinicaltrials.gov).

Post-tuberculosis lung disease (PTLD) is an increasingly recognized condition that significantly affects survivors' quality of life, creating disability and incrementing the risk of mortality. PTLD includes a spectrum of structural and functional lung impairments such as obstructive, restrictive, and mixed patterns, bronchiectasis, and pulmonary fibrosis that persist beyond microbiological cure. Global prevalence data highlight a heavy burden of PTLD, especially in high-incidence regions, driven by late diagnosis and suboptimal treatment. Functional and radiological evaluation remains critical for timely diagnosis, with spirometry and imaging revealing lasting abnormalities in a large proportion of TB survivors. Multidisciplinary care is essential and includes bronchodilator therapy, infections/complications management and prevention, pulmonary rehabilitation, and, in selected cases, surgical intervention. Despite increasing recognition, standardized diagnostic and therapeutic pathways for PTLD are still lacking, and data on optimal follow-up, rehabilitation strategies, and preventive measures remain limited. Prospective studies, better stratification tools, and patient education initiatives are urgently needed to reduce PTLD morbidity and mortality. This narrative review synthesizes current evidence on PTLD epidemiology, clinical evaluation and management while offering practical suggestions for clinicians taking care of people with TB and addressing research needs.

No previous study described adolescents and young adults (AYAs) with HIV in Italy. Aims were to investigate the temporal trend of AYAs enrolment in the ICONA cohort over 2014-2023, and to compare their baseline characteristics and antiretroviral therapy (ART) outcomes with adults. All subjects enrolled in ICONA, the Italian cohort enrolling HIV-1 positive individuals from ART-naïve, over 2014-2023 were grouped into: AYAs (18-24 years old) and adults (≥25). Study outcomes were: time to first ART start, time to treatment discontinuation (TD) of first-line regimen, cause-specific TD, virologic failure, and loss-to-follow-up (LTFU). Overall, 9519 participants: 653 AYAs (6.9%) and 8,866 adults (93.1%). Excluding the decline recorded in 2020, the percentage of AYAs enrolled showed a similar trend before- and after-COVID. Compared with adults, AYAs had a milder clinical presentation, a better viro-immunological status, a higher mean change of cluster of differentiation 4 count over 24 months and, after adjusting, a higher risk of TD for patient's choice/adherence-related issues and LTFU. The less advanced clinical presentation and more robust immune recovery of AYAs, might depend upon more recent HIV infection, better thymic function, and lower immune activation. The higher risk of TD due to patient's choice/adherence-related issues and LTFU among AYAs is a major concern and suggests the need to create ad hoc clinical care pathways.

The genetic variability of a large collection of European samples of the zoonotic pathogen Cryptosporidium parvum has been recently explored on the basis of a novel multi-locus sequence typing (MLST) scheme. In this work, we assessed the usefulness of this scheme to type C. parvum samples from Italy, a country where this pathogen is widespread and associated with human infections. Polymerase chain reaction (PCR) and sequencing for the eight markers of the MLST scheme were performed on 31 human- and 21 animal-derived C. parvum samples. MLST data from 27 samples of animal origin previously sequenced at the genome level were also included. Sequence data for the glycoprotein 60 (gp60) gene were also generated. Phylogenetic and cluster analyses were conducted. Full genotyping data were obtained for 72 of 79 samples, and 39 different profiles were categorized, 28 of which were found in individual samples (singletons). A new allele was found at the marker on chromosome 2 in a human-derived sample. When compared with the 154 profiles previously described in Europe, 30 of the 39 profiles (76%) were found to be restricted to Italy, a result compatible with a model of isolation by distance, with geographically structured populations. Analysis of the gp60 sequences identified 19 different subtypes among the 55 samples belonging to family IIa, and 7 different subtypes among the 16 samples belonging to family IId. Phylogenetic and haplotype analyses did not identify clusters related to the host, the geographic origin (i.e., the Italian regions), or the time of collection of the samples but did identify two different populations, mirroring data obtained from whole genome comparative analyses. The MLST scheme appears to be a promising method for genotyping C. parvum samples, as it provided higher discrimination compared with gp60 and enabled the recognition of the two major populations circulating in Europe and in Italy.

Background: Accurate assessment of prolonged disorders of consciousness (pDOC) is a critical clinical challenge. Misdiagnosis in pDOC can occur in up to 40% of cases, highlighting the need for more objective and reproducible biomarkers to support neurophysiological scales, thereby improving diagnosis and guiding therapeutic and prognostic decisions. Electroencephalography (EEG) microstate analysis is a promising, non-invasive method for tracking large-scale brain dynamics, but research in pDOC has predominantly relied on a canonical 4-class model. This methodological constraint may limit the ability to capture the full complexity of neural alterations present in these patients. Objective: This pilot study aimed to offer an objective method for assessing consciousness, complementing and enhancing the existing approaches established in the literature. The classical 4-class and an extended 7-class microstate model were compared to determine which more accurately characterizes the complexity of resting-state brain dynamics across different levels of consciousness in pDOC patients and healthy controls (HCs). Methods: Retrospective resting-state EEG (rsEEG) data from a cohort of pDOC patients and HC subjects were analyzed. Microstate analysis was performed using both 4-class and 7-class templates. The models were evaluated and compared based on three criteria: spatial correspondence with canonical maps (shared variance), the number of significant intra-group correlations between temporal features (Spearman test), and their ability to discriminate between the pDOC and HC groups (Wilcoxon test). Results: The 7-class microstate model provided a more accurate description of brain activity for most participants, with a greater number of microstate classes exceeding the 50% shared variance threshold compared to the 4-class model. In the pDOC group, both the 4-class and 7-class models showed a mean shared variance <50% in class D, which is associated with executive functioning across both templates. For the HC group, a prevalence of classes B and D emerged in both models, indicating higher engagement of executive functions. Furthermore, the 7-class model allowed for a group-specific analysis, which demonstrated that microstates A and F were consistently shared among 86% of pDOC patients. This suggests the potential preservation of specific intrinsic brain networks, particularly the sensory and default networks, even in the presence of severely impaired consciousness. Moreover, the 7-class model yielded a higher number of significant correlations within both groups and identified a broader set of temporal features that were significantly different between pDOC patients and HCs. These results highlight the enhanced sensitivity of the 7-class model in distinguishing subtle brain dynamics and improving the diagnostic capability for pDOC. Conclusions: The 7-class microstate model provides a more fine-grained and sensitive characterization of brain activity in both pDOC patients and healthy individuals. It demonstrated better performance in capturing individual brain dynamics, identifying shared network patterns, and discriminating between clinical populations. These findings suggest that the extended 7-class model holds greater potential for clinical utility and could lead to the development of more robust biomarkers for assessing consciousness.

Objectives: To investigate the profile of Th1- and Th2-type cytokines in response to Epstein–Barr virus (EBV) antigens and to correlate this immune signature with clinical relapses in Multiple Sclerosis (MS). Specifically, we aimed to evaluate the cellular and humoral immune response following stimulation with a pool of lytic and latent EBV proteins. Methods: We employed ELISpot and ELISA to quantify Interferon-gamma (IFN-γ), Interleukin-18 (IL-18), Interleukin-10 (IL-10), and the B-cell activation marker soluble CD23 (sCD23). Measurements were performed on peripheral blood mononuclear cells (PBMCs) from MS patients and controls following stimulation with EBV peptide antigens. Results: MS patients exhibited significantly higher levels of all tested cytokines compared to controls. A statistically significant positive correlation was noted between IL-10 and sCD23 levels (p < 0.03), with significant correlations also found between IL-10 and IFN-γ (r = −0.56) and between IFN-γ and IL-18 (p < 0.02), a finding that warrants cautious interpretation. Crucially, both IL-10 and sCD23 levels strongly correlated with the Expanded Disability Status Scale (EDSS) score (p = 0.0003 and p = 0.0001, respectively). Conclusions: Our findings suggest a chronic, dysregulated immune response to EBV antigens in MS patients, characterized by the co-activation of inflammatory Th1 pathways and robust B-cell activation. These results support a pathogenetic model where the EBV-specific immune response, perpetuated by infected B-cells, may directly contribute to the immunopathological processes driving central nervous system (CNS) damage and clinical relapses.

Severely burned patients are at high risk of local and systemic infections due to skin barrier loss. Their clinical management is complex and requires coordinated intensive care and infection prevention strategies. Diagnosing infective endocarditis (IE) in this population is particularly difficult due to overlapping symptoms and limited diagnostic specificity. Common pathogens include Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii. We conducted a retrospective cohort study on 543 patients with burns affecting >18% of total body surface area (TBSA), admitted to our Burn Intensive Care Unit (BICU) from 2019 to 2024. The incidence of infective endocarditis was 1.47%, involving aortic (75%), mitral (12.5%), and tricuspid (12.5%) valves. Pathogens identified included S. aureus, Klebsiella pneumoniae, A. baumannii, and P. aeruginosa. This incidence is significantly higher than that in the general population. Mortality reached 50%, with an overall 3-month mortality of 75%. The literature on IE in burn patients is scarce, and the role of antibiotic prophylaxis remains controversial. Infective endocarditis in burn patients, although rare, represents a severe complication with high mortality. Early diagnosis and coordinated multidisciplinary care are essential to improve patient outcomes.

Fracture-related infections (FRIs) represent a significant complication in orthopedic trauma care, often leading to delayed bone healing, prolonged hospital stays, and increased patient morbidity. Pathogenesis involves microbial contamination during injury or surgery, compounded by patient-related risk factors such as diabetes, smoking, or immunosuppression. Diagnosis of FRI relies on a combination of clinical, radiological, and microbiological criteria. Common signs include persistent pain, swelling, erythema, purulent discharge, and non-union of the fracture. FRIs are classified based on the timing of infection onset into acute, delayed, and chronic forms, each requiring tailored management strategies. Treatment generally involves aggressive surgical debridement, possible hardware removal or retention, and targeted antibiotic therapy. In cases of severe tissue loss, reconstructive procedures may be necessary to restore bone and soft tissue integrity. Treatment strategies include early administration of prophylactic antibiotics, meticulous surgical technique, and timely soft tissue coverage in open fractures. A multidisciplinary approach involving orthopedic surgeons, infectious disease specialists, and microbiologists is essential for successful management. Early recognition and appropriate intervention are crucial to improving outcomes and minimizing long-term disability in patients with fracture-related infections.

ABSTRACT Previous studies demonstrated that integrase-strand-transfer-inhibitors (INSTIs) promote adipocyte differentiation, while nucleoside-reverse-transcriptase-inhibitors (NRTIs) tenofovir-alafenamide-fumarate (TAF) and tenofovir-disoproxil-fumarate (TDF), inhibit adipogenesis. NRTIs were shown to counteract the pro-adipogenic effects of INSTIs[6]. However, the effects of non-nucleoside-reverse-transcriptase-inhibitors (NNRTIs) and of the novel long-acting INSTI cabotegravir (CAB), on adipogenesis, alone or in combination with NRTIs or other INSTIs, remain unclear. This study aims to elucidate the impact of NNRTIs and recent INSTIs on adipogenesis. 3T3-L1 cells were used as an adipogenesis in vitro model. The NNRTIs doravirine (DOR) and rilpivirine (RPV) were tested alone and in combination with DTG, CAB, TDF, TAF. Adipogenesis was assessed by Oil-Red-O-staining and by measuring expression-levels of peroxisome-proliferator-activated-receptor-gamma (PPARγ) and CCAAT/enhancer-binding-protein-alpha (C/EBPα). Moreover, Fibroblast-marker ER-TR7 was assessed by immunohistochemistry. CAB, DOR, and RPV promoted adipogenesis, with CAB and DOR showing greater effects. In combination, NNRTIs enhanced the adipogenic effects of CAB and DTG. Conversely, TAF and TDF, when paired with RPV or DOR, inhibited adipogenesis. NNRTIs and CAB increased ER-TR7 expression, suggesting fibroblastic differentiation. Finally, NNRTIs and INSTIs promote adipogenesis and induce fibroblastic features in 3T3-L1 cells. Contrarily, TAF and TDF exhibited an antagonistic effect on adipogenesis when combined with certain antiretrovirals, supporting our previous research.