Cristina Scollo

Background: Determining infection eradication before reimplantation remains challenging during two-stage revision for chronic periprosthetic joint infections (PJI). This exploratory study investigated the association between serial postoperative C-reactive protein (CRP) trajectories and treatment outcome following prosthesis explantation during two-stage revision for chronic periprosthetic joint infection (PJI). Methods: We retrospectively reviewed patients undergoing two-stage revision for chronic hip or knee PJI between January 2020 and August 2024. Patients with weekly CRP measurements and at least 12 months of follow-up were included. Treatment failure was defined according to modified Delphi criteria. Weekly CRP concentrations and percentage changes from postoperative Week 1 (ΔCRP) were compared between groups. ROC analysis assessed CRP discrimination weekly. Results: Ninety-one patients were included; 50 (54.9%) achieved infection eradication and 41 (45.1%) experienced treatment failure. CRP increased during the first post-operative week in both groups. Week 1 CRP concentrations were not significantly different between groups (5.24 vs. 6.79 mg/dL, p = 0.108). From Week 2 onwards, postoperative CRP trajectories and relative reductions from Week 1 differed between patients with treatment success and those experiencing treatment failure. From Week 2 onward, CRP remained significantly higher in patients with treatment failure (Week 2: 3.91 vs. 2.27 mg/dL, p = 0.0017; Week 4: 3.28 vs. 0.94 mg/dL, p < 0.0001; Week 6: 2.16 vs. 0.70 mg/dL, p = 0.0007). Relative CRP reduction was significantly higher in the success group from Week 2 onward. Discriminatory performance improved over time, with AUCs of 0.699–0.782 at Weeks 2–6. Conclusions: In this exploratory cohort, postoperative CRP trajectories differed according to treatment outcome. A slower decline in CRP was associated with treatment failure, but these findings do not establish an independent prognostic effect. CRP should not determine reimplantation timing in isolation, but an unfavourable trajectory should prompt reassessment and consideration of repeat debridement and spacer exchange. Larger prospective multicentre studies are needed to confirm these associations and determine their clinical utility.

Helicobacter pylori (H. pylori) infection has been investigated as a potential contributor to extra-gastric vascular injury, although its cardiovascular relevance remains uncertain and context-dependent. This state-of-the-art narrative review synthesizes clinical, translational, and experimental evidence linking H. pylori infection to endothelial dysfunction and arterial stiffness, two complementary phenotypes of early vascular aging. Evidence is strongest for endothelial dysfunction, particularly in the presence of active or cytotoxin-associated gene A (CagA)-positive infection, extracellular-vesicle-mediated signaling, oxidative stress, impaired endothelial repair, selective attenuation of endothelium-dependent vasodilation, and short-term improvement after eradication. Associations with arterial stiffness are less consistent and appear more evident in selected settings characterized by younger age, inflammatory or metabolic vulnerability, and severe gastric injury. Conversely, serology-based studies and studies using late structural vascular endpoints frequently report null or discordant findings. Overall, H. pylori should not be considered a universal cardiovascular risk factor, but it may amplify early vascular injury in susceptible subgroups. Prospective studies using active-infection testing, virulence profiling, gastric histology, and prespecified vascular endpoints are needed to determine whether eradication produces sustained vascular benefit.

Local antibiotic delivery has gained a central role as an adjunct to radical debridement in chronic osteomyelitis, allowing high antimicrobial concentrations at the infection site while reducing systemic toxicity. This narrative review summarizes the current clinical evidence on commercially available antibiotic-loadable bone substitutes, with particular focus on calcium sulfate (CaSO₄)-based systems and biphasic calcium sulfate/hydroxyapatite (CaS/HA) composites. Nineteen studies were included. Differences in formulation, resorption kinetics, antibiotic elution profile and osteoconductive behavior are discussed, alongside clinical outcomes including recurrence of infection, reoperation rates and complication patterns. Finally, based on the currently available evidence and expert recommendations, practical guidance is proposed to support carrier selection in different clinical scenarios (cavitary vs. corticomedullary defects; high-risk soft tissue; polymicrobial or resistant infections). Across published series, although heterogeneous, infection eradication rates are generally high when local carriers are integrated into structured surgical protocols. Calcium sulfate carriers provide rapid resorption and robust early antibiotic release but are associated with higher rates of sterile wound drainage. In contrast, CaS/HA biocomposites demonstrate more gradual remodeling and radiographic integration, potentially improving defect consolidation and reducing wound-related morbidity, although leakage and cost considerations remain relevant.

Mild fasting hypertriglyceridemia is often accompanied by early insulin resistance and atherogenic dyslipidemia, making it an attractive target for pragmatic dietary prevention. This trial aims to determine whether substituting common cereal-based staples with functional low-glycemic index (low-GI) products improves the triglyceride–glucose (TyG) index in adults with fasting triglycerides >150 mg/dL. The GLOW study is an exploratory, randomized, double-blind, single-center crossover trial. Adults aged ≥18 years with fasting triglycerides >150 mg/dL and body mass index ≤30 kg/m² will be enrolled. Participants will follow a stabilized Mediterranean-style diet and will complete two 28-day intervention periods in random sequence: (i) functional low-GI Altograno^® pasta, pizza base and flatbread; and (ii) conventional standard wholegrain products. Intervention periods will be separated by a 28-day washout. Study foods will be consumed as fixed daily substitutions of usual staple servings (one bread portion and one pasta or pizza portion). The primary endpoint is the between-intervention difference in TyG response over each period, defined as the period-specific change from the corresponding period baseline to the end-of-period assessment. The primary analysis will compare end-of-period TyG between interventions while adjusting for the period-specific baseline value. Secondary endpoints include fasting triglycerides and glucose, atherogenic lipoproteins (non–high-density lipoprotein cholesterol and apolipoprotein B), inflammation (high-sensitivity C-reactive protein), endothelial reactivity assessed with the Endocheck^®/Vicorder^® system, and food acceptability. Safety endpoints include adverse event recording. Treatment effects will be estimated using linear mixed-effects models accounting for treatment, period and sequence, with prespecified carryover sensitivity analyses. A total of 40 participants will be recruited to generate feasibility data and effect size estimates. This protocol will provide crossover evidence on whether pragmatic, product-level low-GI staple substitution improves TyG and related cardiometabolic and vascular biomarkers in adults with suboptimal triglyceridemia, informing larger trials. Trial registration: ClinicalTrials.gov NCT07198789.

Vitamin D insufficiency remains common in adults, and supplementation with cholecalciferol (vitamin D₃) is widely used to improve circulating 25-hydroxyvitamin D [25(OH)D]. At the same time, circular-economy strategies are increasingly applied to nutraceutical production, including the valorization of fish processing by-products as sources of lipid-soluble bioactives. However, clinical evidence directly comparing fish processing by-product-derived vitamin D₃ with conventional synthetic vitamin D₃ at commonly used nutritional doses remains limited. D-FISH is a single-center, randomized, double-blind, parallel-group, non-inferiority trial enrolling adults aged 18–60 years with a baseline plasma of 25(OH)D 20–40 ng/mL. Participants will be randomized (1:1) to receive either fish processing by-product-derived or synthetic vitamin D₃ at the same nutritional dose (600 IU once daily with the evening meal) for 12 weeks. The primary endpoint is the between-group difference in the change in plasma 25(OH)D from day 0 to day 84, assessed against a pre-specified non-inferiority margin of 5 ng/mL, with analyses conducted in full analysis and per-protocol populations. Secondary endpoints include markers of mineral metabolism (calcium, phosphorus, PTH), fasting lipid profile, anthropometrics, and tolerability/safety outcomes; early 25(OH)D kinetics will be explored at 72 h, day 7, and day 28. The study will inform biochemical non-inferiority and short-term tolerability but is not powered to evaluate clinical outcomes (NCT07127796).

Background: Biologic graft infection (BGI) is one of the main complications in graft reconstructions. However, very little evidence exists regarding the epidemiology of BGI, as most of the data come from sparse reports. Moreover, most of the series did not detail the treatment and outcome of graft infections. The aim of this systematic review of the literature is to provide a comprehensive data collection on BGI after oncologic resections. Methods: Three different databases (PubMed, Scopus, and Web of Science) were searched for relevant articles, and further references were obtained by cross-referencing. Results: 139 studies met the inclusion criteria. A total of 9824 grafts were retrieved. Among these, 684 (6.9%) were in the humerus, 365 (3.7%) in the pelvis, 2041 (20.7%) in the femur and 1660 (16.8%) in the tibia. Most grafts were osteoarticular (2481, 26.7%) and intercalary 2112 (22.7%) allografts. In 461 (5.0%), vascularized fibula grafts (VFGs) were used in combination with recycled autografts. Recycled grafts were reported in 1573 (16.9%) of the cases, and allograft-prosthetic composites in 1673 (18.0%). The pelvis and the tibia had the highest incidence of BGI (20.4% and 11.0%, respectively). The most reported first treatment was debridement and implant retention (DAIR) in 187 (42.8%) cases and two-stage revision with graft removal in 152 (34.8%). Very little data are reported on the final outcome specified by site or type of graft. Conclusions: This systematic review of the literature confirms a high incidence of infections in biologic reconstructions after resections of primary bone tumors. Despite DAIR being a viable attempt, in most cases, a two-stage approach with graft removal and reconstruction with endoprosthesis presented the highest chance to overcome infection, guaranteeing a reconstruction. We emphasize the need for future multicentric studies to focus on the management of infections after biological reconstructions in bone sarcomas.