Mediterranean Journal of Hematology and Infectious Diseases最新文献

Background: In the ICU, distinguishing immune-mediated thrombotic thrombocytopenic purpura (iTTP) from sepsis-associated thrombotic microangiopathy (TMA) is time-critical. We tested whether serial ADAMTS-13 combined with targeted coagulation and inflammation markers improves iTTP risk stratification in a Sepsis-3 ICU cohort and whether a pragmatic rule-out is feasible.

Methods: Prospective single-center study of adults meeting Sepsis-3 with thrombocytopenia and schistocytes ≥ 1% or LDH > 2× ULN within 24 h of ICU admission. ADAMTS-13 activity and VWF: Ag were assayed at 0/24/48/72 h alongside a thrombo-inflammatory panel. We derived a Dynamic ADAMTS-13 Index (DAI), a Coagulation Consumption Index (CCI) anchored to ISTH DIC and fibrinogen/antithrombin III, and an Inflammation Index (IL-6/HBP). The prespecified main rule-out required a ≥ 15% ADAMTS-13 rise by 48 h plus low CCI. A prespecified RCV-anchored sensitivity analysis required ≥ 35% relative rise or ≥ 10 absolute % points plus low consumption. For decision-making, pre-treatment (pre-plasma exchange, PEx) analyses are emphasized. Intent-to-diagnose (care-embedded) analyses are exploratory, and internal validation used a bootstrap optimism correction.

Results: Of 1,274 screened, 330 were included (iTTP = 34). Discrimination improved from baseline ADAMTS-13 (AUROC 0.78) to DAI (0.93), with smaller gains after adding CCI (0.95) and the Inflammation Index (0.96). With the main rule-out (≥ 15% + low CCI) in the intent-to-diagnose analysis, sensitivity was 97.1%, specificity was 86.1%, and NPV was 99.6%. The RCV-anchored sensitivity analysis preserved 100.0% sensitivity and NPV with 76.0% specificity. A 72-h phenotype (ADAMTS-13 < 10% with high IL-6/HBP) was associated with higher 28-day mortality (adjusted HR 2.6).

Conclusions: In Sepsis-3 ICU patients with TMA features, serial ADAMTS-13 testing, along with targeted coagulation/inflammation markers, enhances early iTTP risk stratification and supports a pragmatic rule-out framework. External validation and implementation studies remain essential. These findings also support investment in rapid/automated ADAMTS-13 activity assays and decision-support workflows to enable timely adoption beyond tertiary centers.

Background: Transfusion-dependent thalassemia (TDT) is a transfusion-dependent anemia frequently associated with iron overload, which may disrupt liver function and glucose metabolism.

Objective: This study aimed to evaluate glucose dysregulation and the effects of iron chelation therapy in pediatric TDT patients.

Methodology: This retrospective study included 31 children and adolescents (aged 7-23 years) with TDT who were followed at a tertiary-care pediatric hematology center with available oral glucose tolerance test (OGTT) data. Clinical and laboratory data were analyzed, including oral glucose tolerance test (OGTT), serum ferritin, alanine aminotransferase (ALT), glycated hemoglobin (Hb A1c), C-peptide, homeostatic model assessment for insulin resistance (HOMA-IR), abdominal ultrasonography (USG), and liver and cardiac magnetic resonance imaging (MRI). Diagnosis of diabetes mellitus (DM) and prediabetes was based on American Diabetes Association (ADA) criteria.

Results: OGTT was performed in 28 patients; impaired fasting glucose (IFG) was observed in 10.7%, impaired glucose tolerance (IGT) in 3.6%, and 85.7% had normal glucose regulation. All received consistent oral chelation with film-coated deferasirox. ALT showed significant correlation with age at chelation onset (r=0.49, p=0.00), C-peptide (r=0.45, p=0.02), and age at diagnosis (r=0.56, p=0.001). Duration of chelation correlated with hepatomegaly severity (r=0.61, p=0.00), 30-minute glucose (r=0.39, p=0.03), and insulin levels at 30 (r=0.37, p=0.04) and 90 minutes (r=0.39, p=0.03). No significant association was found between ferritin and OGTT values (p>0.05).

Conclusions: Overt glucose metabolism disorders were uncommon and should be interpreted cautiously. These results highlight the critical role of adherence to chelation and metabolic monitoring to prevent DM in children with TDT.

The gut microbiota, a vast community of symbiotic microorganisms inhabiting our gut, has been recognized as a key-lever for human health, shaping immune system resilience and being essential for immunological homeostasis throughout the life course. Gut microbiota composition may influence both initiation and/or perpetuation of intestinal inflammation, but recent research has highlighted its contribution to both rising and progression of protean non-intestinal inflammatory diseases: indeed, a perturbation of host-associated microbiota during critical developmental stages like early childhood can directly condition many cellular dynamics and impact long-term health. This narrative review explores the interactions among gut microbiota, physiologic healthy equilibrium, dysbiosis, and immune-mediated non-intestinal inflammatory diseases occurring in childhood, such as inflammasome-based disorders, juvenile idiopathic arthritis, Kawasaki disease, and IgA vasculitis, focusing on how microbial changes may alter disease outcomes and suggesting potentially novel therapeutic approaches. Additionally, this review examines the evolution of immune recognition mechanisms and their role in maintaining the gut microbiota-host mutualism as a result of millennia of human co-evolution with the microbial counterpart.

Background: Stenotrophomonas maltophilia (S. maltophilia) is a multidrug-resistant pathogen frequently isolated in hospital-acquired pneumonia and represents a significant clinical challenge. This study aimed to investigate the risk factors associated with 30-day mortality in patients diagnosed with S. maltophilia pneumonia.

Methods: This retrospective, single-center study included patients aged 18 years and older who were hospitalized between January 2018 and December 2021, had S. maltophilia isolated from respiratory samples, and demonstrated clinical and radiological evidence of pneumonia. Patients were grouped by 30-day survival status, and comparisons were made for demographic characteristics, risk factors, and antibiotic regimens.

Results: Among the 200 evaluated patients, colonization was detected in 48%. A total of 104 patients met the inclusion criteria, of whom 75% required ICU admission. The 30-day mortality rate was 55.7%. Malignancies were present in 62.5%. Polymicrobial infections and coinfections were observed in 39.4% and 82.4%, respectively. Multivariate analysis identified SOFA (Sequential Organ Failure Assessment) score (OR = 1.293, 95% CI [1.113-1.501], p = 0.001), mechanical ventilation (OR = 5.005, 95% CI [1.379-18.157], p = 0.014), and a high Charlson Comorbidity Index (OR = 1.353, 95% CI [1.103-1.650], p = 0.004) as independent predictors of mortality. Combination antibiotic therapy had no significant effect on mortality. No resistance to trimethoprim-sulfamethoxazole was detected.

Conclusion: S. maltophilia pneumonia is a serious nosocomial infection with high mortality, particularly in ICU patients with malignancies. SOFA score, mechanical ventilation, and a high Charlson Comorbidity Index were independently associated with increased mortality.

Background: Radiologic complications of pediatric Mycoplasma pneumoniae pneumonia (MPP), consolidation, and necrotizing pneumonia (NP) are difficult to anticipate early. We tested whether admission cytokines and short-term changes predict imaging outcomes.

Methods: A retrospective cohort (Oct 2022-Sep 2024) of hospitalized children with PCR-confirmed MPP. Multiplex cytokines (including IL-6, IL-10, CXCL10/IP-10) were assayed from residual samples at admission (T0) and days 3-5 (T1). NP analyses were conditional on undergoing computed tomography (CT). Primary outcomes were WHO end-point CXR consolidation ≤14 days and CT-defined NP ≤28 days. Full-cohort 14-day CXR-consolidation risk (admission), post-T1 consolidation risk among event-free children (day 3-5 landmark), and 28-day NP risk conditional on being scanned. Penalized logistic models evaluated T0 and Δ(T0-T1) predictors among children event-free at T1, with AUC (bootstrap-corrected) and BH-FDR control.

Results: Of 286 enrollments, 268 were analyzed; consolidation occurred in 96/268 (35.8%), CT was performed in 124/268 (46.3%), and identified NP in 28/124 (22.6%; 10.4% overall). In the Admission model, IL-6 (adjusted OR [aOR] 1.45, 95% CI 1.16-1.83; q=0.01), IP-10 (1.52, 1.21-1.93; q<0.01), and IL-10 (1.28, 1.03-1.60; q=0.04) predicted consolidation (AUC 0.78, 95% CI 0.73-0.83). In event-free children at T1 (n=180), ΔIL 6 (1.40, 1.12-1.76) and ΔIP 10 (1.48, 1.18-1.88) improved discrimination (AUC 0.84, 0.79-0.88). In CT-subset models, T0 IL-6 (1.67, 1.09-2.58) and ΔIL-6 (1.89, 1.22-3.00) were associated with NP (AUC 0.79). Findings were robust in prespecified sensitivity analyses.

Conclusions: Admission cytokines and early rises, especially IL-6 and IP-10, enable pragmatic early risk stratification for consolidation, with ΔIL-6 also signaling NP risk in the CT-scanned subset. These results support external validation of a cytokine-based tool to inform imaging and triage.