Search Results (1,626)

Background and Methods: Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a severe complication of allogeneic stem cell transplant (allo-SCT). Given the increased use of allo-SCT and variability of SOS/VOD incidence in published reports, cases of allo-SCT from two major transplant centers in Ontario, Canada (2019–2021), were reviewed to identify risk factors prognostic for SOS/VOD onset and to assess outcomes. Results: This study included 536 allo-SCT cases, with a mean age of 53.4 years [min–max: 17–76], including 322 male recipients and 214 female recipients. There were 17 SOS/VOD cases diagnosed during the first 100 days, representing 3% of allo-SCT cases, with a median age of 48 years [18–72] and equally distributed between genders. All cases were classical SOS/VOD, with onset prior to day 21 [1–20]. These cases were graded as one mild, six moderate, six severe, and four very severe cases. The mild case of SOS/VOD recovered after treatment with diuretics. In respect to the 16 cases graded as ≥moderate SOS/VOD, the average inpatient stay was 56 days [24–178], and eight patients were in the ICU for an average of 6 days [0–42], with a median of zero days. Five of the sixteen ≥moderate SOS/VOD patients died within 100 days [9–59]—four from SOS/VOD. After day +100, five remained alive, and six died between days 125 and 419. Treatments for ≥moderate SOS/VOD included diuretics [n = 15], steroids [n = 3], and defibrotide [n = 9]. The nine patients treated with defibrotide were graded as moderate [n = 2], severe [n = 4], and very severe [n = 3]. Three of the nine patients treated with defibrotide died before day 100, and the other six survived beyond day 100. None of the six surviving patients died from SOS/VOD. Univariable regression analysis identified a higher baseline absolute neutrophil count (ANC) of 4.2 × 10⁹/L compared to 2.6 × 10⁹/L [p = 0.035] and lower baseline platelet count of 104 × 10⁹/L compared to 140 × 10⁹/L [p = 0.034] in SOS/VOD and non-SOS/VOD cases, respectively, as independent risks for ≥moderate SOS/VOD. Treatment with inotuzumab ozogamicin was also identified as a risk factor for ≥moderate SOS/VOD (p = 0.016). The absence of late-onset SOS/VOD in the cohort of 536 patients prompted a retrospective analysis of the data to identify potentially missed cases. Seven cases were identified as meeting the diagnostic criteria for SOS/VOD: four classical and three late-onset. One case would have been graded as severe, and the remaining six would have been graded as very severe. Six patients were reported to have died between days 11 and 107, with four deaths before day 100. The clinical diagnoses of patients meeting diagnostic criteria for SOS/VOD included infection (n = 3), graft-versus-host disease (GVHD) (n = 3), and pulmonary hemorrhage (n = 1). The inclusion of potentially missed cases in the analysis again suggested a lower baseline platelet count (p = 0.002) and prior treatment with inotuzumab ozogamicin (p = 0.003) as potential risk factors for SOS/VOD. The baseline ANC was lower in this combined cohort but did not reach statistical significance (p = 0.089) as it did in the confirmed SOS/VOD cohort (p = 0.035). Additional clinical features that were identified as statistically significant for the onset of SOS/VOD (potential and confirmed cases) included a lower Karnofsky Performance Status (p = 0.01), the presence of pulmonary hypertension (p = 0.012), lower baseline hemoglobin (p = 0.017), and higher baseline serum ferritin (p = 0.01). Conclusions: The incidence of classical SOS/VOD in this cohort was consistent with recent published reports and carried a high fatality rate. A higher ANC, lower platelet count at the start of the preparative regimen, and prior treatment with inotuzumab ozogamicin were identified as potential risk factors for diagnosed SOS/VOD. Hospital and intensive care unit stays were longer in SOS/VOD patients. There were no cases of late-onset VOD diagnosed within the first 100 days of allo-SCT transplant, which is inconsistent with recently reported incidence rates. Potentially missed cases of SOS/VOD were identified, suggesting that this disease may be under-diagnosed and underscoring the need for ongoing education and resources to allow for early intervention. Full article

β-thalassemia minor, often referred to as the β-thalassemia trait, is among the most prevalent hemoglobinopathies globally, impacting around 80–90 million carriers, with a prevalence of up to 15% among Mediterranean, Middle Eastern, and Asian populations. Although traditionally regarded as clinically benign, pregnancy imposes hematologic and metabolic stressors that may unmask latent vulnerabilities. This review combines the latest data and findings about the pathophysiology of β-thalassemia minor during pregnancy, its short-term outcomes on the mother and fetus, and its long-term impact on the child, as well as management techniques. A narrative review of PubMed-indexed studies (2000–2025) was conducted, including cohort and case–control studies, systematic reviews, meta-analyses, and international guidelines. Outcomes were organized by theme, and quantitative findings (prevalence, relative risks, odds ratios) were combined when available. Anemia is a common health issue for mothers. Literature mentions that the pooled incidence is between 30% and 40% during the third trimester, with ~5%of carriers needing a blood transfusion (mainly in iron-deficient or baseline Hb 6–8 g/dL cases). Meta-analyses have shown elevated risks of pre-eclampsia (odds ratio (OR) ~ 1.4, 95% confidence interval (CI) 1.1–1.8) and postpartum hemorrhage (PPH); however, estimates differ by region. The odds of preterm delivery (OR ~ 1.4), small-for-gestational-age (SGA) (OR ~ 1.5), and low birth weight (LBW) are slightly increased for carriers, and neonatal intensive care unit (NICU) admission rates are also higher for carriers. However, the risk of stillbirth is not always increased. The usual approach is iron supplementation guided by ferritin levels to prevent overload, personalized transfusion thresholds, and regular folate support. There is not much evidence for long-term consequences for children of carrier mothers since no research has followed more than 200 children born to carrier mothers into adulthood. However, maternal anemia is linked to slower growth, neurodevelopmental issues, and a higher risk of cardiometabolic problems in larger groups of pregnant women. However, maternal anemia is associated with slower growth, neurodevelopment, and higher cardiometabolic risk in larger groups of pregnant women. β-thalassemia minor during pregnancy usually has a mild, though significant, impact. While most pregnancies proceed without complications, this condition is associated with a significantly higher prevalence of anemia and other adverse postnatal outcomes. Consequently, the implementation of risk-stratified monitoring, smart supplementation, and standardized management protocols is essential. Prospective registries, mechanistic placental research, and long-term offspring cohorts are necessary to better understand long-term trends. Full article

Background: Iron overload cardiomyopathy (IOC) is a major determinant of outcomes in hemochromatosis, and conventional echocardiography may miss early myocardial toxicity. Comparative data on primary (PH) versus secondary hemochromatosis (SH) using myocardial work (MW) indices are limited. Methods: We performed a retrospective cross-sectional study of 34 adults (16 PH and 18 SH patients) at a tertiary center. They all underwent echocardiography with speckle-tracking to obtain LV global longitudinal strain (GLS) and non-invasive MW indices from pressure-strain loops: global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Echocardiographic phenotypes were classified as a Normal, Dilated, Restrictive, or right ventricular/pulmonary hypertension (RVPH) phenotype. Results: SH patients showed higher iron burden and neurohormonal activation than PH patients (maximum ferritin 2954 vs. 444 ng/mL; BNP 93 vs. 13.5 pg/mL; both p < 0.001) and accounted for all deaths (33% vs. 0%) despite similar 3D LVEFs and GLSs. PH patients predominantly exhibited Normal phenotypes (81%), whereas SH patients more often showed advanced phenotypes, mainly RVPH and Dilated. GWI correlated inversely with ferritin (ρ ≈ −0.40), particularly ferritin at echocardiography in SH patients, while PH patients showed no significant correlations. GWW was higher in Dilated/RVPH compared to Normal phenotypes, and in SH patients, higher maximum ferritin was associated with impaired right ventricular free-wall strain. Conclusions: PH and SH patients exhibit distinct IOC phenotypes, with SH patients showing more advanced remodeling and worse outcomes. In this exploratory analysis, MW indices showed modest associations with iron burden markers, suggesting they may provide complementary information beyond LVEF and GLS. These preliminary findings require validation in larger, prospective studies. Full article

Background/Objectives: Oral iron supplementation is widely used to treat iron deficiency but frequently causes gastro-intestinal side effects that limit treatment adherence. Unabsorbed luminal iron has been proposed to influence intestinal microbial communities, yet the effects of different oral iron doses on the human gut microbiome remain insufficiently characterized. Methods: In this randomized open-label study, 30 healthy premenopausal women with iron deficiency without anaemia received either low-dose oral iron supplementation (6 mg twice daily) administered under fasting conditions or standard-dose iron supplementation (100 mg once daily) taken with a meal for four weeks. Stool samples were collected before and after treatment and analyzed using 16S rRNA sequencing to evaluate microbiome composition. Results: Baseline characteristics, including age, body mass index, hemoglobin concentration and serum ferritin, were comparable between groups. After four weeks of treatment, distinct alterations in gut microbiome composition were observed between the low-dose and standard-dose groups. The genera Colidextribacter and GCA-900066575 decreased in the low-dose group but increased in the standard-dose group, whereas Oscillospira showed the opposite pattern. Gastrointestinal adverse events were reported by 87% of participants receiving standard-dose iron supplementation compared with 7% receiving low-dose iron supplementation (p < 0.0001). Conclusions: Oral iron supplementation induces dose-dependent changes in the intestinal microbiome and higher doses are associated with substantially increased gastrointestinal intolerance. These findings suggest that lower iron doses may reduce microbiome disruption and improve treatment tolerability. Full article

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive interstitial lung disease (ILD) is associated with high mortality. While inflammatory markers have been linked to poor outcomes, clinical heterogeneity remains evident, as some patients survive despite marked hyperinflammation. Methods: We retrospectively analyzed consecutive patients with anti-MDA5 antibody-positive ILD treated at our institution between May 2017 and November 2025. In-hospital mortality was assessed in relation to clinical characteristics and laboratory markers, including peak anti-MDA5 antibody titers, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), and KL-6. Analyses were exploratory and hypothesis-generating. Continuous variables were compared using Mann–Whitney U tests, and categorical variables using Fisher’s exact test. Principal component analysis (PCA) and receiver operating characteristic (ROC) analyses were performed for descriptive purposes. Results: Seventeen patients were included (10 survivors and 7 non-survivors). Peak ferritin, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels were significantly higher in non-survivors, whereas peak anti-MDA5 antibody titers showed a non-significant trend toward higher values in non-survivors (p = 0.057). KL-6 levels did not differ significantly between groups. In ROC analyses, LDH and CRP showed the highest discriminative performance for in-hospital mortality, followed by ferritin, whereas KL-6 showed the lowest discriminative performance. Despite these overall trends, substantial overlap between survivors and non-survivors remained across all biomarkers. Principal component analysis (PCA) demonstrated partial separation of outcomes along an inflammation-dominant axis, but with persistent overlap, indicating marked outcome heterogeneity. Conclusions: Inflammatory biomarkers, particularly LDH, CRP, and ferritin, were associated with in-hospital mortality in anti-MDA5 antibody-associated ILD. However, persistent overlap between survivors and non-survivors suggests that single-biomarker assessment is insufficient for precise prognostication. These findings should be interpreted as hypothesis-generating and require validation in larger multicenter cohorts. Full article

X-ray crystallography is still the most widely used and versatile method for structural studies of biological macromolecules. This study concerns the application of nanogels to facilitate protein crystallization, a prerequisite for X-ray crystallography. Nanogels (NGs) are nano-sized, highly crosslinked polymeric particles that have been extensively studied for chemical catalysis and drug delivery but not for protein crystal nucleation. The efficacy of six types of nanogels (three N-isopropylacrylamide-based and three acrylamide-based) was tested, with promising results. They were subsequently functionalised with active hydroxyl groups for further testing. Both functionalised and non-functionalised nanogels were tested on model (trypsin, thaumatin, proteinase K, ferritin and catalase) and target proteins (glulisine, α-crustacyanin and acriflavine resistance protein subunit AcrB) using both manual and automated techniques. All nanogels were found to be effective in promoting protein crystallization in both screening and optimization trials, giving crystal ‘hits’ that would have otherwise been missed. Overall, the functionalised nanogels were more effective. Nanogel effects are proposed to be due to a combination of surface porosity and surface chemistry. Full article

This case-control study investigated the association between polymorphisms in the dedicator of cytokinesis 2 (DOCK2) gene and susceptibility to COVID-19 in a Mexican population. Methods: Genotyping of five single-nucleotide polymorphisms (SNPs) in the DOCK2 gene (rs9307 A/G, rs1045176 G/T, rs1045168 C/T, rs2112703 A/C, and rs2287727 A/C) was performed using TaqMan assays in 248 COVID-19 patients and 288 healthy controls. Results: No significant differences were observed in the allelic or genotypic distributions of rs1045176 G/T and rs2287727 A/C between cases and controls. However, under multiple genetic inheritance models (co-dominant, dominant, recessive, heterozygous, and additive), the rs9307 A, rs1045168 C, and rs2112703 A alleles were significantly associated with a reduced risk of COVID-19 (p < 0.05). Furthermore, sub-analyses stratified by genotype in COVID-19 patients revealed that the rs9307 AA, rs1045168 CC, and rs2112703 AA genotypes correlated with altered plasma concentrations of lactic acid dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ferritin. Conclusions: The DOCK2 SNPs rs9307 A/G, rs1045168 C/T, and rs2112703 A/C are associated with decreased susceptibility to COVID-19 in this population and influence plasma levels of LDH, ALT, AST, and ferritin, suggesting a potential role in disease pathogenesis and severity. Full article

Background/Objectives: Previous cross-sectional studies investigated the associations of low handgrip strength (HS), a primary indicator of probable sarcopenia (PS), with biomarkers related to anemia. However, existing evidence is inconsistent, and data establishing causality remain limited. The present prospective study aimed to evaluate whether serum vitamin B12, folate, homocysteine (Hcy), and ferritin levels are associated with PS risk. Methods: This study analyzed data from 1930 adults aged 45–76 years who had normal muscle quantity at baseline. Serum biomarkers were assessed at baseline and PS defined by low HS was determined at 6-year follow-up. The modified Poisson regression method was employed to calculate multivariable risk ratios (RRs) and 95% confidence intervals (CIs). Results: Among all participants, PS risk was inversely related to serum vitamin B12 levels (p = 0.06), while it was lowest in the high-normal ranges of serum Hcy (12.1–15 μmol/L) and ferritin (101–200 ng/mL) levels. The RRs (95% CIs) for PS risk were 0.73 (0.60, 0.89) and 0.75 (0.64, 0.87) for high-normal Hcy and ferritin categories, respectively, compared with the lowest category. On examining the associations of elevated Hcy and ferritin levels with PS risk, age was identified as a significant modifier for elevated Hcy levels (>15 μmol/L) (p for interaction < 0.05); a reduced risk was observed in younger participants, whereas an increased risk was noted in older participants. Conclusions: These findings suggest that high-normal ferritin levels may be optimal for alleviating PS risk, irrespective of age, and that elevated Hcy levels could be detrimental for older adults in preventing PS risk. Full article

Dysregulated iron handling—including catalytic iron and ferroptosis, hepcidin–ferroportin signaling, ferritin dynamics, and neutrophil gelatinase-associated lipocalin (NGAL)-mediated siderophore transport—has been implicated in the initiation and propagation of acute kidney injury (AKI) across ischemia–reperfusion, sepsis, and nephrotoxic contexts. To provide a SANRA-aligned narrative synthesis of mechanistic and translational evidence on iron biology in AKI, clarifying biomarker readiness and therapeutic prospects while explicitly separating preclinical from human findings. PubMed, Scopus, and Web of Science (1 January 2000 to 30 September 2025), plus appraised grey literature (guidelines/registries) using predefined criteria (authority, update recency, and methodological transparency). Narrative review with comprehensive database searches, single-reviewer screening/extraction (acknowledged as a limitation), and qualitative synthesis. Evidence is organized by pathway (catalytic iron/ferroptosis, transferrin (Tf)/transferrin receptor (/TfR), ferritin/ferritin heavy chain (FtH), hepcidin–ferroportin and NGAL) and translational domain (biomarkers and therapeutics). Statements are tagged as [Preclinical] or [Human]. [Preclinical] Robust signals support roles for catalytic iron and ferroptosis, protection by iron chelation, hepcidin modulation, heme oxygenase 1 (HO-1)/FtH induction, and apotransferrin/NGAL-based strategies. [Human] Biomarkers such as NGAL show clinical utility for kidney injury detection, whereas catalytic iron assays (labile plasma iron [LPI]/bleomycin-detectable iron [BDI]) remain investigational with limited standardization. Observational links between iron-regulatory pathways and AKI risk exist, but interventional trials are sparse; dose, timing, and safety of iron-targeted strategies in defined AKI settings remain to be established. Iron-handling pathways are compelling targets for AKI prevention/mitigation, yet high-quality human trials are limited. Priorities include standardized catalytic-iron assays, biomarker-guided enrichment, and pragmatic trials of tractable interventions (e.g., peri-contrast or cardiopulmonary bypass settings). Until such evidence accumulates, recommendations beyond standard care should be avoided. Full article

Obesity is characterized by low-grade systemic inflammation and alterations in gut-related immune pathways that may contribute to metabolic dysfunction. Composite biomarker indices may better capture these complex processes than individual markers, although their performance may differ across biological domains. In this cross-sectional study, 88 adults without diabetes or infection were categorized as BMI < 25 kg/m² (n = 20), BMI 25–29.9 kg/m² (n = 34), or BMI ≥ 30 kg/m² (n = 34). Circulating biomarkers reflecting systemic inflammation (high-sensitivity C-reactive protein, ferritin, interleukin-6, presepsin) and intestinal barrier-related activity (β-defensin-2, regenerating islet-derived protein 3 alpha) were measured and subsequently combined into two composite indices: the Inflammatory Load Index, derived from inflammatory markers, and the Barrier Activation Index, derived from barrier-related markers. Group differences were assessed using analysis of variance with post hoc testing. Additional analyses included effect size estimation, receiver operating characteristic (ROC) analysis, and logistic regression. Individual biomarkers showed limited differences across BMI categories. The Inflammatory Load Index differed significantly across BMI categories (p = 0.040), with higher values observed in individuals with BMI ≥ 30 kg/m² compared with those with BMI 25–29.9 kg/m² (p = 0.032; Cohen’s d = 0.80), while the Barrier Activation Index did not differ (p = 0.257). In ROC analysis, the Inflammatory Load Index discriminated BMI ≥ 30 kg/m² with an area under the curve of 0.720 (95% confidence interval 0.576–0.851), yielding 77.8% sensitivity and 67.7% specificity. Each one standard deviation increase in the index was associated with higher odds of obesity (odds ratio 2.34, 95% confidence interval 1.22–4.49; p = 0.011). In conclusion, a composite inflammatory biomarker index, but not a barrier-related index, differentiates degrees of BMI in individuals without diabetes. These findings support integrated biomarker approaches for reflecting obesity-related biological burden beyond single markers. However, these observations are based on cross-sectional data and do not imply causality. Full article

Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure. Full article

Background: Brucellosis is a globally distributed zoonotic disease characterized by highly variable clinical manifestations that may mimic systemic autoimmune and inflammatory disorders. In Europe, where the incidence of brucellosis is relatively low, limited clinical awareness may contribute to delayed diagnosis and inappropriate management. In addition to zoonotic transmission, Brucella species are a well-recognized cause of laboratory-acquired infections (LAIs) among microbiology laboratory personnel. Methods: We report a case of laboratory-acquired Brucella abortus infection in a young woman presenting with undulant fever, arthralgia, systemic inflammation, elevated ferritin levels, and antinuclear antibody (ANA) positivity. Microbiological confirmation was achieved through serological testing (ELISA), repeat blood cultures, species-specific quantitative PCR, and whole-genome sequencing (WGS) followed by core genome multilocus sequence typing (cgMLST). Results: Initial laboratory evaluation revealed elevated C-reactive protein, mildly increased ferritin levels (146 ng/mL), abnormal liver enzyme levels, and rising ANA titers (from 1:160 to 1:320), raising suspicion of a systemic autoimmune disorder and prompting consideration of corticosteroid therapy. Although the initial blood culture was negative, subsequent molecular diagnostics and repeat cultures confirmed B. abortus infection. Epidemiological investigation suggested a possible occupational exposure in a diagnostic microbiology laboratory, consistent with a laboratory-acquired infection. Genomic analysis classified the isolate as sequence type 1 (ST1) and demonstrated zero allelic differences compared with the ST1 reference strain. Targeted antimicrobial therapy resulted in complete clinical recovery, supporting an infection-triggered immune response rather than primary autoimmunity. Conclusions: Acute brucellosis should be considered in the differential diagnosis of febrile syndromes accompanied by autoimmune-like laboratory abnormalities, even in low-incidence regions. This case highlights the diagnostic challenges posed by laboratory-acquired brucellosis and underscores the importance of early microbiological investigation and strict biosafety awareness in laboratory settings. Full article

We evaluated the interplay between systemic total antioxidant capacity (TAC), oxidative stress (OS) (lipid hydroperoxides), inflammation, iron status, and oral contraception (OC) use in 182 healthy 23-year-old women (76 OC-users, and 106 non-OC-users). In all women, blood TAC (FORD units) values were significantly inversely associated with OS (FORT units), high-sensitivity C-reactive protein (hsCRP), and transferrin; and positively associated with transferrin saturation (TfS%). No significant associations were observed for hemoglobin, hematocrit, red blood cells, serum iron, soluble transferrin receptor (sTfR), sTfR/log(ferritin) ratio (sTfR-F index), ferritin, folate, uric acid, or creatinine. OS hydroperoxides were positively associated with hsCRP and transferrin, and inversely associated with TfS%. sTfR was positively correlated with hydroperoxides in non-OC-users and with folate in all women and non-OC-users, but was not associated with hsCRP in any group. The combined abnormal condition of low TAC and elevated OS (n = 71) was significantly more frequent among OC-users (OR = 39.0), women with hsCRP ≥ 3 mg L⁻¹ (OR = 10.1), transferrin ≥ 330 mg dL⁻¹ (OR = 6.58), and smokers (OR = 3.76). OC use modulated the TAC/OS balance and inflammation. Low TAC and elevated OS may impact health status. Enhanced TAC/OS knowledge may increase awareness of effects of OC use among fertile-age women. Ferritin was independent of TAC/OS status and OC use, supporting its reliability as an iron biomarker. Full article

Background/Objectives: This study aimed to investigate the impact of allergic diseases (AD) or obstructive sleep apnea (OSA) risk, as a host factor, on the development of severe Mycoplasma pneumoniae Pneumonia (SMPP) in children by analyzing the clinical data of pediatric patients with Mycoplasma pneumoniae Pneumonia (MPP). Methods: This retrospective study enrolled children hospitalized with Mycoplasma pneumoniae pneumonia (MPP) at Shanghai Ninth People’s Hospital from November 2024 to November 2025. Patients were classified into severe (SMPP) and mild (MMPP) groups. Demographic, clinical, laboratory, and questionnaire data were collected and compared between groups. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of SMPP and construct a nomogram. The model was validated for discrimination, calibration, and clinical utility using ROC curves, calibration plots, and decision curve analysis, with internal validation by bootstrap resampling. Results: Among the 150 enrolled children with MPP, 35 (23.3%) were classified as severe (SMPP) and 115 (76.7%) as mild (MMPP). Patients with SMPP exhibited significantly higher frequencies of allergic diseases, prolonged fever and steroid use, elevated inflammatory markers (CRP, LDH, D-dimer, ferritin, ALT), and higher PSQ and RQLQ scores (all p < 0.05). Disease severity was positively correlated with these clinical, laboratory, and questionnaire-based parameters. Multivariate logistic regression identified allergic diseases, PSQ score, LDH, and ferritin as independent predictors of SMPP. A nomogram incorporating these four factors demonstrated good predictive performance, with an internally validated C-index of 0.827, satisfactory calibration (Hosmer–Lemeshow p = 0.116), and clinical utility within a 0–25% threshold probability range on decision curve analysis. Conclusions: Children with MPP and comorbid AD or OSA risk are more likely to develop SMPP. Among children aged 6–12 years, RQLQ score is positively correlated with the severity of MPP. AD, PSQ score, LDH, and ferritin are independent risk factors for SMPP. Clinicians should be alert to the development of SMPP when children with MPP present with a history of AD, PSQ score >3.5, LDH >327.50 U/L, or ferritin >120.05 ng/mL. The visual nomogram model constructed by combining these risk factors demonstrates improved predictive performance for SMPP, with high predictive efficacy and accuracy. It has great clinical value and can be used for individualized risk assessment and early intervention. However, our proposed nomogram requires external validation prior to broader implementation. Full article

Background: Test descriptions from major diagnostic manufacturers do not include ferritin reference intervals (RIs) for individuals aged 60 and older. The absence of older adults-specific RIs contrasts with the widespread use of serum ferritin testing in older adults. We aimed to establish and verify RIs using two common analytical methods. Methods: For this study, 1467 older adults were prospectively enrolled and monitored for morbidity and mortality, and exclusion criteria were applied. Ferritin was measured using chemiluminescent microparticle immunoassay (CMIA) and transferred to an electrochemiluminescence immunoassay (ECLIA) using method comparison. RIs were evaluated using a direct method with a prospective observational study based on healthy individuals according to the Clinical and Laboratory Standards Institute (CLSI) 28-A3c guideline and compared with RIs obtained using an indirect approach based on data obtained in clinical routine outpatients, where normal and abnormal values are supposed to be statistically differentiated to determine RIs. When applied within a countrywide population-based setting in Liechtenstein, the impact of novel RIs on the frequency of abnormal values was analyzed. Results: A total of 386 men and 532 women were included in the direct RI determination. Women (W) had significantly lower ferritin levels than men (M), while age over the age of 60 years had no significant association with ferritin in men and women. RIs were 23–241 ng/mL (W) and 19–396 ng/mL (M) for CMIA and 27–293 ng/mL (W) and 23–480 ng/mL (M) for ECLIA. These RIs are higher than those mentioned in the test descriptions in both tests. In comparison, the indirect method for both assays showed comparably lower reference limits, whereas upper reference limits were only approximately similar. The prevalence of high abnormal ferritin levels was considerably lower with this study’s RIs compared with manufacturer RIs. Conclusions: Employing older adults-specific RIs in clinical routine seems to be advisable. This reduces the frequency of abnormal high values in comparison with the widely applied practice of extrapolating RIs obtained from younger age groups to older adults and therefore leads to fewer follow-up investigations. Full article