INTRODUCTION:Vancomycin is a critical antibiotic for treating severe Gram-positive infections. Due to its narrow therapeutic window, reliable plasma concentration measurements are essential for dose adjustment and avoiding toxicity. However, method-dependent analytical variability between immunoassay platforms may compromise result comparability. METHODS:Data from 78 external quality assurance (EQA) samples distributed between 2016 and 2025 by Labquality (Helsinki, Finland) and Equalis (Uppsala, Sweden) were analyzed. Results from laboratories using immunoassays from Abbott Laboratories (n = 1391), Beckman Coulter (n = 172), Roche Diagnostics (n = 3584), Ortho Clinical Diagnostics (n = 78), Siemens Healthineers (n = 1670), Thermo Fisher (n = 152), and ARK Diagnostics (n = 33) were included (total = 7104). The mean consensus value for each sample was used as reference. RESULTS:Across the study period, Abbott Laboratories (+4.7%), Thermo Fisher (+12%), Ortho Clinical Diagnostics (-4.6%), and Siemens Healthineers (-4.9%) showed systematic biases relative to the consensus mean, whereas Beckman Coulter (-0.3%), Roche Diagnostics (<0.1%), and ARK Diagnostics (-2.4%) displayed good agreement. Temporal trends indicated method-specific drifts, most notably for Beckman Coulter (-20.2%) and Siemens Healthineers (+12.5%). Coefficients of variation ranged from 0.9% (ARK Diagnostics) to 12.1% (Beckman Coulter). CONCLUSION:Considerable intermethod bias and temporal drift exist among commonly used vancomycin immunoassays, underscoring the need for improved calibration harmonization and traceability to ensure consistent therapeutic drug monitoring.

OBJECTIVES:Albuminuria is a key biomarker of kidney damage, yet preanalytical challenges with conventional liquid urine testing, limiting its utility for decentralized and large-scale screening. This study evaluated the analytical performance of a novel dried urine spot (DUS) device, for measuring urinary albumin-to-creatinine ratio and assessed its agreement with standard liquid urine analysis. METHODS:One hundred routine urine samples were analysed both as liquid and dried specimens prepared with the DUS device. After drying, discs were eluted and tested on three clinical chemistry platforms (Roche Cobas Pro, Abbott Alinity, Siemens Atellica). Albumin-to-creatinine ratio (ACR) was calculated. Statistical analyses included duplicate precision (coefficient of variation), linear regression, and Bland-Altman comparison. A stability study was conducted under multiple temperature conditions. RESULTS:ACR values obtained from DUS samples showed strong concordance with liquid urine results (Roche Cobas Pro: y=1.024×-1.427; R2=0.997; Siemens Atellica y=0.983 + 0.336; R2=0.958 and Abbott Alinity: y=1.062×-0.360; R2=0.991). Across ACR intervals (<3 mg/mmol, 3-30 mg/mmol >30 mg/mmol), Cobas demonstrated small positive median differences (0.46, 0.25, 0.62 mg/mmol), Alinity showed variable differences (-0.87, 0.27, -0.24 mg/mmol), and Atellica yielded consistently positive, slightly larger differences (0.47, 2.42, 1.33 mg/mmol). CONCLUSIONS:The DUS device provides a robust and reproducible alternative to liquid urine sampling for albumin and creatinine measurement. Its ability to enable decentralized, ambient-temperature collection with strong analytical agreement supports its application in population screening, remote monitoring, and kidney disease research.

Quantification of serum free light chains (FLCs) is essential for the diagnosis and monitoring of plasma cell disorders. This study evaluated the analytical performance of a novel avian IgY-based particle-enhanced turbidimetric immunoassay (PETIA) for measuring free kappa (κ) and lambda (λ) light chains in serum and plasma. The assay was evaluated on the Cobas Pro c503 (Roche Diagnostics, Basel, Switzerland) and Abbott Architect c4000 (Abbott Laboratories, Abbott Park, IL) platforms using samples from patients with monoclonal components and healthy donors. Performance characteristics included precision, limit of quantification (LoQ), linearity, interference, measuring interval, reagent stability, high-dose hook effect, method comparison with the Diazyme FLC assay, and reference interval verification in 70 healthy individuals. Within-run precision was acceptable at clinically relevant concentrations. Functional LoQs (15% CV) were 1.94 mg/L for κ and 3.74 mg/L for λ. Linearity was demonstrated on the Abbott platform, with no significant interference from haemolysis, lipaemia or bilirubin. Reagents were stable for 38 days on-board, and no hook effect was observed at very high FLC concentrations. Method comparison showed strong correlation with the Diazyme assay (κ: r = 0.953; λ: r = 0.881) and substantial agreement for κ/λ ratios (Cohen's κ = 0.64). Verified reference intervals aligned with established standards. The IgY-based PETIA provides precise, interference-resistant measurement of free κ and λ light chains across a wide dynamic range, supporting its suitability for routine clinical use.

Introduction Acute kidney injury (AKI) criteria and staging are based on serum creatinine and urine output, but serum cystatin C performs better at estimating glomerular filtration rate in critically ill patients. Accordingly, a cystatin C-based AKI staging system was developed and its performance studied in critically ill patients. Methods AKI stages according to KDIGO creatinine criteria were converted to corresponding cystatin C-based stages using 14-day mortality in 9424 critically ill patients from three Swedish hospitals followed for 5.6 (2.8–7.2, median IQR) years. Model performance was evaluated using Cox regression on long-term mortality adjusted for age, gender, comorbidities and unit type. An independent cohort (n=434) was used for validation. Results KDIGO stages corresponded to: Stage 1: increase in cystatin C 1.40–1.59 times baseline within seven days or ≥0.44 mg/L within 48 hours; Stage 2: 1.60–2.09 times baseline; Stage 3: above 2.10 times baseline or ≥2.80 mg/L. Cystatin C-based vs. creatinine-based staging identified 11 percent more AKI and 10 percent more Stage 3. Patients reclassified to AKI by cystatin C from no AKI had a higher risk of death of 1.36 (1.24–1.49), while those reclassified vice versa had a lower risk 0.71 (0.56–0.91). These findings were consistent irrespective of infection status for 30-day mortality. In the validation cohort, reclassification to a higher stage by cystatin C was an independent predictor of increased risk of death. Conclusions In critically ill patients, cystatin C-based staging identified more AKI than KDIGO criteria, and these patients had increased short- and long-term mortality.

Anemia is a common and debilitating complication of chronic kidney disease (CKD), but its pathogenesis remains incompletely understood. Endostatin, an anti-angiogenic peptide that is elevated in CKD, may impair erythropoiesis through vascular dysfunction. We investigated the relationship between circulating endostatin and both prevalent and incident anemia in older adults, as well as whether kidney function modified this association. We analyzed data from 2,008 participants aged ≥ 75 years enrolled in the Screening for CKD among Older People across Europe (SCOPE) prospective cohort. Cross-sectional associations between standardized log-transformed endostatin and hemoglobin levels or prevalent anemia were assessed using linear and logistic regression, respectively. Dose-response relationships were explored across endostatin tertiles. Longitudinal analyses included 1,394 non-anemic individuals followed for two years; incident anemia was assessed using Fine-Gray competing risk models, with death treated as a competing event. Models were progressively adjusted for demographics, comorbidities, kidney function, iron status, medications, and baseline hemoglobin. Sensitivity analyses included Winsorization and subgroup interaction testing. At baseline, 405 participants (20.2

BACKGROUND:Carbamazepine is an antiepileptic and mood-stabilizing drug with complex pharmacokinetics and a narrow therapeutic index, making therapeutic drug monitoring (TDM) essential. The therapeutic reference range for carbamazepine at our laboratory is 20-40 µmol/L (4.7-9.4 mg/L). Long-term laboratory data may help identify population trends, seasonal or demographic variation, and the suitability of patient-derived medians as a quality-assurance tool. METHODS:This retrospective study analyzed 12 577 serum carbamazepine results obtained between May 2007 and December 2025 at Uppsala University Hospital. The total number of unique individuals providing the test results was 3147. Demographic variables (age, sex) and sampling dates were included. Yearly percentiles were used to evaluate long-term trends, and monthly variation was assessed for seasonal effects. Equivalence of analytical results was examined during the transition from the Architect ci8200 to the Cobas Pro c503 platform (February 2021). RESULTS:Annual test volume peaked in 2010 (n = 955) and declined to 160 by 2025. Despite reduced testing, carbamazepine concentrations increased steadily over time, with median values rising from 25.2 µmol/L (5.9 mg/L) in 2007 to 31.2 µmol/L (7.4 mg/L) in 2025. Seasonal analysis showed predictable drops in sampling during the Swedish summer vacation period but no meaningful variation in drug concentrations. The method transition in February 2021 showed strong agreement between platforms, with slightly higher values on the Cobas system (Cobas = 1.049 × Architect - 0.164; R2 = 0.946). CONCLUSIONS:Carbamazepine concentrations in routine patient samples have gradually increased over 2 decades, independent of declining test frequency. Seasonal workload fluctuations did not affect observed levels. Patient-derived medians were stable and sensitive to method changes, supporting their role as complementary internal quality-control tools. Long-term TDM databases provide valuable insights for both clinical interpretation and laboratory quality assurance.

Skeletal muscle capillary density is correlated with physical performance and whole-body metabolic properties. Thus, we performed a genome-wide association study of skeletal muscle capillary-to-fiber ratio (C:F) (n = 603 males) and found that the rs115660502 G allele was associated (p < 5 × 10-8) with increased C:F and reduced skeletal muscle expression of RAB3 GTPase-activating non-catalytic protein subunit 2 (RAB3GAP2). The capillary-increasing G allele was more prevalent in elite endurance athletes than in power athletes and non-athlete controls in two independent cohorts. Low-muscle-expressing RAB3GAP2 expression quantitative trait locus (eQTL) alleles were associated with muscle damage in athletes. In healthy individuals, RAB3GAP2 expression was reduced by high-intensity intermittent training. RAB3GAP2 protein was not uniformly expressed in muscle but predominantly expressed in the endothelium and capillaries. RAB3GAP2 expression was lower in endurance compared with power athletes and was negatively associated with type I (oxidative) muscle fiber density. Experimental reduction of RAB3GAP2 in human endothelial cells led to (1) increased proliferation and tube formation in vitro, (2) regulation of secreted factors (e.g., CD70 and TNC) promoting angiogenesis and T cell activation, and (3) increased in vivo endothelial cell density in mice. RAB3GAP2 expression in skeletal muscle was negatively correlated with exercise-induced release of TNC in vivo in humans. In conclusion, RAB3GAP2 is expressed in the microvascular endothelium and is suggested to be a negative regulator of angiogenesis through a decrease in endothelial cell proliferation, possibly mediated by RAB18, with its low-expressing variant associated with higher muscle C:F and elite endurance performance.

Background/Objectives: Therapeutic drug monitoring (TDM) of cyclosporine is essential due to its narrow therapeutic index and pronounced pharmacokinetic variability. Long-term surveillance of patient results may provide insight into analytical stability and clinical practice patterns beyond conventional quality control approaches. Methods: This retrospective observational study included 48,835 routine whole blood cyclosporine concentrations analyzed at a tertiary university hospital laboratory between January 2006 and December 2025. Yearly patient percentiles (10th, 25th, 50th, 75th and 90th percentiles) were calculated to assess longitudinal trends, variability, and potential effects of analytical platform transitions. Results were analyzed overall and by sex. Results: The yearly number of reported cyclosporine results declined modestly over the study period. The overall median cyclosporine concentration was 134.4 µg/L, with negligible differences between female and male patients. The 10th, 25th, and 50th percentiles remained highly stable across the 20-year period, with coefficients of variation between 6.1% and 6.8%. Upper percentiles exhibited greater variability, but the total coefficient of variation for the 90th percentile remained below 8%. No systematic shifts associated with analytical platform transitions were observed. Conclusions: Long-term patient median and percentile analysis demonstrated remarkable temporal stability of cyclosporine concentrations over two decades, despite changes in analytical platforms and clinical practice. Continuous monitoring of patient medians and percentiles may serve as a valuable complementary quality indicator, particularly for assays with limited commutable quality control materials.

Abstract Background Monitoring end-tidal carbon dioxide (EtCO 2 ) and respiratory rate (RR) is a non-invasive and reliable, continuous breathing assessment method in intubated and spontaneously breathing patients. The prehospital spreading of this technique in awake patients has been limited by mainstream capnographs´ dimensions and costs. Yet the potential prehospital applications of a wearable mainstream capnograph are many. This study aims to assess the ability to measure EtCO 2 of the novel mainstream MARIE capnograph in normal ambulance transport conditions. Methods A single-centre, observational, exploratory feasibility study conducted in Region Uppsala between December 2024 and January 2025. First 20 healthy adult volunteers were transported approximately 10 min by ambulance, having EtCO 2 and RR continuously measured by the mainstream device. Three measurements were performed (in the beginning, in the middle and at the end of the transport). A fourth value was noted on arrival in the Emergency Department (ED) with a reference capnograph for comparison with the third value by the mainstream device. The same measurement procedure was then repeated on 30 clinically stable adult patients transported by ambulance to the ED. Results A total of 20 volunteers and 29 patients were included in the final analysis. The comparison between the mainstream and reference capnograph showed that median EtCO 2 values were 4.6 [4.1–5.2] vs. 4.9 [4.4–5.2] kPa respectively ( p = 0.35). Bland Altman analysis showed a mean difference between the mainstream capnograph and reference device of 0.16 kPa (95% CI -0.07-0.41), with moderate correlation between measurements. The median values of breaths per minute were 17 [14–21] vs. 19 [15–22] respectively ( p < 0.01). Conclusion This study suggests that the mainstream capnograph MARIE is able to measure credible EtCO 2 values in standard ambulance transport conditions. Clinical trial registration ClinicalTrials.gov, TRN NCT06905613, Registration date 16th December 2024.

Abstract Advances in ultrasensitive immunoassays have enabled reliable quantification of neuroglial biomarkers in blood, providing valuable insights into neurological disorders. However, cross-platform evaluations are necessary to ensure comparability and standardization. This study aimed to compare the analytical performance of a Single Molecule Array (Simoa) and an ultrasensitive electrochemiluminescence (ECL) assay for quantifying neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in human serum. Baseline serum samples from 174 participants in the RIFUND trial were analyzed in parallel on both platforms. Concentrations of NfL and GFAP were compared using Spearman correlation, Bland–Altman analyses, reproducibility assessments, dilution linearity, and cross-platform recovery. All samples were quantifiable on both platforms. NfL concentrations correlated strongly between methods (Spearman correlation r = 0.88, p < 0.0001), whereas GFAP correlated moderately (r = 0.77, p < 0.0001). Inter- and intra-assay coefficients of variation were comparable between platforms for both analytes. The relationship between the two assays could be described with the following equations: NfLECL = 7.63 × NfLSIMOA + 1.71 and GFAPECL = 0.332 × GFAPSIMOA + 4.22. Dilution linearity was excellent on both platforms (R2 > 0.99), although cross-platform recovery varied systematically across the analytical range. Both Simoa and ECL demonstrated strong analytical performance for neuroglial biomarker quantification in serum. Despite systematic differences in absolute concentrations, relative agreement was high, particularly for NfL. These findings highlight the need for platform harmonization and provide empirically derived conversion factors to support analytical comparability in research and clinical applications.

IntroductionHigh salt intake is associated with adverse health outcomes. Emerging evidence highlights the importance of the gut microbiome in human health, but large-scale human data on salt intake and the microbiome are limited. We examined the cross-sectional association between estimated 24-h sodium excretion (est24hNa) and the gut microbiome in a population-based cohort.MethodsWe included 9,220 participants from the Swedish SCAPIS cohort with available shotgun metagenomic sequencing of fecal samples and urine analyses. We estimated the 24-h sodium excretion using the Kawasaki formula. Alpha diversity was assessed using the Shannon and inverse Simpson indices, and beta diversity using Bray–Curtis dissimilarity. Functional potential was evaluated using Gut Microbial Modules. Associations were analyzed using mixed linear regression models.ResultsAlpha diversity was inversely associated with est24hNa, but associations were attenuated after adjustment for BMI and were not significant in fully adjusted models. Beta diversity was associated with est24hNa, although the explained variance was small (R2 < 0.001). Higher est24hNa was associated with 75 microbial species, including lower abundance of 27 species and higher abundance of oral–associated taxa such as Streptococcus spp. and Veillonella. It was also associated with increased abundance of pathways involved in microbial energy metabolism and carbohydrate fermentation.ConclusionHigher est24hNa was associated with selected gut microbiome features, including a higher abundance of several oral-associated taxa and differences in inferred functional capacity for energy metabolism and carbohydrate fermentation. These findings identify microbial patterns associated with sodium exposure that may be relevant to cardiometabolic health.

Abstract Background and aims Biomarkers reflecting neuroplasticity, inflammation, and vascular integrity may explain variability in post-stroke recovery. This exploratory substudy of the PRACTISE trial (NCT05355831) examined longitudinal biomarker changes during stroke rehabilitation and their associations with upper-extremity (UE) motor recovery. Methods A total of 24 patients with subacute ischemic stroke (21 completers) received patient-tailored transcranial direct current stimulation (TDCS) or sham during four weeks of UE rehabilitation. UE motor function (FMA-UE) and clinical outcomes - including cognition (MoCA), depression (BDI-II), and quality of life (EQ-5D-5L) - were assessed at baseline, end-of-treatment, and at 12-weeks along with the biomarkers plasma Cathepsin-B, Cathepsin-S, E-selectin, and high-sensitivity C-reactive protein (hsCRP). Baseline MRI was rated for small-vessel-disease (SVD) burden using STRIVE criteria. Longitudinal biomarker changes were evaluated using mixed-effects regression. Results Despite substantial interindividual variability, increases in hsCRP were associated with less FMA-UE improvement from baseline to end-of-treatment (β = –0.75 ± 0.26, p = 0.01). The remaining biomarkers were not significantly related to FMA-UE improvement. Four participants who later experienced major adverse cardiovascular events showed marked elevations in hsCRP and Cathepsin-S at baseline. Sensitivity analyses revealed no significant associations with changes in cognition, depression, or quality-of-life, although a trend-level positive association was observed between E-selectin and MoCA-score. Conclusions Inflammatory activation—particularly elevated hsCRP and Cathepsin-S—was linked to poorer motor recovery and characterized individuals who later experienced major adverse cardiovascular events. These findings support further investigation of inflammatory biomarkers as indicators of both recovery potential and vascular risk during subacute stroke rehabilitation. Conflict of interest All authors have nothing to disclose.

Abstract Background Bacteremia caused by Pseudomonas aeruginosa carries a high mortality rate. P. aeruginosa also possesses several resistance mechanisms to antibiotics, mandating studies of novel therapies. Specific polyclonal anti- P. aeruginosa IgY-antibodies ( Pa -IgY) have been reported to decrease P. aeruginosa concentration in the airways. In this study, we investigated the effects of intravenous Pa -IgY on P. aeruginosa septic shock. Method Pigs were anaesthetized, mechanically ventilated, and allocated to receive either intravenous P. aeruginosa only, P. aeruginosa + low dose Pa- IgY, P. aeruginosa + high dose Pa- IgY or high dose Pa- IgY only. The experiment lasted 6 h with repeated blood cultures, blood tests, monitoring of physiological parameters and postmortem organ cultures. We performed in vitro cultures of P. aeruginosa +/- porcine neutrophils and +/- Pa- IgY and flow cytometry of FITC-marked inactivated P. aeruginosa cultured with porcine blood +/- Pa- IgY. Results The pigs developed septic shock with accompanying respiratory failure as a result of the P. aeruginosa infusion. Treatment with Pa- IgY increased bacterial concentrations, both in the porcine model in blood ( p = 0.004) and when P. aeruginosa was cultured after pre-treatment with Pa- IgY +/- neutrophils in vitro ( p < 0.001). The phagocytosis of P. aeruginosa in porcine blood was similar with and without Pa- IgY. Pa- IgY had no effect on the development or severity of septic shock. Animals with high dose Pa- IgY had higher PaO 2 /FiO 2 -ratio and static compliance. The inflammatory response was similar apart from higher IL-10 in animals treated with Pa- IgY ( p = 0.007). Conclusion In pigs with P. aeruginosa septic shock, treatment with Pa- IgY was associated with higher bacterial concentration in blood without an increased inflammatory response.

CONTEXT:Type 2 diabetes is a growing global concern with serious complications, including kidney damage and cardiovascular morbidity and mortality. Monitoring albuminuria, which is associated with these complications, is crucial in optimal diabetes management. Gut microbiota composition has been suggested to impact albuminuria, but large studies with granular data are lacking. METHODS:We investigated the relationship between 1002 gut microbial species, 1308 plasma metabolites, and albuminuria in 752 participants with type 2 diabetes from the Swedish CArdioPulmonary BioImage Study (SCAPIS). To determine the relative abundance of species, we employed deep shotgun metagenomic sequencing of fecal samples. Plasma metabolites were analyzed using mass spectrometry-based methods. RESULTS:We identified 3 species that were associated with albuminuria, including Sellimonas intestinalis, Eggerthellales sp., and Ellagibacter isourolithinifaciens. Two of these species were replicated in an independent prediabetic population (n = 3423) in SCAPIS. In total, 36 annotated metabolites were associated with the 3 albuminuria-signature species. Functional mapping of the signature species suggests a role in the regulation of the metabolites of imidazole propionate and trigonelline, which have previously been reported to play roles in the progression of albuminuria. CONCLUSION:These findings provide additional evidence of the potential impact of microbial species and contribute to our understanding of the complex relationship between the gut microbiome, plasma metabolites, and albuminuria in individuals with diabetes.

Background/Objectives: Lamotrigine is an anticonvulsant and mood stabilizer with wide interindividual pharmacokinetic variability, necessitating therapeutic drug monitoring (TDM). Patient-based quality control (PBQC) strategies, such as tracking median drug concentrations, may complement traditional quality assurance in routine laboratory practice. Methods: We retrospectively analyzed 15,963 lamotrigine results collected between February 2011 and December 2025 at Uppsala University Hospital, Uppsala. Data included age, sex, sampling date, and lamotrigine concentrations. Assays were performed using the Architect platform from February 2011 to January 2021, after which the Cobas Pro c 503 platform was implemented. Yearly patient medians were calculated, and trends, seasonal variation, and method agreement were assessed. Results: Of all the results, 5967 were from males and 9996 from females. Median concentrations were slightly higher in males (15.20 µmol/L) than in females (13.71 µmol/L), representing a weak but statistically significant difference (Spearman R = −0.048; p < 0.0001). The total number of reported results increased steadily over time, from 402 in 2011 to more than 1500 annually by 2024–2025. Median lamotrigine concentrations increased from 11.85 µmol/L in 2011 to 17.40 µmol/L in 2025 (Spearman R = 0.047; p < 0.0001). Seasonal variation in sample volume was observed, with peaks in November and troughs in July and December, but median concentrations remained stable (CV = 3.49%). Method comparison showed strong agreement between Architect and Cobas assays (R2 = 0.97). Conclusions: Patient median lamotrigine concentrations serve as a robust PBQC tool, capable of detecting subtle analytical shifts while remaining resilient to seasonal fluctuations and platform transitions. This approach enhances confidence in assay reliability and supports safer therapeutic decision-making in real-world TDM practice.

INTRODUCTION:The liver is essential for bacterial elimination, preventing intestinal bacteria from entering the systemic circulation, and for producing inflammatory cytokines. Glucocorticoids have been reported to exert heterogeneous effects on bacterial clearance in sepsis. Using a porcine model of gram-negative abdominal sepsis, we investigated how portal venous administration of budesonide, a glucocorticoid with extensive hepatic first-pass metabolism, affects hepatic bacterial and endotoxin elimination as well as the systemic inflammatory response, in comparison with systemic administration and no treatment. METHODS:The Portal Steroid-Sepsis (Sep-Port, n = 8) and Systemic Steroid-Sepsis (Sep-Syst, n = 8) groups were administered budesonide in the portal vein or systemically, followed by an E. coli infusion for 3 h in the portal vein. The Septic Controls (Sep-Ctrl, n = 8) received saline instead of budesonide. Non-septic Controls (NSep-Port, n = 3) were treated only with portal budesonide. Portal, arterial, and hepatic venous bacterial counts were analyzed hourly during the bacterial infusion. The levels of endotoxin and inflammatory cytokines were measured. RESULTS:There was no difference in hepatic/portal venous bacterial count ratios. However, the arterial and hepatic venous bacterial counts were higher in the Sep-Syst compared to Sep-Port group (p < 0.001 and p < 0.01, respectively), while microbiological findings were similar in the Sep-Port and Sep-Ctrl groups. Hepatic endotoxin elimination did not differ between the groups. IL-10 levels were higher in the Sep-Port compared to the Sep-Syst group at 1 h (p < 0.01), and IL-6 levels were lower in the Sep-Port compared to the Sep-Ctrl after the bacterial infusion (p < 0.05). CONCLUSIONS:In this experimental sepsis model, hepatic bacterial elimination was unaffected by portal or systemic budesonide, whereas systemic administration was associated with increased systemic bacterial levels. Endotoxin clearance was unaffected by budesonide. Portal budesonide elicited a more pronounced anti-inflammatory response compared to systemic administration. These findings suggest that hepatic exposure to budesonide may modulate the inflammatory response while limiting adverse effects on systemic bacterial clearance. EDITORIAL COMMENT:Glucocorticoids are widely used in sepsis management, yet their effects on bacterial clearance is incompletely understood. In this porcine model of gram-negative abdominal sepsis, portal venous delivery of budesonide (which has ~90% hepatic first-pass metabolism) preserved bacterial elimination and enhanced the early anti-inflammatory response, without the increase in systemic bacterial levels seen with systemic administration. These results demonstrate that route of delivery as a potentially important determinant of the risk-benefit balance of glucocorticoid therapy in sepsis, and support further investigation of hepatic-targeting strategies.

Background:Calprotectin, a neutrophil activation marker, is a promising diagnostic biomarker for infection and sepsis, but its usefulness in the emergency department (ED) is unclear. The aim of this study was to investigate the diagnostic value of calprotectin for sepsis and the source of infection in the ED. Methods:A total of 583 prospectively included patients presenting with suspected sepsis to the ED of a university hospital in southern Sweden were analyzed. Calprotectin was measured in plasma samples obtained at admission. Results:Mean age was 69 years and 49% were female. Calprotectin discriminated between sepsis and noninfectious systemic inflammatory response syndrome with an area under the curve (AUC) of 0.63, but was not an independent predictor in multivariable analysis including C-reactive protein (CRP). The Modified Early Warning Score did not show any discriminatory ability. Calprotectin and CRP discriminated between lower respiratory tract infection and (1) upper respiratory tract infection, (2) urinary tract infection, and (3) other sources of infection. Addition of calprotectin to CRP significantly increased the AUC for lower versus upper respiratory tract infection and lower respiratory tract infection versus urinary tract infection. Calprotectin was an independent predictor for all outcomes while CRP was only an independent predictor of lower versus upper respiratory tract infection. Conclusions:Calprotectin may improve differentiation of lower respiratory tract infections from upper respiratory tract infections and urinary tract infections in patients presenting to the ED with sepsis. Further research is needed to clarify if calprotectin adds diagnostic value to standard clinical assessment.

Abstract Background Chronic low-grade inflammation plays a central role in cardiometabolic disease, yet the associations between lipid metabolism and inflammatory biomarkers in generally healthy individuals remain incompletely understood. This study aimed to investigate the relationship between blood lipids, high-sensitivity C-reactive protein (hsCRP), and a broad panel of inflammatory cytokines in a healthy adult population. Methods A total of 165 healthy participants aged 18–44 years were recruited at the Falun County Hospital, Sweden. Blood samples were analyzed for a full lipid profile, blood counts, cytokines, and hsCRP. Plasma inflammatory protein levels were quantified using the Olink Proseek Multiplex Inflammation panel, including 92 cytokines. Statistical analysis included Spearman rank correlations and multiple testing correction using the Benjamini–Hochberg false discovery rate (FDR < 0.10). Results hsCRP showed significant correlations with several lipid parameters, particularly remnants, triglycerides, apolipoprotein B (ApoB), and non-HDL cholesterol, as well as with BMI and specific leukocyte counts. Additionally, hsCRP was significantly associated with multiple cytokines, including IL-6, TNF, IL-10, and CXCL10, highlighting a complex pro- and anti-inflammatory milieu. Conclusions This study demonstrates correlations between hsCRP, lipid-related biomarkers, and inflammatory cytokines in healthy adults, underscoring the interplay between lipid metabolism and subclinical inflammation. The significant correlations between hsCRP and remnants, ApoB, and cytokines such as IL-6 support the role of these factors as early indicators of cardiometabolic risk, even in the absence of overt disease.