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Results for “Systemic inflammation response index”

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PubMed2026

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72 h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR = 5.12; 95% CI: 2.57-12.24; p < 0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity < 0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p = 0.045) and significantly improved risk reclassification (cNRI = 0.4778, p < 0.001; IDI = 0.0240, p = 0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans↗

PubMed2026

Associations of clinical and laboratory parameters with pediatric urolithiasis composition: A retrospective, single-center study.

OBJECTIVE: To investigate demographic, clinical, and laboratory factors associated with distinct stone compositions in children. METHODS: This retrospective study included 237 children aged <14 years who underwent stone composition analysis between July 2008 and November 2023. Demographic, clinical, and laboratory data were collected, and propensity score matching (PSM) was used to control for confounding factors. RESULTS: The urate component (uric acid anhydrous, ammonium acid urate, and sodium urate) was most prevalent in infants, males, and non-Han children, whereas the calcium oxalate component predominated in older children. Analysis of coexisting components revealed urate is the most common partner to calcium oxalate (67.6%), and vice versa (82.8%). Struvite most frequently coexisted with carbonate apatite (60%), while carbonate apatite most often coexisted with calcium oxalate (54%). After PSM, the urate component was independently associated with host metabolic dysregulation, including lower high-density lipoprotein (β = -0.175, 95% CI: -0.279 to -0.071, p = 0.001) and with coagulation dysfunction, as evidenced by a prolonged prothrombin time (β = 0.595, 95% CI: 0.125 to 1.064, p = 0.014). Additionally, preoperative urinary tract infection (UTI) and congenital urinary tract anomalies were independently associated with both carbonate apatite and struvite components, with directionally consistent but quantitatively unstable signals in the struvite cohort, whereas the calcium oxalate component exhibited an inverse association with UTI (OR = 0.156, 95% CI: 0.030 to 0.819, p = 0.028). Furthermore, the carbonate apatite component was also independently associated with an elevated systemic immune-inflammation index (β = 416.53, 95% CI: 60.05 to 773.01, p = 0.024) and systemic inflammation response index (β = 1.286, 95% CI: 0.086 to 2.487, p = 0.038). CONCLUSION: Urate component was prevalent in infants, males, and non-Han children, whereas calcium oxalate predominated in older children. After adjusting for confounders, urate composition was associated with metabolic abnormalities, the carbonate apatite component was linked to infection and anatomical malformations, and a similar directional pattern was observed in the struvite cohort.

Humans↗

PubMed2026

Prognostic modeling of overall survival in metastatic pancreatic cancer: an inflammation-based tool validated in PANTHEIA-SEOM cohort.

PURPOSE: To develop and internally validate the PANTHEIA-SIRI prognostic model, which integrates log-transformed systemic inflammation response index (SIRI) with clinical predictors, to estimate overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line chemotherapy. METHODS: We used data from the multicenter PANTHEIA-SEOM registry. OS was defined from chemotherapy start. The model was fitted as a Weibull accelerated failure time model in the survival-analysis population with multiple imputation. Predictors were log-transformed baseline SIRI, modeled with restricted cubic splines, ECOG, tumor burden, chemotherapy regimen, and anorexia-cachexia syndrome. Internal validation used a separate, non-overlapping cohort from the same registry; the centers contributing to each cohort are listed in a supplementary annex. TRIPOD was followed. Discrimination was assessed with Harrell´s C-index and calibration with IPCW Brier scores and IPA. RESULTS: The derivation cohort comprised 672 patients with SIRI data (593 analyzed for survival) across 22 Spanish hospitals (2015-2025); 80.1% had died after a median OS of 9.9 months. The imputation-pooled derivation C-index was 0.654 (95% CI, 0.627-0.681); optimism-corrected, 0.629. Internal validation used 62 separate patients from the same registry; 96.8% had died after a median OS of 9.2 months. The validation C-index was 0.603 (95% CI, 0.518-0.687). Calibration was adequate at 6 and 12 months. CONCLUSIONS: The PANTHEIA-SIRI model provides individualized OS estimates in mPDAC with routine clinical predictors. Its open-access calculator ( https://pantheia-siri.shinyapps.io/calc/ ) may support prognostic communication, treatment-intensity selection, and supportive-care planning. Routine clinical implementation will require further validation in larger, fully independent cohorts.

Cachexia↗

PubMed1975

Prostaglandin F2alpha and human prostatic affinity for testosterone.

Earlier work had shown that the lactogen, LTH and HPL, foster testosterone binding by the prostate. This study was undertaken to see if prostaglandin F2alpha would oppose the effect of the lactogen on the prostate as it does the luteotrophic action of the hormone on the corpus luteum. When it was found instead that the PGF increases steroid binding and that its interaction with lactogen was neither antagonistic nor additive, attention was directed to further characterization of prostaglandin's effect. A dosage/response study of F2alpha alone showed that concentrations of 4 ng/ml and 40 ng/ml increased binding but that 400 ng/ml did not. Glands with stromal hyperplasia and/or inflammation were not responsive than those with epithelial hyperplasia. Assays of water extracts of the tissue revealed concentrations of about 340 ng of F2alpha per gram fresh weight and that the concentration varied inversely as the beta-glucuronidase activity. If the enzyme level is considered an index of the epithelial cell density within the specimen, the inverse relationship suggest a non-epithelial (stromal) site of prostaglandin concentration.

Dose-Response Relationship, Drug↗

PubMed1979

Periodontal status of patients with reduced immunocapacity.

The periodontal status of patients with reduced immunocapacity was assessed. Gingival inflammation, periodontal destruction, and plaque accumulation were compared in three groups--renal transplant patients, dialysis patients, and normal individuals. The levels of all parameters were similar in the three groups indicating that immunosuppression does not affect the clinical appearance of periodontal disease when measurements are made in a single examination. In the transplant group, however, there is a lack of correlation between P.I. and G.I. and between P.I. and P.D.I., indicating a dissociation between plaque accumulation and the tissue response. Long-term longitudinal studies of periodontal disease in such patients are needed in order to obtain more meaningful information on the role of the immune system in affecting the rate of periodontal destruction. This study suggests that nonimmune mechanisms such as the direct effect of bacterial products on supporting tissues can account for at least some of the clinical manifestations of periodontal disease.

Adult↗

PubMed1976

Gingival crevicular fluid: a new diagnostic aid in managing the periodontal patient.

On the whole, the studies on GCF have demonstrated that the flow of this fluid is sufficiently indicative of the inflammatory state that it can be used under a variety of clinical conditions to monitor and control gingival inflammation. Since gingivitis is extremely common, and since some cases of gingivitis presumably do not progress to periodontitis, the question could be posed whether or not a concerted effort to control inflammation (i.e. trying to achieve a GCF flow as near to zero as possible) would be clinically significant. Until there is evidence to the contrary, the answer must be "yes", since few cases are known where periodontitis occurs without being preceded by gingivitis. In other words, the control of all gingivitis, if feasible, should prevent most cases of periodontitis. Although control of all gingivitis would mean the treatment of many cases that would not progress to periodontal breakdown, such efforts would be worth-while if most periodontal destruction were prevented. Even the early destructive lesion exhibiting little or no inflammation may soon be identified, mainly because the minute volume of fluid collected from the gingival crevice can now be measured accurately. Accordingly, the concentration of various constituents in the GCF can be determined, which should lead to the development of tests to differentiate between pockets undergoing active destruction with minimal inflammation from the majority of active lesions that are intimately involved with frank inflammation. Thus, a clinician would measure sub-clinical gingival inflammation by measuring GCF flow, then differentiate destructive from quiescent lesions by analyzing the GCF sample for some constituent(s), chemical or microbial (Listgarten et al. 1975) indicative of the periodontal destructive process. Monitoring the flow of GCF might be of value in other clinical situations. For example, one could monitor the response of gingival tissues to various restorative and prosthetic procedures (Strauss et al. 1975) to ensure that these procedures do not aggravate the periodontal tissues and induce gingivitis or periodontitis. The education of the patient should be easier since patients can read their own numbers on the GCF meter at each examination and self-evaluate their personal periodontal condition and the effectiveness of their home care. Even the education of the dental student should be easier since he or she would have the means of self-evaluating the effectiveness of treatment, and not be as dependent upon the subjective assessment of his efforts by an instructor. Finally, monitoring GCF for various components could provide the dentist with a valuable means of easily screening patients for systemic disease. Obviously, this area of investigation is in its infancy, but does promise an exciting future for the oral diagnostician.

Ammonia↗

PubMed2026

Single-nucleus profiling reveals hepatocyte identity and immune features associated with corticosteroid response in severe alcohol-related hepatitis.

BACKGROUND & AIMS: Severe alcohol-related hepatitis (sAH) is associated with high short-term mortality. However, 30-40% of patients fail to respond to corticosteroids, the only proven pharmacological treatment. The pathophysiological mechanisms underlying sAH and the marked heterogeneity in treatment response remain incompletely understood. We aimed to define cellular changes associated with corticosteroid response in sAH and to identify baseline markers predictive of treatment outcome. METHODS: Single-nucleus RNA sequencing was performed on liver biopsies from patients with biopsy-proven sAH (n = 17), including paired baseline and day 8 biopsies in a subset of patients (n = 8). Patients were classified as corticosteroid responders (sAH-R; Lille score <0.45) or non-responders (sAH-NR; Lille score ≥0.45). Liver biopsies from patients with acute decompensation of alcohol-related cirrhosis (AD; n = 5) and healthy controls (n = 4) were included for comparison. Findings were validated using immunohistochemistry and spatial proteomics in a large multicenter validation cohort (n = 172). RESULTS: At baseline, sAH-R exhibited a significantly higher proportion of liver-infiltrating S100A8+ monocytes compared to sAH-NR, a difference that persisted at day 8. sAH livers showed a marked reduction in mature hepatocytes and an expansion of stressed and intermediate hepatocyte populations, indicating progressive loss of mature hepatocyte identity. This loss was more pronounced in sAH-NR, who also exhibited fewer cycling hepatocytes at day 8, consistent with impaired regenerative capacity. Expression of SULT2A1, a marker of mature hepatocyte identity, was significantly reduced in sAH-NR at baseline. Finally, liver biopsies with ≥50% SULT2A1-positive hepatocytes at baseline were strongly predictive of corticosteroid response. CONCLUSIONS: This study delineates distinct immune and hepatocyte changes associated with corticosteroid response in sAH. Baseline SULT2A1 expression may facilitate stratified treatment approaches in sAH. IMPACT AND IMPLICATIONS: Severe alcohol-related hepatitis (sAH) represents one of the most devastating manifestations of alcohol-related disorders. sAH is characterized by acute hepatic inflammation and high short-term mortality. Clinical management remains challenging, as corticosteroids - the only pharmacological therapy currently applied - are ineffective in a substantial proportion of patients and are associated with significant adverse effects. These limitations highlight the need for a more detailed understanding of sAH pathophysiology and for approaches that enable improved patient stratification and therapeutic decision-making. In this study, we identify distinct pre-treatment differences between corticosteroid responders and non-responders at the level of both hepatocytes and myeloid cells, providing new insight into the cellular mechanisms underlying treatment heterogeneity in sAH. Furthermore, leveraging these findings, we developed a histology-based SULT2A1 scoring system using a commercially available antibody, which predicts corticosteroid response at baseline and may support stratified treatment approaches in clinical practice.

Humans↗

PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗

PubMed2026

Exerkine dysregulation links visceral adiposity to skeletal muscle impairment in end-stage heart failure with reduced ejection fraction: proteomic evidence for a cardio-adipose-muscle axis.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is associated with profound alterations in body composition, skeletal muscle dysfunction, and impaired exercise capacity. Exerkines representing exercise-responsive signaling molecules released by skeletal muscle, adipose tissue, and other organs may mediate systemic metabolic communication between tissues. However, their role in advanced HFrEF and their relationship with adiposity and skeletal muscle characteristics remain poorly understood. METHODS: We studied 73 patients with end-stage HFrEF and 16 healthy controls. Body composition was assessed using computed tomography, including visceral (VAT), subcutaneous (SAT), and epicardial adipose tissue (EAT), as well as skeletal muscle quantity (psoas muscle index, PMI) and quality (psoas muscle density, PMD). Functional performance was evaluated using handgrip strength (HGT) and the 6-min walk test (6MWT). Circulating exerkines were quantified using the Olink technology. Associations between proteins and clinical variables were assessed using age- and creatinine-adjusted linear models with false discovery rate correction. RESULTS: Among patients with HFrEF, 36% were obese and 38% exhibited central obesity independent of BMI. Muscle strength and muscle quality were strongly associated with functional capacity. VAT correlated with muscle mass but not with muscle quality or performance. Compared with controls, HFrEF patients demonstrated elevated inflammatory and metabolic stress-related exerkines including CXCL8, CCL2, IL-6, TNF, IL-15, GDF15, FGF21, ANGPTL4, CTSB, DCN, and resistin. In contrast, proteins associated with muscle integrity and regenerative signaling (myostatin, BDNF, IL-7, SPARC) were significantly reduced. In HFrEF patients leptin strongly correlated with adiposity measures. Metabolic stress mediators (GDF15, IL-15, FGF21, CTSB) were inversely associated with muscle quality and functional performance, whereas myostatin positively correlated with muscle quality, strength, and exercise capacity. BDNF was inversely associated with frailty. CONCLUSIONS: Advanced HFrEF is characterized by a dysregulated exerkine network linking adiposity, skeletal muscle quality, and functional performance. Four biologically coherent axes were identified: a leptin-driven adiposity axis, a metabolic stress-muscle quality axis, a myostatin-related muscle function axis, and a neurotrophic frailty axis. These findings support the presence of a systemic cardio-adipose-muscle signaling network in end-stage HFrEF and identify candidate molecular mediators of sarcopenia and functional decline.

Humans↗