Systemic Response Research Articles

Pancreatic Stone Protein in the Diagnosis of Sepsis in Children Admitted to High-Dependency Care: A Single-Center Prospective Cohort Study.

Blood level of pancreatic stone protein (PSP) is a promising biomarker of sepsis both in adults and children. The aim of our study was to investigate the diagnostic accuracy of PSP in children with suspected sepsis and to compare diagnostic performance with other sepsis biomarkers approved for clinical use, that is, procalcitonin (PCT) and C-reactive protein (CRP). Prospective study. PICU and pediatric emergency department. Blood levels of PSP were measured using a nanofluidic point-of-care immunoassay (abioSCOPE, Abionic SA, Switzerland) within 24 hours of admission. We studied 99 children aged between older than 1 month and younger than 18 years with signs and symptoms of systemic inflammatory response syndrome (irrespective of associated organ dysfunction). The prevalence of sepsis was 35 of 99 (35.4%). Patients with sepsis had higher PSP levels (p < 0.001) than patients with systemic inflammation of noninfectious cause. In this analysis, the optimal cutoff for the diagnosis of sepsis using PSP was 123 ng/mL, which resulted in a sensitivity of 0.63 (95% CI, 0.43-0.80), specificity of 0.89 (95% CI, 0.77-0.95). The PSP test area under the receiver operating characteristic curve (AUROC) was 0.82 (95% CI, 0.73-0.91) and, by comparison, procalcitonin and CRP AUROC were 0.70 (95% CI, 0.58-0.82) and 0.72 (95% CI, 0.60-0.84), respectively. Overall, the pretest to posttest probability of sepsis with a positive test changed from 0.35 to 0.73. In this single-center prospective pediatric cohort, admitted to the high intensive care and to the PICU, our findings suggested the potential use of PSP as a sepsis biomarker. However, because of the clinical diagnostic uncertainty with a positive result, further investigation is needed particularly in combination with other biomarkers.

Association between house dust endotoxin and kidney injury: findings from the national health and nutrition examination survey (NHANES) 2005-2006.

House dust endotoxin is thought to be associated with systemic inflammatory responses and respiratory diseases. Previous studies have indicated that lung injury and systemic inflammation could lead to kidney damage. However, the potential link between house dust endotoxin and the increased risk of kidney injury remains unexplored. This cross-sectional study and retrospective study aim to investigate the relationship between house dust endotoxin levels and renal markers, specifically the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR), utilizing data from the NHANES 2005-2006 survey cycle. Proteinuria was assessed using the UACR, with values categorized into negative (UACR ≤ 30mg/g) and positive (UACR > 30mg/g) groups. Significant differences in house dust endotoxin levels were observed between these groups (p value = 0.003). Weighted logistic regression analysis indicated that higher levels of house dust endotoxin were associated with an increased rate of positive UACR (OR [95% CI]: 1.57 [1.20, 2.05]; p value = 0.003). This association remained significant after adjusting for covariates such as age, gender, race, poverty income ratio (PIR), Type 2 Diabetes Mellitus (T2DM), and hypertension (OR [95% CI]: 1.46 [1.08, 1.97]; p-Value = 0.021). However, no significant correlation was found between house dust endotoxin levels and eGFR (Estimate [95% CI]: 1.19 [-1.28, 3.66]; p value = 0.32). Our findings suggest a significant association between house dust endotoxin levels and proteinuria, based on data from the NHANES 2005-2006 survey cycle. This association indicates that elevated levels of house dust endotoxin may be linked to kidney damage. Further research is necessary to elucidate the specific relationship between exposure to house dust endotoxin and the risk of developing kidney disease.

Unveiling systemic responses in kidney transplantation: interplay between the allograft transcriptome and serum proteins

Immunity, as defined by systems biology, encompasses a holistic response throughout the body, characterized by intricate connections with various tissues and compartments. However, this concept has been rarely explored in kidney transplantation. In this proof-of-concept study, we investigated a direct association between the allograft phenotype and serum protein signatures. Time-matched samples of graft biopsies and blood serum were collected in a heterogeneous cohort of kidney-transplanted patients (n = 15) for bulk RNA sequencing and proteomics, respectively. RNA transcripts exhibit distinct and reproducible, coregulated gene networks with specific functional profiles. We measured 159 serum proteins and investigated correlations with gene expression networks. Two opposing axes—one related to metabolism and the other to inflammation—were identified. They may represent a biological continuum between the allograft and the serum and correlate with allograft function, but not with interstitial fibrosis or proteinuria. For signature validation, we used two independent proteomic data sets (n = 21). Our findings establish a biological link between the allograft transcriptome and the blood serum proteome, highlighting systemic immune effects in kidney transplantation and offering a promising framework for developing allograft-linked biomarkers.

Discovery of a Novel Benzimidazole Necroptosis Inhibitor from an In-House Compound Library

AbstractNecroptosis, a caspase-independent regulated cell death, is primarily mediated by the serine/threonine kinases RIPK1 and RIPK3, and the mixed lineage kinase domain-like protein (MLKL). Targeting necroptosis is a validated therapeutic strategy for various diseases. We screened compound 1, a novel benzimidazole-based necroptosis inhibitor, from our in-house compound library. We assessed its inhibitory roles and mechanisms in blocking HT-29 cell necroptosis. HT-29 cells were treated with pan caspase inhibitor Z-VAD-FMK + Smac mimetic (TSZ), or Z-VAD-FMK + cycloheximide (TCZ), then with tumor necrosis factor α (TNFα) to induce necroptosis in vitro. Prior to stimulation, cells were exposed to compound 1. GSK'843 served as a control drug. HT-29 cells were treated with TNFα + Smac mimetic (TS) or TNFα + cycloheximide (TC) to induce apoptosis in vitro. Cell viability, cell death, and necroptotic cells were evaluated by luminescence-based CellTiter-Lumi assay or flow cytometry. Western blots, immunoprecipitation, and KINOMEscan technology were used to assess RIPK1, RIPK3, and MLKL's involvement in compound 1's mechanisms. Compound 1's roles in mouse TNFα induced systemic inflammatory response syndrome (SIRS) in mice were also investigated by assessing body temperature, mouse survival rate, and interleukin (IL)-β and IL-6 levels in respective tissues. We found that necroptosis triggered by TSZ or TCZ was effectively mitigated by compound 1, showing a dose-responsive inhibition, and it could protect mice from TNF-induced SIRS. The mechanism study showed that compound 1 could interact with RIPK1, inhibiting RIPK1 phosphorylation activation to block necrosome formation in necroptotic cells. In summary, compound 1 is a promising lead compound for developing treatments targeting diseases associated with necroptosis.

Preoperative systemic inflammation response index enhances the prognostic value of tumor multifocalityin upper tract urothelial carcinoma

Preoperative systemic inflammation response index enhances the prognostic value of tumor multifocalityin upper tract urothelial carcinoma

A Diketopyrrolopyrrole-Based All-in-One Nanoplatform for Self-Reinforcing Mild Photothermal Therapy Cascade Immunotherapy for Tumors.

Mild photothermal therapy (PTT) has attracted attention for effectively avoiding the severe side effects associated with high-temperature tumor ablation. However, its progress is hindered by the limited availability of high-performance photothermal agents (PTAs) and the thermoresistance of cancer cells induced by heat shock reactions. Herein, this work proposes a new strategy to expand the library of high-performance organic small-molecule PTAs and utilize it to construct a multifunctional nano-theranostic platform. By incorporating additional acceptors and appropriate π-bridges, a diketopyrrolopyrrole-based dye BDB is developed, which exhibits strong absorption and bright fluorescence emission in the near-infrared (NIR)region. Subsequently, BDB is co-coated with the heat shock protein (HSP) inhibitor tanespimycin (17-AAG) using the functional amphiphilic polymers DSPE-Hyd-PEG2000-cRGD to form an all-in-one nanoplatform BAG NPs. As a result, BAG NPs can precisely target tumor tissue, guide the treatment process in real-time through NIR-II fluorescence/photoacoustic/photothermal imaging, and release 17-AAG on demand to enhance mild PTT. Additionally, the mild PTThas been demonstrated to induce immunogenic cell death (ICD) and activate a systemic anti-tumor immune response, thereby suppressing both primary and distant tumors. Overall, this study presents a multifunctional nanoplatform designed for precise mild PTT combined with immunotherapy for effective tumor treatment.

Autologous haematopoiesis stem cell transplantation (AHSCT) for treatment-refractory autoimmune diseases in children

ObjectivesTo evaluate the long-term effectiveness and safety of autologous haematopoiesis stem cell transplantation (AHSCT) for severe, refractory autoimmune diseases in paediatric patients.MethodsA single-centre study of consecutive children and adolescents with...

Surface Display of Duck Hepatitis A Virus Type 1 VP1 Protein on Bacillus subtilis Spores Elicits Specific Systemic and Mucosal Immune Responses on Mice.

Duck viral hepatitis, primarily caused by duck hepatitis A virus type 1 (DHAV-1), poses a significant threat to the global duck industry. Bacillus subtilis is commonly utilized as a safe probiotic in the development of mucosal vaccines. In this study, a recombinant strain of B. subtilis, designated as B. subtilis RV, was constructed to display the DHAV-1 capsid protein VP1 on its spore surface using the outer coat protein B as an anchoring agent. The immunogenicity of this recombinant strain was evaluated in a mouse model through mixed feeding immunization. The results indicated that B. subtilis RV could elicit specific systemic and mucosal immune responses in mice, as evidenced by the high levels of serum IgG, intestinal secretory IgA, and potent virus-neutralizing antibodies produced. Furthermore, the recombinant strain significantly upregulated the expression levels of IL-2, IL-6, IL-10, TNF-α, and IFN-γ in the intestinal mucosa. Thus, the recombinant strain maintained the balance of the Th1/Th2 immune response and demonstrated an excellent mucosal immune adjuvant function. In summary, this study suggests that B. subtilis RV can be a novel alternative for effectively controlling DHAV-1 infection as a vaccine-based feed additive.

The clinical value of nutritional and inflammatory indicators in predicting pneumonia among patients with intracerebral hemorrhage

Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079–0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.

Higher systemic inflammation response index is associated with increased risk of heart failure in adults: An observational study.

Inflammation has been established to play a crucial role in the onset of heart failure (HF) for many years, and the systemic inflammation response index (SIRI) is a new and comprehensive indicator reflecting the inflammation status in human body. The aim of this investigation was to determine the potential relationship between HF and SIRI in adults. For this investigation, we used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2009 to 2018. The study utilized multivariable linear regression models to examine the potential independent relationship between HF and SIRI. Additionally, a subgroup analysis and interaction test were carried out. To illustrate the nonlinear relationship, threshold effect analysis and fitted smoothing curves were also used. 26,303 eligible subjects aged ≥ 20 years were enrolled as the final samples. HF participants exhibited significant higher SIRI compared with non-HF participants [1.89 ± 1.33 vs 1.25 ± 0.95 (1000 cells/μL), P < .0001]. Multivariate logistic regression showed that those in the highest SIRI quartile had a significantly greater risk of HF by 130% (OR = 2.30, 95% CI 1.41-3.76; P < .0001). In addition, nonlinear relationship between HF and SIRI with the inflection point of 2.2 (1000 cells/μL) was observed. According to our research, adult HF prevalence and SIRI are positively correlated. This implies that SIRI could be a valuable biomarker for determining HF risk in the clinic.

T Cells Immune Imbalance Present in Patients With Multiple Intracranial Aneurysms.

Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to development of MIAs.

Immune response to cold exposure: Role of γδ T cells and TLR2-mediated inflammation.

The mammalian body possesses remarkable adaptability to cold exposure, involving intricate adjustments in cellular metabolism, ultimately leading to thermogenesis. However, cold-induced stress can impact immune response, primarily through noradrenaline-mediated pathways. In our study, we utilized a rat model subjected to short-term or long-term mild cold exposure to investigate systemic immune response during the cold acclimation. To provide human relevance, we included a group of regular cold swimmers in our study. Our research revealed complex relationship between cold exposure, neural signaling, immune response, and thermogenic regulation. One-day cold exposure triggered stress response, including cytokine production in white adipose tissue, subsequently activating brown adipose tissue, and inducing thermogenesis. We further studied systemic immune response, including the proportion of leukocytes and cytokines production. Interestingly, γδ T cells emerged as possible regulators in the broader systemic response, suggesting their possible contribution in the dynamic process of cold adaptation. We employed RNA-seq to gain further insights into the mechanisms by which γδ T cells participate in the response to cold. Additionally, we challenged rats exposed to cold with the Toll-like receptor 2 agonist, showing significant modulation of immune response. These findings significantly contribute to understanding of the physiological acclimation that occur in response to cold exposure.

Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Analysis of the immune-inflammatory indices for patients with metastatic hormone-sensitive and castration-resistant prostate cancer

BackgroundInflammation plays a pivotal role in the progression of prostate cancer (PCa). Several immune-inflammatory indices, including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), lymphocyte to monocyte ratio (LMR) and platelet to lymphocyte ratio (PLR), lung immune prognostic index (LIPI), systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), have demonstrated their prognostic values in several solid malignancies. However, Comparisons of superiority with these seven indices’ predictive efficacy within metastatic hormone-sensitive PCa (mHSPC) and metastatic castration-resistant PCa (mCRPC) remain uncertain.MethodsWe retrospectively included 407 patients diagnosed with mHSPC and 158 patients with mCRPC at West China Hospital from 2005 to 2022. The seven immune-inflammatory indices were computed based on hematological data of mHSPC at initial diagnosis and mCRPC at progression to CRPC. Prognostic value for castration-resistant prostate cancer-free survival (CFS), overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS) and prostate-specific antigen (PSA) response was assessed using Kaplan–Meier curves, Cox regression models, and chi-square tests. The predictive performance of each immune-inflammatory index was assessed using the area under the curve (AUC) in time-dependent receiver operating characteristic curve (ROC) analysis and C-index calculation.ResultsAll seven immune-inflammatory indices were significantly associated with CFS and OS in the mHSPC cohort, as well as with PSA response, PSA-PFS, and OS in the mCRPC cohort. In the mHSPC cohort, LIPI consistently exhibited higher AUC values compared to NLR, dNLR, LMR, PLR, SII, and SIRI for predicting CFS and OS. This indicates that LIPI had a superior discriminative ability compared to the other indices (C-index of LIPI: 0.643 and 0.686 for CFS and OS, respectively). Notably, the predictive advantage of LIPI over other indices in the mHSPC stage diminished in the mCRPC stage.ConclusionsThis study firstly confirmed the prognostic value of SII, SIRI and LIPI in mHSPC and mCRPC, and revealed that LIPI had a higher predictive power than NLR, dNLR, LMR, PLR, SII and SIRI in mHSPC. These non-invasive indices can enable clinicians to quickly assess the prognosis of patients.

Limited impact of traumatic brain injury on the post-traumatic inflammatory cellular response.

Trauma triggers a systemic inflammatory cellular response due to tissue damage, potentially leading to a secondary immune deficiency. Trauma severity is quantified by the Injury Severity Score (ISS). Severe Traumatic Brain Injury (TBI) is associated with high ISSs due to high lethality, despite limited tissue damage. Therefore, ISS might overestimate the post-traumatic inflammatory cellular response. This study investigated the effect of TBI on the occurrence of different systemic neutrophil phenotypes as alternative read-out for systemic inflammation. A single-center retrospective cohort study was conducted at a level-1 trauma center. Patients aged ≥ 18 years, admitted between 01-03-2021-01-11-2022 and providing a diagnostic blood sample were included. Four groups were created: isolated TBI, isolated non-TBI, multitrauma TBI and multitrauma non-TBI. Primary outcome was occurrence of different neutrophil phenotypes determined by automated flow cytometry. Secondary outcome was infectious complications. In total, 404 patients were included. TBI and non-TBI patients demonstrated similar occurrences of different neutrophil phenotypes. However, isolated TBI patients had higher ISSs than their isolated non-TBI controls who suffered similar post-traumatic inflammatory cellular responses. Regardless of the type of injury, patients exhibiting higher systemic inflammation had a high infection risk. When TBI is involved, ISS tends to be higher compared to similar patients in the absence of TBI. However, TBI patients did not demonstrate an increased inflammatory cellular response compared to non-TBI patients. Therefore, TBI does not add much to the inflammatory cellular response in trauma patients. The degree of the inflammatory response was related to the incidence of infectious complications.

Blood-Count-Derived Inflammatory Markers as Predictors of Response to Biologics and Small-Molecule Inhibitors in Psoriasis: A Multicenter Study

Background: Psoriasis is an immune-mediated chronic disorder associated with various comorbidities. Even though biologics and small-molecule inhibitors are the mainstay treatment for moderate-to-severe psoriasis, there is no current consensus regarding which agent should be used for a specific type of patient. This paper aims to test the reliability of blood-count-derived inflammatory markers in assessing treatment response to biologics and small-molecule inhibitors in psoriasis. Material and Methods: Bio-naïve adult patients diagnosed with chronic plaque psoriasis fulfilling the inclusion criteria were enrolled. They were divided into study subgroups based on treatment of choice, and blood-count-derived inflammatory markers were analyzed at baseline, three-month, six-month, and at twelve-month visits. Results: A total of 240 patients were included. The highest number of patients underwent treatment with ixekizumab. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI) all varied significantly (p &lt; 0.005) between the four visits. The psoriasis area severity index (PASI) score correlated with PLR, d-NLR, and SII, while the psoriasis scalp severity index (PSSI) score correlated with AISI and SIRI. More than half of patients reached the target goal of PASI90 at the six-month visit. A total of 77 patients were super-responders, with the highest number undergoing treatment with ixekizumab. Higher baseline values of d-NLR and SIRI are independent predictors of the super-responder status. Conclusions: Blood-count-derived inflammatory markers can serve as indicators of treatment response to biologics in psoriasis, while d-NLR and SIRI were independent predictors of super-responders in our study.

Comparison of Inflammatory Marker Scoring Systems and Conventional Inflammatory Markers in Patients over 65 Years of Age Admitted to the Intensive Care Unit: A Multicenter, Retrospective, Cohort Study

Background: The aim of the current study is to evaluate the effects of inflammation markers on infection and mortality in patients over 65 years of age monitored in the intensive care unit (ICU). In this study, we attempted to determine the significance of the pan-immune–inflammation value (PIV); the neutrophil–lymphocyte ratio (NLR); the platelet–lymphocyte ratio (PLR); the monocyte–lymphocyte ratio (MLR); the systemic immune–inflammatory index (SII); the systemic immune response index (SIRI); multi-inflammatory indices (MIIs) 1, 2, and 3; and the CRP/albumin ratio (a new biomarker) as prognostic and mortality markers in patients over 65 years of age being monitored in the ICU. Methods: This multicenter, retrospective, cohort study was conducted on patients aged 65 and over who were admitted to two tertiary-level ICUs. Patients with cirrhosis, bone marrow transplantation, hematologic malignancy, steroid intake, current chemotherapy treatment, and neutropenia upon admission to the ICU were excluded from this study. Results: A total of 333 patients were included in this study. The group’s 28-day mortality was found to be 31.8%. When each inflammatory marker associated with 28-day mortality was examined, the CRP/albumin ratio was found to be a better indicator than both the NLR and the SIRI, and the results were statistically significant (AUC: 0.665, 95% CI: 0.604–0.726, and p &lt; 0.001). The NLR showed moderate discriminative ability in distinguishing mortality risk (AUC: 0.593, 95% CI: 0.526–0.660, and p = 0.006). Although the SIRI was lower than the NLR, it produced a statistically significant result (AUC: 0.580, 95% CI: 0.514–0.646, and p = 0.019). The CRP/albumin ratio was the most effective inflammatory marker in predicting mortality risk in older patients admitted to the ICU. Conclusions: It is important to monitor inflammatory markers (especially CRP/albumin ratio, NLR, SIRI, and MII 1-2-3) in older patients admitted to the ICU in order to accurately predict 28-day mortality. In the current study, the effects of PIV, MLR, PLR, and SII on the prediction of 28-day mortality in older ICU patients could not be demonstrated. We believe that more clinical studies are needed to determine the effects of PIV, MLR, PLR, and SII on short- and long-term prognoses and survival in older ICU patients.

Systemic immune-inflammatory index and systemic inflammation response index in predicting renal impairment in children with type 1 diabetes mellitus

BackgroundThe aim of this study was to investigate the role of systemic immune-inflammatory index and systemic inflammation response index in predicting early renal impairment in children with type 1 diabetes mellitus (T1DM).MethodsThis is a retrospective cohort study which searched the electronic medical records of patients consecutively admitted to Pediatric Endocrinology Unit with the diagnosis of type 1 diabetes mellitus between August 2022 and July 2023.ResultsA total of 100 children with the diagnosis of T1DM were enrolled in the study. Early stage diabetic nephropathy (DN) was found in 34 patients. Patients with DN showed significantly higher HbA1C, microalbuminuria, cholesterol, TLC, platelet, neutrophil count, NLR, PLR, SII, and SIRI than the DM without DN. It was discovered that DN was independently correlated with NLR, PLR, SII, and SIRI.ConclusionsSIRI and SII are easily available and affordable inflammatory markers that may serve as independent early predictors of diabetic nephropathy in individuals with type 1 diabetes.

Machine learning models to predict systemic inflammatory response syndrome after percutaneous nephrolithotomy

ObjectiveThe objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL).MethodsWe retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance.ResultsAmong the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890–0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count.ConclusionMachine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.

Novel predictors of intravenous immunoglobulin resistance in patients with Kawasaki disease: a retrospective study

ObjectiveThe aim of this study was to investigate the predictive value of systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV) in predicting intravenous immunoglobulin (IVIG) resistance in children diagnosed with Kawasaki disease (KD).MethodsThe clinical data of pediatric patients diagnosed with Kawasaki disease and admitted to our hospital between January 2006 and December 2022 were retrospectively analyzed.ResultsIn total, 771 children diagnosed with KD were included in this study, 86 (11.2%) of whom were diagnosed with IVIG resistance. The correlation between SII, SIRI, PIV and IVIG resistance was evaluated using univariate testing, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. Our study found that the SII, SIRI, and PIV were independent risk factors (p=0.001, p&amp;lt;0.001, and p=0.02, respectively). The area under the ROC curve (AUC) values of the SII, SIRI, and PIV were 0.626 (95% confidence interval (CI): 0.553–0.698, p&amp;lt;0.001), 0.571 (95% CI: 0.500–0.642, p=0.032), and 0.568 (95% CI: 0.495–0.641, p=0.040), respectively, and the cutoff values were 2209.66, 3.77, and 1387.825, respectively.ConclusionThe SII, SIRI, and PIV have potential value in predicting IVIG resistance in patients with KD.