Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-analysis.

INTRODUCTION: The systemic inflammatory response index (SIRI) is a novel indicator of systemic inflammation derived from the absolute counts of neutrophils, monocytes, and lymphocytes. The aim of this meta-analysis was to evaluate the association between SIRI and functional outcome in patients with acute ischemic stroke (AIS). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Relevant cohort studies were retrieved by a search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure from database inception to February 9, 2024. A poor functional outcome was defined as a modified Rankin Scale ≥ 3 within 3 months after disease onset. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. The protocol of the meta-analysis was not prospectively registered in PROSPERO. RESULTS: Fourteen cohort studies were included. Pooled results showed that a high SIRI at admission was associated with increased risk of poor functional outcome within 3 months (odds ratio [OR]: 1.57, 95% confidence interval: 1.39 to 1.78, p < 0.001; I2 = 0%). Results of the meta-regression analysis suggested that the cutoff for defining a high SIRI was positively related to the OR for the association between SIRI and the risk of poor functional outcome (coefficient = 0.13, p = 0.03), while other variables including sample size, mean age, severity of stroke at admission, percentage of men, current smokers, or patients with diabetes did not significantly modify the results. Subgroup analyses according to study design, main treatments, and study quality scores showed similar results. CONCLUSION: A high SIRI may be associated with a poor functional outcome in patients after AIS.

Inhibitor of bromodomain and extraterminal domain proteins decreases transcription of Cd33 in the brain of mice subjected to systemic inflammation; a promising strategy for neuroprotection.

The neuroinflammation is a crucial component of virtually all neurodegenerative disorders, including Alzheimer's disease (AD). The bacterial lipopolysaccharide (LPS), a potent activator of the innate immune system, was suggested to influence or even trigger the neuropathological alterations in AD. LPS-induced neuroinflammation involves changes in transcription of several genes, thus controlling these molecular processes may be a potentially efficient strategy to attenuate the progression of AD. Since genome-wide association studies showed that the majority of AD-related genetic risk factors (AD-GRF) are connected to the immune system, our aim was to identify AD-GRF affected in the hippocampus by LPS-induced systemic inflammatory response (SIR). Moreover, we analysed the role of bromodomain and extraterminal domain (BET) proteins, the readers of the acetylation code, in controlling the transcription of selected AD-GRF in the brain during neuroinflammation. In our study, we used a mouse model of LPS-induced SIR and mouse microglial BV2 cells. JQ1 was used as an inhibitor of BET proteins. The level of mRNA was analysed using microarrays and qPCR. Our data demonstrated that among the established AD-GRF, only the expression of Cd33 was significantly upregulated in the hippocampus during SIR. In parallel, we observed an increase in the expression of Brd4, a BET family member. JQ1 prevented an LPS-evoked increase in Cd33 expression in the hippocampus of mice. Moreover, JQ1 reduced Cd33 expression in BV2 microglial cells stimulated with blood serum from LPS-treated mice. Our study suggests that LPS-evoked SIR may increase Cd33 gene expression in the brain, and inhibition of BET proteins through suppression of Cd33 expression could be a promising strategy in prevention or in slowing down the progression of neuroinflammation and may potentially affect the pathomechanism of AD.

Pancreatic cancer - epidemiology, risk factors, nutritional and infl ammatory prognostic and predictive factors.

BACKGROUND: Pancreatic cancer remains one of the most challenging malignancies to treat, with consistently low survival rates despite advances in medical research. The identification and validation of effective prognostic biomarkers are crucial for improving diagnostic accuracy and treatment outcomes. OBJECTIVE: The aim of the work is to analyze the latest data of the pancreatic cancer incidence and mortality, comparing them with global epidemiological data. The narrative review also aims to summarize current knowledge about various prognostic biomarkers in the pancreatic cancer treatment, including indicators of performance status, nutritional and inflammatory markers. METHODS: The most recently available national epidemiological data on pancreatic cancer are analyzed. The literature review is focused on markers that evaluate the general condition of patients, such as performance status, body mass index, prognostic nutritional index and markers of the inflammatory response, such as Glasgow prognostic score, C-reactive protein, neutrophil to lymphocyte ratio, systemic inflammatory response index and systemic immune inflammation index. These biomarkers are analyzed for their role in predicting prognosis and response to systemic therapy for pancreatic cancer. RESULTS: Both the Slovak Republic and the Czech Republic are globally ranked in the leading places in terms of pancreatic cancer incidence and mortality, both in estimates and real data. Indicators of nutritional and performance status play a critical role in patient assessment and influence treatment decisions, with potential impact on treatment outcomes. Inflammatory markers have shown significant prognostic value, correlating with the patient's immune response to the tumor and inflammatory processes that may promote disease progression. However, despite their promising predictive capabilities, these biomarkers are not routinely used in clinical practice due to the need for further validation. CONCLUSION: Integration of new biomarkers into clinical practice could lead to more personalized therapeutic decisions and improved treatment outcomes. Further research is needed for a more comprehensive assessment of the validity of these biomarkers and their use in common clinical conditions.

Investigation of Predictors of Systemic Inflammatory Response Syndrome After Endourological Procedure of Upper Urinary Tract Stones.

Background: In order to prevent infectious complications following endourological procedure of upper urinary tract stones, it is essential to determine which patients are at high risk of developing this complication. We aimed to identify predictors that may cause systemic inflammatory response syndrome (SIRS) after the endourological procedure of upper urinary tract stones. Materials and Methods: Patients who underwent percutaneous nephrolithotomy (PNL), flexible ureteroscopy (F-URS), or semirigid ureteroscopy (SR-URS) in our center between January 2011 and June 2020 were evaluated retrospectively. After surgery, patients were pursued for SIRS criteria. Logistic regression analyses were applied to identify predictors of SIRS. Results: A total of 1471 patients were included in the study. The rates of SIRS after PNL, F-URS, and SR-URS were 12.9%, 6.3%, and 1.7%, respectively. In multivariate analysis, predictors for SIRS were determined to be stone volume, operative time, and history of recurrent urinary tract infection (UTI) in the PNL group; ipsilateral stone surgery history, stone volume, and operative time in the F-URS group; and stone volume, operative time, and history of recurrent UTI in the SR-URS group. Conclusion: Stone volume and operative time were determined to be independent predictors of SIRS in endourological surgery of upper urinary tract stones.

Association of Systemic Inflammation Level on Admission with Total and Cardiovascular­Specific Death in Heart Failure with Preserved Ejection Fraction: A Large Multi­Center Retrospective Longitudinal Study.

Purpose: Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF. Patients and Methods: Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular­specific mortality, respectively. Results: 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01-1.35], 1.31[1.13-1.52], 1.51[1.30-1.76], respectively; P for trend <0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99-1.51], 1.50[1.20-1.86], 1.73[1.37-2.18], respectively; P for trend <0.001). Conclusion: Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.

Association of systemic inflammatory response index and clinical outcome in acute traumatic spinal cord injury patients.

Systemic inflammatory response index (SIRI) has been proven to be associated with the prognosis of coronary artery disease and many other diseases. However, the relationship between SIRI and acute traumatic spinal cord injury (tSCI) has rarely been evaluated. The study aims to assess the prognostic value of SIRI for clinical outcomes in individuals with acute tSCI. A total of 190 patients admitted within eight hours after tSCI between January 2021 and April 2023 were enrolled in our study. Logistic regression analysis was used to analyze the association between SIRI and American Spinal Injury Association Impairment Scale (AIS) grade at admission and discharge, as well as neurological improvement in tSCI patients, and receiver operating characteristic (ROC) analysis was performed to assess the discriminative ability of SIRI in predicting AIS grade at discharge. After adjusting for confounding factors, SIRI positively correlated with the AIS grade (A to C) at admission and discharge, and negatively correlated with neurological improvement. The area under the curve values in ROC analysis was 0.725 (95% CI 0.647, 0.803). The study suggests that SIRI is significantly associated with an increased risk of poor clinical outcome at discharge in tSCI patients and has a certain discriminative value.

Association of Systemic Inflammatory Response Index and Neutrophil-to-lymphocyte Ratio on Unfavorable Functional Outcomes in Acute Ischemic Stroke Patients after Endovascular Therapy.

BACKGROUND: Inflammatory markers for the prognosis of acute ischemic stroke (AIS) with endovascular therapy remain unclear. The purpose of this study was to investigate the association between the Systemic Inflammatory Response Index (SIRI) and Neutrophil-to-Lymphocyte Ratio (NLR) with unfavorable functional outcomes at 90-day in individuals of AIS who underwent endovascular therapy. METHODS: 128 AIS patients who had endovascular therapy were enrolled from the Nanjing Stroke Registry between September 2019 and November 2022. Peripheral venous blood was collected from patients within 24 h of admission for information on the following parameters: neutrophil count, lymphocyte count, monocyte count. Then, the SIRI and NLR values were calculated, and the association among SIRI, NLR, and modified Rankin Scale (mRS) scores 90 days after endovascular therapy was examined via univariate and multivariate logistic analyses. ROC curves were utilized to determine the best threshold for SIRI and NLR in predicting negative neurological outcomes following endovascular treatment for patients with AIS. RESULTS: 128 participants were evaluated, among which 50% had unfavorable outcomes. Linear regression analysis showed that the best threshold for SIRI was >1.407 (OR = 1.265; 95% CI, 1.071-1.493; P = 0.006), and for NLR it was >5.347 (odds ratio; OR = 1.088; 95% confidence interval [CI], 1.007-1.175; P = 0.033). These results revealed NLR and SIRI as significant predictors of unfavorable outcomes at 90 days. The AUC for SIRI and NLR in predicting 90-day adverse outcomes was 0.643 and 0.609, respectively. CONCLUSIONS: Higher SIRI and NLR levels at admission may lead to unfavorable outcomes at 90 days for AIS patients with endovascular therapy.

State of the art of sepsis care for the emergency medicine clinician.

Sepsis impacts 1.7 million Americans annually. It is a life-threatening disruption of organ function because of the body's host response to infection. Sepsis remains a condition frequently encountered in emergency departments (ED) with an estimated 850,000 annual visits affected by sepsis each year in the United States. The pillars of managing sepsis remain timely identification, initiation of antimicrobials while aiming for source control and resuscitation with a goal of restoring tissue perfusion. The focus herein is current evidence and best practice recommendations for state-of-the-art sepsis care that begins in the ED.

A systematic review of the role of systemic inflammation-based prognostic scores in patients with abdominal aortic aneurysm.

BACKGROUND AND AIMS: Activation of the systemic inflammatory response (SIR) is associated with inferior outcomes across a spectrum of disease. Routinely available measures of the SIR (neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory grade (SIG)) have been shown to provide prognostic value in patients undergoing surgical intervention. The present study aimed to review the literature describing the prognostic association of NLR, PLR, SII and SIG in patients undergoing intervention for abdominal aortic aneurysm (AAA). METHODS: This PRISMA guidelines were followed. The MEDLINE database was interrogated for relevant studies investigating the effect of peri-operative systemic inflammation-based prognostic systems on all-cause mortality in patients undergoing OSR and EVAR for AAA. Inter-study heterogeneity precluded meaningful meta-analysis; qualitative analysis was instead performed. RESULTS: There were 9 studies included in the final review reporting outcomes on a total of 4571 patients; 1256 (27 %) patients underwent OSR, and 3315 (73 %) patients underwent EVAR. 4356 (95 %) patients underwent a procedure for unruptured AAA, 215 (5 %) patients underwent an emergency procedure for ruptured AAA0.5 studies reported early (inpatient or 30-day) mortality; 2 of these found that elevated NLR predicted inferior survival, however PLR did not provide prognostic value. 6 studies reported long-term mortality; elevated NLR (5 studies), PLR (1 study), and SIG (1 study) predicted inferior survival. CONCLUSIONS: It appears that activation of the SIR is associated with inferior prognosis in patients undergoing intervention for AAA, however the evidence is limited by heterogenous methodology and lack of consensus regarding optimal cutoff. PROSPERO DATABASE REGISTRATION NUMBER: CRD42022363765.

Systemic inflammatory response index as a predictor of stroke-associated pneumonia in patients with acute ischemic stroke treated by thrombectomy: a retrospective study.

BACKGROUND: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy. METHODS: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis. RESULTS: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774). CONCLUSIONS: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP.

Association between systemic inflammatory response index and bone turnover markers in Chinese patients with osteoporotic fractures: a retrospective cross-sectional study.

Background: The systemic inflammatory response index (SIRI) is a novel composite biomarker of inflammation. However, there is limited information on its use in the context of osteoporotic fractures. Hence, this study aimed to investigate the association between baseline SIRI values and bone turnover markers (BTMs) in Chinese patients diagnosed with osteoporotic fractures (OPFs), to offer a more precise method for assessing bone health and inflammation in clinical settings. Methods: A retrospective cross-sectional study was conducted on 3,558 hospitalized patients with OPFs who required surgery or hospitalization at the First People's Hospital of Kunshan City from January 2017 to July 2022. Baseline measurements of SIRI, ß-CTX (beta-C-terminal telopeptide of type I collagen), and P1NP (procollagen type I N-terminal propeptide) were obtained. The analyses were adjusted for variables, including age, sex, body mass index (BMI), and other initial laboratory and clinical findings. Furthermore, multivariable logistic regression, smooth curve fitting, and threshold analysis were also performed. Results: The results revealed a negative correlation between baseline SIRI values and both ß-CTX and P1NP levels. After adjusting for covariates in the regression analysis, each unit increase in SIRI was found to be inked to a reduction of 0.04 (ß = -0.04; 95% confidence interval [CI], -0.05 to -0.03; with p-value <0.001) in ß-CTX levels and a decrease of 3.77 (ß = 3.77; 95% CI, 5.07 to 2.47; with p-value <0.001) in P1NP levels. Furthermore, a curvilinear relationship and threshold effect were also identified. Turning points were identified at SIRI values of 1.41 and 1.63 on the adjusted smooth curve. Conclusion: The results showed a negative correlation between the baseline SIRI value and ß-CTX level, as well as the level of P1NP. This suggests a possible link between the systemic inflammatory response and reduced bone metabolism. If these findings are verified, SIRI has the potential to function as a predictive indicator for BTMs. Nevertheless, additional research is necessary to verify these findings.

Inflammatory markers in systemic immune-inflammatory index and inflammatory response index to predict early pregnancy loss.

OBJECTIVES: To uncover the predictive value of systemic immune-inflammatory index (SII) and systemic inflammatory response index (SIRI) on early pregnancy loss. METHODS: A total of 535 individuals were enrolled in this retrospective analysis. The early pregnancy losses (EPL) group included patients between 18-35 years old who experienced EPL. The control group comprised healthy pregnant women who gave birth at ≥37 weeks. RESULTS: The EPL group had significantly lower plateletcrit (p=0.04), platelet distribution width (PDW, p<0.0001), and RDW (p<0.0001) and higher monocyte (p<0.0001) and SIRI (p<0.0001) values than the control group. The hemoglobin, white blood cells, platelet count, neutrophil count, lymphocyte count, mean platelet volume, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and SII values were not significantly different between the EPL and control groups (p>0.05). The cut-off value for the SIRI that offers the best sensitivity/specificity balance was 1.48 (sensitivity of 63%; specificity of 63%) in the receiver operating characteristics curve. Among the inflammatory parameters for predicting EPL, PDW had highest specificity (84%), and RDW had the highest sensitivity (80%). CONCLUSION: This study provides compelling evidence that various inflammatory pathways may significantly contribute to EPL pathogenesis. Moreover, our findings suggest that SIRI could be a more effective marker than NLR, PLR, MLR, and SII in predicting EPL in an ongoing pregnancy, thereby potentially revolutionizing early pregnancy loss diagnostics.

High systemic inflammatory response index (SIRI) is an independent risk factor for poor outcome in IgA nephropathy patients.

BACKGROUND: The systemic inflammatory response index (SIRI), a straightforward and easily accessible measure of inflammation and prognosis, has drawn more attention lately. It is unknown, however, if SIRI is important for IgA nephropathy (IgAN) patients' outcomes. To better clarify these concerns, we conducted this investigation. METHOD: This retrospective study involved 981 patients with biopsy-confirmed IgAN from West China Hospital of Sichuan University between 2008 and 2019. The patients were divided into two groups based on the SIRI's optimal cut-off value calculated by the X-tile: the low SIRI group (SIRI ≤ 0.63, n = 312) and the high SIRI group (SIRI > 0.63, n = 669). Basic clinical characteristics at the time of renal biopsy were evaluated, and the relationship between SIRI and the combined endpoint was analyzed. We also used the Cox proportional hazard model and Kaplan‒Meier curve to evaluate the renal prognosis of IgAN. RESULTS: A total of 981 IgAN patients were included. During a median follow-up period of 56.7 months (36.8-80.4 months), 122 patients progressed to the combined endpoint (12.4%). Patients were divided into a low SIRI group (SIRI ≤ 0.63, n = 312) and a high SIRI group (SIRI > 0.63, n = 669) according to the optimal cut-off value of the systemic inflammatory response index (SIRI). Further analysis showed that a higher SIRI value was significantly associated with the risk of IgAN patients reaching the composite endpoint (HR 1.62, 95% CI 1.02-2.56, p = 0.041). CONCLUSION: High SIRI is a significant and independent risk factor for renal disease progression in IgAN patients.

Mixed Shock Complicating Cardiogenic Shock: Frequency, Predictors, and Clinical Outcomes.

BACKGROUND: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity. METHODS: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters. RESULTS: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure (P=0.043), hepatic injury (P=0.049), and suspected/definite infection (P=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P=0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; Padj=0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; Padj<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; Padj=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; Padj=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; Padj=0.008). CONCLUSIONS: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.

A Novel Inflammatory Indicator for Tuberculosis-Associated Obstructive Pulmonary Disease (TOPD): The Systemic Inflammatory Response Index (SIRI).

Background: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients. Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD. Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM. Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.

The Association of Pretreatment Systemic Immune Inflammatory Response Index (SII) and Neutrophil-to-Lymphocyte Ratio (NLR) with Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma.

Objective: Immunoinflammatory response can participate in the development of cancer. To investigate the relationship between pretreatment systemic immune inflammatory response index (SII), systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and lymph node metastasis in patients with papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 547 PTC patients treated in Meizhou People's Hospital from January 2018 to December 2021. Clinicopathological data were collected, including gender, age, Hashimoto's thyroiditis, maximum tumor diameter, extra-membrane infiltration, disease stage, BRAF V600E mutation, pretreatment inflammatory index levels, and lymph node metastasis. The optimal cutoff values of SII, SIRI, NLR, PLR and LMR were calculated by receiver operating characteristic (ROC) curve, and the relationship between inflammatory indexes and other clinicopathological features and lymph node metastasis was analyzed. Results: There were 303 (55.4%) PTC patients with lymph node metastasis. The levels of SII, SIRI, NLR, and PLR in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis, while the levels of LMR were significantly lower than those in patients without lymph node metastasis (all p<0.05). When lymph node metastasis was taken as the endpoint, the critical value of SII was 625.375, the SIRI cutoff value was 0.705, the NLR cutoff value was 1.915 (all area under the ROC curve >0.6). The results of regression logistic analysis showed that age <55 years old (OR: 1.626, 95% CI: 1.009-2.623, p=0.046), maximum tumor diameter >1cm (OR: 2.681, 95% CI: 1.819-3.952, p<0.001), BRAF V600E mutation (OR: 2.709, 95% CI: 1.542-4.759, p=0.001), SII positive (≥625.375/<625.375, OR: 2.663, 95% CI: 1.560-4.546, p<0.001), and NLR positive (≥1.915/<1.915, OR: 1.808, 95% CI: 1.118-2.923, p=0.016) were independent risk factors for lymph node metastasis of PTC. Conclusion: Age <55 years old, maximum tumor diameter >1cm, BRAF V600E mutation, SII positive, and NLR positive were independent risk factors for lymph node metastasis in PTC.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

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

OBJECTIVE: The 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). METHODS: We 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. RESULTS: Among 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. CONCLUSION: Machine 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.

Graft-to-recipient weight ratio and risk of systemic inflammatory response syndrome early after liver transplantation in children.

BACKGROUND: Systemic inflammatory responses soon after liver transplantation in children can lead to complications and poor outcomes, so here we examined potential risk factors of such responses. METHODS: Data were retrospectively analyzed for 69 children who underwent liver transplantation at a single center between July 2017 and November 2019 through follow-up lasting up to one years. Numerous clinicodemographic factors were compared between those who suffered early systemic inflammatory response syndrome (SIRS) or not. RESULTS: Of the 69 patients in our analysis, early SIRS occurred in 35 [50.7%, 95% confidence interval (CI), 38.6-62.8%]. Those patients showed significantly higher graft-to-recipient weight ratio (3.69 ± 1.26 vs. 3.12 ± 0.99%, P = 0.042) and lower survival rate at one year (85.7% vs. 100%, P = 0.023). Multivariate analysis found graft-to-recipient weight ratio > 4% to be an independent risk factor for early SIRS [odds ratio (OR) 3.8, 95% CI 1.08-13.371, P = 0.037], and a cut-off value of 4.04% predicted the syndrome in our patients, and area under the receiver operating characteristic curve of 0.656 (95% CI 0.525-0.788, P = 0.026). CONCLUSIONS: Graft-to-recipient weight ratio > 4% may predict higher risk of SIRS soon after liver transplantation in children.