Systemic Inflammatory Response Research Articles

HL-204 Systemic Inflammatory Response Syndrome (SIRS) Induced by Bendamustine – A Case Series

HL-204 Systemic Inflammatory Response Syndrome (SIRS) Induced by Bendamustine – A Case Series

Risk assessment with gene expression markers in sepsis development

Infection is a commonplace, usually self-limiting, condition but can lead to sepsis, a severe life-threatening dysregulated host response. We investigate the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole-blood RNA sequencing analysis was performed on preoperative samples from 267 patients. These patients developed postoperative infection with (n= 77) or without (n= 49) sepsis, developed non-infectious systemic inflammatory response (n= 31), or had an uncomplicated postoperative course (n= 110). Machine learning classification models built on preoperative transcriptomic signatures predict postoperative outcomes including sepsis with an area under the curve of up to 0.910 (mean 0.855) and sensitivity/specificity up to 0.767/0.804 (mean 0.746/0.769). Our models, confirmed by quantitative reverse-transcription PCR (RT-qPCR), potentially offer a risk prediction tool for the development of postoperative sepsis with implications for patient management. They identify an individual predisposition to developing sepsis that warrants further exploration to better understand the underlying pathophysiology.

Inflammatory indices—Systemic Immune-Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI)—during Pregnancy and Associations with Gestational Diabetes Mellitus

Inflammatory indices—Systemic Immune-Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI)—during Pregnancy and Associations with Gestational Diabetes Mellitus

Correlation study of multiple inflammatory indices and vertebral compression fracture: A cross-sectional study

BackgroundVertebral compression fractures (VCFs) are prevalent in patients with osteoporosis and pose significant health risks. Although chronic low-grade inflammation plays a crucial role in the pathogenesis of osteoporosis, the relationship between various inflammatory indices and the occurrence of fractures remains unclear. ObjectiveThis study aims to evaluate the correlation between multiple inflammatory indices, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI), and VCFs, to explore the significance of these indices in clinical application. MethodsClinical data of 310 patients diagnosed with osteoporosis from November 2020 to June 2023 in the hospital were collected. The general conditions between fracture and non-fracture groups were described. Spearman analysis and binary logistic regression analysis were used to assess the relationship between inflammatory indices and VCFs. Receiver operating characteristic curve was used to evaluate the diagnostic efficacy of these inflammatory indices for VCFs. ResultsVCFs were diagnosed in 43.55 % of patients with osteoporosis. NLR(ρ = 0.169, P=0.003), MLR(ρ = 0.293, P<0.001), SII(ρ = 0.126, P=0.027), and SIRI(ρ = 0.273, P<0.001) were positively correlated with the occurrence of VCFs. NLR(OR=1.480, 95 %CI 1.114 ∼ 1.966, P=0.007), MLR(multiplied by 100, OR=1.048, 95 %CI 1.011 ∼ 1.087, P=0.011), and SIRI(OR=3.327, 95 %CI 1.510 ∼ 7.330, P=0.003) were independent risk factors for VCFs, hip bone mineral density (BMD) (OR=0.011, 95 %CI 0.001 ∼ 0.151, P=0.001) was an independent protective factor for VCFs. MLR(AUC 0.671, 95 % CI=0.610 ∼ 0.732, P <0.001) had relatively high clinical diagnostic efficacy. ConclusionThe neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index (SIRI) are independent risk factors for vertebral compression fractures.

Predictive factors for prolonged operative time in ureteroscopic lithotripsy for ureteral stones A retrospective cohort study.

A prolonged operative time of lithotripsy with ureteroscopy for urolithiasis increases the risk of infectious complications; however, few reports have investigated the factors prolonging the operative time for ureteral stones. We investigated the factors associated with longer operative time in ureteroscopy for ureteral stones. This retrospective cohort study analyzed patients who underwent retrograde ureteroscopic lithotripsy for ureteral stones and achieved an endoscopic stone-free status between April 2019 and July 2022. Patients were classified into two groups based on an operative time of ≥90 minutes or <90 minutes. We compared the patient and stone characteristics and surgical outcomes, and investigated the factors associated with a prolonged operative time. The cohort comprised 519 patients, with 58 patients in the group with an operative time of ≥90 minutes. Compared to the shorter operative time group, the longer operative time group had a significantly greater proportion of males, stone diameter, stone volume, and Hounsfield units of stone; additionally, the longer operative time group had higher prevalences of endoscopic findings of edema, polyps, and mucosa-stone adherence. Multivariable analysis showed that stone size >10 mm (odds ratio 4.05), polyps (odds ratio 2.40), and mucosal adherence (odds ratio 3.51) were significantly associated with an operative time exceeding 90 minutes. There were no significant differences between the two groups in the incidences of postoperative fever and systemic inflammatory response syndrome. Stone size, endoscopic findings of polyps, and mucosa-stone adherence were independent factors associated with a longer operative time.

Prognostic significance of diffuse increased fluorine-18-fluorodeoxyglucose (18F-FDG) uptake within the reticuloendothelial system in lymphoma patients.

As constituents of the reticuloendothelial system, the spleen and bone marrow (BM) have been recognized as integral components of the systemic inflammatory response in cancer contexts, thereby serving as predictive indicators for assessing cancer prognosis. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has attained widespread utilization for staging, assessing treatment response, and prognostication in lymphoma patients. Several investigations have proposed that focal increased 18F-FDG uptake in the BM or spleen may correlate with malignant involvement in lymphoma. However, scant data exist regarding the implications of diffuse BM and splenic uptake. This study aimed to explore the relationships between metabolic parameters of the spleen and BM on 18F-FDG PET/CT and inflammatory markers, and to assess their prognostic value in patients with lymphoma. A retrospective analysis was conducted on 118 patients newly diagnosed with malignant lymphoma, who underwent 18F-FDG PET/CT and exhibited diffuse increased splenic or BM uptake in 18F-FDG PET/CT imaging. The mean standardized uptake value (SUV) of the spleen, BM, and liver was calculated. The association between metabolic variables and systemic inflammatory markers was investigated, and the prognostic significance of clinicopathological and PET parameters was assessed using overall survival (OS) and progression-free survival (PFS). A statistically significant correlation was found between the spleen-to-liver SUV ratio (SLR) and inflammatory markers such as C-reactive protein (r=0.264, P=0.007) and platelet-to-lymphocyte ratio (r=0.227, P=0.021). No significant correlation was observed between BM-to-liver SUV ratio (BLR) and hematologic parameters, while concordance analysis revealed a fair agreement between BLR and bone marrow biopsy (BMB) (Cohen's Kappa-κ =0.271, P=0.002). In patients with aggressive non-Hodgkin lymphoma, both SLR [P=0.017, HR 2.715, 95% confidence interval (CI): 0.875-8.428] and BLR (P=0.044, HR 0.795, 95% CI: 0.348-1.813) were significantly linked to OS, while SLR (P=0.019, HR 2.223, 95% CI: 1.139-4.342) emerged as a significant prognostic factor for PFS. This study highlighted that diffuse increased splenic 18F-FDG uptake in lymphoma patients was closely associated with inflammation, whereas diffuse BM uptake was likely attributable to BM infiltration rather than inflammatory changes. Furthermore, both parameters held promise as prognostic indicators for patients with aggressive lymphoma.

Interpretable prediction of acute ischemic stroke after hip fracture in patients 65 years and older based on machine learning and SHAP

BackgroundHip fracture and acute ischemic stroke (AIS) are prevalent conditions among the older population. The prognosis for older patients who experience AIS subsequent to hip fracture is frequently unfavorable. MethodsPatients were categorized into the AIS group and the non-AIS group. A predictive model was developed using six different machine learning algorithms. The SHapley Additive exPlanations (SHAP) method was then utilized to provide both local and global explanations. We performed adjusted mediation analyses. Furthermore, a nomogram was created to present the outcomes obtained from the LASSO regression examination. The main objective was to ascertain influential elements that can predict the occurrence of AIS. To alleviate the influence of confounding variables, propensity score matching was utilized to compare the occurrence of additional complications. Survival was compared by Kaplan-Meier methods. ResultsThe AUC of 6 ML models ranged from 0.73 to 0.87. The SVM model exhibited the greatest efficacy in forecasting AIS among older individuals with hip fractures. The leading 6 variables in the support vector machines (SVM) model were identified as systemic inflammatory response index (SIRI), carotid atherosclerosis, prior stroke, C-reactive protein (CRP), fibrinogen (FIB), and hypertension. The leading 2 variables in SHAP were identified as FIB at admission and SIRI index. There wasn't potential mediating effect of admission FIB between the SIRI index and AIS. There were statistically significant differences between the two groups in survival (P=0.003). ConclusionsThe model displayed good performance for prediction of AIS after hip fracture in patients 65 years and older, which might facilitate to establishment of a better clinical assessment plan.

Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics

BackgroundCancer cachexia (CCx) presents a multifaceted challenge characterized by negative protein and energy balance and systemic inflammatory response activation. While previous CCx studies predominantly focused on mouse models or human body fluids, there's an unmet need to elucidate the molecular inter-organ cross-talk underlying the pathophysiology of human CCx. MethodsSpatial metabolomics were conducted on liver, skeletal muscle, subcutaneous and visceral adipose tissue, and serum from cachectic and control cancer patients. Organ-wise comparisons were performed using component, pathway enrichment and correlation network analyses. Inter-organ correlations in CCx altered pathways were assessed using Circos. Machine learning on tissues and serum established classifiers as potential diagnostic biomarkers for CCx. ResultsDistinct metabolic pathway alteration was detected in CCx, with adipose tissues and liver displaying the most significant (P ≤ 0.05) metabolic disturbances. CCx patients exhibited increased metabolic activity in visceral and subcutaneous adipose tissues and liver, contrasting with decreased activity in muscle and serum compared to control patients. Carbohydrate, lipid, amino acid, and vitamin metabolism emerged as highly interacting pathways across different organ systems in CCx. Muscle tissue showed decreased (P ≤ 0.001) energy charge in CCx patients, while liver and adipose tissues displayed increased energy charge (P ≤ 0.001). We stratified CCx patients by severity and metabolic changes, finding that visceral adipose tissue is most affected, especially in cases of severe cachexia. Morphometric analysis showed smaller (P ≤ 0.05) adipocyte size in visceral adipose tissue, indicating catabolic processes. We developed tissue-based classifiers for cancer cachexia specific to individual organs, facilitating the transfer of patient serum as minimally invasive diagnostic markers of CCx in the constitution of the organs. ConclusionsThese findings support the concept of CCx as a multi-organ syndrome with diverse metabolic alterations, providing insights into the pathophysiology and organ cross-talk of human CCx. This study pioneers spatial metabolomics for CCx, demonstrating the feasibility of distinguishing cachexia status at the organ level using serum.

Brain and Lung Biomarker Responses to Hyperoxic Hypobaric Decompression.

INTRODUCTION: Biomarker responses to intensive decompression indicate systemic proinflammatory responses and possible neurological stress. To further investigate responses, 12 additional brain and lung biomarkers were assayed.METHODS: A total of 15 healthy men (20 to 50 yr) undertook consecutive same-day ascents to 25,000 ft (7620 m), following denitrogenation, breathing 100% oxygen. Venous blood was sampled at baseline (T0), after the second ascent (T8), and next morning (T24). Soluble protein markers of brain and lung insult were analyzed by enzyme-linked immunosorbent assay with plasma microparticles quantified using flow cytometry.RESULTS: Levels of monocyte chemoattractant protein-1 and high mobility group box protein 1 were elevated at T8, by 36% and 16%, respectively, before returning to baseline. Levels of soluble receptor for advanced glycation end products fell by 8%, recovering by T24. Brain-derived neurotrophic factor rose by 80% over baseline at T24. Monocyte microparticle levels rose by factors of 3.7 at T8 and 2.7 at T24 due to early and late responses in different subjects. Other biomarkers were unaffected or not detected consistently.DISCUSSION: The elevated biomarkers at T8 suggest a neuroinflammatory response, with later elevation of brain-derived neurotrophic factor at T24 indicating an ongoing neurotrophic response and incomplete recovery. A substantial increase at T8 in the ratio of high mobility group box protein 1 to soluble receptor for advanced glycation end products suggests this axis may mediate the systemic inflammatory response to decompression. The mechanism of neuroinflammation is unclear but elevation of monocyte microparticles and monocyte chemoattractant protein-1 imply a key role for activated monocytes and/or macrophages.Connolly DM, Madden LA, Edwards VC, Lee VM. Brain and lung biomarker responses to hyperoxic hypobaric decompression. Aerosp Med Hum Perform. 2024; 95(9):667-674.

Systemic Immune-Inflammation Indices Could Be Additional Predictive Markers for Cesarean Scar Pregnancy.

Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP. In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination. The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (p<0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (p<0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity). Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP.

Combination of neutrophil-to-lymphocyte ratio and serum CA 19-9 as a prognostic factor in pancreatic cancer.

Traditionally, serum carbohydrate antigen 19-9 (CA 19-9) has been used as a key biomarker for pancreatic cancer and recently other biomarkers which reflect the systemic immune and inflammatory responses also have been explored as potential prognostic factors. The study aims to evaluate the significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and serum CA 19-9 as prognostic factor in pancreatic cancer patients. A retrospective analysis was conducted in 153 consecutive patients with pancreatic cancer in Instituto Nacional de Cancerología from 2013 to 2018. Pretreatment NLR and serum CA 19-9 values were recorded as well as survivals. The cut-off value determined for NLR was 2.4 and for serum CA 19-9 was 553 U/mL. Survival analysis showed that the 5-year overall survival (OS) was 9% in patients with low-NLR compared with 2% for patients with high-NLR (P=0.008), and 5-year progression-free survival (PFS) was 5.7% in patients with low-NLR compared with 1.3% in patients with high-NLR (P=0.007). For patients with low-CA 19.9, 5-year OS was 8.5% compared with 0% for patients with high-CA 19-9 (P=0.002), and 5-year PFS was 4.1% in patients with low-CA 19-9 compared with 0% in patients with high-CA 19-9 (P=0.005). Classification groups created showed that 5-year OS in Group 1 (low-NLR and low-CA 19-9) was 11.8% compared with 1.9% for patients in Group 2 (either one or both high-NLR or CA 19-9) (P<0.001), and 5-year PFS was 8.6% in Group 1 and 0% in Group 2 (P=0.001). High-NLR and high-CA 19-9 values used separately are both independently associated with worse OS and PFS in patients with pancreatic cancer. The classification groups created combining both biomarkers showed better prognostic significance than when used separately as demonstrated by survival analysis and multivariate analysis.

Short-term feed restriction induces inflammation and an antioxidant response via cystathionine-β-synthase and glutathione peroxidases in ruminal epithelium from Angus steers.

Decreased intake is induced by stressors such as parturition, transportation, dietary transitions, and disease. An important function of one-carbon metabolism (OCM) is to produce the antioxidant glutathione to help reduce oxidative stress. Although various components of OCM are expressed in the bovine rumen and small intestine, the relationship among reduced feed intake, one-carbon metabolism, and antioxidant mechanisms in gut tissues is unknown. This study aimed to assess alterations in immune and antioxidant pathways in ruminal epithelium due to acute feed restriction (FR). Seven group-housed ruminally-cannulated Angus steers (663 ± 73kg body weight, 2-year old) had ad libitum access to a finishing diet (dry-rolled corn, corn silage, modified wet distiller's grains) during 15 days of a pre-FR period (PRE). Subsequently, steers were moved to a metabolism barn with tie-stalls and individually-fed at 25% of estimated intake in PRE for 3 days (FR period, FRP). This was followed by 15-days of recovery (POST) during which steers had ad libitum access to the same diet as in PRE and FRP. Plasma and ruminal tissue biopsies were collected during each period. Plasma free fatty acid and IL1-β concentrations were higher (P ≤ 0.03) in FRP than PRE or POST. The mRNA abundance of the pro-inflammatory genes TNF, TLR2, and TLR4 in ruminal epithelium peaked (P < 0.05) at FRP and remained higher at POST. These responses agreed with the higher (P < 0.05) abundance of phosphorylated (p)-MAPK (an inflammation activator) and p-EEF2 (translational repressor) in FRP than PRE and POST. Although ruminal GPX enzyme activity did not increase at FRP compared with PRE and POST, protein abundance of GPX1 and GPX3 along with the antioxidant response regulator NFE2L2 were highest (P < 0.01) and the activity of cystathione-beta synthase tended (P = 0.06) to be highest during FR. Although FR had minimal negative effects on tissue integrity-related genes (only filamin A was downregulated), it led to a systemic inflammatory response and triggered inflammation and antioxidant mechanisms within ruminal epithelium. Thus, deploying anti-inflammatory and antioxidant mechanisms via molecules that feed into OCM (e.g., dietary methyl donors such as methionine, choline, betaine, folate) could potentially counteract the stressors associated with FR.

Predictive value of inflammatory markers (NLR, PLR, MLR, SII, SIRI, PIV, IG, and MII) for latency period in Preterm premature rupture of membranes (PPROM) pregnancies

BackgroundOur study aimed to investigate the value of inflammatory indices in predicting the latency period until birth in patients with preterm premature rupture of membranes (PPROM).MethodsThis retrospective study was conducted on PPROM cases between 24 and 34 weeks of gestation at Ankara Etlik City Hospital Perinatology Department from October 2023 to April 2024. A total of 146 participants were divided into two groups: Group 1 included 73 patients who gave birth within 72 hours (h) of PPROM diagnosis, and Group 2 included 73 patients who gave birth after 72 h.ResultsThis study evaluated the prognostic significance of various inflammatory markers neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), pan-immune inflammation value (PIV), immature granulocytes (IG), multi-inflammatory index (MII)-1, MII-2, and MII-3 in predicting the latency period in patients with PPROM. Only MII-1, MII-2, and MII-3 reliably predicted labor within 72 h. The cut-off value for MII-1 was > 48.3, with a sensitivity of 57.7% and specificity of 57.3% (AUC: 0.598, 95% CI: 0.503–0.692, p = 0.042). For MII-2, the cut-off was > 1037.6, with a sensitivity of 57.7% and specificity of 57.3% (AUC: 0.611, 95% CI: 0.516–0.705, p = 0.021). MII-3 had a cut-off of > 10919.9, with a sensitivity of 53.5% and specificity of 52% (AUC: 0.595, 95% CI: 0.501–0.690, p = 0.046).ConclusionOur findings show that, among NLR, PLR, MLR, SII, SIRI, PIV, IG, MII-1, MII-2, and MII-3, only MII-1, MII-2, and MII-3 levels are statistically significant in predicting birth timing.

Aspirations Dashed: Conventional Synovial Fluid Analysis Is Superior to Synovial Fluid and Blood Neutrophil-to-Lymphocyte Ratios in Diagnosing Pediatric Septic Arthritis of the Hip and Knee.

Recent research suggests that synovial fluid neutrophil-to-lymphocyte ratio (SF-NLR) is a superior diagnostic for pyogenic septic arthritis (SA) in adults compared with synovial fluid white blood cell count (SF-WBC) ≥50,000 cells/μL or ≥90% polymorphonuclear leukocytes (SF-%PMN). Other research also indicates that the neutrophil-to-lymphocyte ratio in the blood (B-NLR) may be of diagnostic significance. However, it is not known whether these findings extend to the pediatric population. Medical records at a large urban tertiary-care children's hospital were queried for emergency department visits between 2012 and 2023, where synovial fluid (SF) analysis was performed to evaluate for SA of the hip or knee. Patients 18 years old and above were excluded. The "conventional composite test" (CCT) for SA was considered positive if SF analysis showed any of the following: (1) SF-WBC ≥50,000 cells/μL, (2) ≥90% PMNs, or (3) organisms reported on gram stain. Patients with aspirate and/or operating room (OR) cultures (or supplemental testing, ie, nucleic acid identification) revealing an offending organism were considered to have culture-positive septic arthritis (CPSA). The remaining patients were considered culture-negative (CN). Serum and SF test data were analyzed to assess their diagnostic utility in identifying CPSA. Receiver operating characteristic (ROC) curves were examined to compare the predictive value of SF-NLR and B-NLR versus conventional indicators of SA. A total of 394 patients met the inclusion criteria. In all, 58.6% (n=231) were male, 67.5% (n=266) involved the knee, and 20.1% (n=79) had CPSA. Those with CPSA had higher ESR and CRP compared with CN patients (P<0.01). Bivariate testing did not show a difference in SF-NLR or B-NLR between those with CPSA and CN patients (P=0.93 and 0.37, respectively). The CCT showed 91% sensitivity and 35% specificity using conventional thresholds. ROC analysis showed that SF-WBC was superior to SF-NLR and B-NLR in the diagnosis of CPSA (AUC=0.71 vs. 0.50 and 0.53, respectively; both P<0.01). Among CCT (+) patients who ended up culture negative, Lyme testing was positive in 48.8% (100/205). In contrast to adults, SF-NLR and B-NLR were not found to be strong diagnostic indicators of SA of the hip or knee in pediatric patients. This may be because competing diagnoses in children come with systemic inflammatory responses similar to that seen in pyogenic SA, while noninfectious conditions that might represent the major alternate diagnoses in adults do not increase systemic inflammatory markers as significantly. Given the high incidence of Lyme disease seen among patients in this study, this topic should be further studied at pediatric centers outside Lyme-endemic areas to better understand the generalizability of these findings. Despite excitement regarding SF-NLR and B-NLR as diagnostics for adult SA, these criteria appear less useful in the diagnosis of pyogenic SA in pediatric patients in Lyme-endemic areas.

Systemic inflammatory markers and volume of enhancing tissue on post-contrast T1w MRI images in differentiating true tumor progression from pseudoprogression in high-grade glioma

BackgroundHigh-grade glioma (HGG) patients post-radiotherapy often face challenges distinguishing true tumor progression (TTP) from pseudoprogression (PsP). This study evaluates the effectiveness of systemic inflammatory markers and volume of enhancing tissue on post-contrast T1 weighted (T1WCE) MRI images for this differentiation within the first six months after treatment. Material and MethodsWe conducted a retrospective analysis on a cohort of HGG patients from 2015 to 2021, categorized per WHO 2016 and 2021 criteria. We analyzed treatment responses using modified RANO criteria and conducted volumetry on T1WCE and T2W/FLAIR images.Blood parameters assessed included neutrophil/lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). We employed Chi-square, Fisher’s exact test, and Mann-Whitney U test for statistical analyses, using log-transformed predictors due to multicollinearity. A Cox regression analysis assessed the impact of PsP- and TTP-related factors on overall survival (OS). ResultsThe cohort consisted of 39 patients, where 16 exhibited PsP and 23 showed TTP. Univariate analysis revealed significantly higher NLR and SII in the TTP group [NLR: 4.1 vs 7.3, p = 0.002; SII 546.5 vs 890.5p = 0.009]. T1WCE volume distinctly differentiated PsP from TTP [2.2 vs 11.7, p < 0.001]. In multivariate regression, significant predictors included NLR and T1WCE volume in the “NLR Model,” and T1WCE volume and SII in the “SII Model.” The study also found a significantly lower OS rate in TTP patients compared to those with PsP [HR 3.97, CI 1.59 to 9.93, p = 0.003]. ConclusionElevated both, SII and NLR, and increased T1WCE volume were effective in differentiating TTP from PsP in HGG patients post-radiotherapy. These results suggest the potential utility of incorporating these markers into clinical practice, though further research is necessary to confirm these findings in larger patient cohorts.

Low platelet to high-density lipoprotein ratio predicts poor short-term prognosis in hepatitis B-related acute-on-chronic liver failure

BackgroundAcute-on-chronic liver failure (ACLF) is characterized by a systemic inflammatory response, predominantly associated with hepatitis B virus in the Asia-Pacific region, with a high short-term mortality rate. The platelet to high-density lipoprotein ratio (PHR) has been used to predict the prognosis of patients with various inflammatory diseases. We aim to is to use the PHR to predict the short-term prognosis of patients with HBV-ACLF.MethodIn this study, we retrospectively analyzed clinical data from 270 HBV-ACLF patients. Using logistic regression, we identified independent risk factors for short-term mortality and developed a prognostic model. This model was then validated, compared, and its clinical utility assessed via decision curve analysis (DCA).ResultsAmong the 270 HBV-ACLF patients, 98 patients died within 28 days. The deceased group exhibited a higher proportion of severe hepatic encephalopathy and ascites. Additionally, there was a statistically significant difference (P = 0.046) in the novel inflammation scoring system, PHR, between the two groups. Following stringent variable selection, PHR was identified as a predictive factor for short-term mortality in HBV-ACLF patients using logistic regression analysis (OR: 0.835 (0.756–0.999), P = 0.009), and it exhibited a synergistic effect with certain traditional scores. The prognostic model constructed based on PHR demonstrated a superior ability to predict short-term mortality compared to traditional scores such as Child-Turcotte-Pugh (AUC: 0.889). Evaluation using calibration curves and decision curve analysis (DCA) suggested its practical utility.ConclusionPHR can predict short-term mortality in patients, with a low PHR upon admission being associated with an increased risk of death.

Significance of Fibrillin-1, Filamin A, MMP2 and SOX9 in Mitral Valve Pathology.

Genetic factors play a significant role in the pathogenesis of mitral valve diseases, including mitral valve prolapse (MVP) and mitral valve regurgitation. Genes like Fibrillin-1 (FBN1), Filamin A (FLNA), matrix metalloproteinase 2 (MMP2), and SRY-box transcription factor 9 (SOX9) are known to influence mitral valve pathology but knowledge of the exact mechanism is far from clear. Data regarding serum parameters, transesophageal echocardiography, and genetic and histopathologic parameters were investigated in 54 patients who underwent cardiovascular surgery for mitral valve regurgitation. The possible association between Fibrillin-1, Filamin A, MMP2, and SOX9 gene expressions was checked in relationship with the parameters of systemic inflammatory response. The mRNA expression levels (RQ-relative quantification) were categorized into three distinct groups: low (RQ < 1), medium/normal (RQ = 1-2), and high (RQ > 2). Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 (p < 0.05). The myxoid degeneration level was associated with the mRNA expression level for FBN1 and a low lymphocyte-monocyte ratio was associated with an increased mRNA expression of FBN1 (p < 0.05). A high number of monocytes was associated with high values of FBN1 whereas the increase in the number of lymphocytes was associated with high levels of MMP2. In addition, we observed that the risk of severe hyalinization was enhanced by a low mRNA expression of FLNA and/or SOX9. In conclusion, a lower FLNA mRNA expression can reflect the aging process that is highlighted in mitral valve pathology as a higher risk for hyalinization, especially in males, that might be prevented by upregulation of the SOX9 gene. FBN1 and MMP2 influence the inflammation-related fibrotic degeneration of the mitral valve. Understanding the genetic base of mitral valve pathology can provide insights into disease mechanisms, risk stratification, and potential therapeutic targets.

Anti-OJ antibody-positive anti-synthetase syndrome following SARS-CoV-2 infection: a case report and literature review

BackgroundCOVID-19 can induce a systemic inflammatory response with variable clinical manifestations. Similar to various viruses, COVID-19 has been implicated in the pathogenesis of autoimmune diseases. This article highlights the potential for infections including the SARS-CoV-2 virus to induce exacerbations of pre-existing autoimmune diseases or even potentially unmask de novo autoimmune diseases in particular anti-synthetase syndrome (ASSD) in predisposed individuals. Although there are other case reports of ASSD following SARS-CoV-2 infection, here we present the first reported case of a gentleman with a newly diagnosed anti-OJ positive anti-synthetase syndrome following SARS-CoV-2 infection.Case presentationDescribed is a case of a 70-year-old man presenting to the emergency department with worsening dyspnea in the context of a recent COVID-19 infection. CT-chest revealed changes suggestive of fibrotic lung disease, consistent with usual interstitial pneumonitis (UIP) pattern. Despite recovery from his COVID-19 illness, the patient subsequently developed proximal myopathy with cervical flexion weakness on further assessment with persistently elevated creatinine kinase (CK). Myositis autoantibodies found a strongly positive anti-OJ autoantibody with MRI-STIR and muscle biopsy performed to further confirm the diagnosis. The patient received pulse methylprednisolone 1 g for 3 days with a long oral prednisolone wean and in view of multiple end-organ manifestations, loading immunoglobulin at 2 g/kg administered over two days was given. In addition, he was then commenced and escalated to a full dose of azathioprine given a normal purine metabolism where he remains in clinical remission to this date. At least 267 cases of rheumatic diseases has been associated with SARS-CoV-2 infection as well as COVID-19 vaccination. A literature search on PubMed was made to determine the amount of case reports describing myositis associated with SARS-CoV-2 infection. We found 3 case reports that fit into our inclusion criteria. Further literature searches on diagnostic approach and treatment of ASSD were done.ConclusionAlthough SARS-CoV-2 infection itself can cause a directly mediated viral myositis, this case report highlights the possibility of developing virus-triggered inflammatory myositis through multiple aforementioned proposed mechanisms. Therefore, further studies are required to explore the relationship and pathophysiology of SARS-CoV-2 infection and the incidence of inflammatory myopathies.

Potential and place of efferent therapy in patients with myocardial infarction complicated by cardiogenic shock

Myocardial infarction complicated by cardiogenic shock (MI CS) is the terminal stage of the cardiovascular disease continuum, leading to the death of every second patient in its severe course. Over the past decades, there are no improvement in inhospital mortality rates for MI CS, despite the widespread introduction of early and effective revascularization methods and intensive care techniques. Recently, more and more data have emerged on the significant contribution of the systemic inflammatory response (SIR) to the pathogenesis of acute coronary syndrome and its complications. The characteristics and impact of SIR in MI CS on its course and outcome have not been sufficiently studied. One of the strategies to influence the SIR course, along with the use of anti-inflammatory therapy, is efferent treatment. However, despite all the above-mentioned fundamental prerequisites for the use of an extracorporeal therapy in CS patients, the introduction of these techniques into clinical guidelines and practice requires exploratory and multicenter randomized studies. This review article summarizes modern ideas and characterizes the existing possibilities of using efferent therapy in MI CS.

High-exchange ULTrafiltration to enhance recovery after paediatric cardiac surgery (ULTRA): study protocol for a Canadian double-blinded randomised controlled trial

IntroductionSurgical repair is the standard of care for most infants and children with congenital heart disease. Cardiopulmonary bypass (CPB) is required to facilitate these operations but elicits a systemic inflammatory...