Higher Levels Of Inflammation Research Articles

A Prospective Study of the Association of IL6 with the Critical Unit and Their Effect on in-Hospital Mortality in Critically Ill Patients.

We previously proposed a new concept, the "critical unit", which covers the structural integrity and function of mitochondria and endothelium. Injury of the critical unit plays a key role in the development of critical illnesses. High levels of inflammation may lead to abnormalities of the critical unit, which is an important mechanism for critical illnesses, and both inflammation and critical unit dysfunction may affect patient prognosis. Here we evaluated the correlation between interleukin-6 (IL6) and the critical unit biomarkers in critically ill patients and the impact of both on prognosis. This study included adult patients admitted to the intensive care unit for various reasons from January 1st to May 31st, 2023. Baseline characteristics, intensive care unit parameters, and laboratory test and outcome data were obtained from the electronic medical records system. Critical unit parameters were measured using polymerase chain reaction and enzyme-linked immunosorbent assay methods. Correlations were examined between IL6, critical unit parameters, and various outcomes. In critically ill patients, IL6 was closely associated with all the critical unit biomarkers (activated partial thromboplastin time, sphingosine 1-phosphate, mitochondrial DNA, mitochondrial fission 1, and Parkin) and the prognoses of patients. A nomogram was constructed using the critical unit biomarkers to predict the in-hospital mortality of critically ill patients. The area under the curve for the mortality prediction model was 0.708. In sensitivity analyses, the predictive effect was better in the non-surgery and tumor groups compared with the surgery and non-tumor groups, with area under the curve values of 0.885 and 0.891, respectively. Our study innovatively integrated mitochondrial and endothelial markers in the critical unit to comprehensively evaluate patient prognosis, which may be a trend in the future assessment of critically ill patients. There are few such studies, and ours may promote the progress of related research.

Imaging-based detection of anterior chamber inflammation: a comparative diagnostic accuracy study

PurposeWe investigated the impact of operator parameters on the diagnostic performance of danterior segment optical coherence tomography (AS-OCT) in anterior uveitis. DesignProspective comparative diagnostic analysis. MethodsSetting: Single site.Study Population: Children aged under 18 years with anterior uveitis, recruited consecutively.Observation Procedures: Index testing: Optovue RTVue80 AS-OCT using ‘low-volume’ (LV, horizontal and vertical cross-sections) and ‘high-volume’ (HV, 68 horizontal cross-sections) protocols. Reference testing: slit lamp examination with anterior chamber inflammation graded using standardisation of uveitis nomenclature (SUN).Main Outcome Measure: Index test performance metrics (sensitivity, specificity, likelihood ratios), utility for ‘ruling-in’ and ‘ruling-out’ disease (positive / negative predictive values, PPV/NPV), receiver operating characteristic (ROC) curves to explore the impact of different imaging derived metrics, multivariable multilevel regression analyses to quantify correlation of index to reference testing, and repeatability indices across protocols. Results40 children (77 eyes: 51 eyes at SUN grade 0, 10 at SUN0.5+, 8 at SUN1+, 8 SUN≥2+ or higher) were included. There was high repeatability across protocols (0.98, p<0.001, 95% CI 0.75-1.0). OCT resulted in strong predictive values for ‘ruling-out’ (LV-scan NPV 82.9%, 95% CI 71.5 - 90.4%; HV-scan NPV 100%, 95% CI 3% to 100%), and but less predictive value for ‘ruling-in’ SUN≥0.5+ (LV-scan PPV 52.8% 95% CI 41.5 - 63.7%; HV-scan PPV 34.2%, 95% CI 33.3 to 35.1%). Detection of more than 1 cell within a cross sectional scan was strongly suggestive of clinical activity, with area under the curve of 0.76 (95% CI 0.62 - 0.89) for SUN≥0.5+, and 0.85 (95% CI 0.73- 0.98), for the detection of SUN≥1+. Cell count correlated with SUN grades at higher levels of inflammation (SUN≥2+ both protocols, SUN≥1+ HV-scans). There was an independent positive association between age and AS-OCT cell (adjusted correlation coefficient 0.2 cells for each additional year of age). ConclusionsOperator dependent factors impact the diagnostic and quantification performance of AS-OCT for anterior chamber inflammation. However, the strong, ‘dose-respondent’ correlation of low-volume protocols with SUN grading promises clinical utility without the storage and analysis burden of high-volume approaches. Further work will involve exploration of the need for age-specific image metric interpretation.

Guava polysaccharides attenuate high fat and STZ-induced hyperglycemia by regulating gut microbiota and arachidonic acid metabolism

This study investigated the hypoglycemic mechanism of guava polysaccharides (GP) through the gut microbiota (GM) and related metabolites. Our findings demonstrated that GP significantly mitigated high-fat diet- and streptozotocin-induced hyperglycemia, insulin resistance, hyperlipidemia, elevated alanine aminotransferase, high hepatic inflammation levels, and prevented pancreatic atrophy and hepatomegaly. Interestingly, the benefits of GP were attributed to alterations in the GM. GP decreased the ratio of Firmicutes to Bacteroidetes, significantly inhibiting deleterious bacteria, including Uncultured_f_Desulfovibrionaceae, Bilophila, and Desulfovibrio, while promoting the proliferation of probiotic Bifidobacterium and Bacteroides. In addition, GP promoted the generation of short-chain fatty acids. Notably, the arachidonic acid (AA) metabolism pathway was enriched in liver metabolites. GP significantly elevated hepatic AA and 15-hydroxyeicosatetraenoic acid, while reducing prostaglandin E2 and 5- and 12-hydroxyeicosatetraenoic acid. This modulation is accompanied by the downregulation of hepatic cyclooxygenase-1, 12-lipoxygenase, P38, and c-Jun N-terminal kinase mRNA expression, and the upregulation of cytochrome P4502J5 and insulin receptor substrate 1/2 mRNA expression. However, GP antibiotic treatment did not induce significant alterations in FBG and AA levels or gene expression. Overall, our findings suggest that the hypoglycemic effect of GP may be intricately linked to alterations in AA metabolism, which depends on the GM.

Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: a placebo-controlled double-blind clinical trial

BackgroundSubjects with metabolic syndrome and obesity have higher levels of inflammation with depression of the vitamin D (VD) hydroxylase/metabolising genes (CYP2R1/CYP27A1/CYP27B1/VDR) required to convert VD consumed in the diet into...

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study.

Neuroinflammatory processes in depression are associated with treatment resistance to conventional antidepressants. Ketamine is an effective new therapeutic option for treatment-resistant depression (TRD). Its well-established immunomodulatory properties are hypothesized to mediate its antidepressant effect. In this context, higher levels of inflammation may predict a better treatment response. However, conclusive evidence for this hypothesis is lacking. We thus investigated whether standard peripheral inflammatory cell markers and C-reactive protein (CRP) levels could predict symptom improvement during intravenous ketamine therapy in TRD patients. 27 participants with TRD were treated with six weight-adjusted intravenous ketamine infusions (0.5 mg/kg bodyweight) over three weeks. Baseline assessments included CRP, absolute monocyte count (AMC), and absolute neutrophil count (ANC). Depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (D1), after the first (D3) and before the last ketamine infusion (D18). Raters were blinded for the baseline laboratory assessments. 13 participants responded to ketamine treatment, and 8 participants partially responded. Baseline AMC showed a strong negative correlation with MADRS change at D3 (r=-0.57, p=0.002) and at D18 (r =-0.48, p=0.010), indicating that a high baseline AMC was associated with greater symptom improvement. A generalized linear model confirmed the association of baseline AMC with symptom improvement during ketamine treatment when additionally accounting for age, sex, and body mass index. Specifically, baseline AMC demonstrated predictive value to discriminate responders and partial responders from non-responders, but lacked discriminative ability between partial responders and responders. Baseline ANC correlated with the MADRS changes at D3 (r=-0.39, p=0.046), while CRP values did not correlate at all. Our prospective single-arm open-label observational study demonstrated that baseline AMC reliably predicted symptom improvement during intravenous ketamine treatment in TRD patients. AMC could therefore serve as a simple and easily accessible marker for symptom improvement during ketamine therapy in daily clinical practice. Future studies with larger sample sizes and a more detailed longitudinal assessment of AMC subtypes are needed to better understand the specific relationship between monocytes and the neuromodulatory effects of ketamine.

Chlorogenic acid can improve spermatogenic dysfunction in rats with varicocele by regulating mitochondrial homeostasis and inhibiting the activation of NLRP3 inflammasomes by oxidative mitochondrial DNA and cGAS/STING pathway

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS–STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1β, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

Gut microbiome and inflammation among athletes in wheelchair in a crossover randomized pilot trial of probiotic and prebiotic interventions

Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.

Screening of Oxidative Stress Biomarkers and Inflammatory Cytokines in the Pathogenesis of Diabetic Neuropathy

Diabetic neuropathy is a neurological syndrome characterized by severe pain and significant mortality caused primarily by somatosensory nerve system damage. In DN patients, the structural and functional damages of neurons are caused by variety of factors. Among these factors, the production of free radicals serves as significant contributors to DN. In addition, hyperglycemia causes chronic inflammation and metabolic changes in neuronal tissues by producing variety of proinflammatory cytokines which serve a significant role in the pathophysiology of DN. Hence, the present study aimed to determine the levels of oxidative stress indicators like SOD, CAT, GR and GPX, as well as proinflammatory cytokines like IL-2, IL-4 and IL-6 in patients with DN in comparison to healthy subjects. The results demonstrated that the mean glucose levels in DN patients range from 142.6±7.2 to 168.1±8.2 mg/dl. The Hb levels exhibited negative correlation in both the DN patients and healthy controls with age. In DN patients, enzymatic antioxidants including SOD, CAT, GR and GPX exhibited significantly decreased activity than the healthy individuals and they exhibited strong negative correlations such as r = -0.943, r = -0.819, r = -0.969 and r = -0.973 respectively. The mean TAS levels in DN patients range from 0.93±0.1 to 0.37±0.02 mM FE with increasing age. Additionally, proinflammatory cytokines such as IL-2, IL-4 and IL-6 levels in DN patients were observed in the ranges of 2.48±1.2 to 3.97±1.5, 41.15±3.7 to 56.43±4.3, 7.61±2.1 to 10.24±1.8 pg/ml respectively with increasing age. The present study concluded that patients with high inflammatory marker levels had elevated oxidative stress, demonstrating that oxidative stress and inflammation are important pathophysiological factors in DN.

Differences in maternal subgingival microbiome between preterm and term births: The MOHEPI study.

Periodontitis is a potential risk factor for preterm birth (PTB) in women; however, the causal relationship or the exact mechanism remain unknown. This study aimed to compare the oral microbiome features of mothers with full-term birth (FTB) with those who had preterm delivery. This study prospectively enrolled 60 women (30 mothers with PTB and 30 mothers with FTB), and subgingival plaque samples were collected and analysed by metagenomic 16S rDNA sequencing. Clinical measurements, including periodontal probing depth, clinical attachment level, modified gingival index (mGI) and plaque index, were performed to determine the periodontal state of the participants. Medical and obstetric data were collected as well. Among the periodontal measurements, mGI score, reflecting the level of gingival inflammation, exhibited a statistically significant association with PTB (adjusted odds ratio 2.705, 95% confidence interval 1.074-6.811, p = .035). When subgroup analysis was conducted based on mean mGI scores (mGI ≥ 2, high inflammation [HI] versus mGI < 2, low inflammation [LI]), microbiome analysis revealed clear distinctions in microbial compositions between PTB and FTB mothers in both the HI and LI groups. Especially in the HI group, alpha diversity exhibited a decreasing trend in PTB mothers compared to FTB mothers. Beta diversity also revealed significant differences between the two groups. In Linear Discriminant Analysis Effect Size analysis, certain anaerobic taxa, including the genera Spirochaetes, Treponema and Porphyromonas, were relatively abundant in the FTB/HI group, whereas the PTB/HI group showed a high abundance of the order Actinomycetales. Network analysis showed that the FTB/HI had relatively stronger connectivity in microbial composition than the PTB/HI group. Dysbiosis ratio of plaque microbiome, in terms of periodontitis, was significantly lower in PTB/HI group compared to FTB/HI group. The compositions of maternal subgingival microbiomes differed between PTB and FTB mothers in both the high and low levels of gingival inflammation groups. In the presence of high level of gingival inflammation, dysbiosis in plaque microbiome, in terms of periodontitis, was decreased in PTB mothers compared to FTB mothers.

Emergency right lower lobectomy for severe pulmonary abscess in a pregnant woman at the 25th week of gestation: a case report

BackgroundPulmonary abscess is a severe infection commonly seen in patients with chronic obstructive pulmonary disease, interstitial pneumonia, immune deficiency disease, drug-induced immunocompromised state, and congenital pulmonary disease. The treatment strategy in pregnant women with a pulmonary abscess is considered challenging since adverse effects on the fetus must be avoided to ensure safe delivery.Case presentationA 34-year-old female patient at 24 weeks of gestation (G2P1) was admitted to the Department of Obstetrics and Gynecology due to sudden right chest pain. The patient had no significant medical history, including congenital anomalies, and no history of drug addiction or smoking. Laboratory data indicated high levels of inflammation (white blood cell 12,000/µL, C-reactive protein 16.0 mg/dL), and computed tomography demonstrated a large intrapulmonary cyst located in the middle of the right lower lobe, with some fluid collection. As the patient had no medical history of congenital pulmonary anomalies, she was initially diagnosed with a pulmonary cyst infection and treated with intravenous antibiotics. However, the infection did not resolve for over a week, and a spike in fever developed after admission. There was no definitive evidence concerning the risk of preterm delivery and fetal abortion during non-obstetric surgery. However, to control the severely infected pulmonary abscess that was refractory to antibiotics and obtain a pathological diagnosis while saving the life of both the mother and fetus, we elected to perform an emergent right lower lobectomy by open thoracotomy with a fissureless maneuver after receiving informed consent. Postoperatively, the infection gradually improved, and the patient was discharged on the 16th postoperative day without any major complications in the mother or fetus. Although she later experienced coronavirus disease-19 at 29 weeks of gestation, a boy was born at 40th weeks of gestation without any complications. Pathologically, no infectious agents, malignancies, or congenital anomalies other than lung abscesses associated with the pulmonary infarction were observed. The mother and child were healthy 1 year postoperatively.ConclusionsWe experienced a rare case of a pulmonary abscess in a pregnant woman who needed an emergent right lower lobectomy to control the severe infection and obtain a correct pathological diagnosis. Under cooperation from an obstetrician and anesthesiologist, emergency pulmonary resection can be performed safely for serious abscess formation even for pregnant women who have several months left until delivery.

#1849 Returning to dialysis after kidney transplant failure: preliminary findings of a multi-centre database

Abstract Background and Aims Kidney transplant failure contributes to a considerable proportion of new dialysis starters. In some centres there are dedicated clinics for patients with failing kidney transplants, however, the specific needs of patients with dialysis after graft loss (DAGL) may be lost in the non-specific clinical review practiced in the general dialysis community. This study examines the mortality and morbidity risk in patients returning with DAGL and compares it to transplant-naïve (T-N) dialysis starters, to determine if the former warrant a more specialised approach. Method This is a retrospective observational study of mortality in all adult patients who started dialysis treatments in Fresenius Medical Care (North America, Latin America, Europe, Middle East, Africa, and Asia Pacific) from 1st January 2018 to 31st March 2021, were identified in the Apollo Dial DB dataset. DAGL was identified from the ICD-10 codes ‘Kidney transplant failure’, ‘Unspecified complication of kidney transplant’ and ‘Other complication of kidney transplant’ at dialysis start. The T-N control group had not previously received a kidney transplant and had not received immunosuppressive medication during the first six months of dialysis start. The first six months on dialysis were defined as baseline, months 7 to the end of year 5 were defined as the follow-up period. All-cause mortality was recorded during follow-up. Cox proportional hazards models were applied to explore the association between DAGL and all-cause mortality. Results A total of 360 469 dialysis starter patients from 41 countries were included in the analysis. 10 010 patients had DAGL and were compared with 350 459 in the T-N control group. In univariate analysis, DAGL patients were significantly younger in all age categories and had a higher proportion of male sex. Serum creatinine, ferritin, phosphate and neutrophil-to-lymphocyte ratio were higher in the DAGL group. Haemoglobin was lower in the DAGL group (Table 1). In the Cox proportional model adjusted for age, gender, and other laboratory and clinical markers, patients with DAGL had an equivalent survival probability compared with T-N dialysis starters (HR: 0.93, 95% CI: 0.86, 1.02) (Table 2). Conclusion DAGL patients appeared to have an increased mortality compared to T-N dialysis starters historically in the literature. Our large and recent study is in line with other recent publications suggesting a more equivalent survival in the two groups. Our results are compatible with younger patients receiving kidney transplantation early in their renal replacement therapy journey, thus constituting a significant proportion of DAGL patients. We posit that DAGL patients may start dialysis at a lower level of renal function, with higher levels of inflammation. Our analysis is preliminary and limited, not fully accounting for confounding factors. Future analysis of this large and well recorded dataset will allow us to examine these interesting associations and design a more specialised management approach to DAGL more closely.

Adverse Health Effects of the Long-Term Simultaneous Exposure to Arsenic and Particulate Matter in a Murine Model.

PM2.5 and arsenic are two of the most hazardous substances for humans that coexist worldwide. Independently, they might cause multiple organ damage. However, the combined effect of PM2.5 and arsenic has not been studied. Here, we used an animal model of simultaneous exposure to arsenic and PM2.5. Adult Wistar rats were exposed to PM2.5, As, or PM2.5 + As and their corresponding control groups. After 7, 14, and 28 days of exposure, the animals were euthanized and serum, lungs, kidneys, and hearts were collected. Analysis performed showed high levels of lung inflammation in all experimental groups, with an additive effect in the coexposed group. Besides, we observed cartilaginous metaplasia in the hearts of all exposed animals. The levels of creatine kinase, CK-MB, and lactate dehydrogenase increased in experimental groups. Tissue alterations might be related to oxidative stress through increased GPx and NADPH oxidase activity. The findings of this study suggest that exposure to arsenic, PM2.5, or coexposure induces high levels of oxidative stress, which might be associated with lung inflammation and heart damage. These findings highlight the importance of reducing exposure to these pollutants to protect human health.

α-Tocopherol inhibits atherogenesis and improves cardiac function in mice independently of its antioxidant properties.

The impact of α-tocopherol on atherosclerosis is unclear and controversial. While some studies suggest potential benefits, such as antioxidant properties that may reduce oxidative stress, other studies indicate no significant preventive effects. The intricate interplay of various factors, including dosage, individual differences, and study methodologies, contributes to the ongoing uncertainty surrounding α-tocopherol's role in atherosclerosis. Further research is needed to clarify its impact and establish clearer guidelines. Therefore, we aimed to evaluate the impact of α-tocopherol on atherogenesis in ApoE-/- fibrillin (Fbn)1C1039G/+ mice, which is a unique mouse model of advanced atherosclerosis with typical features, such as large necrotic cores, high levels of inflammation, and intraplaque neovascularization, that resemble the unstable phenotype of human plaques. ApoE-/- Fbn1C1039G+/- mice were fed a western-type diet (WD) supplemented with a high dose of α-tocopherol (500 mg/kg diet), while control mice were fed a WD containing a low dose of α-tocopherol (50 mg/kg diet). The high dose of α-tocopherol reduced plaque thickness and necrotic core area in the right common carotid artery (RCCA) after 24 weeks WD. Moreover, α-tocopherol decreased plaque formation and intraplaque neovascularization in the RCCA. In addition to its antiatherogenic effect, chronic supplementation of α-tocopherol improved cardiac function in ApoE-/- Fbn1C1039G/+ mice. However, chronic supplementation of α-tocopherol did not decrease lipid peroxidation. On the contrary, α-tocopherol acted as a prooxidant by increasing plasma levels of oxidized LDL and plaque malondialdehyde, an end product of lipid peroxidation. Our data indicate that α-tocopherol inhibits atherogenesis and improves cardiac function independent of its antioxidant properties.

Abstract 1068: Peak Gamma' Fibrinogen Levels Are Associated With Death In COVID-19 Patients

Introduction: COVID-19 is associated with high levels of inflammation and high rates of thrombosis. We have shown previously that the inflammatory biomarker gamma' fibrinogen (GPF) is significantly associated with COVID-19 severity, as judged by SpO 2 levels. In addition, up to 70% of long COVID patients have GPF levels above the range of normal, even 6 weeks after infection. Hypothesis: We assessed the hypothesis that high GPF levels, by virtue of GPF's ability to bind and sequester active thrombin and prevent its inhibition by heparin/antithrombin III, would be associated with thrombotic events and adverse outcomes in COVID-19 patients. Methods: 52 COVID-19 patients at a tertiary care medical center in the IMPACC and Biobank studies were retrospectively enrolled, and GPF levels were measured using a commercial ELISA. Results: 11 patients died, and they had significantly higher peak levels of GPF, 135.2 ± 18.3 mg/dL (mean ± SE), compared to patients who lived, 87.5 ± 7.3 mg/dL, using a Wilcoxon rank-sum test (p = 0.013). Ten patients developed a VTE, either a deep vein thrombosis or a pulmonary embolism. The patients that developed a VTE had a trend towards higher levels of GPF, 125.4 ± 19.1 mg/dL (mean ± SE), compared to patients who did not develop a VTE (91.0 ± 7.7 mg/dL), but these results did not reach statistical significance (p = 0.067). ROC curve analysis revealed an area under the curve of 0.74 for GPF and death, whereas the area under the curve for GPF and VTE was 0.69. Conclusions: In conclusion, GPF levels are significantly associated with death in COVID-19 patients. Monitoring GPF levels in COVID-19 patients may therefore be warranted. Further studies are necessary to determine if the heparin resistance associated with GPF is involved.

The Risk of and Associated Demographic and Laboratory Variables for Amputations for Inpatients with Diabetic Foot Ulcers

ObjectiveDiabetic foot ulcers (DFUs) are a leading cause of morbidity and mortality, which disproportionately impacts underserved populations. This study aimed to provide data regarding the rates and outcomes of amputation in patients admitted with DFU in our health system, which cares for an ethnically diverse and underserved population. MethodsThis retrospective study examined the electronic medical records of adult patients hospitalized with DFU at 3 hospitals in our health system between June 1, 2016, and May 31, 2021. ResultsAmong 650 patients admitted with DFU, 88% self-identified as non-White race. Male sex (odds ratio [OR], 0.62), low body mass index (OR, 0.98), and history of smoking (OR, 1.45) were significantly associated with amputation during the study period. A higher erythrocyte sedimentation rate (OR, 1.01), C-reactive protein level (OR, 1.05), and white blood cell count (OR, 1.11) and low albumin level (OR, 0.41) were found to be significantly associated with amputation versus no amputation during admission. The amputation risk during the index admission for DFU was 44%. ConclusionOur study identified a high DFU-related amputation risk (44%) among adult patients who were mostly Black and/or Hispanic. The significant risk factors associated with DFU amputation included male sex, low body mass index, smoking, and high levels inflammation or low levels of albumin during admission. Many of these patients required multidisciplinary care and intravenous antibiotic therapy, necessitating a longer length of stay and high readmission rate.

The loneliness factor in eating disorders: Implications for psychopathology and biological signatures

ObjectivesEating disorders (ED) are severe psychiatric conditions. While the biological consequences of EDs are well established, including an increase in inflammatory biomarkers, the influence of psychological factors, such as loneliness, has only recently gained attention in research. Loneliness has been associated with more severe psychopathology in ED patients, while its association with inflammatory biomarkers has only been explored in the general population. For these reasons, we aimed to investigate any possible associations between psychological features, trauma, and inflammatory biomarkers with loneliness in people with ED. MethodsThis study examined the interaction between loneliness, eating psychopathology, and biological markers in people with EDs. A group of 97 female patients with various diagnoses of ED was assessed for loneliness, general and eating psychopathology, traumatic history during childhood, and clinical biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and urinary-free cortisol (UFC). ResultsThe results indicated that individuals with ED who reported moderate to severe loneliness also displayed greater general psychopathology (p = 0.001), weight concerns (p = 0.007), and physical neglect during childhood (p = 0.006). Furthermore, people with higher levels of loneliness also had higher inflammatory indexes (ESR p = 0.001, CRP p = 0.027) and were positively correlated with markers of stress reaction such as UFC (p < 0.05). ConclusionThe findings underscore the importance of considering loneliness in the assessment of individuals with an ED. We observed notable associations between loneliness and increased psychopathology (both general and specific to eating), as well as higher levels of inflammation and childhood physical neglect. Addressing loneliness may contribute to improving overall well-being and potentially support recovery. This consideration encompasses both psychological and physical factors that interplay in the clinical presentation of individuals.

Layered plaque is associated with high levels of vascular inflammation and vulnerability in patients with stable angina pectoris.

Layered plaque, a signature of previous plaque destabilization and healing, is a known predictor for rapid plaque progression; however, the mechanism of which is unknown. The aim of the current study was to compare the level of vascular inflammation and plaque vulnerability in layered plaques to investigate possible mechanisms of rapid plaque progression. This is a retrospective, observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) for stable angina pectoris (SAP) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Perivascular inflammation was measured by pericoronary adipose tissue (PCAT) attenuation at the plaque levels on CTA. Features of plaque vulnerability were assessed by OCT. Layered plaques were defined as plaques presenting one or more layers of different optical densities and a clear demarcation from underlying components on OCT. A total of 475 plaques from 195 patients who presented with SAP were included. Layered plaques (n = 241), compared with non-layered plaques (n = 234), had a higher level of vascular inflammation (-71.47 ± 10.74 HU vs. -73.69 ± 10.91 HU, P = 0.026) as well as a higher prevalence of the OCT features of plaque vulnerability, including lipid-rich plaque (83.8% vs. 66.7%, P < 0.001), thin-cap fibroatheroma (26.1% vs. 17.5%, P = 0.026), microvessels (61.8% vs. 34.6%, P < 0.001), and cholesterol crystals (38.6% vs. 25.6%, P = 0.003). Layered plaque was associated with a higher level of vascular inflammation and a higher prevalence of plaque vulnerability, which might play an important role in rapid plaque progression.Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT04523194 .

Exploring the association between dietary Inflammatory Index and chronic pain in US adults using NHANES 1999–2004

Chronic pain, a substantial public health issue, may be influenced by dietary patterns through systemic inflammation. This cross-sectional study explored the association between Dietary Inflammatory Index (DII) and chronic pain among 2581 American adults from NHANES data. The DII, ranging from − 4.98 to 4.69, reflects the inflammatory potential of the diet, with higher scores indicating greater pro-inflammatory capacity. Our findings showed no significant association between the continuous DII score and chronic pain prevalence. However, a nonlinear relationship emerged. When the DII was categorized, a significant association between higher DII scores (DII ≥ 2.5) and chronic pain prevalence was observed. The analysis uncovered a U-shaped pattern, with an inflection point at a DII score of − 0.9, indicating an association between both low and high levels of dietary inflammation are associated with higher pain prevalence. This nuanced interaction between dietary inflammation and chronic pain indicates the possibility of incorporating dietary modification into pain management strategies and underscores the need for further research into the long-term effects of diet on chronic pain.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p=.001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Abstract LB092: Novel tumor gene expression signatures predictive of outcome in large B cell lymphoma treated with CAR T cell therapy (axicabtagene ciloleucel)

Abstract We leveraged ZUMA-7, the first and largest, phase III randomized CAR-T cell clinical study of relapsed/refractory large B cell lymphoma (LBCL) in the 2nd line setting, to discover tumor gene expression (GE) signatures associated with outcome to anti-CD19 CAR-T cell therapy, Axicabtagene Ciloleucel (axi-cel). We performed GE profiling on pre-treatment LBCL tumor samples from 134 axi-cel-treated (safety dataset) patients using IO-360 Nanostring panel (769 genes). Multivariate analysis with penalized Cox models was conducted to identify genes whose expression (transcripts) associated with event-free survival (EFS), progression-free survival (PFS), and duration of response (DOR), leading to identification of two predictive GE signatures. For technical validation, the predictive value of these signatures was reproduced in a subset of ZUMA-7 samples profiled by RNA-seq (n=124). High levels (&amp;gt; median) of a favorable 6-transcript GE signature (6-GES) composed of CD19, CD45RA, CCL22, KLRK1, SOX11, and SIGLEC5 positively correlated with EFS (HR: 0.27, 95% CI: 0.16–0.44; P=1.82 × 10−8) and PFS (HR: 0.27, 95% CI: 0.16–0.46; P=1.35 × 10−7) in patients treated with axi-cel. The 6-GES may capture lymphomas with abundant adhesion molecules, a relatively low inflammation, and abundant expression of the targeted antigen (CD19). Conversely, high levels of an unfavorable 17-transcript GE signature (17-GES; CD45RO, BCL2, IL-18R1, TNFSF4 [OX40L], KLRB1 [CD161], KIR3DL2, ITGB8, DUSP5, GPC4, PSMB5, RPS6KB1, SERPINA9, NBN, GLUD1, ESR1, ARID1A, and SLC16A1) negatively correlated with Axi-cel EFS (HR: 6.19, 95% CI: 3.60–10.65; P=1.51 × 10−13) and PFS (HR: 7.58, 95% CI: 4.16–13.81; P=2.70 × 10−14). The 17-GES signature is consistent with a high level of immune infiltration and inflammation paralleled by the activation of immune-escape mechanisms, such as the upregulation of anti-apoptotic genes. Notably, the 17-GES was elevated at progression after axi-cel treatment (n=18). These signatures did not associate with outcome to 2nd-line SOC from ZUMA-7 (n = 122 for nanostring and n = 125 for ZUMA-7 RNAseq datasets, respectively), nor with outcome to 1st -line R-CHOP from two online datasets, indicating their predictive rather than prognostic value. In conclusion, our transcriptomic analysis of ZUMA-7 dataset identified novel GE signatures predictive of outcome with axi-cel. These GE signatures could support risk-stratification of LBCL patients. Citation Format: Yuan Tian, Justin Budka, Frederick L. Locke, Jason R. Westin, Christina To, Shilpa Shahani, Davide Bedognetti, Rhine R. Shen, Jorge Andrade, Simone Filosto. Novel tumor gene expression signatures predictive of outcome in large B cell lymphoma treated with CAR T cell therapy (axicabtagene ciloleucel) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB092.