Assessing myocardial indices and inflammatory factors to determine anxiety and depression severity in patients with chronic heart failure

BACKGROUND Patients with chronic heart failure(CHF)have a progressive disease that is associated with poor quality of life and high mortality.Many patients experience anxiety and depression(A&D)symptoms,which can further accelerate disease progression.We hypothesized that indicators of myocardial function and inflammatory stress may reflect the severity of A&D symptoms in patients with CHF.Changes in these biomarkers could potentially predict whether A&D symptoms will deteriorate further in these individuals.AIM To measure changes in cardiac and inflammatory markers in patients with CHF to determine A&D severity and predict outcomes.METHODS We retrospectively analyzed 233 patients with CHF treated at the Jingzhou Hospital,Yangtze University between 2018-2022 and grouped them according to Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)scores.We compared clinical data in the no-A&D,mild-A&D,moderate-A&D,and severe-A&D groups,the SAS and SDS scores with the New York Heart Association(NYHA)functional classification,and cardiac markers and inflammatory factors between the no/mild-A&D and moderate/severe-A&D groups.Regression analysis was performed on the markers with P<0.05 to determine their ability to predict A&D severity in patients and the area under the receiver operating characteristic curve(AUROC)was used to evaluate their accuracy.RESULTS In the inter-group comparison,the following variables had an effect on A&D severity in patients with CHF:NYHA class,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-6(IL-6),and tumor necrosis factor-alpha(P<0.05).Other variables did not differ significantly between the A&D groups(P>0.05).In addition,we found that higher NYHA classes were associated with higher the SAS and SDS scores(P<0.05).Regression analysis showed that LVEF,NTproBNP,and IL-6 were independent risk factors for A&D severity(P<0.05).Among them,NT-proBNP had the best predictive ability as a single indicator(AUROC=0.781).Furthermore,the combination of these three indicators exhibited a good predictive effect toward discriminating the extent of A&D severity among patients(AUROC=0.875).CONCLUSION Cardiac and inflammatory biomarkers,such as LVEF,NT-proBNP,and IL-6,are correlated with A&D severity in patients with CHF and have predictive value.

Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.

Effects of Wuwei Xiaodu Decoction on Uterine Energy Metabolism and Serum Inflammatory Factors in Rats with Acute Pelvic Inflammatory Disease

[Objectives]To observe the effects of Wuwei Xiaodu Decoction on uterine energy metabolism and serum inflammatory factors in the acute pelvic inflammatory disease(APID)model.[Methods]75 Wistar rats(females)were randomly divided into control group,model group and Wuwei Xiaodu Decoction low,medium and high dose groups(n=15).Except for the control group,the rat APID model was established by right uterine inoculation.On the fifth day after inoculation,the low,medium and high dose groups of Wuwei Xiaodu Decoction were administered at 4,8 and 16 g/kg,and the control group and model group received normal saline.Rats were killed 12 h after nondose administration,blood was collected from the abdominal aorta and measured by ELISA for serum interleukin-6(interleukin-6,IL-6),IL-8,and C-reactive proteins(CRP);the right uterus of rats was tested for high-energy phosphate adenosine phosphate(AMP),adenosine diphosphate(ADP),adenosine triphosphate(ATP)and total adenine nucleotides(TAN)level to evaluate the uterine energy metabolism.[Results]AMP,ADP,ATP and TAN were significantly higher in the Wuwei Xiaodu Decoction of low,medium and high dose than the model group,while the serum IL-6,IL-8 and CRP were significantly lower than the model group,and the difference between the low,medium and high doses(P<0.05).[Conclusions]The Wuwei Xiaodu Decoction can dose-dependent promote uterine energy metabolism and inhibit inflammatory response in APID model rats.

Clinical effects of nonconvulsive electrotherapy combined with mindfulness-based stress reduction and changes of serum inflammatory factors in depression

BACKGROUND Depression is a common and serious psychological condition,which seriously affects individual well-being and functional ability.Traditional treatment methods include drug therapy and psychological counseling;however,these methods have different degrees of side effects and limitations.In recent years,nonconvulsive electrotherapy(NET)has attracted increasing attention as a noninvasive treatment method.However,the clinical efficacy and potential mechanism of NET on depression are still unclear.We hypothesized that NET has a positive clinical effect in the treatment of depression,and may have a regulatory effect on serum inflammatory factors during treatment.AIM To assess the effects of NET on depression and analyze changes in serum inflammatory factors.METHODS This retrospective study enrolled 140 patients undergoing treatment for depression between May 2017 and June 2022,the observation group that received a combination of mindfulness-based stress reduction(MBSR)and NET treatment(n=70)and the control group that only received MBSR therapy(n=70).The clinical effectiveness of the treatment was evaluated by assessing various factors,including the Hamilton Depression Scale(HAMD)-17,self-rating idea of suicide scale(SSIOS),Pittsburgh Sleep Quality Index(PSQI),and levels of serum inflammatory factors before and after 8 wk of treatment.The quality of life scores between the two groups were compared.Comparisons were made using t and χ^(2) tests.RESULTS After 8 wk of treatment,the observation group exhibited a 91.43%overall effectiveness rate which was higher than that of the control group which was 74.29%(64 vs 52,χ^(2)=7.241;P<0.05).The HAMD,SSIOS,and PSQI scores showed a significant decrease in both groups.Moreover,the observation group had lower scores than the control group(10.37±2.04 vs 14.02±2.16,t=10.280;1.67±0.28 vs 0.87±0.12,t=21.970;5.29±1.33 vs 7.94±1.35,t=11.700;P both<0.001).Additionally,there was a notable decrease in the IL-2,IL-1β,and IL-6 in both groups after treatment.Furthermore,the observation group exhibited superior serum inflammatory factors compared to the control group(70.12±10.32 vs 102.24±20.21,t=11.840;19.35±2.46 vs 22.27±2.13,t=7.508;32.25±4.6 vs 39.42±4.23,t=9.565;P both<0.001).Moreover,the observation group exhibited significantly improved quality of life scores compared to the control group(Social function:19.25±2.76 vs 16.23±2.34;Emotions:18.54±2.83 vs 12.28±2.16;Environment:18.49±2.48 vs 16.56±3.44;Physical health:19.53±2.39 vs 16.62±3.46;P both<0.001)after treatment.CONCLUSION MBSR combined with NET effectively alleviates depression,lowers inflammation(IL-2,IL-1β,and IL-6),reduces suicidal thoughts,enhances sleep,and improves the quality of life of individuals with depression.

The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.

Efficacy and Impact on Inflammatory Factors and Lung Function in Pediatric Bronchial Asthma Treated with Modified Dingchuan Decoction

Objective:To study the efficacy of treating pediatric bronchial asthma with a modified Dingchuan Decoction and its effect on inflammatory factors and lung function levels.Methods:Sixty cases of bronchial asthma admitted to the hospital between January and December 2023 were divided into two groups using a computerized randomization method.One group of 30 cases received basic treatment with a salmeterol ticarcoson powder inhaler(control group),while the observation group received the same treatment plus a modified Dingchuan Decoction.The disappearance time of symptoms,levels of inflammatory factors,lung function indexes,and clinical efficacy were compared between the two groups.Results:The disappearance time of symptoms in the observation group was shorter than that in the control group.The levels of inflammatory factors after treatment were lower,and lung function indexes were higher in the observation group compared to the control group.Additionally,the total effective rate of treatment in the observation group was higher than that in the control group(P<0.05).Conclusion:In the clinical treatment of pediatric bronchial asthma,supplementing conventional Western medicine with a modified Dingchuan Decoction is effective,as it actively reduces inflammatory factor levels and improves lung function.

The effect of Jiangan Xiaozhi Formula on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease

Objective:To investigate the effects of Jiangan Xiaozhi Formula(JGXZ)on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease(NAFLD).Methods:Between September 2022 and December 2023,our hospital admitted a total of 58 patients with NAFLD.These patients were split into two groups at random:one for experimentation and the other for control.There were 27 patients in the experimental group at the end,compared to 26 in the control group,reasonable exercise,weight management,lipid regulation,and oral polyene phosphatidylcholine capsules(PPC).The experimental group received JGXZ in addition to the above treatments for 12 consecutive weeks.Changes in Traditional Chinese Medicine(TCM)syndrome scores,blood lipids,liver function indicators,the levels of oxidative stress markers,such as malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and superoxide dismutase(SOD),as well as serum inflammatory factors,such as interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α),were measured both before and after treatment.Results:After treatment,both groups showed significant reductions in TCM syndrome scores(P<0.05)and improvements in blood lipids,liver function indicators,inflammatory factors,and oxidative stress markers(P<0.05).Improvements were noticeably better in the experimental group than in the control group.(P<0.05).Conclusion:JGXZ can significantly improve clinical symptoms,regulate blood lipids,and protect liver function in patients with NAFLD.Its mechanism may be related to inhibiting inflammatory responses and regulating the balance of the oxidation-antioxidation system.

Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease:A literature review

Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells

BACKGROUND Mesenchymal stem cells(MSCs)have great potential for the treatment of various immune diseases due to their unique immunomodulatory properties.However,MSCs exposed to the harsh inflammatory environment of damaged tissue after intravenous transplantation cannot exert their biological effects,and therefore,their therapeutic efficacy is reduced.In this challenging context,an in vitro preconditioning method is necessary for the development of MSC-based therapies with increased immunomodulatory capacity and transplantation efficacy.AIM To determine whether hypoxia and inflammatory factor preconditioning increases the immunosuppressive properties of MSCs without affecting their biological characteristics.METHODS Umbilical cord MSCs(UC-MSCs)were pretreated with hypoxia(2%O_(2))exposure and inflammatory factors(interleukin-1β,tumor necrosis factor-α,interferon-γ)for 24 h.Flow cytometry,polymerase chain reaction,enzyme-linked immunosorbent assay and other experimental methods were used to evaluate the biological characteristics of pretreated UC-MSCs and to determine whether pretreatment affected the immunosuppressive ability of UC-MSCs in coculture with immune cells.RESULTS Pretreatment with hypoxia and inflammatory factors caused UC-MSCs to be elongated but did not affect their viability,proliferation or size.In addition,pretreatment significantly decreased the expression of coagulationrelated tissue factors but did not affect the expression of other surface markers.Similarly,mitochondrial function and integrity were retained.Although pretreatment promoted UC-MSC apoptosis and senescence,it increased the expression of genes and proteins related to immune regulation.Pretreatment increased peripheral blood mononuclear cell and natural killer(NK)cell proliferation rates and inhibited NK cell-induced toxicity to varying degrees.CONCLUSION In summary,hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics.

Correlation analysis of anxiety with psoriasis severity, oxidative stress and inflammatory factors in patients with psoriasis vulgaris

Objective:To investigate the anxiety status of patients with psoriasis vulgaris,and analyze the correlation between anxiety and severity of the disease,oxidative stress factors and inflammatory factors.Methods:From August 2021 to February 2022,84 patients with psoriasis in the Dermatology Department of Dongzhimen Hospital of Traditional Chinese Medicine were recruited.Hamilton anxiety scale(HAMA),psoriasis lesion area and severity index(PASI),VAS pruritus scale(VAS)were collected to detect serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH px),interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α).Based on the HAMA score,a group controlled study and correlation analysis were conducted.In addition,the HAMA scores of 84 healthy people were collected for a controlled study.Results:HAMA score of patients with psoriasis vulgaris was higher than that of healthy people(Z=-7.730,P<0.05).There were differences in PASI,VAS scores,MDA,SOD,GSH px,IL-6,IL-17A secretion levels between psoriasis vulgaris patients with anxiety and psoriasis vulgaris patients without anxiety.HAMA score was positively correlated with PASI and VAS scores in patients with psoriasis vulgaris(r=0.564,0.513,P<0.05).It was positively correlated with MDA,IL-6,IL-17A in serum(r=0.390,0.355,0.248,P<0.05).It was negatively correlated with SOD and GSH px(r=-0.313,-0.502,P<0.05);and TNF-αnot relevant.Conclusion:The anxiety risk of psoriasis patients was higher than that of healthy people;anxiety is closely related to psoriasis,and is reflected in the skin lesions,itching,oxidative stress and inflammatory factor levels of psoriasis patients.The comorbidity mechanism of anxiety and psoriasis may be related to oxidative stress and up regulation of inflammatory factors.

Effect of hepatocyte growth factor on inflammatory factors associated with CCL_(4)-induced hepatocyte injury

Objective:The aim of this study is to investigate the effects of Hepatocyte Growth Factor(HGF)on the expression levels of IL-8,TNF-α,IL-4,and IL-21 in mice with liver injury induced by CCL_(4).Methods:An acute liver injury mouse model was established using CCL_(4),and hepatocytes and white blood cells were separated by gradient density centrifugation.Different concentrations of HGF were added in vitro,and the expression levels of cytokines were detected using ELISA.Results:In the in vivo injury model,the hepatocyte experiment results showed that the expression level of IL-8 was reduced in the 10 ng/mL HGF group compared to the injured hepatocyte group(P<0.05),and increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.05).For IL-4,the expression levels were reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the injured hepatocyte group.The white blood cell experiment results showed that the expression levels of TNF-αwere reduced in both the 10ng/ml HGF group(P<0.05)and the 25 ng/mL HGF group(P<0.05)compared to the injured white blood cell group.In the in vitro injury model,hepatocyte experiment results showed that the expression levels of TNF-αwere reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the normal control group.For IL-4,the expression level was reduced in the 25 ng/mL HGF group compared to the normal control group(P<0.05).The white blood cell experiment results showed that the expression level of TNF-αwas increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.001);for IL-21,the expression levels were reduced in the CCL_(4) model group(P<0.05),10 ng/mL HGF group(P<0.05),25 ng/mL HGF group(P<0.05),and 50 ng/mL HGF group(P<0.05)compared to the normal control group.Conclusion:when the liver of mice is acutely damaged by CCL_(4),HGF can reduce the expression levels of inflammatory cytokines IL-8,TNF-α,IL-4 in hepatocytes,and TNF-αin liver white blood cells.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease:A review of the literature

Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.

Effect of inflammatory response on joint function after hip fracture in elderly patients:A clinical study

BACKGROUND Excellent hip joint function facilitates limb recovery and improves the quality of survival.This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management.AIM To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients.METHODS The elderly patients who had hip fracture surgery at our hospital between January 1,2021,and December 31,2022 were chosen for this retrospective clinical investigation.Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared.Age,gender,fracture site,surgical technique,laboratory indices,and other variables that could have an impact on postoperative joint function were all included in a univariate study.To further identify independent risk factors affecting postoperative joint function in hip fractures,risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis.In addition to this,we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups.RESULTS A total of 119 elderly patients with hip fractures were included in this study,of whom 37 were male and 82 were female.The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin(IL)-6,IL-8,IL-10,C-reactive protein(CRP),and complement C1q(C1q)between the fair and excellent joint function groups(P<0.05).The results of multiple logistic regression analysis showed that IL-6>20 pg/mL[Odds ratio(OR)3.070,95%CI:1.243-7.579],IL-8>21.4 pg/mL(OR 3.827,95%CI:1.498-9.773),CRP>10 mg/L(OR 2.142,95%CI:1.020-4.498)and C1q>233 mg/L(OR 2.339,95%CI:1.094-5.004)were independent risk factors for poor joint function after hip fracture surgery(all P<0.05).CONCLUSION After hip fractures in older patients,inflammatory variables are risk factors for fair joint function;therefore,early intervention to address these markers is essential to enhance joint function and avoid consequences.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

Association between inflammatory bowel disease and all-cause dementia:A two-sample Mendelian randomization study

BACKGROUND Numerous observational studies have documented a correlation between inflammatory bowel disease(IBD)and an increased risk of dementia.However,the causality of their associations remains elusive.AIM To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization(MR)method.METHODS Genetic variants extracted from the large genome-wide association study(GWAS)for IBD(the International IBD Genetics Consortium,n=34652)were used to identify the causal link between IBD and dementia(FinnGen,n=306102).The results of the study were validated via another IBD GWAS(United Kingdom Biobank,n=463372).Moreover,MR egger intercept,MR pleiotropy residual sum and outlier,and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity.Finally,multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia,with the inverse variance weighted approach adopted as the primary analysis.RESULTS The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS.No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted[odds ratio(OR)=0.980,95%CI:0.942-1.020,P value=0.325],weighted median(OR=0.964,95%CI:0.914-1.017,P value=0.180),and MR-Egger(OR=0.963,95%CI:0.867-1.070,P value=0.492)approaches.Consistent results were observed in validation analyses.Reverse MR analysis also showed no effect of dementia on the development of IBD.Furthermore,MR analysis suggested that IBD and its subtypes did not causally affect allcause dementia and its four subtypes,including dementia in Alzheimer's disease,vascular dementia,dementia in other diseases classified elsewhere,and unspecified dementia.CONCLUSION Taken together,our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes.Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.

Progress in the Study of Inflammatory Bowel Disease Patients with Primary Non-Responsiveness

Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.

Environmental risk factors for inflammatory bowel diseases: Evidence based literature review

AIM: To advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases(IBD). METHODS: The current opinion on the pathogenesis of IBD suggests that genetically susceptible individuals develop intolerance to dysregulated gut microflora(dysbiosis) and chronic inflammation develops as a result of environmental insults. Environmental exposures are innumerable with varying effects during the life course of individuals with IBD. Studying the relationship between environmental factors and IBD may provide the missing link to increasing our understanding of the etiology and increased incidence of IBD in recent years with implications for prevention, diagnosis, and treatment. Environmental factors are heterogeneous and genetic predisposition, immune dysregulation, or dysbiosis do not lead to the development of IBD in isolation. RESULTS: Current challenges in the study of environmental factors and IBD are how to effectively translate promising results from experimental studies to humans in order to develop models that incorporate the complex interactions between the environment, genetics, immunology, and gut microbiota, and limited high quality interventional studies assessing the effect of modifying environmental factors on the natural history and patient outcomes in IBD.CONCLUSION: This article critically reviews the current evidence on environmental risk factors for IBD and proposes directions for future research.

Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks

Hepatocyte nuclear factor 4-alpha(HNF4-α)is a nuclear receptor regulating metabolism,cell junctions,differentiation and proliferation in liver and intestinal epithelial cells.Mutations within the HNF4A gene are associated with human diseases such as maturityonset diabetes of the young.Recently,HNF4A has also been described as a susceptibility gene for ulcerative colitis in genome-wide association studies.In addition,specific HNF4A genetic variants have been identified in pediatric cohorts of Crohn’s disease.Results obtained from knockout mice supported that HNF4-αcan protect the intestinal mucosae against inflammation.However,the exact molecular links behind HNF4-αand inflammatory bowel diseases remains elusive.In this review,we will summarize the current knowledge about the role of HNF4-αand its isoforms in inflammation.Specific nature of HNF4-αP1 and P2 classes of isoforms will be summarized.HNF4-αrole as a hepatocyte mediator for cytokines relays during liver inflammation will be integrated based on documented examples of the literature.Conclusions that can be made from these earlier liver studies will serve as a basis to extrapolate correlations and divergences applicable to intestinal inflammation.Finally,potential functional roles for HNF4-αisoforms in protecting the intestinal mucosae from chronic and pathological inflammation will be presented.