LDH Levels Research Articles

CNS RELAPSE OF DIFFUSE LARGE B‐CELL LYMPHOMA AND ROLE OF UPFRONT PROPHYLAXIS: A 10‐YEAR SINGLE CENTER EXPERIENCE

Introduction: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare event, occurring in about 5% of patients (pts) and correlating with a very dismal prognosis. Much debate has surrounded the use of strategies to avert CNS disease recurrence. Nowadays, CNS prophylaxis is mostly based on high-dose intravenous (iv) methotrexate (HD-MTX), but its effectiveness is controversial. Our study focuses on pts with CNS relapse of DLBCL in order to evaluate their clinical and biological features, the validity of known prognostic scores, the efficacy of CNS prophylaxis, prognosis and treatment at the time of relapse. Methods: All pts with DLBCL diagnosed between January 2010 and December 2021 at AOU Città della Salute e della Scienza di Torino and treated with curative intent were selected: 498 cases with at least 12 months of follow-up were identified. Pts with primary mediastinal lymphoma, primary testicular lymphoma or CNS disease at diagnosis were excluded. Results: The case series included 406 pts. Mean age was 67 years, 56/400 had ECOG PS ≥ 2 (14%), 231/400 elevated LDH levels (58%), 251/404 were stage IV (62%), 192/374 IPI score ≥ 3 (51%), 189/373 CNS-IPI 2–3 (51%), 91/373 CNS-IPI 4–6 (24%). 95/397 pts received CNS prophylaxis (24%): 59 by intrathecal (IT) route only (15%) (n 26 CNS-IPI 2-3; n 29 CNS-IPI 4-6), 25 by iv MTX only (6%) (n 17 HD-MTX ≥3 g/mq; n 6 CNS-IPI 2-3; n 16 CNS-IPI 4-6), and 11 by combined route (3%) (n 5 CNS-IPI 2-3, n 6 CNS-IPI 3–6). 12 pts experienced CNS relapse; 8/12 exclusively CNS and 4/12 along with systemic recurrence. The cumulative incidence at 3 years was 2.8%. In univariate analysis CNS relapse risk was significantly influenced by ECOG PS and elevated LDH levels, while the use of prophylaxis was not shown to impact the risk of CNS recurrence. However, none of the pts who received systemic MTX prophylaxis had subsequent CNS disease, while 2/59 pts who received exclusive IT prophylaxis had CNS relapse with an incidence superimposable to the whole cohort (3.3%). In multivariate analysis, only ECOG PS confirmed significant correlation with the risk of such disease recurrence (Figure 1). With a mean follow-up of 36 months, the 3-year overall survival for pts with SNC recurrence was 30%. Encore Abstract—previously submitted to EHA 2023 Keyword: aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Key factors associated with response in the treatment of liver metastatic melanoma by cryoablation combined with PD-1 blockade therapy: The Cryo-Fire-001 study.

e21500 Background: Liver metastasis remains a challenge in the treatment of advanced stage melanoma through immunotherapy. Although our previous study showed cryoablation could enhance the efficacy of PD-1 blockade therapy in the treatment of melanoma patients with liver metastasis, the key factors correlated with survival and treatment response remains unknown. Methods: Between 2018 and 2022, 45 melanoma patients receiving combined PD-1 blockade therapy and cryoablation of liver metastasis were retrospectively analyzed. The technical parameters of cryoablation, the sequence of the combined treatment, tumor characteristics, important immune markers and their correlations with treatment response were evaluated. The associations between key factors and overall survival (OS) were determined by Cox regression. Results: Of the 45 patients, the 3-month overall response rate (RECIST 1.1 criteria) is 26.7%. Multivariate analysis showed the number of metastatic organs ( > 2 vs ≤2; HR 3.54; 95% CI 1.32-9.49; P = 0.012), pretreatment LDH level ( > 300 vs ≤300 U/L; HR 4.59; 95% CI 1.78-11.85; P = 0.002) and diameter of ablated lesion ( > 30 vs ≤30 mm; HR 3.27; 95% CI 1.17-9.15; P= 0.024) were independent unfavorable prognostic factors for OS. Further analysis showed patients with larger intrahepatic tumors ablated had larger tumor size (P < 0.001). A scatter plot by the two key variables showed patients with intrahepatic tumor size less than 45 mm and size of ablated lesion less than 30 mm had a marginally higher rate of 3-month response (10/28, 35.7%) compared to those not (2/17, 11.7%; P = 0.076). Large diameter of ablated lesion ( > 30 mm) require more ablation needles and cause greater elevation in the level of IL-6, CD8+T cell to Treg cell ratio and neutrophil to lymphocyte ratio after cryoablation while these changes disappeared when tested one month later. Conclusions: Fine selection based on baseline characteristics of patients and size of intrahepatic lesion for cryoablation are essential to achieve a high response rate during cryoablation-PD-1 combination treatment for liver metastatic melanoma.

Carcinoembryonic antigen kinetics predict response to first-line treatment in metastatic colorectal cancer: Analysis from PRODIGE 9 trial.

To examine the relationship between carcinoembryonic antigen (CEA) kinetics and prognosis in metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the PRODIGE9 trial. Associations between monthly CEA measurements within 6 months since baseline and progression-free survival (PFS) were evaluated using a joint-latent class-mixed model. A validation set was used to test our prognosis model. Correlations between CEA trajectories (classes) and baseline characteristics were also investigated. Three classes were identified. Class 1 had low baseline CEA with small variations. Class 2 had high baseline CEA with a rapid decrease reaching the same CEA level at 6 months as in class 1. Class 3 had high baseline CEA with a transient decrease followed by an increase to reach, at 6 months, the same CEA level as at baseline. Six-month PFS was significantly lower in class 3 than in classes 1 and 2 (57% vs. 91% and 93% respectively; p<0.01). Class 3 was significantly associated with ECOG 2 status, a high LDH level and non-resected primary tumor. Variations in CEA kinetics correlate with prognosis in patients receiving first-line chemotherapy for mCRC. We propose here a user-friendly application to classify CEA trajectory.

ANTIPROLIFERATIVE POTENTIAL OF ESCITALOPRAM IN DIMETHYLHYDRAZINE (DMH) INDUCED COLON CANCER IN SWISS ALBINO MICE

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems.This research emphasizes on pharmacological evaluation of anti-colon cancer effect of escitalopram in albino mice by using behavioral and hematological models. Animal House, Aryakul College of Pharmacy &amp; Research, Lucknowprovided albino mice of either sex weighing 70-90g. All the animals were divided into 5 groups (n=6) Group 1 (NC): Mice are administered only 0.25% CMC once a week up to 28 days. Group 2 (CC): Mice are administered DMH (40mg/kg, o.d.) once a week up to 28 days. Group 3 (PC): Mice are administered DMH (40mg/kg, o.d.) once a week up to 28 days + Fluorouracil (10mg/kg) once a day for 15 days. Group 4 (T1): Mice are administered DMH (40mg/kg) once a week up to 28 days + Escitalopram (5mg/kg) once a day for 15 days. Group 5 (T2): Mice are administered DMH (40mg/kg) once in a week up to 28 days + Escitalopram (10mg/kg) once a day for 15 days.They were evaluated for parameters like determination of pH, acidity, of ALT, AST &amp; LDH levels and estimation of lipid profile. The results of the current study demonstrate that Escitalopram administration influences ameliorating anticancer effects by altering several processes, including Phase I &amp; II biotransformation. lipid peroxidation, enzymes, antioxidants, and histopatholgical alterations. It concluded that Escitalopram is effective in management of colon cancer in animal model. This study suggests that Escitalopram can also be given in the treatment of colorectal cancer in human beings after successful clinical trials.

Dynamic changes of phenotype and function of natural killer cells in peripheral blood before and after thermal ablation of hepatitis B associated hepatocellular carcinoma and their correlation with tumor recurrence

BackgroundThermal therapy induces an immune response in patients with hepatocellular carcinoma (HCC), but the dynamic characteristics of the natural killer (NK) cell immune response post-thermal ablation remain unclear. We conducted a prospective longitudinal cohort study to observe the dynamic changes of phenotype and function of NK cells in peripheral blood before and after thermal ablation of hepatitis B-associated HCC and their correlation with tumor recurrence.MethodsFifty-six patients clinically and pathologically confirmed with hepatitis B-associated HCC were selected for thermal ablation. Peripheral blood was collected on day 0, day 7, and month 1. NK cell subsets, receptors, and killing function were detected by flow cytometry, and the LDH levels were examined. Overall recurrence and associated variables were estimated using Kaplan–Meier, log-rank, and Cox proportional-hazards analyses.ResultsThe frequency of CD3−CD56+ cells was increased on day 7 (P < 0.01) without significant differences between D0 and M1. NKG2D, NKp44, NKp30, CD159a, and CD158a expression was increased on M1 (all P < 0.05). The granzyme B and IFN-γ expression in NK cells were higher on M1 vs. D0 (P < 0.05). On day 7, the NK cell lysis activity of the target K562 cells was increased (P < 0.01) but decreased on M1 (P < 0.05). Survival analysis showed that CD158a expression and IFN-γ and perforin release on day 0 were associated with the risk of HCC recurrence. Cox regression analysis showed that the expression changes in CD56, NKp46, granzyme B, and perforin (D7-D0) induced by thermal ablation were associated with recurrence-free survival (RFS) of patients with HCC.ConclusionThermal ablation increased the frequency and function of CD3−CD56+ NK cells in the peripheral blood of patients with HCC. These cells tended to be more differentiated and activated. Notably, expression levels of NK cell receptors NKp46, perforin, and granzyme B were associated with RFS.

Inhibition of the lectin pathway of complement activation reduces LPS-induced acute respiratory distress syndrome in mice.

Acute respiratory distress syndrome (ARDS) is a life-threatening disorder with a high rate of mortality. Complement activation in ARDS initiates a robust inflammatory reaction that can cause progressive endothelial injury in the lung. Here, we tested whether inhibition of the lectin pathway of complement could reduce the pathology and improve the outcomes in a murine model of LPS-induced lung injury that closely mimics ARDS in human. In vitro, LPS binds to murine and human collectin 11, human MBL and murine MBL-A, but not to C1q, the recognition subcomponent of the classical pathway. This binding initiates deposition of the complement activation products C3b, C4b and C5b-9 on LPS via the lectin pathway. HG-4, a monoclonal antibody that targets MASP-2, a key enzyme in the lectin pathway, inhibited lectin pathway functional activity in vitro, with an IC50 of circa 10nM. Administration of HG4 (5mg/kg) in mice led to almost complete inhibition of the lectin pathway activation for 48hrs, and 50% inhibition at 60hrs post administration. Inhibition of the lectin pathway in mice prior to LPS-induced lung injury improved all pathological markers tested. HG4 reduces the protein concentration in bronchoalveolar lavage fluid (p<0.0001) and levels of myeloid peroxide (p<0.0001), LDH (p<0.0001), TNFα and IL6 (both p<0.0001). Lung injury was significantly reduced (p<0.001) and the survival time of the mice increased (p<0.01). From the previous findings we concluded that inhibition of the lectin pathway has the potential to prevent ARDS pathology.

Oxidative stress, genotoxic effects, and other damages caused by chronic exposure to silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs), and their mixtures in zebrafish (Danio rerio)

This study assessed the oxidative stress impacts of Ag NPs and ZnO NPs and their mixtures in zebrafish (Danio rerio). Zebrafish were exposed to sublethal concentrations of each NP and a mixture for 28 days followed by a 28-day recovery period (without NP exposure) and measurements made on hepatic levels of antioxidant enzymes (CAT, SOD, and GPx), MDA levels, expression of the genes for the Hsp70 and Hsp90, and MT, blood biochemical parameters (total protein, globulin, albumin, AST, ALT, ALP, and LDH), and genotoxicity in erythrocytes (via measurement of micronuclei (MN) and nuclear (NA) abnormalities). There was a tendency for an increase in the variation in the responses of antioxidant defense systems and there were higher MDA levels with increasing exposure concentration of Ag NPs and with increasing exposure time. Total protein, globulin, and albumin decreased during the exposure period, especially on the days of 28. Moreover, levels of AST and LDH increased significantly in the NPs co-exposure treatments, while levels of ALT and ALP significantly decreased. The highest expression levels for these genes occurred on day 14 and in the NPs co-exposure treatments. For exposure to both NPs individually and as a mixture, the frequency of MN and other NA were significantly increased (p < 0.05). During the recovery periods, most of the effects seen were reduced, most notably in the individual NPs treatments. The overall results suggest that the toxic effects of Ag NPs and ZnO NPs in combination significantly increase their toxicity in zebrafish.

The plant-derived alkaloid aloperine prevents ischemia/reperfusion injury-induced sudden cardiac death.

Sudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from Sophora alopecuroides plants, exhibits antioxidant, anti-inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury-associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion-provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage-gated potassium (Kv) channels were performed using two-electrode voltage clamp analysis of cloned channels expressed in Xenopus laevis oocytes. Aloperine pretreatment (10 mg/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK-MB, α-HBDH, and cTnI post-I/R, and stimulated phosphorylation of ventricular ERK1/2 and STAT-3, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1/2 (with U0126) or STAT-3 (with Ag490) abolished aloperine-induced anti-arrhythmic effects and ERK1/2 and STAT-3 phosphorylation. Interestingly, while aloperine (100 μM) had no effect on cloned Kv4.3 activity, aloperine (1 μM and up) negative-shifted the voltage dependence of hERG activation by ~10 mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti-arrhythmic effects against myocardial ischemia and reperfusion injury-induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1/2/STAT-3 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.

Clinical and laboratory factors associated with hospitalization and mortality in the COVID-19 pandemic

Introduction: This study aimed to investigate the relationship between MPV and disease prognosis in patients with COVID-19, the chronic diseases that affect the prognosis of COVID-19, and the laboratory data that can help diagnose this disease and provide information about the course of the disease during the treatment process. Methods: The study was conducted in a cross-sectional format. All participants gave written, informed consent to participate. A questionnaire consisting of two parts, including categorical (socio-demographic) data and laboratory data, was applied to people who had COVID-19 who applied to the internal medicine outpatient clinic of the hospital. The Pearson chi-squared test and Fisher exact test were used for comparing categorical variables. The Mann-Whitney U test, or Kruskal-Wallis test with Bonferroni post hoc comparisons, was used to compare numerical variables between the groups. All analyses were performed using the SPSS 25.0 (SPSS Inc., Chicago, IL, ‎USA) software package. Results: The participants' mean (±SD) age was 40.8±13.7 years (median: 40, range: 18 – 72). Almost half of the participants (48.0%, n=98) were male, the majority (76.0%, n=155) were married, and 24.0% (n=49) were single. Of the 204 patients, 28 (13.7%) were hospitalized, and five died (2.5%). Of the five patients who died, three had chronic lung disease, one had diabetes and chronic lung disease, and one had no chronic disease. Conclusion: Older age and the presence of chronic diseases are important factors affecting hospitalization in patients with COVID-19. LDH, CRP, and ferritin levels were high, and the mean platelet volume levels were significantly higher in hospitalized patients. Keywords: COVID -19, pandemics, prognosis of COVID -19

NLRP3 inflammasome activation contributes to fungal clearance and lung injury during Talaromyces marneffei infection

The increased levels of IL-1β and IL-18 cytokines have been associated with the severity of sepsis and outcomes of patients infected with Talaromyces marneffei. Previous studies have suggested that NLRP3 plays an important role in caspase-1 activated secretion of IL-1β and IL-18 in fungal-infected macrophages. In the present study, the role of the NLRP3 inflammasome in talaromycosis is investigated in an in vitro assay and in vivo with a mice systemic infection model. We found that the NLRP3 inflammasome pathway in infected mice is activated along with increased production of IL-1β. Such an activation of the NLRP3 inflammasome is also observed in either mice or human macrophages challenged with T. marneffei conidia. Our results indicate that IL-1β release by infected macrophages is NLRP3 inflammasome-dependent and NLRP3 contributes to death of mice at the early stage of pulmonary infection. Moreover, a greater number of MPO-positive cells are found in the lungs of infected Nlrp3−/− mice and WT mice with reduced LDH levels, especially at the last stage of infection. Therefore, we conclude that the NLRP3 Inflammasome activation is important for fungal clearance, neutrophil recruitment and lung injury during T. marneffei Infection.

Protective effect of dihydromyricetin against lipopolysaccharide-induced HK2 cells by upregulating HIF-1α

ABSTRACT Sepsis complicated by acute kidney injury (AKI) carries an extremely high mortality rate. The present study aimed to investigate the protective effect and underlying mechanism of dihydromyricetin (DHM) on human renal tubular epithelial cells (HK2) during AKI. To simulate an in vitro model of AKI, HK2 cells were treated with lipopolysaccharide (LPS) and divided into four groups: Control, LPS, LPS+DHM, and LPS+DHM+si-HIF-1α. The cellular viability of HK2 cells was determined by the CCK-8 assay after treatment with LPS and DHM (60 μmol/L). The expression of Bcl-2, Bax, Cleaved Caspase-3, and HIF-1α was measured by Western blotting. The expression of Bcl-2, Bax, and HIF-1α mRNA was assessed by PCR. The apoptosis rate of each group was determined by flow cytometry, while different kits were used to measure the levels of MDA, SOD, and LDH in each group of HK2 cells. DHM was found to increase the expression of HIF-1α in HK2 cells after treatment with LPS. the expression of HIF-1α mRNA and protein, Cleaved Caspase-3, Bax protein, MDA and LDH levels, and apoptosis rate were significantly decreased, while Bcl-2 protein, cell viability, and SOD activity were markedly increased in the LPS+DHM group compared with the LPS and LPS+DHM+si-HIF-1α groups. Thus, DHM can reduce apoptosis and oxidative stress damage in HK2 cells by increasing HIF-1α expression after LPS treatment. DHM may be a treatment for AKI, but in vitro studies must be validated in animal models and clinical trials before drawing conclusions. Caution must be exercised in interpreting in vitro results.

LncRNA NKILA Exacerbates Alzheimer's Disease Progression by Regulating the FOXA1-Mediated Transcription of TNFAIP1.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the world, which seriously affects AD patients' life quality. Recently, long non-coding RNAs (lncRNAs) have been reported to play a key role in AD pathogenesis, however, the specific mechanism remains unclear. Herein, we aimed to investigate the role of lncRNA NKILA in AD.The learning and memory performance of rats from streptozotocin (STZ)-treated or other treated groups were tested by Morris water maze test. Relative levels of genes and proteins were measured using RT-qPCR and Western blotting. Mitochondrial membrane potential was tested by JC-1 staining. Levels of ROS, SOD, MDA, GSH-Px, and LDH were measured using corresponding commercial kits. Apoptosis was evaluated by TUNEL staining or Flow cytometry assay. RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays were utilized to test the interaction between indicated molecules.STZ treatment caused learning and memory impairment in rats and oxidative stress damage in SH-SY5Y cells. LncRNA NKILA was found to be elevated in the hippocampal tissues of rats and SH-SY5Y cells after STZ exposure. Knockdown of lncRNA NKILA alleviated STZ-induced neuronal damage. Furthermore, lncRNA NKILA could bind to ELAVL1, which regulate the stability of FOXA1 mRNA. Moreover, TNFAIP1 transcription process was controlled by FOXA1, which targeted the promoter of TNFAIP1. In vivo results demonstrated that lncRNA NKILA accelerated STZ-induced neuronal damage and oxidative stress by FOXA1/TNFAIP1 axis.Our findings indicated that knockdown of lncRNA NKILA inhibited the neuronal damage and oxidative stress induced by STZ through the FOXA1/TNFAIP1 axis, thereby alleviating the development of AD, revealing a promising therapeutic axis for AD treatment.

Based on CT radiomics model for predicting the response to first-line chemotherapy of diffuse large B-cell lymphoma

Objective: To investigate the potential value of CT Radiomics model in predicting the response to first-line chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods: Pre-treatment CT images and clinical data of DLBCL patients treated at Shanxi Cancer Hospital from January 2013 to May 2018 were retrospectively analyzed and divided into refractory patients (73 cases) and non-refractory patients (57 cases) according to the Lugano 2014 efficacy evaluation criteria. The least absolute shrinkage and selection operator (LASSO) regression algorithm, univariate and multivariate logistic regression analyses were used to screen out clinical factors and CT radiomics features associated with efficacy response, followed by radiomics model and nomogram model. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the models in terms of the diagnostic efficacy, calibration and clinical value in predicting chemotherapy response. Results: Based on pre-chemotherapy CT images, 850 CT texture features were extracted from each patient, and 6 features highly correlated with the first-line chemotherapy effect of DLBCL were selected, including 1 first order feature, 1 gray level co-occurence matrix, 3 grey level dependence matrix, 1 neighboring grey tone difference matrix. Then, the corresponding radiomics model was established, whose ROC curves showed AUC values of 0.82 (95% CI: 0.76-0.89) and 0.73 (95% CI: 0.60-0.86) in the training and validation groups, respectively. The nomogram model, built by combining validated clinical factors (Ann Arbor stage, serum LDH level) and CT radiomics features, showed an AUC of 0.95 (95% CI: 0.90-0.99) and 0.91 (95% CI: 0.82-1.00) in the training group and the validation group, respectively, with significantly better diagnostic efficacy than that of the radiomics model. In addition, the calibration curve and clinical decision curve showed that the nomogram model had good consistency and high clinical value in the assessment of DLBCL efficacy. Conclusion: The nomogram model based on clinical factors and radiomics features shows potential clinical value in predicting the response to first-line chemotherapy of DLBCL patients.

Xuebijing injection protects against sepsis-induced myocardial injury by regulating apoptosis and autophagy via mediation of PI3K/AKT/mTOR signaling pathway in rats.

Apoptosis and autophagy are significant factors of sepsis induced myocardial injury (SIMI). XBJ improves SIMI by PI3K/AKT/mTOR pathway. Present study is devised to explore the protective mechanism of XBJ in continuous treatment of SIMI caused by CLP. Rat survival was first recorded within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and XBJ group. The animals in each group were divided into 12 h group, 1 d, 2 d, 3 d and 5 d according to the administration time of 12 hours, 1 day, 2 days, 3 days or 5 days, respectively. Echocardiography, myocardial injury markers and H&E staining were used to detect cardiac function and injury. IL-1β, IL-6 and TNF-α in serum were measured using ELISA kits. Cardiomyocyte apoptosis was assayed by TUNEL staining. Apoptosis and autophagy related proteins regulated by the PI3K/AKT/mTOR signaling pathway were tested using western blot. XBJ increased the survival rate in CLP-induced septic Rat. First of all, the results of echocardiography, H&E staining and myocardial injury markers (cTnI, CK, and LDH levels) showed that XBJ could effectively improve the myocardial injury caused by CLP with the increase of treatment time. Moreover, XBJ significantly decreased the levels of serum inflammatory cytokines IL-1β, IL-6 and TNF-α in SIMI rats. Meanwhile, XBJ downregulated the expression of apoptosis-related proteins Bax, Cleaved-Caspase 3, Cleaved-Caspase 9, Cytochrome C and Cleaved-PARP, while upregulated the protein levels of Bcl-2 in SIMI rats. And, XBJ upregulated the expression of autophagy related protein Beclin-1 and LC3-II/LC3-I ratio in SIMI rats, whereas downregulated the expression of P62. Finally, XBJ administration downregulated the phosphorylation levels of proteins PI3K, AKT and mTOR in SIMI rats. Our results showed that XBJ has a good protective effect on SIMI after continuous treatment, and it was speculated that it might be through inhibiting apoptosis and promoting autophagy via, at least partially, activating PI3K/AKT/mTOR pathway in the early stage of sepsis, as well as promoting apoptosis and inhibiting autophagy via suppressing PI3K/AKT/mTOR pathway in the late stage of sepsis.

Mitoprotective effect of mesenchymal stem cells-derived conditioned medium in myocardial reperfusion injury of aged rats: role of SIRT-1/PGC-1α/NRF-2 network.

The aged myocardium experiences various forms of stress that cause reduction of its tolerance to injury induced by ischemia/reperfusion (I/R). Developing effective cardioprotective modalities to prevent the amplification of I/R injury during aging is under focus of investigation. Mesenchymal stem cells (MSCs) have the ability to regenerate infarcted myocardium mostly by producing multiple secretory factors. This study aimed to explore the mechanisms of mitoprotection by MSCs-conditioned medium (CM) in myocardial I/R injury of aged rats. Male Wistar rats (n = 72, 400-450g, 22-24months old) were randomized into groups with/without I/R and/or MSCs-CM treatment. To establish myocardial I/R injury, the method of LAD occlusion and re-opening was employed. MSCs-CM was administered intramyocardially (150μl) at the onset of reperfusion in recipient group. After 24h reperfusion, myocardial infarct size, LDH level, mitochondrial functional endpoints, expression of mitochondrial biogenesis-associated genes, and the levels of pro-inflammatory cytokines were evaluated. After 28days reperfusion, echocardiographic assessment of cardiac function was performed. MSCs-CM treatment improved myocardial function and decreased infarct size and LDH level in aged I/R rats (P < .05 to P < .001). It also decreased mitochondrial ROS formation, enhanced mitochondrial membrane potential and ATP content, upregulated mitochondrial biogenesis-related genes including SIRT-1, PGC-1α, and NRF-2, and lessened TNF-α, IL-1β, and IL-6 levels (P < .05 to P < .01). MSCs-CM treatment attenuated myocardial I/R injury in aged rats, in part by improving mitochondrial function and biogenesis and restraining inflammatory reaction. the upregulation of SIRT-1/PGC-1α/NRF-2 profiles is a possible target for the mitoprotective effects of MSCs-CM following I/R injury during aging.

P435 THE IMPORTANCE OF CORRELATION BETWEEN HEART FAILURE AND THYROID: A CASE REPORT

Abstract A 39–year–old African man was admitted to our department within a four days symptoms of short of breath, cough, tachycardia and lower limb edema. He also complained headache for about a month. He denied fever, chest pain and loss of consciousness. Clinical and family history were unremarkable. Blood tests showed moderate microcytic anemia ( Hb 9.6 g/dl, MCV 93.3 fL), hypoalbuminemia ( Albumin: 3.20 g/dl), elevated levels of LDH ( LDH: 246 U/L), mild C–reactive protein (CRP) and pro–Brain Natriuretic Peptide (pro–BNP) increase (CRP: 1.14 mg/dl); (PRO–BNP: 1133 pg/mL) and negative troponin. Given the clinical picture suggestive of heart failure, we immediately started diuretic therapy with benefit. Chest–x ray revealed a modest thickening of the pulmonary interstitium, electrocardiogram (ECG) a sinus rhythm and early repolarization changes. Chest CT highlighted a bilateral apical–basal pleural effusion, a bilateral hilar ectasia and interstitial markings due to stasis. He underwent an ultrasound of the abdomen that was normal. Thyroid function tests showed high levels of thyroid hormones with suppressed TSH and elevated levels of Ab anti–receptor TSH ( FT3: 8.73 pg/mL; FT4: 2.35 ng/dL; TSH&amp;lt;0.01 mUI/ml; TRAB: 3.62 UI/L). Thyroid ultrasound showed a multinodular goiter. The patient began therapy with Tapazole. Echocardiogram didn’t show any evidence of acute heart disease and systolic function was normal. After discharge he performed a heart MRI with evidence of no alteration of global systolic function, of regional left and right ventricular kinetics or of pathological areas of delayed enhancement in relation to myocardial edema/fibrosis/necrosis. Hyperthyroid patients can show signs and symptoms of heart failure that are due to the hyperdynamic circulatory state and/or to the frequent pulmonary arterial hypertension and our case report demonstrates that this clinical status tends to improve with the restoration of euthyroidism, but if left untreated, can worsen over the time leading to heart failure.

Towards Predicting Length of Stay and Identification of Cohort Risk Factors Using Self-Attention-Based Transformers and Association Mining: COVID-19 as a Phenotype.

Predicting length of stay (LoS) and understanding its underlying factors is essential to minimizing the risk of hospital-acquired conditions, improving financial, operational, and clinical outcomes, and better managing future pandemics. The purpose of this study was to forecast patients' LoS using a deep learning model and to analyze cohorts of risk factors reducing or prolonging LoS. We employed various preprocessing techniques, SMOTE-N to balance data, and a TabTransformer model to forecast LoS. Finally, the Apriori algorithm was applied to analyze cohorts of risk factors influencing hospital LoS. The TabTransformer outperformed the base machine learning models in terms of F1 score (0.92), precision (0.83), recall (0.93), and accuracy (0.73) for the discharged dataset and F1 score (0.84), precision (0.75), recall (0.98), and accuracy (0.77) for the deceased dataset. The association mining algorithm was able to identify significant risk factors/indicators belonging to laboratory, X-ray, and clinical data, such as elevated LDH and D-dimer levels, lymphocyte count, and comorbidities such as hypertension and diabetes. It also reveals what treatments have reduced the symptoms of COVID-19 patients, leading to a reduction in LoS, particularly when no vaccines or medication, such as Paxlovid, were available.

Prognostic significance of laboratory parameters in assessment the severity of the course and outcome of coronavirus disease (COVID-19)

The objective – to evaluate the dynamics and prognostic value of inflammatory markers and other laboratory parameters in the blood of patientswith COVID-19 and to assess the severity of the course and mortality in this disease. Materials and Methods. The clinical and laboratory data of 819 patients with COVID-19 treated in a hospital were retrospectively analyzed. In 700 (85.5 %) patients, the disease occurred in a moderate form, these patients were recovered. Patients with severe course (n = 119) were treated in the intensive care unit, of which 47 (39.5 %) patients had a favorable outcome and 72 (60.5 %) patients died. All patients underwent clinical, biochemical (including IL-6) and coagulological studies at admission and in dynamics. The concentration of IL-1ß, IL-8, IL-10, tumor necrosis factor TNF-α were additionally measured in patients with severe COVID-19. Results. Initially, patients with severe disease, compared with moderate, had higher levels of C-reactive protein (p &lt; 0.001), LDH (p = 0,007), D-dimers (p = 0.028), fibrinogen (p = 0.014), the number of white blood cells (p = 0.018), as well as lower levels of albumin (p &lt; 0.001). In the group of patients with fatal outcome, higher levels of LDH (p = 0.008), creatinine (p = 0.009), urea (p &lt; 0.001), troponin (p = 0.024), D-dimers (p = 0.002), fibrinogen (p = 0.009), the relative content of immature leukocytes (p = 0.004), neutrophil to lymphocyte ratio (p = 0.022) were found than in survivors. On the 7th day of hospitalization, an acute increase in ferritin, urea, D-dimers, LDH, interleukins was noted in the group of deceased patients. Using the observer’s operating curves method, predictors of an unfavorable outcome in COVID-19 were determined: IL-10 above 9.46 pg/ml (area under the ROC curve AUC = 0.902), urea above 6.6 mmol/L (AUC = 0.815), TNF-α above 12.6 pg/ml (AUC = 0.799), C-reactive protein above 59.6 mg/L (AUC = 0.714), LDH above 348 U/L (AUC = 0.702), neutrophil to lymphocyte ratio above 4.94 (AUC = 0.700), IL-6 above 62.2 pg/ml (AUC = 0.686), ferritin above 772 μg/L (AUC = 0.654). Conclusions. Baseline levels of LDH, D-dimers, and fibrinogen have a discriminatory ability to determine both the severity and the outcome of COVID-19. The severity of the inflammatory response upon admission correlates with the severity of the disease, but has no prognostic value. At the time of admission, patients with an unfavorable outcome already have initial manifestations of organ dysfunction (assessed by creatinine, urea, and troponin levels). On the 7th day of hospitalization, the relationship of values and the outcome appears in ferritin and interleukin 6. The presence of a strong correlation between the levels of interleukins IL-6, IL-8, IL-10, TNF-α makes it possible to measure any of them.

Intravascular hemolysis in phenol poisoning: An unforeseen and rare complication

The black phenyl is a powerful germ killer used for homes, hospitals, which is easily accessible and can be consumed with the intention of self harm. Cases of intravascular hemolysis through inhalation or spillage has been reported, but intravascular hemolysis following ingestion is rarely reported. A 25 year old previously healthy male presented after alleged ingestion of black phenyl and was asymptomatic at presentation. By day 4, he developed fever, icterus, tachycardia, fatigue and dark brown urine. Labs were Hgb 3.6g/dl, platelet count 2.75 lakhs/ul, creatinine 1.1mg/ dI, AST 244U/L, ALT 69U/L, Total Bilirubin 4.65g/dl (Indirect 3.35) PT 14.6, INR 1.23. By Day 6, urine color darkened, suggestive of ongoing hemolysis with LDH level of 3614 U/L. Over the full hospital stay, urine output was maintained, and he didn't develop acute kidney injury. By Day 9, patient's symptoms improved &amp; he was discharged on day 12. These compounds interfere with oxidative phosphorylation in cells, making red blood cells losing osmotic equilibrium. This metabolic handicap may lead to premature red blood cell lysis. Though asymptomatic at presentation, patient developed serious intravascular hemolysis and hemoglobinuria by day 4. This suggests the need for admission of asymptomatic patients, constant monitoring and to anticipate toxic potentials of the compound. The dearth of enough literature on this rare complication made us report this first case from North East India.

Correlation between Ubiquinone Levels, Lactate Dehydrogenase, and Lactate on Acute Myocardial Infarction

Ubiquinone is an antioxidant that plays a role in preventing endothelial damage, thereby reducing the risk of myocardial infarction. In myocardial infarction, there is a decrease in ubiquinone levels and energy production in the form of ATP. Both stimulate anaerobic metabolism, which increases lactate dehydrogenase and lactate levels. This study aimed to analyze the correlation between ubiquinone levels, lactate dehydrogenase levels, and lactate levels in patients with acute myocardial infarction. This study was an analytical observational study with a cross-sectional approach. The normality of data was analyzed using the Kolmogorov-Smirnov test, and the correlation among variables was analyzed using the Spearman Rank test. The number of research subjects was 52, consisting of 25 research subjects with STEMI and 27 with NSTEMI. The median of ubiquinone, LDH, and lactate levels was 12.52 ng/mL (5.6–412.2); 310 U/L (3-1212); and 4 mmol/L (0.8 – 22), respectively. The correlation test results between ubiquinone levels with LDH levels obtained p=0.4 with r=-0.35; correlation test results between LDH levels and lactate levels obtained p=0.09, with r = -0.14. There was no correlation between acute myocardial infarct patients' ubiquinone levels, LDH levels, and lactate levels in AMI patients.