LDH Levels Research Articles

Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study.

The optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group, 89.2% of CT-group and 78.8% of no-bridge-group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT-group, 28.2% in the CT-group, and 47.6% in the no-bridge-group (p = 0.044, CT-bridging vs RT-bridging); 1-year OS was 86.7% in the RT-group, 52.7% in the CT-group and 69% in the no-bridge-group (p = 0.025, CT-bridging vs RT-bridging). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT-group, 3.3% RT-group, 7.7% no-bridge group; p = 0.05). In conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site.

Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer

Background: Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin- E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated. Methods: The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin- E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin- E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined. Results: The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 μg/ml. LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors. Conclusions: These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.

Free Fatty Acids and Biochemical Changes in Iraqi patients with Chronic Renal Failure

Chronic renal failure (CRF) is progressive irreversible destruction of kidney tissue by disease which, if not treated by dialysis or transplant, will result in patient's death. This study was carried out on 30 patients (17 male and 13 female) with chronic renal failure. The aim of this research was studied the changes in the level of total protein ,albumin, calcium ,ionized calcium, phosphorous , iron ,ALP, LDH ,CK and FFA in patients with CRF before and after hemodialysis .The obtained results have been compared with 30 healthy subjects as control group (18male and 12 female). The results showed that there was significant increase in the level of calcium ,ionized calcium, phosphorous ,iron ,ALP,LDH,CK and FFA ,while there was a significant decrease in the level of total protein ,albumin before hemodialysis comparison to control group . Non significant changes was observed in the level of total protein ,albumin, calcium ,ionized calcium, phosphorous and significant increase in the level of iron ,ALP,LDH,CK and FFA after hemodialysis as compared to control group. This study shows significant positive correlation between FFA and each of albumin and total protein in pre and post-dialysis patients ,and a significant positive correlation with calcium and non significant with ionized calcium in pre-dialysis patients where as there were non significant correlation with calcium and a significant negative correlation with ionized calcium in post-dialysis patients. The conclusion of this study is hemodialysate composition (concentration of electrolytes, free –ionized calcium and some other plasma constituents), the increase concentration of other biochemical changes after renal dialysis because of amissibility a much of amounts of body fluids, and the change in acidosis status may be affect on the correlation between FFA and other parameters used in this study.

New model to predict survival in advanced pancreatic ductal adenocarcinoma patients by measuring GGT and LDH levels and monocyte count.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor survival outcome. Predicting patient survival allows physicians to tailor treatments to specific individuals. Thus, a simple and cost-effective prognosis model is sorely needed. This retrospective study assesses the prognostic value of blood biomarkers in advanced and metastatic PDAC patients (n=96) from Spain. Cut-off points for hematological parameters were calculated and correlated with overall survival (OS) using Kaplan-Meier, log-rank test, robust Cox proportional hazards and logistic regressions. In univariate analysis, individuals with low levels of GGT, LDH, ALP, leukocyte-, neutrophil- and monocyte counts showed significantly longer survival than patients with higher levels. In multivariate analysis, lower levels of GGT (HR (95%CI), 2.734 (1.223-6.111); p=0.014), LDH (HR (95%CI), 1.876 (1.035-3.400); p=0.038) and monocyte count (HR (95%CI), 1.657 (1.095-2.506); p = 0.017) remained significantly beneficial. In consequence, we propose a prognostic model based on logistic regression (AUC=0.741) of these three biomarkers as a pioneer tool to estimate OS in PDAC. This study has demonstrated that the joint use of GGT (<92.00), LDH (<220.00) and monocyte count (<800) are independent positive prognostic factors in PDAC that can predict one-year survival in a novel prognostic logistic model.

Identification of novel variants in hereditary spherocytosis patients by whole-exome sequencing

Defects in erythrocyte membrane proteins can cause the most common type of inherited hemolytic anemia, so called hereditary spherocytosis (HS). It is characterized by the appearance of spherocytes in peripheral blood, hemolytic anemia, splenomegaly, jaundice and gallstones. Due to difficulty of diagnosis solely based on aforementioned parameters, the addition of genetic testing seems to be effective and most acknowledged. Up to date, pathogenic variations in five genes encoding membrane proteins (ANK1, SPTA1, SPTB, SLC4A1, EPB42) are identified to cause HS. Here, we have studied the genetic spectrum in forty-one patients with clinically suspected HS and their families, as well as their genotype-phenotype correlations. Pathogenic mutations in ANK1, SPTB, SLC4A1 and SPTA1 were found in 17 (41.5 %), 12 (29.3 %), 7 (17.1 %) and 5 (12.2 %) patients, respectively. Deleterious variants include 12 missense, 15 nonsense, 12 frameshift, and 4 splicing variants. Among these variations 32 were novel. In our genotype-phenotype analysis, platelet levels in SPTB (p = 0.021) and SLC4A1 (p = 0.02) patients were found to be significantly lower than ANK1 patients. In addition, LDH levels in SPTB patients were remarkably lower than patients with ANK1 mutations (p = 0.025).

Clinical Features and Prognosis of Patients with Diffuse Large B-Cell Lymphoma of the Breast

To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast. The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed. There were significant differences in IPI score, LDH level and β2- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was （59.1±19.8）% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05). Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and β2-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.

The Activation of PKM2 Induces Pyroptosis in Hippocampal Neurons via the NLRP3/Caspase-1/GSDMD Pathway in Neonatal Rats With Hypoxic-Ischemic Brain Injury.

The presence of hypoxic-ischemic brain damage (HIBD) in neonates triggers a strong neuroinflammatory reaction. Pyroptosis, a programmed cell death mechanism associated with inflammation, plays a crucial role in HIBD. Pyruvate kinase M2 (PKM2) plays a significant role in connecting metabolic processes and inflammatory responses, but whether it affects hippocampus pyroptosis in HIBD is unclear. The aim of this study is to elucidate the role of PKM2 in HIBD and to propose a novel therapeutic approach for neonatal ischemic-hypoxic encephalopathy. In this study, we employed neonatal 7-day-old Sprague Dawley rats to establish a model of HIBD using the Rice-Vannucci surgical technique and a hypoxia device. To inhibit the elevation of PKM2, we utilized the PKM2 inhibitor shikonin. The rats were categorized into four groups: Sham, Shikonin, HIBD, and Shikonin+HIBD. Behavioral tests, hematoxylin eosin staining, immunofluorescence staining, ELISA (IL-1β, IL-18), and LDH were conducted in each group to evaluate neurological function, hippocampal damage, the occurrence of neuronal pyroptosis, and the neuroinflammation. Western blot was used to assess the expression levels of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN, and IL-1β. The expression of PKM2 elevated in hippocampal tissues of the HIBD model and the localization of PKM2 in the hippocampus was activated in neurons instead of microglia during the HIBD. Meanwhile, the inhibition of PKM2 improved the behavioral test scores and the body weight of rats, the neuronal damage in the CA1 region of hippocampal tissue was also attenuated. In addition, inhibiting PKM2 alleviated neuronal pyroptosis by decreasing the expression of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN. Furthermore, serum levels of LDH and inflammatory factors IL-1β and IL-18 decrease with PKM2 inhibition. Based on these findings, we can conclude that PKM2 plays a crucial role in regulating hippocampal neuronal pyroptosis of HIBD rats via NLRP3/Caspase-1/GSDMD pathway. Therefore, inhibiting PKM2 could be a promising therapeutic strategy for the treatment of neonatal ischemic-hypoxic encephalopathy.

Codonopsis pilosula polysaccharide suppresses the progression of non-small cell lung cancer by triggering NLRP3/GSDMD-dependent pyroptosis

BackgroundNon-small cell lung cancer (NSCLC) represents a prevalent and challenging malignancy, often posing difficulties in treatment due to late-stage diagnosis and limited therapeutic options.ObjectiveThis study aims to elucidate the impact of Codonopsis pilosula polysaccharide (CPP) on NSCLC, exploring its potential anticancer molecular mechanisms.Materials and methodsPurchase A549 cells and treat them with varying concentrations of CPP, dividing them into groups. Use CCK-8 assays for cell proliferation and TUNEL assays for apoptosis detection. Perform Western blot (WB) to detect NF-κB p65, pNF-κB p65, and pyroptosis-related proteins. Measure ROS, inflammatory factors, and LDH levels using kits. Observe pyroptosis morphology under a microscope. Inoculate A549 cells subcutaneously into nude mice to create a xenograft model and treat them with daily CPP injections. Collect tumor tissues, measure tumor volume and mass. Perform TUNEL immunohistochemistry for apoptosis and H&E staining for tumor histology. Detect pyroptosis-related proteins with Western blot and immunohistochemistry, and assess inflammatory factors using ELISA and immunohistochemistry.ResultsThe research reveals a concentration-dependent inhibitory effect of CPP on A549 cell viability, with optimal efficacy observed at 40 μmol/L CPP. CPP demonstrates the capacity to induce apoptosis, mediate NF-κB activation, and accumulate reactive oxygen species (ROS). Notably, CPP promotes pyroptosis in A549 cells and in vivo, upregulating pyroptosis-related proteins. In vivo administration of CPP significantly inhibits tumor growth, accompanied by notable morphological and histological alterations. Additionally, both in vitro and in vivo studies confirm elevated levels of IL-1β and IL-18 in tumor tissues following CPP treatment.Discussion and conclusionIn conclusion, CPP, as a multifaceted agent, suppresses the progression of NSCLC by inducing NLRP3/GSDMD-dependent pyroptosis. This research provides valuable insights into the therapeutic potential of CPP and stimulates further exploration for its integration into future NSCLC treatments.

SS-31 modification alleviates ferroptosis induced by superparamagnetic iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes

Superparamagnetic iron oxide nanoparticles (SPION) are widely used in cardiovascular applications. However, their potential to induce ferroptosis in myocardial cells post-ischemia-reperfusion hinders clinical adoption. We investigated the mechanisms behind SPION-induced cytotoxicity in myocardial cells and explored whether co-loading SPION with SS-31 (a kind of mitochondrial-targeted antioxidant peptide) could counteract this toxicity.To create SPION@SS-31, SS-31 was physically adsorbed onto SPION. To study the dose- and time-dependent cytotoxic effects and assess the influence of SS-31 on reducing SPION-induced damage, hypoxia/reoxygenation(H/R) H9C2 cells were treated with either SPION or SPION@SS-31. We examined the relationship between SPION and ferroptosis by measuring mitochondrial ROS, mitochondrial membrane potential (MMP), lipid peroxidation products, ATP, GSH, GPX4, mitochondrial structure, nonheme iron content, cellular iron regulation, and typical ferroptosis markers.The findings showed that SPION induced concentration- and time-dependent toxicity, marked by a significant cell viability loss and an increase in LDH levels. In contrast, SPION@SS-31 produced results comparable to the H/R group, implying that SS-31 can notably reduce cell damage induced by SPION. SPION disrupted cellular iron homeostasis, with FtH and FtMt expression increased and reduced levels of FPN1 and ABCB8, which led to the overload of mitochondrial iron. This iron dysregulation damaged mitochondrial function and integrity, causing ATP depletion, MMP loss, and decreased GPX4 and GSH levels, accompanied by a burst of mitochondrial lipid peroxidation, ultimately resulting in ferroptosis in H/R cardiomyocytes. Notably, SS-31 significantly alleviated SPION-induced ferroptosis by decreasing mitochondrial MDA production and maintaining GSH and GPX4 levels, indicating its possibility to reverse SPION-induced cytotoxicity. The viability of H/R cells and cells treated with SPION and Fer-1 did not differ statistically, whereas cells exposed to SPION along with inhibitors like 3-MA, zVAD, or Nec-1 showed a substantial loss in viability, implying that ferroptosis is the primary mechanism behind SPION-induced myocardial toxicity.SPION triggers mitochondrial lipid peroxidation by causing overload of iron, leading to ferroptosis in H/R H9C2 cells. Mitochondria appear to be the primary target of SPION-induced toxic effects. SS-31 demonstrates potential in inhibiting this ferroptosis by acting as a mitochondria-targeted antioxidant, suggesting that the modification of mitochondria-targeted antioxidant peptides represents an innovative and practical approach to attenuate the myocardial toxicity associated with SPION.

Curcumin ameliorates ischemic stroke injury by downregulating GMFB expression: An in vitro study.

Ischemic stroke (IS) is a cerebrovascular sickness, and cerebral ischemia-reperfusion (I/R) damage often occurs, but there is still a lack of drugs that can significantly alleviate it. Curcumin (Cur) exerts pharmacological effects such as antioxidative stress, anti-inflammation, and the promotion of apoptosis through regulating various pathways, but its efficacy and specific mechanism of action in IS have not been fully clarified. The purpose of this paper is to study the influence of Cur on IS. Brain microvascular endothelial cells (BMECs) were used to create an oxygen-glucose deprivation/reoxygenation (OGD/R) model to simulate I/R damage. The cell viability was assessed using an MTT assay. The LDH level and ROS positive rate were measured using commercial kits. The cell invasion was examined using a transwell assay. The apoptosis was assessed by flow cytometry. The contents of GMFB, Bax, and Bcl2 were measured using western blot. We confirmed that in the OGD/R-induced IS cell model, the abundance of GMFB was enhanced in the OGD/R group versus the control group. GMFB overexpression promoted OGD/R-induced cell viability diminution, increased LDH and ROS levels, lessened cell invasion ability, enhanced cell apoptosis, enhanced Bax levels, and decreased Bcl2 levels. Silencing GMFB ameliorated OGD/R-induced cell damage. Cur ameliorated OGD/R-induced cell damage. Cur curbed OGD/R-induced cell damage by downregulating GMFB expression. In conclusion, Cur cured ischemic stroke-induced cell damage by downregulating GMFB expression.

Association between laboratory markers, clinical and radiological findings in patients with idiopathic intracranial hypertension: case–control study

BackgroundIdiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure. Contribution of inflammatory mediators has been suggested in IIH pathophysiology. The aim of this study was to estimate certain serum inflammatory markers in IIH patients compared to normal subjects. Also, to examine the correlation between these laboratory parameters and the clinical and radiological characteristics of IIH patients.ResultsBody mass index (BMI) was significantly higher among IIH patients compared to controls. Serum LDH, CRP, NLR and PLR were significantly higher, whereas serum iron was significantly lower in IIH patients compared to healthy controls. IIH patients with stenosis in brain MRV had significantly higher mean serum CRP compared with patients with normal MRV. There was a statistically significant positive correlation between serum CRP and the presence of stenosis in MRV, between serum LDH level and grade of papilledema, and between CRP, TIBC, and NLR with BMI.ConclusionsThere is a significant elevation of inflammatory markers in IIH patients. Moreover, cerebral venous sinus stenosis and BMI were positively associated with higher markers of inflammation as CRP, LDH and NLR indicating the role of inflammation in thrombosis and obesity associated with IIH.

Outcomes and predictors of progression in progressive pulmonary fibrosis

Background Progressive pulmonary fibrosis (PPF) is a general term for a class of interstitial lung diseases (ILDs) characterized by a progressive fibrosing (PF) phenotype. Patients with PPF have decreased lung function, exercise ability, and quality of life. The purpose of this study was to investigate the clinical characteristics, potential associated factors for disease progression, and survival outcomes of patients in the PPF population. Methods This study retrospectively reviewed the data of patients diagnosed with ILD between January 2011 and December 2022 at The First Affiliated Hospital of Ningbo University. A PF phenotype was defined based on the criteria that were used in the PPF clinical practice guidelines, which led to the identification of 92 patients with a PF phenotype among the 177 patients with fibrotic ILD. Baseline clinical information and laboratory parameters were collected and analysed in our cohort. Results Patients in the PPF group had higher tumour marker levels and lower pulmonary function test results at baseline than did those in the non-PPF group. According to the multivariate logistic regression analysis, age >65 years (OR 2.71, 95% CI 1.26-5.89; p = 0.011), LDH >245 U/L (OR 3.07, 95% CI 1.39-6.78; p = 0.006), CA-153 > 35 U/mL (OR 3.16, 95% CI 1.25-7.97; p = 0.015), FVC <60% predicted (OR 4.82, 95% CI 1.60-14.51; p = 0.005), DLCO <50% predicted (OR 3.21, 95% CI 1.43-7.21; p = 0.005), and the UIP-like pattern on chest HRCT (OR 3.65, 95% CI 1.33-10.07; p = 0.012) were potentially associated with the progression of fibrotic interstitial lung diseases (f-ILDs) to PPF. Furthermore, the PPF group had a poorer survival rate than the non-PPF group (p = 0.0045). According to the multivariate Cox regression analysis, an SPAP ≥ 37 mmHg (HR 2.33, 95% CI 1.09-5.00; p = 0.030) and acute exacerbation (HR 2.88, 95% CI 1.26-6.59; p = 0.012) were identified as significant prognostic factors for mortality in patients with PPFs. Conclusions Patients who were older, had high CA-153 and LDH levels, had poor pulmonary function test results, or had a UIP-like pattern on chest HRCT were more likely to have indications for the progression of f-ILD to PPF. Increased SPAP and AE are independent risk factors for the prognosis of PPF patients, so additional attention should be given to such patients.

Revealing ferritin's significance: A prognostic marker in COVID-19 at a tertiary care hospital in Rawalpindi

Amid the global COVID-19 crisis with over 762 million cases by 2023, reaching 775 million by 2024, this study examines the critical role of ferritin in diagnosing and managing COVID-19, emphasizing its correlation with disease severity and patient outcomes, especially in Pakistan, where data is scarce. At Benazir Bhutto Hospital in Rawalpindi, this study analyzed medical records of 376 COVID-19 patients aged 25-87 between April 2020 to August 2021, categorizing them by severity. Biochemical parameters, as well as ferritin, AST, ALT, urea, creatinine, and LDH, be assessed using Beckman Coulter AU480, with group differences analyzed via nonparametric tests and SPSS 25. Among 376 patients, predominantly aged 45-65 with a male majority (56.6%), 88.2% had comorbidities and 34.8% deceased during hospitalization. Elevated levels of ferritin, AST, urea, creatinine, and LDH were strongly linked to mortality (p &lt; 0.001). The patients in the 66-90 age group had significantly increased risk of death from COVID-19 than those aged 45-65, by an adjusted odds ratio (AOR = 4.973; 95% CI: 2.517, 9.826; p = 0.0001). Additionally, individuals in the upper ferritin tertile were more susceptible to death, with an AOR of 3.443(95% CI: 2.012, 5.892; p = 0.0001) in contrast to those in middle and lower ferritin tertiles. These findings underscore the predictive value of age and ferritin levels in COVID-19 mortality. Increased ferritin levels stand out as a vital indicator, along with age, for forecasting mortality in COVID-19 patients, highlighting the pressing need for prompt intervention and customized treatment approaches.

A comparative retrospective study of pre-fibrotic primary myelofibrosis versus overtly fibrotic stage in Qatar: clinicopathological, genetic landscape, risk stratification and survival data (2008–2021) – a single center experience

ABSTRACT Background In MENA region, there is a lack of evidence on Primary Myelofibrosis (PMF), leading to its underrepresentation in medical literature. This study marks the first comprehensive report on PMF data in Qatar, presenting findings from a single-center study spanning 13 years (2008-2021). Methods Clinicopathological data, genetic features, and disease progression parameters of pre-PMF and overt PMF subgroups were collected. Overall survival (OS), progression-free survival (PFS), DIPSS plus four categories and merged low and high-risk DIPSS scoring groups were assessed. Results Pre-PMF patients showed higher hemoglobin (P < 0.001), and platelet counts (P < 0.05) but lower blast counts, LDH levels, constitutional symptoms (P < 0.0001), and splenomegaly (P < 0.010) than overt PMF patients. JAK2 V617F mutation was more common in pre-PMF (P = 0.059), while unfavorable karyotypes were exclusive to overt PMF (P = 0.028). Median overall survival was significantly longer at 276.9 months (IQR: 315.9, 276.9 months) to what was previously reported. Overt PMF patients predominantly fell into the higher DIPSS risk category (P < 0.001) and showed greater disease progression than pre-PMF (P < 0.0001). Complications including refractory anaemia (P < 0.001) and leukemic transformation (P = 0.043), increased notably in the high-risk group. Furthermore, 86.2% of high-risk patients required treatment versus 59.4% of the lower-risk group (P = 0.020). Conclusions To the best of our knowledge our research represents the first and largest published dataset on PMF in MENA region to be published. Merged DIPSS plus scoring came to be a pragmatic tool for defining high-risk patients who significantly differ in mortality, progression, need for treatment and leukemic transformation.

Musculoskeletal Symptoms and Misdiagnoses in Children With Acute Myeloid Leukaemia: A Nationwide Cohort Study.

Childhood cancer often presents with non-specific signs and symptoms that might mimic non-malignant disorders including musculoskeletal diseases, potentially leading to rheumatic and orthopaedic misdiagnoses. We aimed to compare clinical presentation, diagnostic interval and survival in paediatric acute myeloid leukaemia (AML) with and without initial musculoskeletal symptoms. This nationwide retrospective, cohort study reviewed medical records of 144 children below 15 years diagnosed with AML in Denmark from 1996 to 2018. Musculoskeletal symptoms occurred in 29% (42/144) of children with AML and 8% (11/144) received an initial musculoskeletal misdiagnosis, being mainly non-specific and pain-related. The children with and without musculoskeletal symptoms did not differ markedly up to the diagnosis of AML and blood counts were affected equally in both groups. However, the children with prior musculoskeletal symptoms were more likely to have elevated levels of LDH and ferritin. Furthermore, they revealed a tendency towards a longer total interval (median 53 days vs. 32 days, p = 0.07), but the overall survival did not differ. AML should be considered as an underlying cause in children with unexplained musculoskeletal symptoms and abnormal blood counts. Concomitant elevation of LDH and ferritin should strengthen the suspicion.

Neuroblastoma with high ASPM reveals pronounced heterogeneity and poor prognosis

ObjectiveWe explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB).MethodsThis retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity.ResultsThere were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS.ConclusionASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients.

4-Phenylbutyric acid suppresses psoralen-induced hepatotoxicity by inhibiting ERS and reestablishing mitochondrial fusion-fission balance in mice

Psoralen is a main active molecule of the traditional Chinese herb medicine Fructus Psoraleae. Our previous studies have shown that psoralen induced liver injury through the endoplasmic reticulum stress (ERS) signaling pathways. In this article, we studied whether the ERS inhibitor, 4-phenylbutyrate acid (4-PBA) could inhibit the liver toxicity caused by psoralen, and explored the underlying mechanisms. Mice were given the solvent, 20 mg/kg, 40 mg/kg, 80 mg/kg of psoralen, or 80 mg/kg of psoralen plus 4-PBA for 14 days. We found that 4-PBA significantly reduced the serum LDH and liver tissue MDA level, increased the activities of SOD and CAT, reduced liver weight and coefficient, repaired histopathological damage, and inhibited hepatocytes apoptosis induced by psoralen. RNA-seq transcriptomics found that except for the endoplasmic reticulum, the mitochondria was severely affected by psoralen. And genes involved in mitochondrial fusion, apoptosis, protein folding, and autophagy were found differently expressed in the psoralen group. Further studies found that 4-PBA inhibited the overexpression of GRP78 and CHOP, increased the Bcl-2/Bax ratio, and reduced the expression of Caspase-3. Moreover, 4-PBA reduced the overexpression of mitochondrial fission protein DRP1, increased the expression of fusion proteins Mfn-2 and OPA1, but has no inhibitory effects on autophagy proteins Atg5 or LC3A/B. In conclusion, 4-PBA inhibited ERS and reestablished mitochondrial fusion-fission balance, thereby blocking cell apoptosis, oxidative stress, and mitochondrial dysfunction, thus prevented against psoralen-induced hepatotoxicity.

Efficacy and safety analysis of the OR-CHOP regimen for the treatment of MCD subtype diffuse large B cell lymphoma in the real-world setting

Objective: To investigate the efficacy and safety of orelabrutinib combined with R-CHOP in the treatment of MCD subtype diffuse large B cell lymphoma (DLBCL) . Methods: Twenty-three MCD subtype patients whose gene-subtype classification was based on baseline tumor tissue and/or baseline plasma using the LymphGen algorithm from June 2022 to June 2023 in the First Affiliated Hospital of Nanjing Medical University were retrospectively enrolled in the analysis. All patients were treated with R-CHOP or R-miniCHOP in Course 1, OR-CHOP or OR-miniCHOP (21 days for one course) in Courses 2-6, and R-monotherapy in Courses 7-8. Results: Of the 23 patients, the median age was 58 years (range: 30-81 years), and 11 (47.8% ) aged >60 years. Fifteen cases (65.2% ) had international prognostic index (IPI) scores of 3 to 5. The top 10 mutated genes in the gDNA tissues were PIM1 (78.3% ), MYD88 (69.6% ), ETV6 (43.5% ), BTG1 (39.1% ), CD79B (43.5% ), HIST1H1E (39.1% ), BTG2 (34.8% ), KMT2D (30.4% ), CD58 (26.1% ), and CDKN2B (21.7% ). The consistency rate of the tissue and plasma mutations was 80%, while the baseline plasma ctDNA burden was closely correlated with the LDH levels and IPI scores (P<0.05). All patients received 5 courses of OR-CHOP regimens. The mid-term (after 3 courses) evaluation showed that the overall response rate (ORR) was 100% (23/23), with 22 patients (95.65% ) achieving complete remission (CR), and 1 patient (4.35% ) achieving partial remission (PR). The ORR after the end of treatment (EOT) was 95.65% (22/23). Moreover, 21 patients (91.30% ) obtained CR, 1 patient (4.35% ) obtained PR, and 1 patient (4.35% ) obtained progression disease (PD). Of the 21 patients who had the dynamic EOT-ctDNA burden, only four patients (19.0% ) did not achieve EOT-ctDNA clearance, while the other 17 patients (81.0% ) achieved EOT-ctDNA clearance. The median follow-up time was 20.8 (15.3-30.0) months, while the median progression-free survival (PFS) and overall survival (OS) were not reached. The 2-year PFS rate was 71.8% (95% CI 54.7% -94.2% ), while the 2-year OS rate was 91.3% (95% CI 80.5% -100.0% ). Furthermore, the OR-CHOP regimen was generally well tolerated during clinical use, with hematological toxicity being the main adverse effect. Conclusion: This study revealed that the OR-CHOP regimen can be used as an effective and safe first-line treatment for MCD subtype DLBCL.

Neuropsychiatric manifestations of hospitalized patients with coronavirus disease 2019 during the second wave in Egypt

BackgroundStudies suggested that COVID-19 virus causes neurological and psychiatric manifestations with different mechanisms. However, prevalence of neurological and psychiatric manifestations among COVID-19 patients varies across studies from 18.1%: 82.3%. The objective of this study was to determine neuropsychiatric manifestations in a sample of Egyptian COVID-19 hospitalized patients during the second wave of the pandemic and to detect factors affecting neurological and psychiatric prevalence. This cross-sectional study was conducted at Ain Shams university isolation hospitals and included 110 hospitalized COVID-19 patients, over a 2-month period from June 2021 to August 2021. Patients underwent a careful history taking, full neurological examination including Mini-Mental State Examination, the Structured Clinical Interview for DSM-IV (SCID I), COVID-19 severity criteria. Any available imaging and laboratory tests were recorded.Results83 (75.5%) patients had neurological manifestations. The most common neurological manifestations were headache (50.9%), hypogeusia (24.5%), hyposmia, paresthesia (23.6% each) and coma (15.5%). After exclusion of 17 patients who could not be examined by Mini-Mental State Examination, psychiatric manifestations were seen in 56 patients (61.5%) out of the remaining 91 patients. The most prevalent psychiatric disorders were delirium (30.8%), depression (19%), and adjustment disorder (17.5%). Moreover, hypertension, COVID-19 severity, place of admission, and high levels of LDH and ALT affected neurological manifestations prevalence.ConclusionsCOVID-19 infection and its immune reaction along with its social and psychological effects have a great impact on mental and physical health. Hence, neuropsychiatric evaluation cannot be ignored in any case with COVID-19 infection.

Abnormal expression of circ_0013958 in patients with acute myocardial infarction (AMI) and its influence on prognosis

ObjectiveThe purpose of this study was to investigate the diagnostic value of circ_0013958 in acute myocardial infarction (AMI) patients and its influence on the prognosis of AMI patients.MethodsThe GSE160717 dataset was downloaded from the NCBI database and differentially expressed genes were analyzed between the control group and the AMI group. The up-regulated genes included circ_0013958. The expression of circ_0013958 in both groups was further verified by RT-qPCR. The Receiver Operating Characteristic curve was used to evaluate the diagnostic value of circ_0013958 in AMI. Pearson correlation analysis was used to examine the correlation between circ_0013958 levles and biochemical indicators. Binary logistic regression was used to analyze the risk factors affecting the occurrence of AMI. Prognostic analysis was performed using COX regression analysis and the Kaplan-Meier Curve.ResultsCompared to the control group, the level of circ_0013958 in AMI patients increased. Circ_0013958 can effectively distinguish AMI patients from non-AMI patients. Circ_0013958 levels were positively correlated with cTnI, LDH, CRP and TC levels. The elevated level of circ_0013958 was an independent risk factor for the occurrence of AMI. Higher circ_0013958 levels were also associated with the occurrence of major adverse cardiac events (MACEs) in AMI patients. Additionally, elevated circ_0013958 levels reduced the survival probability of AMI patients.ConclusionCirc_0013958 levels were up-regulated in AMI patients. It can be used as a diagnosis biomarker for AMI. The level of circ_0013958 was correlated with the disease severity and was an independent risk factor for the occurrence of AMI. Elevated circ_0013958 levels were associated with poor prognosis in AMI patients.