Malignancy of Malignant Ascites: A Comprehensive Review of Interplay between Biochemical Variables, Tumor Microenvironment and Growth Factors.

Malignant ascites, a buildup of fluid in the abdominal cavity, is a serious consequence of many malignancies. This review aims to comprehend the biochemical makeup of malignant ascites, such as pH, cholesterol, protein, etc., which is crucial to developing therapeutics with better treatment outcomes and hence correlate with corresponding prognostic value. The unique tumour microenvironment exhibited by malignant ascites and the crosstalk between inflammatory cells, cytokines and chemokines, interactions between tumour and non-tumour cell types, activation of vital cell signalling pathways within the TME for VEGF-regulated sustained angiogenesis, cancer progression and metastasis is highlighted. This review addresses the need to develop comprehensive assay platforms to identify various biochemical aspects of ascites, to discover the interactions of the tumour microenvironment and to study VEGF-regulated permeability that can expedite early diagnosis and progression of ascites.

Targeting NOX2 and glycolytic metabolism as a therapeutic strategy in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a highly heterogeneous malignancy, with a poor 5-year overall survival rate of approximately 30%. Consequently, the search for novel therapeutic strategies is ongoing, and the identification of new vulnerabilities could accelerate progress. Oxidative stress and metabolic rewiring are established hallmarks of cancer, and recent evidence suggests that NADPH oxidases may regulate metabolism, potentially linking these two processes. Increasing research highlights the importance of NOX2 in AML, particularly its role in metabolic regulation. In this study, we investigated the effects of simultaneously inhibiting NOX2 and glycolysis in AML cells. Dual inhibition of NOX2 and glycolysis-by targeting hexokinase or lactate dehydrogenase (LDH)-significantly reduced cell proliferation, markedly impaired clonogenic potential, and induced extensive cell death in a broad panel of AML cell lines. Importantly, these findings were further validated in primary bone marrow samples derived from AML patients, where combined inhibition triggered similar potent anti-leukemic effects. Furthermore, the combined inhibition of NOX2 and LDH enhanced the efficacy of cytarabine (AraC), suggesting this approach could boost the effectiveness of conventional therapies. In an in vivo AML model, targeting NOX2 and LDH in myeloid progenitor cells delayed the onset of leukaemia and extended survival. In conclusion, our findings propose a novel therapeutic strategy for AML through the dual targeting of NOX2 and glycolysis.

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

The application of lung immune prognostic index in predicting the prognosis of 302 STS patients.

Background: Soft tissue sarcoma (STS) are heterogeneous and rare tumors, and few studies have explored predicting the prognosis of patients with STS. The Lung Immune Prognostic Index (LIPI), calculated based on baseline serum lactate dehydrogenase (LDH) and the derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR), was considered effective in predicting the prognosis of patients with pulmonary cancer and other malignancies. However, the efficacy of the LIPI in predicting the prognosis of patients with STS remains unclear. Methods: This study retrospectively reviewed patients with STS admitted to our center from January 2016 to January 2021. Their hematological and clinical characteristics were collected and analyzed to construct the LIPI specific to STS. The correlations between various predictive factors and overall survival (OS) were examined using Kaplan-Meier and Cox regression analyses. Independent risk factors for OS were identified using univariate and multivariate analyses. Finally, a LIPI nomogram model for STS was established. Results: This study enrolled 302 patients with STS, of which 87 (28.9%), 162 (53.6%), and 53 (17.5%) were classified into three LIPI-based categories: good, moderate, and poor, respectively (P < 0.0001). The time-dependent operator curve showed that the LIPI had better prognostic predictive ability than other hematological and clinical characteristics. Univariate and multivariate analyses identified the Fédération Nationale des Centres de Lutte Contre le Cancer grade (FNCLCC/G), tumor size, and LIPI as independent risk factors. Finally, a nomogram was constructed by integrating the significant prognostic factors. Its C-index was 0.72, and the calibration curve indicated that it could accurately predict the three- and five-year OS of patients with STS. The decision and clinical impact curves also indicated that implementing this LIPI-nomogram could significantly benefit patients with STS. Conclusion: This study explored the efficacy of the LIPI in predicting the prognosis of 302 patients with STS, classifying them into three categories to evaluate the prognosis. It also reconstructed a LIPI-based nomogram to assist clinicians in predicting the three- and five-year OS of patients with STS, potentially enabling timely intervention and customized management.

Predictors of relapse of polymyositis/dermatomyositis associated interstitial lung disease.

Background: Polymyositis/dermatomyositis (PM/DM) patients often develop interstitial lung disease (ILD), which can lead to relapse despite anti-inflammatory treatments. This study aims to elucidate the clinical characteristics of relapses in PM/DM-associated ILD patients. Methods: We gathered clinical data, including laboratory results, pulmonary function tests, chest high-resolution computed tomography findings from patients treated at Okinawa Chubu Hospital between January 1, 2010 and December 31, 2018. Results: We identified a total of 74 patients, comprising 21 men and 53 women. Among them, 38 patients remained relapse-free with maintenance therapy, while 36 experienced relapses despite immunosuppressive management. We followed these patients until June 30, 2023, and 13 patients died. The median survival period was 51.4 months (range, 0.3-214 months). When comparing clinical variables, relapsed patients tended to be younger (49.9 vs. 64.1 years), reported myalgia and rash more frequently (63.9% vs. 28.9% and 61.15% vs. 21.1%, respectively). In terms of laboratory findings, lactate dehydrogenase (LDH) levels were higher in relapsed patients (613±464 vs. 381±203 U/L). Radiological findings showed that ground glass opacity (GGO) was more prevalent in relapsed patients (58.3% vs. 16.7%). A Cox-proportional hazards model for relapse demonstrated that serum LDH [hazard ratio (HR) 1.005, 95% confidence interval (CI): 1.000-1.009, P=0.02] and GGO (HR 1.863, 95% CI: 1.103-3.147, P=0.02) were valuable predictors of relapse. Receiver operating characteristic curve analysis of serum LDH indicated that a threshold of 450 correctly classified relapse in PM/DM-associated ILD patients. Conclusions: Serum LDH and GGO may serve as predictors of relapse in PM/DM-associated ILD patients.

Define Critical Parameters of Trastuzumab-Mediated ADCC Assays via Assay Optimization Processes, Focusing on the Impact of Cryopreserved Effector Cells on Assay Performance.

The mechanisms of mAb-induced ADCC have been well established. However, the ADCC bioassays used to quantify mAb-induced ADCC require continued development/refinement to properly assess and compare the potency of newly developed therapeutic mAbs and biosimilars to meet regulatory requirements. We used trastuzumab and a lactate dehydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay, describing how several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can influence the data quality of the ADCC activity. We confirm that a 4 to 24 h recovery cultivation is required to restore peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cell activity toward ADCC when using cryopreserved PBMCs. Furthermore, we delineated the cellular mechanisms underlying the restored ADCC activity following the recovery cultivation. We observed that CD69, an early marker of NK cell activation, was upregulated and a new subset CD56dim/CD16dim population was dramatically increased in the recovered NK cells, which led to an increase in expression and secretion of perforin, granzyme B, and cytokine production. This study provides comprehensive technical insights into ADCC bioassay optimization to inform trastuzumab biosimilar development. The knowledge gained from this study can also be leveraged to guide bioassay development for therapeutic mAbs with ADCC as the primary mechanism of action.

A Case Report of Refractory Hyperlactatemia Secondary to Thiamine Deficiency.

Thiamine is an essential water-soluble vitamin that must be obtained through diet. This vitamin is crucial for various biochemical reactions and is vital for aerobic metabolism. When individuals are deficient in thiamine, which can be due to hypermetabolism (such as in inflammation, ischemia, or malnutrition, among other reasons), anaerobic metabolism may be utilized to maintain energy needs. Such chemical processes produce lactic acid. Excess lactic acid can cause various clinical signs and symptoms, though lactate dehydrogenase (LDH) can typically break down this compound. The following case presents a very unusual instance where a 51-year-old Caucasian woman presented with the chief complaint of ongoing and severe abdominal pain. After an extensive work-up ruling out numerous diagnoses and an eight-day hospital stay, it was believed that she may be suffering from hyperlactatemia secondary to thiamine deficiency, as she improved significantly after administration of this vitamin. It was thought that this was likely due to her previous systemic lupus erythematosus (SLE) diagnosis, vasculitis, chronic inflammation, and a hypermetabolic state, in addition to concurrent LDH malfunction.

Biosafety measures for Alicyclobacillus spp. strains across various levels of biohazard.

Alicyclobacillus bacteria are important contaminants in the beverage industry because their spores remain in the product after usual pasteurization. At the same time, their impact on human health has yet to be characterized, as it is generally assumed to be low or non-existent. However, these bacteria are causing quality concerns mainly due to odor and taste changes of the product. Since potential health effects are not precisely known, an experimental assessment was performed, including a biosafety assessment of six viable and non-viable vegetative and spore forms of Alicyclobacillus spp. strains using cell cultures and rodent study. The monolayer of Caco-2 (Cancer coli-2) cells was investigated for its adsorption effect on the epithelium of the small intestine of mice. Lactate dehydrogenase leakage (LDH) and transepithelial electrical resistance (TEER) tests were used to ensure the integrity of the cell membrane and tight junctions. The methylthiazole tetrazolium bromide (MTT) assay examined in vitro cytotoxicity in Caco-2 and HepG2 cell lines. The hemolysis of erythrocytes was spectrophotometrically measured. The results showed negligible cytotoxicity or non-toxic response in mice. In conclusion, Alicyclobacillus spp. exhibited biocompatibility with negligible cytotoxicity and minimal safety concerns.

Atypical Pulmonary Metastasis of Prostate Adenocarcinoma: A Rare Phenomenon.

Prostate cancer can metastasise to the lung. Most common presentations described in the literature are solitary pulmonary nodules, lymphangitic spread and, rarely, pleural effusion. We describe a case of prostate adenocarcinoma with diffuse bilateral reticulonodular and lymphangitic pulmonary metastasis, and malignant pleural effusion while being on androgen deprivation therapy. LEARNING POINTS: Lymphangitic metastasis of prostate cancer to the lung with diffuse reticulonodular infiltrate is a rare presentation.In chemical castration-sensitive prostate cancer, prostate-specific antigen (PSA) levels can be improving but the patient can still develop new distant metastases.

The relationship between LDH and GLIM criteria for cancer cachexia: Systematic review and meta-analysis.

INTRODUCTION: Cancer cachexia is a clinical condition characterized by recognizable "sickness behaviors" accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed. METHODS: A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS). RESULTS: A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 - 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 - 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 - 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 - 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 - 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 - 2.34; p<0.00001) to low BMI (HR 1.57, 1.29-2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 - 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 - 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64-1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 - 1.77; p<0.00001) or CRP (HR 1.55, 1.43 - 1.69; p<0.00001). CONCLUSION: Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.

Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons.

Oligodendrocytes and astrocytes are metabolically coupled to neuronal compartments. Pyruvate and lactate can shuttle between glial cells and axons via monocarboxylate transporters. However, lactate can only be synthesized or used in metabolic reactions with the help of lactate dehydrogenase (LDH), a tetramer of LDHA and LDHB subunits in varying compositions. Here we show that mice with a cell type-specific disruption of both Ldha and Ldhb genes in oligodendrocytes lack a pathological phenotype that would be indicative of oligodendroglial dysfunctions or lack of axonal metabolic support. Indeed, when combining immunohistochemical, electron microscopical, and in situ hybridization analyses in adult mice, we found that the vast majority of mature oligodendrocytes lack detectable expression of LDH. Even in neurodegenerative disease models and in mice under metabolic stress LDH was not increased. In contrast, at early development and in the remyelinating brain, LDHA was readily detectable in immature oligodendrocytes. Interestingly, by immunoelectron microscopy LDHA was particularly enriched at gap junctions formed between adjacent astrocytes and at junctions between astrocytes and oligodendrocytes. Our data suggest that oligodendrocytes metabolize lactate during development and remyelination. In contrast, for metabolic support of axons mature oligodendrocytes may export their own glycolysis products as pyruvate rather than lactate. Lacking LDH, these oligodendrocytes can also "funnel" lactate through their "myelinic" channels between gap junction-coupled astrocytes and axons without metabolizing it. We suggest a working model, in which the unequal cellular distribution of LDH in white matter tracts facilitates a rapid and efficient transport of glycolysis products among glial and axonal compartments.

Association of Inflammatory Markers With Disease Progression and the Severity of COVID-19.

Introduction In December 2019, there was a massive outbreak of viral pneumonia, which had a high case fatality rate. Genetic sequencing of the virus showed similarity with severe acute respiratory syndrome coronavirus (SARS-CoV). It was later named novel coronavirus 2019 while the disease it caused was given the nomenclature of COVID-19. This deadly pneumonia outbreak was declared a pandemic by the World Health Organization (WHO). Aim To derive the strength of the correlation between blood levels of various inflammatory markers with the severity of COVID-19 pneumonia in patients affected with novel coronavirus 2019. Materials and methodology A prospective study was conducted on 300 confirmed cases of COVID-19 infection from August 2020 to July 2021 in SSG Hospital, Vadodara. Diagnosis of patients as confirmed cases of COVID-19 infection was done according to the WHO interim guidance for COVID-19. Their inflammatory markers were done for this study. All COVID-19-positive patients who had given negative consent for enrollment were excluded from the study. Patients were classified based on the severity of acute respiratory distress syndrome (ARDS). Comprehensive medical record information, encompassing biodata, clinical symptoms, comorbidities, and laboratory investigations, was systematically collected. Patients were given the standard treatment protocol as per guidelines. Patients were subjected to detailed investigations comprising complete blood counts and inflammatory markers like C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, and D-dimer. Patients were further investigated by chest X-ray (posteroanterior view) or high-resolution computed tomography of the thorax. Results A total of 300 confirmed cases of COVID-19 infection were included in this study. Most of them were males (52%) with a mean age of 51 years and 48% were females with a mean age of 55 years. The majority of patients (40%) did not have ARDS, 23.3% of patients had mild, 16.7% of patients had moderate, and 20% of patients had severe ARDS. Higher CRP levels, serum ferritin, and serum D-dimer were significantly associated with the severity of COVID-19 infection as compared to those having no symptoms (p < 0.05). Increased levels were associated with severe clinical manifestations of COVID-19. The sensitivity of CRP is 69% and specificity is 100% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of ferritin is 88% and specificity is 81% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of D-dimer is 94% and specificity is 89% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of LDH is 93% and specificity is 84% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. Conclusions Current evidence from our study showed that higher levels of inflammatory markers such as CRP, LDH, D-dimer, and ferritin are associated with the severity of COVID-19 in terms of ARDS and thus could be used as significant prognostic factors of the disease. These indicators might support clinical decisions to identify high fatality cases and poor diagnosis in the initial admission phase.

PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice.

Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD+-consumption enzyme. PARP-1 hyperactivity causes intracellular NAD+ deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury.

A novel lactate dehydrogenase-based risk score model to predict the prognosis of primary central nervous system germ cell tumor treated with chemoradiotherapy.

BACKGROUND: The prognostic role of lactate dehydrogenase (LDH) has been confirmed in many malignant tumors, but the role of serum LDH in primary central nervous system germ cell tumor (GCT) remains unknown. This study aimed to assess the prognostic value of LDH in GCT patients and develop a nomogram to predict prognosis in patients undergoing chemoradiotherapy. METHODS: A total of 161 patients with GCT were included in this study. Using a restricted cubic spline (RCS) model, the optimal cutoff point for LDH was determined to be 217 U/L. The survival of GCT patients was evaluated using the Kaplan-Meier method and log-rank test to analyze the effects of LDH levels. Univariate Cox regression, multivariate Cox regression, and LASSO Cox regression were conducted to identify prognostic factors, which were incorporated into a nomogram for predicting overall survival (OS). The predictive accuracy of the nomogram was assessed using the C-index, calibration curve, area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and risk group stratification. The net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). RESULTS: The high-LDH group had significantly shorter OS compared to the low-LDH group (P = 0.016). Based on the SYSUCC cohort, three variables were shown to be significant factors for OS and were incorporated in the nomogram: LDH, histopathology, and dissemination. It showed good discrimination ability, with C-index of 0.789 (95% CI, 0.671-0.907). Additionally, the clinical usefulness of the nomogram was confirmed by calibration curves and time-dependent AUC. DCA further highlighted the potential of the nomogram to guide clinical treatment strategies for patients. Moreover, there was a significant difference in OS among patients categorized into different risk groups (P < 0.001). CONCLUSION: LDH levels may serve as a reliable predictor for assessing the therapeutic effect of chemoradiotherapy in GCT. The developed nomogram exhibits high accuracy in predicting survival outcomes, aiding in the classification of prognostic groups, and supporting informed clinical decision-making.

Drainage fluid LDH and neutrophil to lymphocyte ratio as biomarkers for early detecting anastomotic leakage in patients undergoing colorectal surgery.

OBJECTIVES: In this study, we investigated the role of several circulating and drainage fluid biomarkers for detecting postoperative complications (PCs) and anastomotic leakage (AL) in patients undergoing colorectal surgery. METHODS: All consecutive patients undergoing colorectal surgery between June 2018 and April 2020 were prospectively considered. On postoperative days (POD) 1, 3, and 5, we measured lactate dehydrogenase (LDH) in drainage fluid, C-reactive protein (CRP) in serum and drainage fluid, and neutrophil to lymphocyte ratio (NLR). RESULTS: We enrolled 187 patients. POD1 patients with AL had higher serum CRP levels, while on POD3 and on POD5 higher NLR and serum CRP. LDH and CRP in drainage fluid were also significantly higher at both time points. The area under the curves (AUCs) of serum and drainage fluid CRP were 0.752 (0.629-0.875) and 0.752 (0.565-0.939), respectively. The best cut-off for serum and drainage fluid CRP was 185.23 and 76 mg/dL, respectively. The AUC of NLR on POD3 was 0.762 (0.662-0.882) with a sensitivity and specificity of 84 and 63 %, respectively, at a cut-off of 6,6. Finally, drainage fluid LDH showed the best diagnostic performance for AL, with an AUC, sensitivity, and specificity of 0.921 (0.849-0.993), 82 %, and 90 % at a cut-off of 2,186 U/L. Trends in serum parameters between patients with or without PCs or AL were also evaluated. Interestingly, we found that NLR decreased faster in patients without PCs than in patients with PCs and patients with AL. CONCLUSIONS: Drainage fluid LDH and NLR could be promising biomarkers of PCs and AL.

Prognostic value of lactate dehydrogenase, serum albumin and the lactate dehydrogenase/albumin ratio in patients with diffuse large B-cell lymphoma.

OBJECTIVE: To investigate the prognostic value of lactate dehydrogenase (LDH), serum albumin (ALB) and the lactate dehydrogenase/albumin ratio (LAR) in diffuse large B-cell lymphoma (DLBCL) before primary treatment. METHODS: The clinical data of 212 primary adult DLBCL patients admitted to the First People's Hospital of Lianyungang from January 2017 to December 2022 were analyzed retrospectively. The optimal cutoff values of LDH, ALB, and LAR were determined using ROC curves. Survival curves of LDH, ALB, and LAR were plotted and analyzed using the Cox regression model and Kaplan-Meier method with the log-rank test. RESULTS: Among the 212 patients admitted, the study derived the optimal cutoff values for ALB, LDH, and LAR as 38, 301, and 6, respectively. The Kaplan-Meier method and log-rank test analysis indicated a significant association between lower ALB levels, elevated LDH levels, elevated LAR levels, and shorter overall survival (OS) and progression-free survival (PFS) (P < 0.05). Additionally, the critical values of ALB and LDH were grouped into three categories. The differences in OS and PFS among these three groups were statistically significant (P < 0.05). Cox multifactorial analysis revealed that the LAR was an independent factor influencing the prognosis of OS and PFS, with a higher prognostic value than LDH and ALB alone. CONCLUSION: Decreased ALB levels and elevated LDH and LAR levels at the time of initial diagnosis are indicative of a poor prognosis in DLBCL patients. Furthermore, the study highlighted that the LAR has a higher prognostic value than LDH and ALB alone.

Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Adenoviral vector-based COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is rare but carries significant risks of mortality and long-term morbidity. The underlying pathophysiology of severe disease is still not fully understood. The objectives were to explore the pathophysiological profile and examine for clinically informative biomarkers in patients with severe VITT. METHODS: Twenty-two hospitalized patients with VITT, 9 pre- and 21 post-ChAdOx1 vaccine controls, were recruited across England, United Kingdom. Admission blood samples were analyzed for cytokine profiles, cell death markers (lactate dehydrogenase and circulating histones), neutrophil extracellular traps, and coagulation parameters. Tissue specimens from deceased patients were analyzed. RESULTS: There were strong immune responses characterized by significant elevations in proinflammatory cytokines and T helper 1 and 2 cell activation in patients with VITT. Markers of systemic endothelial activation and coagulation activation in both circulation and organ sections were also significantly elevated. About 70% (n = 15/22) of patients met the International Society for Thrombosis and Haemostasis criteria for disseminated intravascular coagulation despite negligible changes in the prothrombin time. The increased neutrophil extracellular trap formation, in conjunction with marked lymphopenia, elevated lactate dehydrogenase, and circulating histone levels, indicates systemic immune cell injury or death. Both lymphopenia and circulating histone levels independently predicted 28-day mortality in patients with VITT. CONCLUSION: The coupling of systemic cell damage and death with strong immune-inflammatory and coagulant responses are pathophysiologically dominant and clinically relevant in severe VITT.

Clinical value of combined predictors of RET%, γ-GT, LDH in the ABO neonatal hemolytic disease.

Objective: The purpose of this study is to examine the prognostic significance of the amalgamated indicators, reticulocyte percentage (RET%), lactate dehydrogenase (LDH), and γ-Glutamyltransferase (γ-GT), in neonatal ABO hemolytic disease. Methods: A total of 137 hospitalized children with pathological jaundice were included. Based on their medical conditions, they were categorized into two groups, hemolytic (67 cases) and non-hemolytic (70 cases). Pearson linear correlation and binary logistic multivariate analysis were used to analyze LDH, γ-GT, RET% and hemolysis. Furthermore, the predictive value of the combined predictors of RET%, LDH, and γ-GT on ABO neonatal hemolytic disease was evaluated using the ROC curve analysis. Results: The laboratory indexes of the two groups were subject to analysis using binary logistic regression to identify suspicious influencing factors. The study revealed that RET%, LDH, and γ-GT were independent risk factors for hemolysis. Pearson linear correlation analysis indicated a positive correlation between LDH and γ-GT with RET% (r = 0.529, P < 0.01; r = 0.526, P = <0.01, respectively). Furthermore, the predictive value of each combined predictor was obtained using the ROC curve, and it was observed that combined predictor L (RET% + LDH + γ-GT)>L1 (RET% + LDH)>L2 (RET% + γ-GT). Conclusion: Combined predictor L (RET% + LDH + γ-GT)demonstrate its optimal diagnostic efficacy, offering a novel approach towards diagnosing early-onset ABO hemolytic disease of the newborn.

The Comparison of the Anti-inflammatory Efficacy of Phytochemical Extracts in Punica granatum and Lawsonia inermis Among Patients Diagnosed With Chronic Periodontitis.

Introduction The oral cavity is the gateway to the human body. Periodontitis is a common inflammatory condition affecting the oral cavity and a known etiological cause of tissue destruction, discomfort, and halitosis. Pomegranate (Punica granatum) and henna (Lawsonia inermis) are herbs known to mankind from time immemorial whose extracts are proven to fight inflammation. The current study was done to evaluate the phytochemical anti-inflammatory efficacy of Punica and Lawsonia in patients with chronic periodontitis and test the potency of herbal mouthwashes in fighting the inflammatory condition affecting the oral cavity using distilled water as a control group. Materials and methods A double-blinded randomized control trial was conducted on 60 patients who were recruited and divided into three groups, in which 20 patients were prescribed with pomegranate (Punica: n=20) mouthwash and 20 patients with henna (Lawsonia: n=20) mouthwash along with distilled water (n=20). All patients were randomly allocated using the coin toss method and advised to use the prescribed mouthwash for a period of two weeks. Unstimulated saliva was collected before using the mouthwash, and salivary enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) and their levels were assessed spectrometrically using the infrared spectrophotoscopy (IFSC) method. Each patient was assigned a mouthwash and recalled after two weeks. Unstimulated saliva was again collected, and salivary activity levels of enzymes AST, ALT, and LDH were analyzed after using mouthwash in a similar method as done before. Later on, the salivary levels of enzymes AST, ALT, and LDH were compared before and after the usage of mouthwashes. Statistical significance was seen in the salivary enzymatic activity of AST, ALT, and LDH before and after using Punica and Lawsonia mouthwashes due to their potent phytochemical action in fighting inflammation. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) 22 (IBM SPSS Statistics, Armonk, NY). The Shapiro-Wilk test was used to determine the normality and significance; intragroup comparison was done using the Wilcoxon signed-rank test and Mann-Whitney U test. Intergroup comparison was done using the Kruskal-Wallis test. Results Punica patients had much lower levels of salivary AST and ALT (p<0.001) and a decrease in LDH (p=0.002) after the usage of mouthwash for a period of two weeks. Also, patients using Lawsonia as herbal mouthwash had reduction in the values of AST (p=0.001) and LDH (p=0.003) and prominent reduction in ALT (p<0.001) after a period of two weeks. But in the case of patients using distilled water, there was an increase in the salivary enzymatic activity of AST and ALT, which was statistically significant (p<0.001), and LDH (p=0.006) depicting the disease progression even after using mouthwash for the given time period of two weeks. Conclusion This study demonstrated that both Punica and Lawsonia were effective in reducing the inflammation in patients diagnosed with chronic periodontitis. However, when intergroup comparison was done, the anti-inflammatory efficacy was superior in Punica with significant reduction in the parameters such as of AST, ALT, and LDH when compared to Lawsonia owing to its potent phytochemical constituency in cutting down the inflammation. Hence, Punica can be used as an implicated effective anti-inflammatory herbal mouthwash.