Serum Lactate Dehydrogenase Level as a Prognostic Factor for COVID-19: A Retrospective Study Based on a Large Sample Size

Background: In this study, we investigated the relationship between serum lactate dehydrogenase (LDH) level and disease progression and prognosis of patients with COVID-19.Methods: We retrospectively reviewed the information of 1,751 patients with COVID-19 from Leishenshan Hospital in Wuhan, China. Univariate and multivariate Cox regression analyses as well as Logistics regression analyses, and Kaplan-Meier curves were used to determine the association between LDH levels and the prognosis of COVID-19 patients.Results: LDH was an independent risk factor for in-hospital death no matter it was taken as classified variable and continuous variable (all P = 0.001) but not for severe or critical illness status. The Kaplan-Meier curves for LDH level showed that an elevated level of LDH was associated with in-hospital death.Conclusions: In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. This will provide a reference for clinicians and researchers to understand, diagnose, and treat patients with COVID-19. Further prospective studies with larger sample sizes are needed to verify these findings.

CYFRA21-1 is a more sensitive biomarker to assess the severity of pulmonary alveolar proteinosis

Background Serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) and CYFRA21-1 are the commonly used biomarkers to identify patients with autoimmune pulmonary alveolar proteinosis (APAP). However, it is not clear which of the biomarkers is more sensitive to the severity of the patient’s condition. Methods APAP patients numbering 151 were enrolled in this study. All patients’ severity was assessed through the severity and prognosis score of PAP (SPSP). According to the respective laboratory upper limits of serum levels of LDH, CEA and CYFRA21-1, APAP patients were divided into higher and lower-level groups. Patients were divided into five groups based on SPSP. 88 patients had completed six months of follow-up. We calculated sensitivity, specificity, and critical point of LDH, CEA and CYFRA21-1 between APAP patients and normal control group, and between grade 1–2 and 3–5 through receiving operating characteristics (ROC) curve. Results Serum LDH, CEA and CYFRA21-1 levels of patients with PAP were higher and distinctly related to PaO2, FVC, FEV1, DLCO, HRCT scores and SPSP. The SPSP of patients in higher-level LDH, CEA and CYFRA21-1 groups were higher than those of corresponding lower-level groups. Based on SPSP results, the patients were divided into five groups (grade I, 20; grade II, 37; grade III, 40; grade IV, 38; grade V, 16). The serum level of CYFRA21-1 of patients with APAP in grade II was higher than that of patients in grade I and lower than that of patients in grade III. Serum CYFRA21-1 of patients with APAP after six months were higher than the baseline among the aggravated group. Serum LDH, CEA and CYFRA21-1 levels after six months among patients in the relieved group of patients with APAP were lower than the baseline. ROC correlating LDH, CEA and CYFRA21-1 values with APAP severity (between grade 1–2 and 3–5) showed an optimal cutoff of LDH of over 203 U/L (< 246 U/L), CEA of over 2.56 ug/L (< 10 ug/L), and CYFRA21-1 of over 5.57 ng/ml (> 3.3 ng/ml) (AUC: 0.815, 95% CI [0.748–0.882], sensitivity: 0.606, specificity: 0.877). Conclusion Serum CYFRA21-1 level was more sensitive in revealing the severity of APAP than LDH and CEA levels among mild to moderate forms of disease.

Serum Lactate Dehydrogenase Level in Pregnancy Induced Hypertension and Fetomaternal Outcome

Hypertensive disorders complicate 5-10% of all pregnancies and associated with potentially dangerous maternal and fetal complications. Studies have shown that pre-eclamptic patients with higher levels of lactate dehydrogenase (LDH) are at high risk of developing subsequent complications with poor maternal and fetal outcome. So with the aim to correlate serum LDH level in pregnancy induced hypertension (PIH) with fetomaternal outcome this hospital based observational descriptive study was done at Tribhuvan University Teaching Hospital (TUTH) for the duration of 1 year from 15th May, 2018 to 14th May, 2019. Women with PIH fulfilling inclusion criteria were enrolled in the study. Serum LDH level was measured and severity of PIH, maternal and perinatal outcome were studied according to the levels of LDH. Results were analyzed using SPSS 18. The incidence of hypertensive disorder in pregnancy was 4.74% in this study and total 180 cases were enrolled. The mean serum LDH level increased with increase in severity of PIH. Thirty two (17.7%) cases had maternal complications and hemolysis elevated liver enzymes and low platelet (HELLP) syndrome was most common complication. More than 2/3rd (62.5%) of cases with LDH level >800 IU/L had complications. The most common perinatal complication was intrauterine growth restriction (IUGR). The perinatal morbidity and mortality were significantly high in patients with PIH with LDH level >800 IU/l. As with the increase in serum LDH level increase in maternal and fetal complications was observed, LDH can be a useful biochemical marker that reflects the severity of PIH.

Lipopolysaccharide-Induced Transcriptional Changes in LBP-Deficient Rat and Its Possible Implications for Liver Dysregulation during Sepsis

Sepsis is an organ dysfunction caused by the dysregulated inflammatory response to infection. Lipopolysaccharide-binding protein (LBP) binds to lipopolysaccharide (LPS) and modulates the inflammatory response. A rare systematic study has been reported to detect the effect of LBP gene during LPS-induced sepsis. Herein, we explored the RNA sequencing technology to profile the transcriptomic changes in liver tissue between LBP-deficient rats and WT rats at multiple time points after LPS administration. We proceeded RNA sequencing of liver tissue to search differentially expressed genes (DEGs) and enriched biological processes and pathways between WT and LBP-deficient groups at 0 h, 6 h, and 24 h. In total, 168, 284, and 307 DEGs were identified at 0 h, 6 h, and 24 h, respectively, including Lrp5, Cyp7a1, Nfkbiz, Sigmar1, Fabp7, and Hao1, which are related to the inflammatory or lipid-related process. Functional enrichment analysis revealed that inflammatory response to LPS mediated by Ifng, Cxcl10, Serpine1, and Lbp was enhanced at 6 h, while lipid-related metabolism associated with C5, Cyp4a1, and Eci1 was enriched at 24 h after LPS administration in the WT samples. The inflammatory process was not found when the LBP gene was knocked out; lipid-related metabolic process and peroxisome proliferator-activated receptor (PPAR) signaling pathway mediated by Dhrs7b and Tysnd1 were significantly activated in LBP-deficient samples. Our study suggested that the invading LPS may interplay with LBP to activate the nuclear factor kappa B (NF-κB) signaling pathway and trigger uncontrolled inflammatory response. However, when inhibiting the activity of NF-κB, lipid-related metabolism would make bacteria removal via the effect on the PPAR signaling pathway in the absence of LBP gene. We also compared the serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels using the biochemistry analyzer and analyzed the expression of high mobility group box 1 (HMGB1) and cleaved-caspase 3 with immunohistochemistry, which further validated our conclusion.

Clinical Role of Serum Lactate Dehydrogenase Assessment in Critically Ill Pediatric Patients with Sepsis

Sepsis is a systemic inflammatory disorder that may be associated with higher rate of morbidity and mortality in pediatric patients admitted to intensive care unit with sepsis. Usage of different biomarkers may be helpful for early detection and appropriate management of sepsis. Our objectives was to investigate the role of serum lactate dehydrogenase in prediction of sepsis in critical pediatric patients, and its relation with prognostic scoring systems. A prospective cohort study was conducted at El Galaa teaching hospital between January 2020 and December 2020. A total of 168 pediatric patients were divided into the septic group (84) critically ill patients with sepsis from the pediatric intensive care unit (PICU)] and control group (84 stable patients admitted to the inpatient word). Demographic and clinical data were collected, routine laboratory investigation including LDH on admission and after 24 hours were performed. Pediatric Risk of Mortality III (PRISMIII) and Sequential Organ Failure Assessment (pSOFA) were assessed. Serum LDH level was significantly higher in septic group than control (P=0.000) and in non-survivor than survivor group (P=0.000). Also there was statistically significant correlation between survivor and non-survivor as regarding length of hospitality, pSOFA score and PRISMIII score. There was statistically significant positive correlation between LDH, PRISMIII (r=0.842, P<0.001) and pSOFA (r=0.785, P<0.001). We concluded that LDH is a useful marker in predicting of sepsis in critically ill pediatric patients especially when combined with prognostic scoring systems.

Maternal serum lactate dehydrogenase level and adverse pregnancy outcomes in women with hypertensive disorder of pregnancy at a tertiary care centre: a retrospective study

Background: Hypertensive disorder of pregnancy affect 6-8% of all pregnancies, contributing immensely to maternal morbidity and mortality. Thus, presence of lactate dehydrogenase (LDH) signifies tissue damage and haemolysis. The aim of the study was to correlate LDH levels with blood pressure ranges and maternal and foetal outcome in women with gestational hypertension, pre-eclampsia.Methods: This retrospective study was conducted in the department of obstetrics and gynaecology of AJ Institute of Medical Sciences and Research Centre, Mangalore for a period of 1 year (January 2020 to January 2021). Based on the eligibility criteria, 52 hypertensive pregnant women were enrolled as cases.Results: Mean±SD period of gestation at delivery was lowest (34.57±1.39 weeks) for pregnant women with S. LDH levels>800 IU/l, whereas with S. LDH<00 IU/l delivered at around 37 weeks of gestation. Mean Apgar scores were lowest for the babies born to hypertensive pregnant women>800 IU/l, mean±SD Apgar scores at the end of 1 min, 5 minutes and 10 min were 4.42±0.79, 4.75±2.26 and 5.50±2.65 respectively.Conclusions: It can be concluded that S. LDH has the potential to be considered as a screening tool or predictor of the outcome of pregnancy in women with hypertensive disorders of pregnancy. However, studies of larger magnitude may be required to confirm the presence and the strength of association of S. LDH levels with pregnancy outcome.

Diabetic COVID -19 Patients are prone to Respiratory Distress Syndrome as compared to Non-Diabetic COVID -19 Patients.

Background: COVID-19 is the alarming problem for all over the world due to its fast spread infection mode and uncertainty in mortality rate. The diabetic population is prone for comorbidity with COVID-19 due to injurious fashion develops in respiratory system. Aim: To compare the serum Lactate dehydrogenase levels in diabetic patients with COVID-19 & non diabetic patients with COVID-19. Methodology: This comparative study was done at Ali medical center Hala New District Matiari Sindh. 42 diabetic & non diabetic clinically suspected cases COVID -19 with fever, cough, shortness of breath, non-pneumonic opacities on digital X.ray with raised TLC, ESR & CRP. The data analyzed for significance on SPSS 19 by applying student t test. Results: The serum LDH levels was significantly raised (p<0.001) in group A contained COVID-19 patients with diabetes as compared to COVID-19 patients with no diabetes mellitus. Conclusion: COVID -19 diabetic population will be more prone to develop the respiratory complications. Keywords: COVID-19, Serum LDH, Diabetes Mellitus, Respiratory Distress Syndrome.

FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice

The incidence of type 2 diabetes mellitus (T2DM) has been increasing globally, and T2DM patients are at an increased risk of major cardiac events such as myocardial infarction (MI). Nevertheless, the molecular mechanisms underlying MI injury in T2DM remain elusive. Ubiquitin-specific protease 10 (USP10) functions as a NICD1 (Notch1 receptor) deubiquitinase that fine-tunes the essential myocardial fibrosis regulator Notch signaling. Follistatin-like protein 1 (FSTL1) is a cardiokine with proven benefits in multiple pathological processes including cardiac fibrosis and insulin resistance. This study was designed to examine the roles of FSTL1/USP10/Notch1 signaling in MI-induced cardiac dysfunction in T2DM. High-fat-diet-treated, 8-week-old C57BL/6J mice and db/db T2DM mice were used. Intracardiac delivery of AAV9-FSTL1 was performed in T2DM mice following MI surgery with or without intraperitoneal injection of crenigacestat (LY3039478) and spautin-1. Our results demonstrated that FSTL1 improved cardiac function following MI under T2DM by reducing serum lactate dehydrogenase (LDH) and myocardial apoptosis as well as cardiac fibrosis. Further in vivo studies revealed that the protective role of FSTL1 against MI injury in T2DM was mediated by the activation of USP10/Notch1. FSTL1 protected cardiac fibroblasts (CFs) against DM-MI-induced cardiofibroblasts injury by suppressing the levels of fibrosis markers, and reducing LDH and MDA concentrations in a USP10/Notch1-dependent manner. In conclusion, FSTL1 treatment ameliorated cardiac dysfunction in MI with co-existent T2DM, possibly through inhibition of myocardial fibrosis and apoptosis by upregulating USP10/Notch1 signaling. This finding suggests the clinical relevance and therapeutic potential of FSTL1 in T2DM-associated MI and other cardiovascular diseases.

Trends of variation of the laboratory parameters during the course of COVID-19 Illness

Background: The coronavirus pandemic which had its origin in the Wuhan China has been spreading across the globe with far reaching complications and a variable clinical course. A variation of the laboratory parameters during the disease course remains a constant parameter to monitor the disease course and progression. Since the laboratory parameters are standardized globally, these may also act as uniform guidelines for the patients monitoring and treatment. Aims and Objectives: The aim of the study was to serial charting of the laboratory parameters in the recovered and expired patients of COVID-19 and to determine an associated prognostic significance. Materials and Methods: A retrospective observational study from the laboratory and medical records was conducted on the patients admitted from March 17, 2020, to May 31, 2020, at the tertiary care center dedicated to the treatment of RT-PCR confirmed COVID-19 positive patients. Results: The group of parameters showing a poor prognosis include a rising WBC count, high neutrophilic percentage, low lymphocyte percentage (<10) an NLR > 15, low lymphocyte monocyte ratio < 3, rising blood urea nitrogen, serum creatinine levels, and serum electrolyte levels. The liver function tests variation reflecting a poor metabolic activity of the liver, namely, a low serum albumin and albumin globulin ratio, rising SGOT levels, and total bilirubin levels. A highly significant variation in the acute phase reactants showing an exponential rise such as the serum lactate dehydrogenase levels, serum ferritin, fibrinogen, C-reactive protein, and IL 6 levels an increased level of D Dimer (>3) and a prolongation of the APTT. Conclusion: The variation of the laboratory parameters acts as a fair marker for the disease progression. Since the disease shows a variable progression with a sudden worsening of the clinical symptoms, a comprehensive monitoring of the laboratory parameters serves to diagnose and treat the disease progression.