Elevated Serum Lactate Dehydrogenase Levels Research Articles

Post-COVID Interstitial Lung Disease: How do We Deal with This New Entity?

In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease. To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD. Multicenter cross-sectional analysis of data from a randomized clinical study. In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT). At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%). The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.

The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

Comprehensive analysis of orbital lymphoma in a Turkish cohort: clinical characteristics, histological subtypes, treatment modalities, prognostic factors, and implications for management.

The study analysed the clinical characteristics, treatment approaches, and survival outcomes of 97 consecutive patients with orbital lymphoma (OL) over a 25-year period at. The median age of the patients was 57.6years, and 59.8% (n = 58) were male. Marginal zone lymphoma constitutes the most prevalent subtype, accounting for 67% of cases, whereas other common subtypes include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, and T-cell lymphomas. Unilateral involvement was observed in the majority of cases (72.3%). Common clinical presentations included mass (30.9%), swelling (26.8%), and epiphora (11.3%). Of the patients, 7.2% received rituximab alone, 14.4% received radiotherapy alone, 48.5% received chemotherapy, 27.8% received radiotherapy plus rituximab, 22.7% received radiotherapy plus chemotherapy, and 5.2% underwent surgery as the first-line treatment. During a median follow-up of 4.3years, 15.5% of patients experienced relapse or disease progression. The 5-year and 10-year progression-free survival rates were 84.1% and 79.1%, respectively. This study contributes to our understanding of OLs and provides a foundation for further investigations in this field. Male gender, presence of B symptoms, advanced stage, secondary orbital lymphoma, aggressive histological subtype, and elevated serum lactate dehydrogenase levels were associated with poorer (either inferior or worse) progression-free survival.

Effect and mechanism of Poria cocos polysaccharides on myocardial cell apoptosis in rats with myocardial ischemia-reperfusion injury by regulating Rho-ROCK signaling pathway

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1β(IL-1β) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1β and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1β and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.

CD70/CD27 Signaling Promotes Expansion of Clonal Plasma Cells in Multiple Myeloma and Is a Promising Therapeutic Target in Advanced Disease

Introduction: Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow (BM). In the last decade, substantial advances in the treatment of MM patients have been made resulting in improved progression-free and overall survival rates. However, to date, MM remains incurable. CD70 and CD27 belong to the TNF receptor family. CD70 is the only known ligand for its receptor CD27. Physiologically, the CD70/CD27 interaction is involved in the regulation of immune cell expansion. However, numerous solid and hematological cancer types overexpress CD70. Aside, CD70 and CD27 co-expression has been described on leukemic stem cells (LSC) in acute myeloid leukemia patients where an autonomous signaling activation drives LSC self-renewal and expansion. While CD70/CD27 signaling plays a key role in the differentiation process of B lymphocytes into plasma cells, only little is known about its impact on myelomagenesis and MM progression. In this study, we analyzed the role of CD70/CD27 signaling in the pathogenesis of MM and studied the possibility to target CD70 by monoclonal antibodies to treat the disease. Materials and Methods: We evaluated CD70 and CD27 gene expression levels and its correlations with overall survival (OS), MM progression and high-risk molecular alterations using different databases (CoMMpass IA15, GSE6477). CD70 and CD27 protein expression patterns were analyzed in a newly established MM tissue microarray (TMA) and a collection of matched BM samples from initial and advanced disease stages (in collaboration with the Institutes of Pathology in Bern, Basel and Tübingen). To assess the functional role of CD70/CD27 signaling on MM initiation and expansion, we generated CD70 knock-out MM cell lines and newly established patient-derived xenografts (PDX) using CRISPR/Cas9 genome editing. CD70-expressing MM cell lines or patient-derived myeloma cells were grown in NOD/SCID (NSG) mice. Moreover, different monoclonal antibodies (Abs) and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab, ArgenX) that activates FcγR-expressing effector cells to assess the therapeutic potential of targeting CD70 in MM. Results: High CD70 gene expression levels correlate with increased MKI67 gene expression and elevated lactate dehydrogenase serum levels indicating a more rapid proliferation of CD70-expressing myeloma cells. In addition, high CD70 expression in MM patients correlated with shorter OS. Longitudinal analyses of CD70 gene expression in the precursor stages monoclonal gammopathy of undetermined significance and smoldering myeloma as well as MM and relapsed MM stages showed highest CD70 gene expression levels in relapsed MM patients. Assessment of the molecular background further revealed increased frequencies of the prognostically unfavorable genomic translocations t(4;14) and t(14;16), as well as gain/amplification of the chromosomal region 1q21 (1q+) in CD70 high expressing MM patients. In line with our previous findings, a TMA analysis of over 200 MM core biopsies as well as a longitudinal analysis of matched biopsies from patients at initial diagnosis and MM relapse indicated that CD70 was overexpressed in advanced disease. Functionally, we found that CD70/CD27 signaling promotes plasma cell survival inducing the expansion of MM cell lines and primary malignant plasma cells. CD70 blockade (αCD70) or CD70 knock-out (CD70 KO) resulted in a significant inhibition or complete abrogation of growth of a CD70-expressing MM patient-derived xenograft (PDX) (EMM01 CD70+) compared to controls (Figure 1). Interestingly, in vivo limiting dilution assays revealed that CD70+CD27+ double-positive myeloma subpopulations showed significantly higher cancer stem cell frequencies compared to CD70 negative fractions suggesting that CD70 expression might be related to an immature or stem-cell like phenotype. The ADCC-optimized CD70 specific antibody custatuzumab efficiently eliminated CD70-expressing MM cells in the presence of PBMC-derived natural killer (NK) cells in vitro and in a PDX model in vivo. Conclusion: Our results indicate that CD70-expressing MM cells have a stem-cell like phenotype and propagate the disease. Targeting CD70 is a promising new therapy especially in advanced disease.

Survival and CNS Relapse in Patients with CD5-Positive Diffuse Large B-Cell Lymphoma: A Multi-Institutional Observational Study in Japan

Background: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is usually characterized by activated B-cell type, poor prognosis, and frequent central nervous system (CNS) relapse. A sandwich therapy of dose-adjusted (DA)-EPOCH-R combined with high-dose methotrexate (HD-MTX) (DA-EPOCH-R/HD-MTX) showed excellent efficacy in a phase II study for newly diagnosed stage II-IV CD5+ DLBCL, including 2-year (yr) overall survival (OS), progression-free survival (PFS), and CNS relapse rates of 89%, 79%, and 9%, respectively (Miyazaki K, et al. Haematologica, 2020). It has been introduced in practice in Japan; however, the current status of treatment and the prognosis in patients with CD5+ DLBCL are unclear. Methods: We retrospectively analyzed the prognosis and CNS relapse rate of consecutive patients with untreated CD5+ DLBCL who were diagnosed at 30 hospitals in Japan from January 2016 to December 2021. Patients who were diagnosed with double-/triple-hit lymphoma, those with CNS involvement at diagnosis, and those who had not received any anthracycline-containing chemotherapy with rituximab (R-chemo) were excluded. We identified risk factors for OS using Cox proportional hazards method. The outcomes in the stage II-IV patients who received DA-EPOCH-R/HD-MTX were compared with those of the phase II study. To evaluate the efficacy of CNS prophylaxis, we divided patients into four groups: HD-MTX alone, intrathecal administration of MTX alone (IT MTX), both HD-MTX and IT MTX (HD/IT MTX), and no CNS prophylaxis. Results: Among the413 enrolled patients, 20 were excluded due to ineligible diagnosis or insufficient clinical information, 18 had CNS involvement at diagnosis, and 27 did not receive R-chemo. As a result, 348 patients were eligible and showed the following features: median age, 71 yrs (range, 23-92); male sex, 54%; stage II-IV, 90%; stage III or IV, 73%; ECOG performance status (PS) > 1, 30%; > 1 extranodal site, 42%; elevated serum lactate dehydrogenase (sLDH) level, 71%; high-intermediate or high International Prognostic Index (IPI), 63%; high CNS-IPI, 41%; and B symptoms, 29%. According to Hans's criteria, the nongerminal center B-cell type accounted for 67% of the 276 cases examined. Among the 348 patients, 62 (18%) received DA-EPOCH-R/HD-MTX, and 286 (82%) were treated with other R-chemo, such as R-CHOP (n = 254). The median age was 63.5 yrs (range, 29-75) in the DA-EPOCH-R/HD-MTX group and 72 yrs (range, 23-92) in the other R-chemo group. The DA-EPOCH-R/HD-MTX group included significantly more patients aged ≤ 60 yrs ( P < 0.001), although it tended to have more patients with ECOG PS > 1 than the other R-chemo group ( P = 0.069). Patients who received IT MTX made up 16% of the DA-EPOCH-R/HD-MTX group and 31% in the other R-chemo group. HD-MTX was used in 100% of patients in the DA-EPOCH-R/HD-MTX group and 17% of patients in the other R-chemo group. Details of CNS prophylaxis were HD-MTX alone in 84 patients (24%), IT MTX alone in 70 (20%), both HD/IT MTX in 28 (8%), and no CNS prophylaxis in 166 (48%). At a median follow-up of 43 months, the 2-yr OS, PFS, and CNS relapse rates of patients with stage II-IV disease in the DA-EPOCH-R/HD-MTX group were 87% (95% CI, 73-94%), 78% (95% CI, 63-87%), and 7.3% (95% CI, 2.8-18.2%), respectively. There were no significant differences in OS or PFS between stage I and stage II-IV patients in the DA-EPOCH-R/HD-MTX group. In all 348 patients with stage I-IV, both the OS ( P = 0.044) and PFS ( P = 0.043) in the DA-EPOCH-R/HD-MTX group were longer than those in the other R-chemo group. The 2-yr OS in these groups were 89% and 78%, and their 2-yr PFS were 78% and 64%, respectively. Multivariate analysis identified elevated sLDH ( P = 0.005), > 1 extranodal involvement ( P < 0.001), no IT MTX ( P = 0.005), and no DA-EPOCH-R/HD-MTX ( P = 0.005) as independent risk factors for OS. The 2-yr CNS relapse rate was 6.5% in the DA-EPOCH-R/HD-MTX group (n = 4) and 10.0% in the other R-chemo group. There were no significant differences in the CNS relapse rate between the two groups ( P = 0.54). The 2-yr CNS relapse rates of HD-MTX, IT MTX alone, both HD/IT MTX, and no prophylaxis were 9.8%, 9.1%, 3.7% (n = 1), and 10.3%, respectively. Conclusions: Our results confirmed favorable survival in the phase II study of DA-EPOCH-R/HD-MTX in clinical settings. DA-EPOCH-R/HD-MTX and IT MTX were associated with longer OS of patients with CD5+ DLBCL in our study cohort, warranting further investigation.

Cyclin D1-Positive Expression Associated with Prognostic Significance and Clinicopathological Characteristics By Paving the Way for Proliferation in Diffuse Large B-Cell Lymphomas

Introduction: Cyclin D1 protein expression in lymphocytes is commonly associated with mantle cell lymphoma. However, it has rarely been reported in patients with diffuse large B-cell leukemia (DLBCL), particularly in Asia where studies on cyclin D1 expression in DLBCL are limited and often small. Furthermore, the clinical implications of cyclin D1 expression in Asia remain unclear. Methods: In this study, a total of 815 patients diagnosed with DLBCL and treated with R-CHOP or R-CHOP-like regimens over a five-year period were reviewed. The authors conducted clinical, immunohistochemical, and genetic analyses, with a specific focus on cyclin D1. Immunohistochemistry was used to identify cyclin D1-positive patients, and fluorescence in situ hybridization was employed to assess cyclin D1 gene (CCND1) rearrangements. A comparison was made between DLBCL patients with and without cyclin D1 expression in terms of clinical, immunohistochemical, and genetic features. Results: Among the DLBCL patients, 16 individuals (2.61%) exhibited cyclin D1 expression without CCND1 gene rearrangements. Cyclin D1-positive DLBCLs were observed in patients with a median age of 58.88 ± 4.07 years, with 93.75% of them classified as stage IV. The majority of cyclin D1-positive patients (81.25%) displayed elevated serum lactate dehydrogenase (LDH) levels and advanced international prognostic index (IPI) scores. Additionally, all cases exhibited a proliferation rate exceeding 80%, and a significant proportion (93.75%) demonstrated MYC expression. Cyclin D1-positive DLBCLs were associated with elevated LDH levels, higher IPI scores, advanced stage, increased Ki-67 proliferation, and MYC expression (p<0.05). However, no significant differences were observed in other clinical characteristics and immunohistochemical features. Patients with cyclin D1 expression experienced shorter progression-free survival (PFS) and overall survival (OS) compared to cyclin D1-negative patients (p<0.05). Next-generation sequencing (NGS) was performed to explore the molecular mechanisms underlying cyclin D1-positive DLBCL. Among the top 50 gene alterations identified, all samples exhibited BRD9 and NOTCH2NL gene mutations, while gene alterations in the PI3K/AKT signaling pathways were evident in cyclin D1-positive DLBCLs. Furthermore, a more pronounced variation in the MTOR gene was observed between cyclin D1-positive and negative patients. Notably, DLBCL patients with cyclin D1 expression frequently exhibited CDKN2A and CDKN2B gene deletions, known to regulate the cell cycle transition from G1 to S phase in tumors. Conclusion: Cyclin D1-positive DLBCL patients exhibited aggressive clinical behavior and inferior survival outcomes compared to DLBCL patients without cyclin D1 expression. NGS studies revealed a potential association between cyclin D1 expression and abnormal cell cycle transition and AKT pathway activation. These findings support the existence of a diagnostically challenging “gray zone” of DLBCL associated with cyclin D1 expression.

Relationship between serum lactate dehydrogenase levels and prognosis in patients infected with omicron and delta variants of COVID-19: A cross-sectional study

Determining the prognosis of COVID-19 is crucial for understanding disease trends and developing effective treatment strategies, particularly for severe cases. However, there is currently insufficient evidence regarding the role of lactate dehydrogenase (LDH) in COVID-19 and its prognostic implications. This retrospective cross-sectional study analyzed data from all patients hospitalized at Urmia Imam Khomeini Hospital between September 2021 and March 2023 with a diagnosis of COVID-19 involving the Delta and Omicron variants. Patient information, including age, sex, duration of hospitalization, admission to the intensive care unit (ICU), strain type, and outcomes, was extracted. Exclusion criteria encompassed myocardial infarction, lung, liver, blood, skeletal muscle diseases, injury, neoplasm, pancreatitis, pregnancy, poisoning, unwillingness to participate in the study, and the use of ascorbic acid. A total of 609 patients with an average age of 54.80 years were included in this study. Among these patients, 56.3% were female, and the mortality rate was 20.7%. The serum LDH levels were significantly higher in patients who succumbed to the disease (P < 0.001), those requiring ICU admission (P < 0.001), and female patients (P = 0.02) compared to other groups. Furthermore, the LDH serum levels exhibited a strong significant correlation with the duration of hospitalization (r = −0.11, P = 0.007). The results revealed that there is a difference in the mean serum LDH levels between deceased patients and discharged patients (P < 0.001). The findings indicate that elevated serum LDH levels are associated with increased mortality, prolonged hospitalization, ICU admission, and infection with the Delta variant of COVID-19.

POSTER: AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

POSTER: AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

AML-002 The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

Study to Determine Correlation of Elevated Serum Creatine Kinase-Muscle Brain Fraction (CK-MB) and Lactate Dehydrogenase (LDH) Levels with Asphyxia Neonatorum and Severity of Hypoxic Ischaemic Encephalopathy

Background: Asphyxia Neonatorum is a significant contributor to neonatal mortality and morbidity. Its burden in resource-poor countries prompts the development of investigative modalities that offers accuracy and affordability. Objective: To determine that serum CK-MB and LDH estimation could be markers of Asphyxia neonatorum, and the elevated levels directly correlate with the grade of severity of Hypoxic Ischemic Encephalopathy (HIE) as defined by Levine. Methods: In this single-center, non-interventional study, we included 100 asphyxiated neonates from level III NICU in the case group, and 100 apparently healthy neonates from the post-natal ward admitted over 18 months at RCSM Government Medical College and CPR Hospital, Kolhapur. 100 healthy neonates were the control group. Results: The median 8-hr serum CK-MB in the case group was 74 U/L and in the control group as 63.5 U/L with P&lt;0.001. Whereas the median serum LDH level in the case group was 597 U/L and the control group was 383.5 U/L with P&lt;0.001. Raised LDH (cut off 580 U/L) had 100% specificity, while CK-MB (cut off 92.6 U/L) had 100% specificity for asphyxia. Amongst the neonates with HIE (n=60), 56% had raised CK-MB (cut off 92.6) and 80% had raised LDH (cut off 580 U/L). 100% of neonates with HIE Grade III (n=9) had elevated CK-MB and LDH levels. Conclusion: The present study concluded that CK-MB and LDH as biochemical markers can be utilitarian in the diagnosis of perinatal asphyxia.

Prognostic Impact of the Immunoscore Based on Whole-Slide Image Analysis of CD3+ Tumor-Infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma

An Immunoscore based on tumor-infiltrating T-cell density was validated as a prognostic factor in patients with solid tumors. However, the potential utility of the Immunoscore in predicting the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) is unclear. Here, the prognostic value of an Immunoscore based on tumor-infiltrating CD3+ T-cell density was evaluated in 104 patients with DLBCL who underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Digitally scanned whole-slide images were analyzed using Aperio ImageScope software. CD3+ cell densities in the whole tumor area were quantitated using 3 different methods, including number of CD3+ cells/area (mm2), ratio of CD3+ cells to total cells, and ratio of CD3+ cells to CD20+ cells. There was a high concordance among the 3 methods. Patients with low CD3+ cell density had an elevated serum lactate dehydrogenase level and a high Ki-67 proliferation index (all, P < .05). Patients with low CD3+ cell density, according to all 3 methods, had worse overall survival (OS) and worse progression-free survival (P < .05, all). They also had poor OS, independent of MYC/BCL2 double expression (DE) status, Eastern Cooperative Oncology Group performance status, or Ann Arbor stage (all, P < .05). These results were validated using 2 publicly available data sets. In both validation cohorts, patients with low CD3E mRNA expression had an elevated serum lactate dehydrogenase level, extranodal site involvement, and DE status (P < .05). They also had worse progression-free survival (P = .067 and P = .002, respectively) and OS (both P < .05). A low CD3E mRNA level was predictive of poor OS, independent of DE status. An Immunoscore based on whole-slide image analysis of CD3+ T-cell infiltration was sufficient to predict survival in patients with DLBCL. Low CD3+ cell density was a poor prognostic factor, independent of other prognostic parameters and DE status.

The role of lactate dehydrogenase in hospitalized patients, comparing those with pulmonary versus non-pulmonary infections: A nationwide study.

Lactic dehydrogenase reflects target organ damage, and is associated with mortality in patients with infectious diseases. The purpose of this study was to examine associations of serum lactic dehydrogenase levels with mortality, target organ damage and length of hospital stay in adults with pulmonary and non-pulmonary infections. This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. Patients with available serum lactic dehydrogenase levels on admission and one week after were included, and stratified by the source of their infection: pulmonary vs. non-pulmonary. Associations of lactic dehydrogenase levels with mortality and target organ damage were analyzed using multivariable logistic regression models. Quantile regression was used for multivariable analysis of the median length of stay. The study included 103,050 patients (45.4% male, median age: 69 years); 44,491 (43.1%) had pulmonary infections. The median serum lactic dehydrogenase levels on admission were higher in patients with pulmonary than non-pulmonary infections (418 vs. 385 units per liter (U/L), p<0.001). In a multivariable logistic regression model, elevated serum lactic dehydrogenase levels (480-700 U/L, 700-900 U/L and >900 U/L), compared with <480 U/L, were associated with in-hospital mortality (OR = 1.81, 2.85 and 3.69, respectively) and target organ damage (OR = 1.19, 1.51 and 1.80, respectively). The median stay increased with increasing elevated lactic dehydrogenase levels (+0.3, +0.5 and +0.4 days, respectively). Among patients with lactic dehydrogenase levels >900 U/L, mortality, but none of the other examined outcomes, was greater among those with pulmonary than non-pulmonary infections. Among hospitalized patients with infectious diseases, lactic dehydrogenase levels were associated with mortality and target organ damage, and were similar in patients with pulmonary and non-pulmonary infections. Among patients with lactic dehydrogenase levels >900 U/L, mortality was prominently higher among those with pulmonary than non-pulmonary infections.

Macrophage activation syndrome in children with Kikuchi-Fujimoto disease

BackgroundKikuchi-Fujimoto disease (KFD) is typically a benign, self-limiting inflammatory disease. However, some patients may have a prolonged or recurrent disease course, or present with life-threatening complications such as macrophage activation syndrome (MAS). In this study, we aimed to describe the incidence and clinical features of MAS in KFD and to access potential laboratory markers for the diagnosis of KFD-associated MAS.MethodsPatients with KFD were retrospectively enrolled from January 2015 to November 2021 at Shenzhen Children’s Hospital. Clinical data were collected from inpatient or outpatient medical records. Data collected included clinical manifestations, laboratory and imaging findings, treatment, and clinical outcomes. Data were analyzed using GraphPad Prism 8.0 statistical software (GraphPad Software Inc., La Jolla, CA, USA). A receiver operating characteristic (ROC) curve analysis was further performed to access the potential predictors for the KFD-MAS diagnosis.ResultsOf 58 patients with a histological diagnosis of KFD, 15 (25.9%) patients had MAS. Compared to patients without MAS, patients with KFD-MAS presented with a higher proportion of skin rash (26.7%, p = 0.01), glucocorticoid treatment (80%, p = 0.003), and disease recurrence (33.3%, p = 0.04). KFD-MAS patients had lower absolute peripheral white blood cell (WBC, p = 0.02), platelet (p = 0.002), serum albumin levels (p = 0.01), and lymphocyte count (p < 0.0001), and higher lactate dehydrogenase (LDH) levels (p < 0.0001). ROC curve analysis showed that the cutoff values of absolute lymphocyte count, an absolute platelet count, serum albumin level, and serum LDH level for KFD-MAS diagnosis were < 1235/μL, < 171 × 106/μL, < 35.6 g/L, and > 679 IU/mL, respectively.ConclusionsThe presence of KFD-MAS in children may be more common than previously expected, especially in those with skin rash. KFD-MAS may be associated with a higher recurrence rate. An extremely elevated serum LDH level and moderate to severe lymphopenia may be useful diagnostic markers for MAS in KFD.Trial registrationNot applicable; this was a retrospective study.

Haemolytic uraemic syndrome with acute kidney injury following paraphenylenediamine-containing hair dye ingestion

Abstract A 20-year-old male patient presented with an alleged history of consumption of 80 mL of paraphenylenediamine (PPD) hair dye. At initial presentation, throat pain, anasarca and reduced urine output were evident. On general physical examination, tachycardia and tachypnoea were evident; blood pressure was 130/80 mm Hg. Oxygen saturation measured with a pulse oximeter (SpO2) on ambient air was 98%. Laboratory investigations revealed haemoglobin (Hb) 14.7 g/dL, platelets 250,000/mm3, neutrophilic leucocytosis, total leucocyte count 23,600/mm3, 86% neutrophils) elevated serum creatinine (6.8 mg/dL), creatine phosphokinase levels (1466 IU/L), hyperkalaemia (6.2 mEq/L) and myoglobinuria. Abdominal ultrasonography revealed normal-sized kidneys and grade 2 renal parenchymal disease changes with maintained corticomedullary differentiation indicating acute kidney injury. Laboratory investigations done on day 7 of admission revealed anaemia Hb 9 g/dL, thrombocytopenia platelets 73,000/mm3, haemoglobinuria and elevated serum lactate dehydrogenase levels (3005 IU/L) with a negative direct and indirect Coombs test and schistocytes (5%) on peripheral smear suggesting microangiopathic haemolytic anaemia. Serum calcium, magnesium and phosphorous were within normal limits. Urinalysis showed plenty of red blood cells with dysmorphia. Haemolytic uraemic syndrome (HUS) was diagnosed and 15 sessions of haemodialysis as well as 7 sessions of plasma exchange were instituted. Clinical improvement was noted with improvement in urinary output; normalisation of laboratory parameters occurred over the next 3 weeks. He was discharged in a haemodynamically stable state. The present case highlights the unusual occurrence of HUS secondary to a hair dye (PPD) poisoning which responded to plasma exchange treatment.

Elevated serum AST and LDH levels are associated with infant death in premature babies with neonatal leukemoid reaction: a cohort study.

Neonatal leukemoid reaction (NLR) is often accompanied by infectious or non-infectious diseases, a low birth weight, sepsis, prematurity, ventricular hemorrhage, and bronchial dysplasia. It has an incidence rate of 1.3-15% and a mortality rate of about 41.4%. Previous studies on NLR have largely focused on its pathogenesis and clinical cases, but little is known about its prognostic laboratory indicators. We found that some of the NLR exhibited obviously elevation in liver function tests like aspartate transaminase (AST) and lactate dehydrogenase (LDH) which were not took by all the LR infants. The necessity for liver function tests for the prognosis of NLR was still unclear. A total of 39 premature infants with NLR at the First Hospital of Jilin University between March 2016 and March 2017 were included in this retrospective cohort study. The infants were divided into death and cured group based on the clinical outcomes. Premature infants with LR and death were defined as the case group (n=14), while infants without death were defined as the control group (n=25). Confounding factors such as age and gender between the two groups were controlled. Blood routine tests, including the white blood cell (WBC) count and subtypes, and liver function, and clinical features were recorded and analyzed. T tests were used to examine the differences in the laboratory indicators between the NLR and control groups. Receiver operating characteristic curves (ROCs) and areas under the curve (AUCs) were used to examine laboratory indicators for prognosis. For predicting clinical outcomes, the ROC curves showed that the cut-off values for AST and LDH were 279 and 1,412 U/L, respectively. The sensitivity and specificity for AST were 92% and 71.43%, respectively, with an AUC of 0.894, while the sensitivity and specificity for LDH were 88% and 78.57%, respectively, with an AUC of 0.911. This innovative study investigated the NLR prognosis depending on laboratory tests. We found that serum AST and LDH levels had reliable predictive value in determining adverse outcomes of NLR.

Prognostic value of lactate dehydrogenase in non-small cell lung cancer patients with brain metastases: a retrospective cohort study.

At present, although there are some known molecular markers for the prognosis of non-small cell lung cancer (NSCLC) brain metastases, but there are still shortcomings in sensitivity and specificity. Lactate dehydrogenase (LDH) is one of the key enzymes involved in malignancy vital glycolytic pathway. Elevated serum LDH levels are reported significantly associated with a poor prognosis in various malignancies. However, there is currently no consensus regarding the prognostic value of LDH in NSCLC patients with brain metastases. We retrospectively analyzed 224 patients diagnosed with lung cancer brain metastases between January 2006 and June 2020 after excluding patients meeting combined with other malignancies and inaccurate clinical information. The LDH cutoff values were obtained using a restricted cubic spline (RCS) model, and the patients were divided into two groups according to the optimal cut-off value (180 U/L). 107 patients with LDH ≤180 (47.77%) and 117 patients with LDH >180 (52.23%) were identified. Univariate and multivariate logistic regression analyses were performed to identify the risk factors. The overall survival (OS) time was defined as the time from the first diagnosis of brain metastases to the last follow-up or death. Of the included patients, 147 survived and 77 died. The Kaplan-Meier method was used to illustrate the OS difference between the two groups. Finally, sensitivity analysis was employed to evaluate the robustness of the results. The OS rate was significantly lower in the high LDH group versus the low LDH group (P=0.009). The median survival times of the high and low LDH groups were approximately 16 and 33 months, respectively. Multivariate analysis showed that high LDH was associated with a significantly worse OS [adjusted hazard ratio (aHR), 1.567; 95% confidence interval (CI): 1.058 to 2.32, P=0.025] with adjustment for covariables that P<0.05 in univariate analysis. Sensitivity analysis indicated that the results of this study are robust, despite potential unmeasured confounders. High level of serum LDH indicates poor prognosis for patients with NSCLC brain metastases. This finding may provide useful prognostic information for patients and clinicians to choose more aggressive treatment strategies.

Creatinine accelerates APAP-induced liver damage by increasing oxidative stress through ROS/JNK signaling pathway.

Serum creatinine is an endogenous biomarker to estimate glomerular filtration rate (GFR) and is commonly used to assess renal function in clinical practice. Acetaminophen (APAP), the most available analgesic and antipyretic medication, is recommended as the drug of choice for pain control in patients with renal diseases. However, an overdose of APAP can lead to severe acute liver injury, which is also the most common cause of acute liver failure in western countries. The role of creatinine in APAP-induced liver injury is unclear and should be further explored. Herein, clinical data on patients with drug-induced liver injury revealed that the creatinine concentration between 82-442 μmol/L for female and 98–442 μmol/L for male is positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST). While there was no correlation between creatinine and ALT and AST when creatinine concentration is over 442 μmol/L. In addition, mice were administrated with creatinine intraperitoneally for 1 week before APAP injection to investigated the pathophysiological role of creatinine in APAP-induced acute liver injury. The results showed that creatinine administration aggravated hepatic necrosis and elevated serum lactate dehydrogenase (LDH) and ALT levels in mice upon APAP injection. The mechanism study demonstrated that creatinine could increase the production of reactive oxygen activation (ROS) and the activation of c-Jun N-terminal kinase (JNK). Furthermore, the liver injury was alleviated and the difference between APAP-treated mice and APAP combined with creatinine-treated mice was blunted after using specific ROS and JNK inhibitors. Significantly, creatinine stimulation aggravates APAP-induced cell death in HepaRG cells with the same mechanism. In summary, this study proposed that creatinine is closely related with liver function of drug-induced liver injury and exacerbates APAP-induced hepatocyte death by promoting ROS production and JNK activation, thus providing new insight into the usage of APAP in patients with kidney problems.

The protective effect of ethanol leaf extract of Annona muricata against doxorubicin toxicity via modulations of hematological, serum biochemical, antioxidant enzymes, and lipid peroxidation

BackgroundDoxorubicin (DOX)-induced organ toxicity is of critical concern in cancer therapy because of its contributions to morbidity and mortality of cancer patients. This study evaluated the beneficial effect of Annona muricata (A. muricata) ethanol leaf extract on the toxic effect of DOX. MethodsScavenging abilities of A. muricata fractions (chloroform, ethyl acetate, ethanol, methanol, and aqueous) were tested against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Male rats (Rattus norvegicus) were randomly allotted into four groups of treatments. Group A served as a control, Group B was treated with 2.5 mg/kg body weight (b.w) DOX intraperitoneally (i.p) twice per week, Group C was treated with 200 mg/kg b.w extract (orally), once per day, and 2.5 mg/kg b.w DOX (i.p) twice per week. While Group D was treated with 200 mg/kg b.w. ethanol leaf extracts orally once daily for 2 weeks. Hematological indices (White blood cells (WBC), Red blood cells (RBC), Platelet (PLT), lymphocyte (LYM), hemoglobin (HGB), and hematocrit (HCT)), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, lactate dehydrogenase (LDH), creatine kinase (CK), cholesterol, CA (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated. ResultsAqueous and ethanol fractions displayed significant DPPH (p < 0.05) and ABTS (P < 0.05) inhibitory activity respectively when compared with other fractions. Ethanol fraction was used for the in vivo study considering significant activity against ABTS. DOX-induced tissue toxicity was shown by significant (P < 0.05) hematological indices unsettling and elevated levels of serum ALT, AST, urea, LDH, CK, and MDA. Serum oxidative stress markers including SOD, CAT, and GSH were significantly (P < 0.05) reduced in DOX treated group. The leaf extract normalized hematological indices and activated levels of ALT, AST, urea, LDH, CK, and MDA due to DOX treatment. Significant elevations of SOD, CAT, and GSH were also observed following extract treatment compared to DOX exposed group. ConclusionThis study suggests that the extract potential to prevent the severity of DOX-induced toxicity may be through oxidative stress suppression.

Predictors of mortality among hospitalized patients with COVID-19: A single-centre retrospective analysis.

BackgroundThe severity of disease and mortality due to coronavirus disease (COVID-19) was found to be high among patients with concurrent medical illnesses. Serum biomarkers can be used to predict the course of COVID-19 pneumonia. Data from India are very scarce about predictors of mortality among COVID-19 patients.MethodologyIn the present retrospective study of 65 RT-PCR confirmed COVID-19 patients, we retrieved data regarding clinical symptoms, laboratory parameters, and radiological grading of severity. Further, we also collected data about their hospital course, duration of stay, treatment, and outcome. Data analysis was done to compare the patient characteristics between survivor and non-survivor groups and to assess the predictors of mortality.ResultsThe mean age of the study population was 56.23 years (SD, 12.91) and most of them were males (63%); 81.5% of patients survived and were discharged, whereas 18.5% of patients succumbed to the disease. Univariate analysis across both groups showed that older age, diabetes mellitus, higher computed tomogram (CT) severity score, and raised levels of laboratory parameters viz, D-dimer, CPK-MB (creatine kinase), and lactate dehydrogenase (LDH) were associated with increased mortality among hospitalized patients. On multivariate analysis, elevated levels of serum D-dimer (odds ratio, 95% CI: 10.98, 1.13–106.62, p = 0.04) and LDH (odds ratio, 95% CI: 19.15, 3.28–111.87, p = 0.001) were independently associated with mortality.ConclusionOlder patients, diabetics, and patients with high CT severity scores at admission are at increased risk of death from COVID-19. Serum biomarkers such as D-dimer and LDH help in predicting mortality in COVID-19 patients.