Elevated Lactate Dehydrogenase Levels Research Articles

Prognostic Factors for Relapse in Patients With Clinical Stage I Testicular Seminoma: A Nationwide, Population-Based Cohort Study.

Approximately 20% of patients with clinical stage I seminoma relapse. Tumor size and rete testis invasion have been identified as risk factors for relapse. However, the level of evidence supporting the use of these risk factors in clinical decision making is low. Previous studies have been hampered by selection bias and variable pathology reporting that limit interpretation and generalization of results. We assessed prognostic factors for relapse in an unselected nationwide population-based setting with centralized pathology review. Patients with clinical stage I seminoma diagnosed from January 2013 to December 2018 were identified in the prospective Danish Testicular Cancer database. By linkage to the Danish National Pathology Registry, histologic slides from the orchiectomy specimens were retrieved and reviewed blinded to the clinical outcome. Clinical data were obtained from medical records with follow-up until July 2022. The association between prespecified potential clinical and histopathologic prognostic factors and relapse was assessed by the use of Cox regression analysis. Of 924 patients included, 148 (16%) patients relapsed during a median follow-up of 6.3 years. Invasion of the testicular hilum (rete testis and hilar soft tissue), lymphovascular invasion, and elevated preorchiectomy levels of β-human chorionic gonadotropin and lactate dehydrogenase were independent predictors of relapse. The estimated 5-year risk of relapse ranged from 6% in patients with no risk factors to 62% in patients with all four risk factors with tumor extension into the hilar soft tissue of the testicular hilum. After internal model validation, the prognostic model had an overall concordance statistic of 0.70. The provided prognostic factors could replace current risk factors in guidelines and be used in future studies investigating risk-adapted follow-up and treatment strategies.

The role of lactate dehydrogenase of the pleural liquid in the cytopathological diagnosis

Elevated serum or pleural fluid lactate dehydrogenase (LDH)enzyme levels can be associated with various conditions, including neoplasia, reticuloendothelial tumors, and leukemia. These conditions can lead to cell damage or death, causing LDH to be released into the bloodstream and pleural fluid. An increase in LDH levels may prompt further investigation into the underlying cause, which could include malignancies or other diseases. Elevated LDH levels in pleural fluid are often associated with certain conditions, and our study seeks to establish a quantitative assessment of LDH in conjunction with cytopathological examination for diagnostic purposes. We show here that the presence of abnormal or malignant cells in pleural fluid, as indicated by positive cytopathological results, can be concerning and often necessitates further evaluation. Elevated LDH levels provide biochemical evidence that supports the cytopathological findings, strengthening the case for a potential underlying disease or condition.

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

Sex Differences among Overweight/Obese Kidney Transplant Recipients Requiring Oxygen Support Amid the COVID-19 Pandemic.

Background and Objectives: Overweight/obesity puts individuals at greater risk for COVID-19 progression and mortality. We aimed to evaluate the impact of overweight/obesity on oxygen (O2) requirement outcomes of male and female kidney transplant recipients (KTRs) during the COVID-19 pandemic. Materials and Methods: We conducted a retrospective analysis of a cohort of KTRs diagnosed with COVID-19. Participants were stratified based on BMI categories, and data on the need for O2 therapy outcome were collected and analyzed separately for male and female KTRs. Results: In total, 284 KTRs (97 males and 187 females) were included in the study. Overweight/obesity was observed in 60.6% of male KTRs and 71% of female KTRs. Strikingly, overweight/obese women had a significantly higher requirement for supplemental O2 (63.3% vs. 41.7%, OR = 2.45, p = 0.03), particularly among older individuals (OR = 1.05, p = 0.04), smokers (OR = 4.55, p = 0.03), those with elevated lactate dehydrogenase (LDH) levels (OR = 1.01, p = 0.006), and those with lower admission and basal estimated glomerular filtration rate (eGFR) levels. Within this cohort, the necessity for O2 supplementation was correlated with more unfavorable outcomes. These included heightened mortality rates, transfers to the intensive care unit, employment of invasive mechanical ventilation, and the emergence of acute kidney injury requiring hemodialysis. On the other hand, although overweight/obese male KTRs had a higher prevalence of hypertension and higher fasting blood glucose levels, no significant association was found with COVID-19-related outcomes when compared to lean male KTRs. Conclusions: Overweight/obesity is highly prevalent in KTRs, and overweight/obese women demonstrated a higher need for supplemental O2. Therefore, the early identification of factors that predict a worse outcome in overweight/obese female KTRs affected by COVID-19 contributes to risk stratification and guides therapeutic decisions.

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<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<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 Factors and Survival Outcomes Among Patients With Mycosis Fungoides in China

There are limited prognostic statistics and data available on survival outcomes for patients with mycosis fungoides (MF) in Asia. To determine the prognostic factors and survival outcomes of patients with MF among a cohort in China. This was a retrospective cohort study of patients with MF who received treatment at a tertiary referral center for skin lymphoma (Peking University First Hospital, Beijing, China) from August 1, 2009, to August 31, 2021. Data were analyzed from September 1, 2021, to December 31, 2022. Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS); for prognostic factors, hazard ratios (HRs), and adjusted HRs (aHRs; adjusted for sex, age, and overall TNMB [tumor, node, metastasis, blood] stage) determined using the Cox proportional hazards model. The study cohort comprised 461 patients with MF (median [range] age at diagnosis, 46 [5-87] years; 275 [59.7%] men and 186 [40.3%] women; 461 [100%] Chinese). The overall 5-year rate was 82.2% for OS, 83.5% for DSS, and 79.6% for PFS. Stage-specific 5-year OS rates were 95.7% for stage IA, 93.2% for IB, 95.7% for IIA, 70.1% for IIB, 55.3% for III, and 23.6% for IV. Compared with a UK cohort, our Chinese cohort had a younger median age at diagnosis (46 years vs 54 years) and a more favorable 5-year OS (82.2% vs 75.0%); however, after adjusting for age, the discrepancy in the 5-year OS rate was diminished (77.3% vs 76.4%). Cox models revealed that unfavorable predictors of OS, PFS, and DSS, respectively, were: age older than 60 years (aHR [95% CI], 2.25 [1.28-3.96]; 2.09 [1.16-3.76]; 2.27 [1.39-3.72]); advanced TNMB stage; advanced overall stage; large-cell transformation (aHR [95% CI], 2.16 [1.17-3.99]; 2.29 [1.21-4.33]; 2.21 [1.26-3.86]); and elevated lactate dehydrogenase levels (aHR [95% CI], 3.92 [1.64-9.36]; 4.77 [1.86-12.22]; 5.05 [2.23-11.42]). Biological sex and plaque lesion type were not associated with prognosis among this study cohort. The findings of this retrospective cohort study of patients with MF in China suggest that Asian patients are diagnosed at a younger age and have a higher 5-year OS compared with patients of other races in studies in other countries (predominantly White). Prognostic factors were similar to those of previous studies, except for patient sex and plaque lesion type.

The Association Between Corrective Surgery for Adult Spinal Deformity and Serum Levels of Hepatobiliary Enzymes.

Background and objective The surgery to correct adult spinal deformity (ASD) is associated with a rare, but life-threatening complication called acute celiac artery compression syndrome (ACACS). To our knowledge, there is currently no study in the literature regarding the abnormal elevation of serum levels of hepatobiliary enzymes after surgery to correct the deformity. In light of this, the purpose of this study was to investigate this potential association. Materials and methods We collected data on 74 patients with ASD who underwent correction surgery at our institution. A Spearman's rank-order correlation was used to assess the association between serum levels of hepatobiliary enzymes and spinal parameters. Factors showing a correlation coefficient of 0.2 or more were combined in a stepwise multiple regression analysis. Results The mean age of the patientswas 68.4 ± 7.7 years; the study comprisedsix men and 68 women. In our stepwise multiple regression analysis, there were two valid models that included spinal parameters as independent variables: changes in lactate dehydrogenase (LDH) - changes in thoracolumbar kyphosis (TLK) (B -0.0025 ± 0.0007, p<0.01), and changes in LDH - preoperative T12-L1 kyphosis (B 0.0031 ± 0.001, p<0.01). Additionally, both valid models contained median arcuate ligament (MAL) overlap defined as MAL crossing the base of the celiac artery (CA) as a significant independent variable. Conclusions Greater sagittal correction of TLK, larger preoperative T12-L1 kyphosis, and MAL overlap were factors associated with an elevated serum level of LDH. Although few patients werereported to have clinically severe symptoms, "potential" ACACS due to a temporary blood flow disturbance can occur in this patient population.

Calycosin Alleviates Lupus Nephritis by Activating the Nrf2/HO-1 Signaling Pathway

Lupus nephritis is a serious condition, for which treatments are limited; hence, there is a need for new cure approaches. The aim of this study was to evaluate the therapeutic effects of calycosin against lupus nephritis induced by lipopolysaccharide (LPS) in human renal cortex proximal convoluted tubule epithelial cells (HK-2). HK-2 cells were stimulated with 1 μg/ml LPS to create a lupus nephritis cell model; the cells were pretreated with calycosin. Cell viability and apoptosis rate were determined using the cell counting kit-8 assay and flow cytometry, respectively. A caspase-3 activity detection kit was used to determine caspase-3 activity. Interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) levels were determined using enzyme-linked immunosorbent assay kits. Lactate dehydrogenase (LDH) level was determined using an LDH assay kit. Finally, western blotting and reverse transcription-quantitative polymerase chain reaction were performed to determine apoptosis-related protein levels and nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Calycosin had no cytotoxic effects on HK-2 cells. Lipopolysaccharide stimulation significantly inhibited cell viability; increased the IL-6, IL-1β, and TNF-α levels; and elevated apoptosis rate, caspase3 activity, and LDH level in HK-2 cells. The protein level of cleaved caspase3 was also increased in LPS-treated HK-2 cells. In addition, the pattern of Nrf2/HO-1 signaling was disturbed by LPS. These effects were reversed by calycosin treatment. Calycosin could alleviate LPS-induced lupus nephritis and may thus be a novel agent for its treatment.Graphical

Cancer and Diabetes: Predictive Factors in Patients with Metabolic Syndrome.

A growing number of epidemiological studies have suggested that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in proinflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of carcinoembryonic antigen (CEA), C-reactive protein (CRP), serum albumin level, hemoglobin, and lactate dehydrogenase (LDH) as biomarkers for cancer risk, and the biological implications of diabetes on the evolution and prognosis of oncological patients. We conducted a retrospective, longitudinal, observational study on a total group of 434 patients, of which 217 were diagnosed with a form of cancer and type two diabetes as a comorbidity, and the other 217 were a control group without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type two diabetes and cancer. The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.

Exploring the role of tryptophanyl-tRNA synthetase and associations with inflammatory markers and clinical outcomes in COVID-19 patients: A case-control study

Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.

Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

Hemophagocytic lymphohistiocytosis–like hyperinflammation due to a de novo mutation in DPP9

Genetic defects in components of inflammasomes can cause autoinflammation. Biallelic loss-of-function mutations in dipeptidyl peptidase 9 (DPP9), a negative regulator of the NLRP1 and CARD8 inflammasomes, have recently been shown to cause an inborn error of immunity characterized by pancytopenia, skin manifestations, and increased susceptibility to infections. We sought to study the molecular basis of autoinflammation in a patient with severe infancy-onset hyperinflammation associated with signs of fulminant hemophagocytic lymphohistiocytosis. Using heterologous cell models as well as patient cells, we performed genetic, immunologic, and molecular investigations to identify the genetic cause and to assess the impact of the identified mutation on inflammasome activation. The patient exhibited pancytopenia with decreased neutrophils and T, B, and natural killer cells, and markedly elevated levels of lactate dehydrogenase, ferritin, soluble IL-2 receptor, and triglycerides. In addition, serum levels of IL-1β and IL-18 were massively increased, consistent with inflammasome activation. Genetic analysis revealed a previously undescribed de novo mutation in DPP9 (c.755G>C, p.Arg252Pro) affecting a highly conserved amino acid residue. The mutation led to destabilization of the DPP9 protein as shown in transiently transfected HEK293T cells and in patient-derived induced pluripotent stem cells. Using functional inflammasome assays in HEK293T cells, we demonstrated that mutant DPP9 failed to restrain the NLRP1 and CARD8 inflammasomes, resulting in constitutive inflammasome activation. These findings suggest that the Arg252Pro DPP9 mutation acts in a dominant-negative manner. A de novo mutation in DPP9 leads to severe infancy-onset autoinflammation because of unleashed inflammasome activation.

Analysis of altered level of blood-based biomarkers in prognosis of COVID-19 patients.

Immune and inflammatory responses developed by the patients with Coronavirus Disease 2019 (COVID-19) during rapid disease progression result in an altered level of biomarkers. Therefore, this study aimed to analyze levels of blood-based biomarkers that are significantly altered in patients with COVID-19. A cross-sectional study was conducted among COVID-19 diagnosed patients admitted to the tertiary care hospital. Several biomarkers-biochemical, hematological, inflammatory, cardiac, and coagulatory-were analyzed and subsequently tested for statistical significance at P<0.01 by using SPSS version 17.0. A total of 1,780 samples were analyzed from 1,232 COVID-19 patients (median age 45 years [IQR 33-57]; 788 [63.96%] male). The COVID-19 patients had significantly (99% Confidence Interval, P<0.01) elevated levels of glucose, urea, alanine transaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), ferritin, D-Dimer, and creatinine phosphokinase-MB (CPK-MB) compared to the control group. However, the levels of total protein, albumin, and platelets were significantly (P<0.01) lowered in COVID-19 patients compared to the control group. The elevated levels of glucose, urea, WBC, CRP, D-Dimer, and LDH were significantly (P<0.01) associated with in-hospital mortality in COVID-19 patients. Assessing and monitoring the elevated levels of glucose, urea, ALT, AST, ALP, WBC, CRP, PCT, IL-6, ferritin, LDH, D-Dimer, and CPK-MB and the lowered levels of total protein, albumin, and platelet could provide a basis for evaluation of improved prognosis and effective treatment in patients with COVID-19.

Circulating Tumor DNA Reflects Histologic and Clinical Characteristics of Various Lymphoma Subtypes.

We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma. Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA. Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage. Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

Integrative genomic and transcriptomic analysis reveals genetic alterations associated with the early progression of follicular lymphoma.

Follicular lymphoma (FL), the most common indolent lymphoma, is a clinically and genetically heterogeneous disease. However, the prognostic value of driver gene mutations and copy number alterations has not been systematically assessed. Here, we analysed the clinical-biological features of 415 FL patients to identify variables associated with disease progression within 24 months of first-line therapy (POD24). Patients with B symptoms, elevated lactate dehydrogenase and β2-microglobulin levels, unfavourable baseline haemoglobin levels, advanced stage, and high-risk FL International Prognostic Index (FLIPI) scores had an increased risk of POD24, with FLIPI being the most important factor in logistic regression. HIST1H1D, identified as a driver mutation, was correlated with POD24. Gains of 6p22.2 (HIST1H1D) and 18q21.33 (BCL2) and loss of 1p36.13 (NBPF1) predicted POD24 independent of FLIPI. Gene expression profiling of FL samples showed that the POD24 cohort was significantly enriched in the inflammatory response (mediated by interferon and tumour necrosis factor), cell cycle regulation (transcription, replication and proliferation) sets and PI3K-AKT-mTOR signalling. This result was further validated with transcriptome-wide information provided by RNA-seq at single-cell resolution. Our study, performed on a large cohort of FL patients, highlights the importance of distinctive genetic alterations and gene expression relevant to disease diagnosis and early progression.

Predictive Factors and Impact of Secondary Pulmonary Infection on Mortality in Patients with Hypoxemic COVID-19 Pneumonia: A Retrospective Cohort Study

Background: Secondary pulmonary infection (SPI) is a severe complication in patients with COVID-19. Objective: To investigate the risk factors, mortality rates, and complications associated with SPI in hypoxemic COVID-19 pneumonia patients. Materials and Methods: A retrospective cohort study was conducted at Saraburi Hospital, analyzing medical records of 512 hospitalized COVID-19 patients. The Fine-Gray model identified risk factors for SPI. Results: SPI was diagnosed in 25.4% of hypoxemic COVID-19 pneumonia patients. SPI patients (mean age of 65.9±15.1 years) had higher inflammation biomarkers, increased in-hospital mortality (IHM), and more complications than non-SPI patients. The primary pathogens causing IHM were gram-negative bacteria in 59.23%. Risk factors for SPI included age of 65 years or older (sHR 1.52; 95% CI 1.03 to 2.25; p=0.032), obesity (sHR 1.52; 95% CI 1.04 to 2.23; p=0.028), invasive mechanical ventilation (sHR 2.87; 95% CI 1.64 to 5.02; p&lt;0.001), lactate dehydrogenase (LDH) level of 520 U/L or more (sHR 2.37; 95% CI 1.69 to 3.33; p=0.027), and catheter-related bloodstream infection (sHR 2.74; 95% CI 1.71 to 4.40; p&lt;0.001). SPI patients had an IHM rate of 74.62%. Multivariable analysis showed higher IHM in SPI patients (aOR 5.29; 95% CI 2.70 to 10.36) compared to non-SPI patients. Conclusion: SPI is a common and harmful complication in hypoxemic COVID-19 pneumonia. Older age, obesity, invasive mechanical ventilation, elevated LDH levels, and catheter-related bloodstream infection are significant risk factors for SPI. Early detection and prevention strategies are crucial to mitigate the short-term consequences of SPI in COVID-19 patients. Keywords: COVID-19; Secondary pulmonary infection; Mortality; Risk factors

Tokat ilinde İki İlçe Hastanesinde Kırım-Kongo Kanamalı Ateşi Ön tanısı ile Takipli Olguların Değerlendirilmesi

Objective: Tokat is one of the cities in Turkey where Crimean–Congo hemorrhagic fever (CCHF) is endemic. Given that CCHF is fatal and contagious, patients should be isolated and hospitalized. This study aimed to compare the epidemiological, clinical, and laboratory findings of CCHF-positive and CCHF-negative cases in two district hospitals in Tokat. Materials and Methods: Patients applied to Turhal and Zile State Hospitals between January 2018 and December 2019 and had a pre-diagnosis of CCHF were included in this case–control study. The patients’ demographic data, symptoms, treatment, and prognosis were recorded. “Pre-diagnosis for CCHF” was defined as the presence of leukopenia or thrombocytopenia, in addition to the presence of at least two symptoms. Cases had antibodies to CCHF virus or CCHF virus-RNA were defined as “CCHF-positive group” and the others were “CCHF-negative group”. Pearson’s chi-square test and Fisher’s test were used to compare the categorical variables. P values that are less than 0.05 were considered statistically significant. Results: Symptoms of headache (20 vs. 18), nausea and vomiting (20 vs. 16), myalgia (18 vs. 16), and diarrhea (11 vs. 5) were more common in the CCHF-positive group than CCHF-negative group. Leukopenia, thrombocytopenia, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels, and prolongated prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels were also more common. AST elevation and PT prolongation were statistically significant (p=0.01 and p=0.003, respectively). The mortality rate in the CCHF-positive group was 3.8%. Conclusion: Even if there is no history of tick bite in patients living in the endemic region and presenting with headache and gastrointestinal symptoms, CCHF probability is high in the presence of leukopenia, thrombocytopenia, elevated liver enzymes and LDH levels, prolonged PT and aPTT. CCHF should always be considered in patients with these symptoms and laboratory findings.

Cold agglutinin syndrome in a patient with human immunodeficiency virus infection

Abstract A 44-year-old female with no prior comorbidities presented with a history of easy fatiguability and yellowish discolouration of eyes of 3 months duration. On examination, she had pallor and icterus. Jugular venous pressure was elevated. Earlier, the patient was diagnosed to have autoimmune haemolytic anaemia and was started on steroids 2 weeks ago elsewhere. Laboratory investigations showed severe anaemia, elevated mean corpuscular volume and lactate dehydrogenase levels. Corrected reticulocyte count was 2.5%. Unconjugated hyperbilirubinaemia was evident. Coomb’s test was positive. In view of suspicion for cold agglutinin syndrome (CAS), monospecific agglutinin test with cold agglutinin titres was done, which tested positive. Serological testing was positive for human immunodeficiency virus (HIV) 1. The patient was diagnosed to have CAS secondary to HIV infection.

Negative Prognostic Impact of High-Dose or Long-Term Corticosteroid Use in Patients with Relapsed or Refractory B-Cell Lymphoma Who Received Tisagenlecleucel

The prognostic impact of corticosteroid therapy in patients receiving tisagenlecleucel (tisa-cel) treatment who are more likely to develop cytokine release syndrome (CRS) remains unclear. This study aimed to evaluate the clinical impact and lymphocyte kinetics of corticosteroid administration for CRS in 45 patients with relapsed and/or refractory B cell lymphoma treated with tisa-cel. This was a retrospective evaluation of all consecutive patients diagnosed with relapsed and/or refractory diffuse large B cell lymphoma, follicular lymphoma with histologic transformation to large B cell lymphoma, or follicular lymphoma who received commercial-based tisa-cel treatment. The best overall response rate, complete response rate, median progression-free survival (PFS), and median overall survival (OS) were 72.7%, 45.5%, 6.6 months, and 15.3 months, respectively. CRS (predominantly grade 1/2) occurred in 40 patients (88.9%), and immune effector cell-associated neurotoxicity syndrome (ICANS) of all grades occurred in 3 patients (6.7%). No grade ≥3 ICANS occurred. Patients with high-dose (≥524 mg, methylprednisolone equivalent; n = 12) or long-term (≥8 days; n = 9) corticosteroid use had inferior PFS and OS to patients with low-dose or no corticosteroid use (both P < .05). The prognostic impact remained even in 23 patients with stable disease (SD) or progressive disease (PD) before tisa-cel infusion (P = .015). but not in patients with better disease status (P = .71). The timing of corticosteroid initiation did not have a prognostic impact. Multivariate analysis identified high-dose corticosteroid use and long-term corticosteroid use as independent prognostic factors for PFS and OS, respectively, after adjusting for elevated lactate dehydrogenase level before lymphodepletion chemotherapy and disease status (SD or PD). Lymphocyte kinetics analysis demonstrated that after methylprednisolone administration, the proportions of regulatory T cells (Tregs), CD4+ central memory T (TCM) cells, and natural killer (NK) cells were decreased, whereas the proportion of CD4+ effector memory T (TEM) cells was increased. Patients with a higher proportion of Tregs at day 7 had a lower incidence of CRS, but this did not affect prognosis, indicating that early elevation of Tregs may serve as a biomarker for CRS development. Furthermore, patients with higher numbers of CD4+ TCM cells and NK cells at various time points had significantly better PFS and OS, whereas the number of CD4+ TEM cells did not impact prognostic outcomes. This study suggests that high-dose or long-term corticosteroid use attenuates the efficacy of tisa-cel, especially in patients with SD or PD. Additionally, patients with high levels of CD4+ TCM cells and NK cells after tisa-cel infusion had longer PFS and OS.