High Lactate Dehydrogenase Levels Research Articles

Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK-RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0-not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4-NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK-RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.

A Clinical Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25–8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12–17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; &gt;4) and a high serum lactate dehydrogenase (LDH) concentration (&gt;260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

A Comparative Study of Vitamin D Level and Lactate Dehydrogenase Activity in Relation to Oxidative Stress in Women with Osteoporosis

Background: Osteoporosis (OP) is a silent disease that affects the microarchitecture of the skeleton bones, leading to a drop in mineral levels and an increase in fracture rates. This condition is more common in women than men, especially postmenopausal women, due to decreased production of estrogen, a hormone that regulates bone formation and bone resorption. Oxidative stress is a known factor in the development of OP, resulting from an imbalance in the production of oxidants and antioxidants. Hip and arm fractures are particularly common in women with OP. Objective: The study aimed to evaluate the activity of Lactate Dehydrogenase (LDH) and oxidative stress (OS) levels in postmenopausal women with osteoporosis and varying levels of vitamin D, and to compare these groups based on the measured parameters. Subjects and Methods: This study was conducted at the Baquba Teaching Hospital in Diyala, Iraq, from October 2022 to January 2023. The study involved 100 women whom were divided into two groups, 50 with normal vitamin D levels and 50 with abnormal vitamin D levels. The malondialdehyde (MDA) level was evaluated using the Satoh-modified approach. Results: According to the statistical analysis conducted with the SPSS program, there was a significant difference (P&lt;0.001) in Vitamin D levels between the groups (OPn. D) and (OPab.D). Additionally, significant increases were observed in LDH activity (P&lt;0.001) and MDA levels (P&lt;0.05) for the group (OPab.D) in comparison to (OPn. D). Conclusion: The current study has indicated that women suffering from osteoporosis (OP) have higher levels of LDH and MDA. Additionally, there is an inverse correlation between vitamin D and these two variables; this correlation suggests that vitamin D may possess antioxidant properties that reduce the effects of oxidative stress (OS) in the body. Therefore, vitamin D may help in reducing LDH levels.

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection – derivation of a clinical risk score

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006-2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age>65 years (2 points), male sex (2 points) and LDH>770U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60-0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41-0.66). A low-risk score of 0-1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.

Association between lactate dehydrogenase and the risk of diabetic kidney disease in patients with type 2 diabetes.

This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). The study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result. A total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings. LDH can serve as a valuable biomarker for screening DKD in patients with T2D.

Analysis of Age-Specific Predictors of Mortality in Patients with Coronavirus Disease 2019.

We investigated predictors of mortality, including demographic, clinical, and laboratory parameters, in hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia. This retrospective, single-center study included 651 consecutive Turkish adults who had been admitted to the emergency department with a diagnosis of COVID-19. We recorded the demographic, clinical, and laboratory parameters of the patients. The patients were divided into two groups: patients aged ≥65 years and patients aged <65 years. The predictors of mortality for hospitalized COVID-19 patients were evaluated. The study included 651 patients (354 [54.4%] men and 297 [45.6%] women; mean age, 56.40 ± 15.70 years). The most common comorbidities were hypertension (37.6%), diabetes mellitus (28.9%), and coronary artery disease (CAD) (16.1%). The overall mortality rate was 10.6% (n = 69); the mortality rate was higher in men than in women. Advanced age; chronic renal failure (CRF); prolonged activated partial thromboplastin time; high serum neutrophil and platelet counts; high C-reactive protein to albumin (CRP/albumin) ratio; and high levels of albumin, lactate dehydrogenase (LDH), and high-sensitivity troponin I (TnI-hs) were independent predictors of mortality in all age groups. Multivariate logistic regression analysis showed that chronic obstructive pulmonary disease (COPD), high serum platelet count, high CRP/albumin ratio, and high levels of albumin, TnI-hs, and D-dimer were independent predictors of mortality in patients aged <65 years. Conversely, advanced age, CAD, CRF, and high levels of serum CRP and LDH were independent predictors of mortality in patients aged ≥65 years.

Laboratory and clinical features of tumor lysis syndrome in children with non-Hodgkin lymphoma and evaluation of long-term renal functions in survivors

ObjectiveThe purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome (TLS) and acute kidney injury (AKI) in childhood non-Hodgkin lymphomas (NHL) and to reveal their impact on long term kidney function in survivors.MethodsOur single-center retrospective study included 107 patients (0-18 years old) with NHL who were admitted and treated at our hospital between 1998 and 2020. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were assessed. The long-term renal functions of the patients were investigated.Results80.3% of the patients were male with a median age of 9.8 years. The most common detected histopathological subgroup was Burkitt lymphoma. Hyperhydration with or without alkalinisation, and allopurinol were used in first-line treatment and prophylaxis of TLS. Laboratory TLS and clinical TLS was observed in 30.8% and 12.1% of patients, respectively. A significant correlation was found between young age, advanced stage, high LDH level at presentation, and TLS. AKI was observed in 12.1% of the patients. When the glomerular filtration rate values of the patients at the first and last admissions were compared after an average of 6.9 years, a mean decrease of 10 mL/min/1.73 m2 was found. It was not, however, found to be statistically significant.ConclusionLower age, advanced stage, and high LDH level at presentation were found to be risk factors for TLS in our study. Long-term renal function loss was not observed in the survivors who received early and careful prophylaxis/treatment for TLS. The survivors are still being followed up.

Real-World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients.

This study aims to describe the overall survival (OS) and to identify associated prognostic factors in patients with inoperable and metastatic cutaneous melanoma of the head and neck (H&N) region, undergoing modern systemic treatments. This is a retrospective single institutional study. Data on all consecutive H&N melanoma patients treated with systemic oncologic treatments between 2015 and 2022 were collected from electronic medical files. Kaplan-Meier curves were used to describe survival and Cox regression analysis was used to identify patient and tumor factors associated with prognosis. A total of 144 patients were included. Median OS was 45 months (95% confidence interval [CI] 28-65 m). On univariable analysis for OS, the primary disease site, specifically the nape and neck (hazard ratio [HR] 3.3, 95% CI 1.4-7.7, p = 0.007), high Eastern Cooperative Oncology Group Performance Status ([ECOG-PS], HR 2.5, 95% CI = 1.9-3.3, p < 0.001), high lactate dehydrogenase (LDH) levels (HR 2.8, 95% CI = 1.7-4.6, p < 0.001), and treatment with targeted therapy (TT) as compared with immunotherapy (HR 2.6, 95% CI = 1.06-6.3, p = 0.03) were all associated with shorter OS. High-grade adverse events (AEs) were associated with a longer OS (HR 0.41, 95% CI = 0.25-0.68, p = 0.001). On multivariable analysis for OS, the ECOG-PS, LDH levels, site of disease, and the development of moderate-severe AEs remained significant. In the era of modern oncologic treatments, the prognosis of inoperable and metastatic cutaneous H&N melanoma aligns with other cutaneous melanomas. Primary tumor site of the nape and neck region emerges as a significant prognostic factor. 3 Laryngoscope, 134:2762-2770, 2024.

1q21+ is associated with poor prognosis in newly diagnosed multiple myeloma patients with extramedullary disease: a retrospective study.

1q21+ is a common cytogenetic abnormality in multiple myeloma (MM) and is considered an independent predictor of poor prognosis; however, its impact on extramedullary disease (EMD) remains unknown. Our study reviewed the clinical relevance and prognostic value of 1q21+ status in 92 patients with NDMM and EMD. 1q21+ was detected in 23.9% (22/92) of patients. Patients with 1q21+ presented with advanced International Staging System stages (P = 0.006), lower level of hemoglobin (P = 0.004), higher percentage of plasma cells in the bone marrow (P < 0.001), higher level of serum β2-microglobulin (7.24g/L vs. 3.85g/L, P = 0.003), and higher levels of lactic dehydrogenase (LDH) (206.5 U/L vs. 177 U/L, P = 0.019). The prevalence of soft tissue-related EMD (EMD-S) (54.5% vs. 18.6%, P < 0.001), renal dysfunction (50.5% vs. 17.7%, P = 0.002), and hypercalcemia (27.3% vs. 7.1%, P = 0.011) was also higher. 1q21+ was strongly associated with other high-risk cytogenetic abnormalities, including IgH/FGFR3 (22.7% vs. 4.3%, P = 0.007) and IgH/MAF translocations (22.7% vs. 1.4%, P < 0.001). 1q21+ patients had significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: 24months vs. 47months, P = 0.002; PFS: 14months vs. 38months, P < 0.001); the poor survival outcomes could not be reversed by autologous hematopoietic stem cell transplantation. Multivariate analysis suggested that 1q21+ , EMD-S, elevated lactate dehydrogenase (LDH) levels, and P53 deletion were independent risk factors for poor prognosis in patients with EMD. In patients with 1q21+ EMD, hypercalcemia, elevated LDH levels, and P53 deletion were independent adverse risk prognostic factors.

Risk factors for the development of bronchiolitis obliterans in children after suffering from adenovirus pneumonia.

Bronchiolitis obliterans (BO) is an irreversible chronic obstructive lung disease in small airways. The aim of this study was to identify the relevant risk factors for the development of BO in children after suffering from adenovirus (ADV) pneumonia. An observational cohort study that included 112 children suffering from ADV pneumonia in our institution from March 2019 to March 2020 was performed. We divided the children into a BO group and a non-BO group based on whether they did develop BO or not. Univariate analysis and multivariate logistic regression analysis were applied to identify risk factors for the development of BO. The prediction probability model was evaluated by receiver operating characteristic (ROC) curve analysis. Twenty-eight children (25%) did develop BO after suffering from ADV pneumonia, while 84 children did not. Respiratory support (OR 6.772, 95% CI 2.060-22.260, P = 0.002), extended length of wheezing days (OR 1.112, 95% CI 1.040-1.189, P = 0.002) and higher lactic dehydrogenase (LDH) levels (OR 1.002, 95% CI 1.000-1.003, P = 0.012) were independently associated with the development of BO. The predictive value of this prediction probability model was validated by the ROC curve, with an area under the curve of 0.870 (95% CI 0.801-0.939, P < 0.001), a standard error of 0.035, a maximum Youden's index of 0.608, a sensitivity of 0.929, and a specificity of 0.679. After suffering an ADV pneumonia, children who have needed respiratory support, had a longer length of wheezing days or had higher LDH levels are more likely to develop BO.

Clinical features and risk factors of liver injury in patients with Chlamydia psittaci pneumonia- a retrospective analysis.

Research into the effects of Chlamydia psittaci pneumonia on the liver has emerged in the last few years. However, no studies have systematically described liver injury in patients with psittacosis. We present the first report on the clinical features and risk factors of liver injury in patients with Chlamydia psittaci pneumonia. We retrospectively collected the clinical parameters for 46 patients with Chlamydia psittaci pneumonia admitted to Jinhua Central Hospital from January 2019 to February 2023. We analyzed the liver function parameters and summarized the clinical characteristics and risk factors of liver injury. Among the 46 patients, 39 (84.8%) had abnormal liver function, and 23 (50.0%) had liver injury. The ratio of patients with a history of alcohol consumption (39.1% vs. 4.3%, P =0.004) or severe pneumonia (56.5% vs. 26.1%, P =0.036) was higher in the liver injury group compared with the non-liver injury group. Laboratory tests showed higher lactate dehydrogenase (LDH) levels in the liver injury group (P <0.001). The optimal cut-off LDH level associated with liver injury was 473 IU/L as determined by ROC curve analysis. Furthermore, multivariate logistic regression analysis demonstrated that a history of alcohol consumption (odds ratio [OR] = 11.251; 95% confidence interval [CI] = 1.022 ~ 123.897, P =0.048) and an LDH level of ≥ 473IU/L (OR = 11.635, 95% CI = 1.832 ~ 73.869, P =0.009) were independent risk factors for liver injury. A history of alcohol consumption and an LDH level of over 473 IU/L are independent risk factors for Chlamydia psittaci pneumonia-related liver injury. It is recommended that particular attention be given to monitoring and evaluating liver function parameters when treating patients with Chlamydia psittaci pneumonia who have a high LDH level and history of alcohol consumption.

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients.

Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83-21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Predictors of Non-invasive Ventilation Failure and Associated Factors Among the COVID-19 Patients Admitted to Intensive Care Unit.

Non-invasive ventilation (NIV) is a method of oxygenation supply that eliminates the need for an endotracheal airway. Non-invasive ventilation failure is defined as the necessity for endotracheal intubation or death during the NIV trial. This study aimed to identify the predictors and associated factors of NIV failure in coronavirus disease 2019 (COVID-19) patients admitted to an intensive care unit (ICU). This retrospective, longitudinal cohort study utilized electronic medical records of COVID-19 patients admitted to the ICU. A total of 150 patients were included in the study. Patient demographics, medical history, laboratory tests, partial pressure of carbon dioxide (PCO2), oxygen saturation (SpO2), heart rate, acidosis, consciousness, oxygenation, and respiratory rate (HACOR score), and the ratio of oxygen saturation (ROX) index (the SpO2/fraction of inspired oxygen [FIO2] to respiratory rate [SF] ratio) were recorded. Non-invasive ventilation failure was determined based on the need for endotracheal intubation or cardiac-respiratory arrest while on NIV. Of 150 patients, 55.3% were male (mean age: 55.9 years), with an NIV failure rate of 67.3%, a mortality rate of 66.7%, and 3.3% of patients requiring tracheostomy after NIV failure. The ROX index consistently decreased over time, and an increase in the HACOR score and PCO2 after 6 hours of commencing NIV were the predictors of NIV failure. Additionally, higher levels of lactate dehydrogenase, lower SF ratios, and higher APACHE scores upon ICU admission were significantly associated with NIV failure. Notably, the erythrocyte sedimentation rate (ESR) as an inflammatory index, SF ratio upon ICU admission, HACOR score, ROX index, and PCO2 after 12 hours were significant predictors of in-hospital mortality in patients receiving NIV. The ROX index, HACOR scale, and PCO2 are significant predictors of both NIV failure and in-hospital mortality.

Primary Thyroid Lymphoma: Clinical Factors Predicting the Possibility of Diffuse Large B-Cell Lymphoma.

Aims: Among primary thyroid lymphomas (PTLs), diffuse large B-cell lymphoma (DLBCL) has a poorer prognosis than other indolent lymphomas such as mucosa-associated lymphoid tissue (MALT) or follicular lymphoma (FL). However, the clinical differences between DLBCL and indolent lymphoma remain unclear. Therefore, this retrospective study on PTL was aimed at investigating the clinical differences between DLBCL and indolent lymphomas and identifying the factors differentiating DLBCL from indolent lymphomas. Materials and Methods: Medical records of 28 patients diagnosed with PTL and treated at our institution between 2005 and 2022 were retrospectively analyzed. Data on the following clinical variables were extracted: sex, age, symptoms (pain and dysphagia), ultrasonographic appearance patterns, the presence of airway stenosis on computed tomography and laryngeal endoscopy, blood test results, disease stage, and pathological diagnosis. Results: In all, 13 patients were histologically diagnosed with DLBCL, 12 with MALT lymphoma, and 3 with FL. Significant differences in disease-specific survival rates were evident between the DLBCL and indolent lymphoma groups (68.2 vs 100%, P = .043). High lactate dehydrogenase levels (>230 U/mL) and airway stenosis were observed only in patients with DLBCL. Multivariate analysis identified that the presence of a linear echoic strand pattern and the absence of an echoic nodular pattern on ultrasound were independently associated with DLBCL (P = .0497 and .012, respectively). Conclusion: DLBCL can cause airway stenosis. The linear echogenic strand pattern and the absence of a nodular pattern should be recognized as predictive factors of DLBCL.

Hyposecretory Progression Pattern Indicates Inferior Survival of Multiple Myeloma

Introduction: The application of novel drugs has significantly enhanced the prognosis of patients with MM. However, most patients will inevitably experience disease progression and relapse. At progressive disease (PD), patients always exhibit distinct features characterized by varying levels of M protein and plasma cells in the bone marrow (BMPC), even in the presence of end-organ damage. Notably, a subgroup of patients initially diagnosed with secretory MM exhibits a higher proportion of BMPC but a lower level of M protein when PD, rendering identification of this subgroup challenging without conducting bone marrow evaluations, leading to many patients experiencing PD but without timely treatment. The identification and comprehension of the hyposecretion at progression remain unclear and require further investigation. Thus, in this study, we aimed to assess the impact of different patterns of disease progression according to M protein and BMPC percentage on the survival and describe the features of the subgroup. Methods: We retrospectively analyzed the baseline and progression clinical features of 268 patients in our hospital between January 1, 2013 to July 1, 2023. We classified the PD patterns into three categories based on the elevated level of M protein and clonal plasma cells in bone marrow at progression: a. hyposecretory progression (HypoP) means &amp;gt;10% increase of the absolute percentage of BMPCs but serum M-protein increase &amp;lt;5g/L (or urine M protein increase &amp;lt; 200 mg/24h) and patients with the non-secretory subtype at diagnosis were excluded.; b. extramedullary progression (EMP) means appearance of a new extramedullary lesion; c. classic progression (ClaP) means any one or more of the other PD criteria according to International Myeloma Working Group (IMWG) criteria. High burden refers to the percentage of BMPC &amp;gt; 50%. Time from the first relapse to death as overall survival (OS) after the first progression (pro-OS). Results: There were 268 patients included in the study, and according to their features of M protein and BMPC at progression, 206 (76.8%) patients were classified in the ClaP group, 39 (14.6%) patients in EMP group and 23 (8.6%) patients in HypoP group. The percentage of female in HypoP group was 52.2%, which was much higher than that in other two groups (36.5% in ClaP and 30.8% in EMP). In general, the patients with MM are predominantly of the IgG subtype. Interestingly, for patients featured by hyposecretion in progression, the M protein types were mainly IgA (47.9%) and light chain type (43.5%) ( P&amp;lt;0.001). Compared to the ClaP and EMP group, there were more patients in HypoP presenting t(11;14) (36.8% vs 16.7% vs 11.8%) and 1q21+ (70% vs 53.8% vs 53.8%) both at diagnosis and progression. And at disease progression, the proportion of patients with t(4;14) in the HypoP group was as high as 50%. Besides, in terms of clinical manifestations, HypoP patients were more likely to suffer from hypercalcemia, renal dysfunction, and lower serum M protein level and EMP experienced high level of lactate dehydrogenase (LDH) both at diagnosis and progression. The median follow-up was 67.0m (7.6-123.0m). Figure 1 demonstrates the progression-free survival (PFS), OS and pro-OS of patients with different progression patterns. Patients in ClaP and EMP groups experienced similar PFS whereas HypoP patients had significantly shorter median PFS ( P=0.003, 23.9m vs. 22.6m vs. 14.1m). We also found that patients with ClaP and HypoP feature had inferior median OS ( P=0.007, 71.4m vs. 48.0m vs. 53.9m for ClaP vs. EMP vs, HypoP) and pro-OS ( P=0.012, 34.2m vs. 17.3m vs. 23.4m for ClaP vs, EMP vs. HypoP). Then we refer to these two as non-ClaP. In the Cox-regression, multivariate analysis showed ISS-III, ASCT and non-ClaP were associated with shorter pro-OS and OS ( Figure 1). Conclusions: In conclusion, our results indicate that the hyposecretory progression pattern is a valuable indicator of inferior survival. In such cases, bone marrow testing plays a crucial role in identifying and detecting this special group. Patients presenting with EMP or HypoP features tend to have a poorer prognosis, representing unmet clinical need. Therefore, it is important to recognize these particular patients as early as possible and to intensify treatment strategies.

Acute Chest Syndrome at the Emory University Georgia Comprehensive Sickle Cell Center at Grady Health System

Background: Individuals who have sickle cell disease (SCD) are susceptible to several severe consequences, such as vasoocclusive crisis (VOC), which may further develop into acute chest syndrome (ACS), a specific type of acute lung injury. Although VOC can result in substantial morbidity, it is important to note that ACS is the primary cause of mortality among individuals with SCD. Despite the devastating consequences of ACS, no interventions exist that directly treat this complication. Consequently, when patients present with ACS, their treatment options are frequently limited to supportive care. The absence of ideal therapeutic interventions for individuals with SCD who are experiencing ACS is a significant factor in their increased rates of illness and death. A cohort of adult patients diagnosed with ACS was examined with the objective to evaluate indicators of disease severity and identify risk factors associated with recurrent ACS. Methods: The Emory University Georgia Comprehensive Sickle Cell Center, located at Grady Health System, offers a dedicated acute care unit (ACU) that operates around the clock. This unit is specifically designed to assess and manage SCD patients who present with sickle cell crises. A pilot retrospective study was undertaken to analyze 25 patients with ACS. The evaluation included the examination of admission laboratory results, demographic information, past medical history, co-morbidity, interventions for each ACS admission for each patient (refer to Table 1). Descriptive statistics were used to report frequencies or median and range (Table 2). Patient characteristics of patients with 1 ACS event versus those with recurrent ACS (&amp;gt;=2) were compared using fishers exact test or the Wilcoxon-rank-sum test. Statistical significance was set at 0.05. Analysis was completed using SAS 9.4 (Cary, NC). Results: A total of 47 ACS episodes were detected in a cohort of 25 individuals, resulting in a median of 1 ACS event per patient (range of 1 to 6). A total of 85% of the patients included in this study had homozygosity for SCD, whereas 36% of the patients were receiving hydroxyurea treatment. Chronic pain was reported in three-fourth of the cohort. Out of all the ACS events observed, only 40% necessitated red cell exchange transfusion. A correlation between a minimum hemoglobin (Hb) level of 3.3 g/dL and lactate dehydrogenase (LDH) levels over 4000 U/L was noted during ACS admission. These findings indicate the presence of intravascular hemolysis. Three individuals died to ACS. Next, we conducted a comparison between a group of 10 patients who experienced recurring ACS events, with a minimum of 2 to a maximum of 6 occurrences, and another group of 15 patients who only had a single ACS episode. The group of patients with recurrent ACS exhibits a median of 5.5 episodes of VOC that necessitate visits to the acute care unit within the year prior. In contrast, the group with a single ACS episode has a median of 1 event. There was a notable disparity in the frequency of transfusions received by patients with recurrent ACS compared to those who experienced only a single episode over the past year. Although no other variable demonstrated statistical significance, the recurrent ACS group exhibited lower levels of hemoglobin and higher levels of LDH in comparison to the group with a single ACS episode. Further examination of our patients with SCD could provide valuable insights into the potential factors that may predict ACS episodes. These factors include a patient's genetic background, the frequency of VOC, the use of hydroxyurea, evidence of hemolysis, and previous blood transfusions. Furthermore, the utilization of acute care unit by patients with SCD has had a positive effect in our cohort, on the reduction of red cell exchange transfusions and mortality rates from ACS, possibly from early identification and episodic transfusion, in comparison to similar cohorts with ACS.

Exposure-Response Relationships between the Complement Factor B Inhibitor Iptacopan and Lactate Dehydrogenase (LDH) and Hemoglobin (Hb) in Patients (Pts) with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Background: PNH is an ultrarare disease characterized by complement-mediated hemolysis and subsequent anemia, bone marrow failure and thrombosis. In pts not treated with complement inhibitors, intravascular hemolysis (IVH) results from unregulated progression of the complement system and membrane attack complex formation. IVH is controlled in pts treated with anti-C5 therapy, but extravascular hemolysis (EVH) may emerge and cause persistent anemia. High LDH levels are a marker of ongoing IVH, while anemia can result from both IVH and EVH. Iptacopan is the first oral proximal complement inhibitor targeting factor B to selectively inhibit the alternative pathway of the complement cascade. As shown in PNH Phase III trials (APPLY-PNH [NCT04558918] and APPOINT-PNH [NCT04820530]), iptacopan can achieve good control of hemolysis. Aim: To support the dose selection for iptacopan, this analysis characterizes the exposure-response relationships between iptacopan and efficacy measures (LDH and Hb) in pts with PNH. The effect of prior anti-C5 treatment status has also been evaluated. Methods: This analysis is based on data from 4 clinical trials enrolling pts with PNH.Final data were used from the completed Phase II trials X2201 (NCT03439839; pts with active hemolysis despite anti-C5 therapy received concomitant iptacopan) and X2204 (NCT03896152; anti-C5-naïve pts received iptacopan monotherapy), in which iptacopan was administered orally in doses ranging from 25 to 200 mg twice daily (bid). Data up to the cut-off dates of 26 September 2022 and 2 November 2022 were used from the Phase III trials, APPLY-PNH (pts previously treated with anti-C5) and APPOINT-PNH (pts not treated with complement inhibitors including anti-C5), respectively, in which oral iptacopan was administered at 200 mg bid. A longitudinal mixed-effects modeling approach was applied to LDH and Hb. To account for the delay between exposure and response, indirect response models were developed for LDH and Hb. The models were used to predict the long-term (6 months) LDH and Hb responses for various iptacopan bid dose levels and to estimate (using simulation) the proportion of pts achieving LDH ≤1.5 × upper limit of normal (ULN) and Hb ≥12 g/dL. Results: The modeling dataset contained 161 pts with PNH; 94 (58%) were female, and median (range) age was 45 (18-84) years. For modeling of LDH and Hb levels, 2812 and 2587 samples were used, respectively, as well as 1577 pharmacokinetic samples. In total, 53 (33%) pts had not received anti-C5 treatment. Of the remaining 108 pts, 16 (15%) received iptacopan as add-on therapy to anti-C5 (pts from X2201) and 92 (85%) had previously received anti-C5 (pts from APPLY-PNH). The indirect response models were considered biologically plausible and adequately described the data using a common EC 50 value to both anti-C5-naïve pts and pts currently receiving or who previously received anti-C5. The estimated concentration of iptacopan required to achieve 90% of the maximum response (EC 90) of LDH was 268 ng/mL (90% confidence interval [CI] 238, 302), irrespective of prior anti-C5 treatment status ( Figure). The estimated typical LDH value after iptacopan treatment at an exposure &amp;gt;EC 90 was 237 U/L (90% CI 224, 250) within the normal LDH range (&amp;lt;250 U/L). Iptacopan 200 mg bid was the dose at which the highest proportion of pts (86%) achieved LDH ≤1.5 × ULN. While baseline LDH levels differed between anti-C5-naïve pts and pts currently receiving or who previously received anti-C5, similar proportions of these pts achieved LDH ≤1.5 × ULN (84% and 88%, respectively). The estimated EC 90 of Hb ≥12 g/dL was 1968 ng/mL (90% CI 1661, 2333) ( Figure); 89% of all pts were expected to reach EC 90 exposure at iptacopan 200 mg bid. The estimated Hb value after treatment with iptacopan at an exposure &amp;gt;EC 90 was 12.7 g/dL (90% CI 12.4, 13.0). 70% of pts were expected to achieve Hb normalization (≥12 g/dL) with iptacopan 200 mg bid. Similar proportions of anti-C5-naïve pts and pts who were currently receiving or who previously received anti-C5 achieved Hb ≥12 g/dL (71% and 68%, respectively). Conclusions: Indirect response models were developed to describe the exposure-response relationships between iptacopan and efficacy measures (LDH and Hb) in pts with PNH. The analysis demonstrated that 200 mg bid is the dose of oral iptacopan that achieves LDH ≤1.5 × ULN and Hb normalization in the highest proportion of patients regardless of prior treatment status.

The genetic landscape of histologically transformed marginal zone lymphomas.

Marginal zone lymphomas (MZLs) comprise a diverse group of indolent lymphoproliferative disorders; however, some patients develop histologic transformation (HT) with rapid progression to aggressive lymphoma. Forty-three MZLs with HT (HT-MZLs), 535 MZLs, and 174 de novo diffuse large B-cell lymphomas (DLBCLs) without rearrangements of MYC, BCL2, and BCL6 were collected. Among these, 22 HT-MZLs, 39 MZLs, and 174 DLBCLs were subjected to 148-gene targeted exome sequencing. The clinicopathologic features of patients who had HT-MZL and their genetic alterations were compared with those of patients who had MZLs and DLBCLs. All 43 HT-MZLs corresponded to DLBCLs. No HT-MZLs harbored BCL2 and MYC and/or BCL6 rearrangements. Bone marrow involvement and higher levels of lactate dehydrogenase were significantly more common in HT-MZLs than in MZLs. Furthermore, upregulated BCL6, MUM1, C-MYC, and Ki-67 expression was observed more frequently in HT-MZLs than in MZLs. TBL1XR1 was the most frequently altered gene (63.6%) in HT-MZLs, followed by CCND3 (31.8%), CARD11, ID3, and TP53 (22.7%). A trend toward worse progression-free survival in patients with TBL1XR1 mutations was observed. Compared with MZLs and non-germinal center B-cell (GCB) type DLBCLs, significantly higher frequencies of TBL1XR1 and ID3 mutations were identified in HT-MZLs. PIM1 mutations frequently occurred in DLBCLs and were significantly associated with TBL1XR1 mutations but were mutated less in HT-MZLs that had TBL1XR1 mutations. The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.

Reporting of biochemical blood values in COVID-19 patients: A retrospective study.

This study aimed to investigate the impact of biochemical blood parameters on the progression of coronavirus disease (COVID-19). This retrospective study analyzed the clinical characteristics and biochemical test parameters of 352 COVID-19 patients treated at Malatya Training and Research Hospital in Turkey between March 3, 2021, and February 28, 2022. The methodological approach of our study included specific analyses and examinations to assess the effect of biochemical blood values on disease progression in COVID-19 patients. To achieve this aim, blood samples were collected from patients and various biochemical tests were performed. The data obtained were evaluated using statistical analyses to examine the relationship between these specific biochemical blood values and the severity of COVID-19. High glucose, urea, alkaline phosphatase and lactate dehydrogenase levels and low albumin and potassium levels were associated with a more severe disease course. The results showed a significant link between certain biochemical blood values and the severity of COVID-19. These findings suggest that these markers may serve as valuable clinical indicators for predicting the disease progression and severity. This study demonstrates the importance of monitoring and analyzing biochemical blood values as essential tools for assessing the severity and progression of COVID-19. The identified markers provide valuable information regarding the prognosis of the disease and may help healthcare professionals make informed decisions regarding patient care.