Lower Lactate Dehydrogenase Levels Research Articles

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.

Differential Upregulation of Th1/Th17-Associated Proteins and PD-L1 in Granulomatous Mycosis Fungoides.

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.

Osmotic response during kidney perfusion with cryoprotectant in isotonic or hypotonic vehicle solution.

Organ cryopreservation would revolutionize transplantation by overcoming the shelf-life limitations of conventional organ storage. To prepare an organ for cryopreservation, it is first perfused with cryoprotectants (CPAs). These chemicals can enable vitrification during cooling, preventing ice damage. However, CPAs can also cause toxicity and osmotic damage. It is a major challenge to find the optimal balance between protecting the cells from ice and avoiding CPA-induced damage. In this study, we examined the organ perfusion process to shed light on phenomena relevant to cryopreservation protocol design, including changes in organ size and vascular resistance. In particular, we compared perfusion of kidneys (porcine and human) with CPA in either hypotonic or isotonic vehicle solution. Our results demonstrate that CPA perfusion causes kidney mass changes consistent with the shrink-swell response observed in cells. This response was observed when the kidneys were relatively fresh, but disappeared after prolonged warm and/or cold ischemia. Perfusion with CPA in a hypotonic vehicle solution led to a significant increase in vascular resistance, suggesting reduced capillary diameter due to cell swelling. This could be reversed by switching to perfusion with CPA in isotonic vehicle solution. Hypotonic vehicle solution did not cause notable osmotic damage, as evidenced by low levels of lactate dehydrogenase (LDH) in the effluent, and it did not have a statistically significant effect on the delivery of CPA into the kidney, as assessed by computed tomography (CT). Overall, our results show that CPA vehicle solution tonicity affects organ size and vascular resistance, which may have important implications for cryopreservation protocol design.

Lactate Dehydrogenase and Hemorrhagic Stroke During Extracorporeal Membrane Oxygenation for COVID-19.

Hemorrhagic stroke (HS) is a devastating complication during extracorporeal membrane oxygenation (ECMO) but markers of risk stratification during COVID-19 are unknown. Lactate dehydrogenase (LDH) is a readily available biomarker of cell injury and permeability. We sought to determine whether an elevated LDH before ECMO placement is related to the occurrence of HS during ECMO for COVID-19. Adult patients with COVID-19 requiring ECMO between March 2020 and February 2022 were included. LDH values prior to ECMO placement were captured.Patientswere categorized into high (> 750 U/L) or low (≤ 750 U/L) LDH groups. Multivariable regression modeling was used to determine the association between LDH and HS during ECMO. There were 520patientsthat underwent ECMO placement in 17 centers and 384 had an available LDH. Of whom, 122 (32%) had a high LDH. The overall incidence of HS was 10.9%, and patients with high LDH had a higher incidence of HS than those with low LDH level (17% vs 8%, p = 0.007). At 100days, theprobabilityof a HS was 40% in the high LDH group and 23% in those with a low LDH, p = 0.002. Afteradjustmentfor clinical covariates, high LDH remained associated with subsequent HS (aHR: 2.64, 95% CI 1.39-4.92). Findings weresimilarwhen restricting topatientssupported byvenovenous ECMOonly. Elevated LDH prior to ECMO cannulation is associated with a higher incidence of HS duringdevicesupport. LDH canriskstratify cases for impending cerebralbleedingduring ECMO.

The neutrophil-to-lymphocyte ratio and lactate dehydrogenase combined in predicting liver metastasis and prognosis of colorectal cancer.

The neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level are inflammatory markers related to tumor growth and metabolism. This study investigated the value of preoperative NLR, LDH and the combination of NLR and LDH (NLR-LDH) for predicting colorectal cancer liver metastasis (CRLM) and tumor prognosis in the early stages of colorectal cancer (CRC). Three hundred patients undergoing CRC resection were included. Logistic regression analysis was used to estimate the correlation between CRLM time and inflammatory markers, and Kaplan-Meier survival and Cox regression analyses were used to estimate overall survival (OS). Forest plots were prepared based on the multivariate Cox analysis model and evaluated by receiver operating characteristic (ROC) curve analysis. The NLR cut-off value was 2.071 according to the ROC curve. The multivariate analysis showed that the elevated LDH level and a high NLR-LDH level were independent predictors of synchronous CRLM and OS (p < 0.05). The combination of a high NLR and elevated LDH and NLR-LDH levels suggested a poor prognosis and a significantly shorter median survival time than a low NLR and low levels of LDH and NLR-LDH. The ROC curve analysis results illustrated that the predictive value of the NLR-LDH score for synchronous CRLM [area under the curve (AUC) = 0.623, p < 0.001] and OS (AUC = 0.614, p = 0.001) was superior to that of the NLR or LDH score used alone. LDH and NLR-LDH are reliable, easy-to-use, independent biomarkers for predicting synchronous or metachronous CRLM and OS in CRC patients. The NLR is an important monitoring index for CRLM. Preoperative NLR, LDH and NLR-LDH may help to guide the use of therapeutic strategies and cancer surveillance.

GLUOSE 6-PHOSPHATE ISOMERASE DEFICIENCY: A RARE ENTITY

A young male presented to us with the chief complaints of jaundice, non-bilious vomiting and intermittent high-grade fever in the background of past history of recurrent blood transfusions.On examination, he had pallor, icterus with a massive non tender splenomegaly and his laboratory parameters were suggestive of indirect hyperbilirubinemia with low haptoglobin and elevated lactate dehydrogenase levels with reticulocytosis and erythroid hyperplasia on bone marrow aspiration. His Direct and indirect coombs test were negative.To rule out hemoglobinopathies, his hemoglobin electrophoresis was sent, which turned out to be normal. Hence, red blood cell membrane and enzyme studies were carried out which revealed Glucose-6-phosphate isomerase deficiency.

Features and Long-Term Outcomes of Stage IV Melanoma Patients Achieving Complete Response Under Anti-PD-1-Based Immunotherapy.

Immune checkpoint inhibition (ICI) has changed the melanoma treatment spectrum. Few studies have examined the characteristics and long-term outcomes of patients achieving complete response (CR) under ICI. We evaluated patients with unresectable stage IV melanoma treated with first-line ICI. The characteristics of those achieving CR were compared with those not achieving CR. Progression-free survival (PFS) and overall survival (OS) were assessed. Late-onset toxicities, response to second-line treatment, the prognostic value of clinicopathologic features, and blood markers were examined. A total of 265 patients were included; 41 (15.5%) achieved CR, while 224 (84.5%) had progressive disease, stable disease, or partial response. At the therapy start, those who had CR were more likely to be older than 65 years of age (p=0.013), have a platelet-to-lymphocyte ratio below 213 (p=0.036), and have lower lactate dehydrogenase levels (p=0.008) than those not achieving a CR. For those who discontinued therapy after CR, the median follow-up time after CR was 56 months (interquartile range [IQR] 52-58) and the median time from CR to therapy end was 10 months (IQR 1-17). Five-year PFS after CR was 79% and 5-year OS was 83%. Most complete responders had a normalization of S100 at the time of CR (p<0.001). In simple Cox regression analysis, age below 77 years at CR (p=0.04) was associated with better prognosis after CR. Eight patients received second-line ICI; disease control was seen in 63%. Late immune-related toxicities occurred in 25% of patients, most being cutaneous immune-related toxicities. Response, according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, is, until now, the most important prognostic factor, and CR is a valid surrogate marker for long-term survival in patients treated with ICI. Our results highlight the importance of investigating the optimal therapy duration in complete responders.

Kleinhovia Hospita Leaf Extract Protects the Heart Against Infarction by Isoproterenol

Background: Isoproterenol, a β-adrenergic agonist, may induce myocardial infarction when used in high dosage in rats. This study was conducted to evaluate the effect of the ethanol extract of Kleinhovia hospita leaves on cardiac biomarkers and myocardial structures of rats induced by isoproterenol. Methods: Male rats (n=30) were assigned as a normal controls or treatment groups. The treatment groups received pretreatments, either placebo or the extract at doses of 250, 500, or 750 mg/kg for 14 days, followed by two isoproterenol injections at 100 mg/kg. After 24 hours, blood samples were taken and the hearts dissected. The tested cardiac biomarkers were creatinine kinase myocardial band (CKMB) and lactate dehydrogenase (LDH). Heart histopathology analysis was performed followed by staining of samples with hematoxylin and eosin. Results: The isoproterenol injections significantly increased CKMB and LDH levels in the placebo group compared to those in normal controls. Pretreatment with the extract at doses of 500 and 750 mg/kg significantly reduced the serum CKMB and LDH levels compared to those of the placebo. The histopathological examinations showed the presence of diffused necrosis and severe inflammation in the placebo group. Pretreatment with the extract at 500 or 750 mg/kg significantly reduced the myocardial tissue damages in rats. Conclusion: The K. hospita extract at doses of 500 or 750 mg/kg significantly reduced the infarctions in the rats’ heart tissue, shown by significantly low levels of CKMB and LDH, and reduced necrotic lesions and inflammation in the rat heart tissue samples induced by isoproterenol pretreatment.

Is the level of serum lactate dehydrogenase a potential biomarker for glucose monitoring with type 2 diabetes mellitus?

Type 2 diabetes mellitus (T2DM) is a metabolic disorder due to defects in insulin secretion or insulin resistance leading to the dysfunction and damage of various organs. To improve the clinical evaluation of short-term blood glycemic variability monitoring, it is critical to identify another blood cell status and nutritional status biomarker that is less susceptible to interference. This study identifies the significance of serum lactate dehydrogenase (LDH) level among T2DM patients treated in outpatient clinics and investigates the relationship of LDH level with other variables. This study comprised 72 outpatients with T2DM over 20 years of age. Blood samples were collected followed by a hematological analysis of serum glycated albumin (GA), LDH, fasting blood glucose, glycosylated hemoglobin, C-peptide, and insulin antibodies (insulin Ab). Serum LDH level was significantly correlated with GA (p < 0.001), C-peptide (p = 0.04), insulin Ab (p = 0.03), and thyroid-stimulating hormone (TSH) levels (p = 0.04). Hence, we performed a linear regression analysis of hematological markers. GA (p < 0.001, r2 = 0.45) and insulin Ab (p < 0.001, r2 = 0.40) were significantly associated with LDH level. Then, we classified patients into low (<200 U/L) and high (≥200 U/L) serum LDH level groups, respectively. GA (p < 0.001), C-peptide (p = 0.001), and TSH (p = 0.03) showed significant differences in patients with high LDH levels compared with those in patients with low LDH levels. In conclusion, we suggested that LDH level was independent of long-term but associated with short-term blood glucose monitoring. The results indicated that changes in serum GA induced cell damage and the abnormal elevation of the serum level of LDH may occur simultaneously with glycemic variability. It has been reported that many biomarkers are being used to observe glucose variability in T2DM. However, LDH could provide a more convenient and faster evaluation of glycemic variability in T2DM.

Predicting COVID-19 progression in hospitalized patients in Belgium from a multi-state model.

To adopt a multi-state risk prediction model for critical disease/mortality outcomes among hospitalised COVID-19 patients using nationwide COVID-19 hospital surveillance data in Belgium. Information on 44,659 COVID-19 patients hospitalised between March 2020 and June 2021 with complete data on disease outcomes and candidate predictors was used to adopt a multi-state, multivariate Cox model to predict patients' probability of recovery, critical [transfer to intensive care units (ICU)] or fatal outcomes during hospital stay. Median length of hospital stay was 9 days (interquartile range: 5-14). After admission, approximately 82% of the COVID-19 patients were discharged alive, 15% of patients were admitted to ICU, and 15% died in the hospital. The main predictors of an increased probability for recovery were younger age, and to a lesser extent, a lower number of prevalent comorbidities. A patient's transition to ICU or in-hospital death had in common the following predictors: high levels of c-reactive protein (CRP) and lactate dehydrogenase (LDH), reporting lower respiratory complaints and male sex. Additionally predictors for a transfer to ICU included middle-age, obesity and reporting loss of appetite and staying at a university hospital, while advanced age and a higher number of prevalent comorbidities for in-hospital death. After ICU, younger age and low levels of CRP and LDH were the main predictors for recovery, while in-hospital death was predicted by advanced age and concurrent comorbidities. As one of the very few, a multi-state model was adopted to identify key factors predicting COVID-19 progression to critical disease, and recovery or death.

Longitudinal Cluster Analysis of Hemodialysis Patients with COVID-19 in the Pre-Vaccination Era.

Coronavirus disease 2019 (COVID-19) in hemodialysis patients (HD) is characterized by heterogeneity of clinical presentation and outcomes. To stratify patients, we collected clinical and laboratory data in two cohorts of HD patients at COVID-19 diagnosis and during the following 4 weeks. Baseline and longitudinal values were used to build a linear mixed effect model (LME) and define different clusters. The development of the LME model in the derivation cohort of 17 HD patients (66.7 ± 12.3 years, eight males) allowed the characterization of two clusters (cl1 and cl2). Patients in cl1 presented a prevalence of females, higher lymphocyte count, and lower levels of lactate dehydrogenase, C-reactive protein, and CD8 + T memory stem cells as a possible result of a milder inflammation. Then, this model was tested in an independent validation cohort of 30 HD patients (73.3 ± 16.3 years, 16 males) assigned to cl1 or cl2 (16 and 14 patients, respectively). The cluster comparison confirmed that cl1 presented a milder form of COVID-19 associated with reduced disease activity, hospitalization, mortality rate, and oxygen requirement. Clustering analysis on longitudinal data allowed patient stratification and identification of the patients at high risk of complications. This strategy could be suitable in different clinical settings.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between survival and biomarkers of hypoperfusion, inflammation, and organ failure

Abstract Background In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). Purpose We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. Methods This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011–2020). Biomarkers at admission and consecutively two days after ECPR initiation were retrieved. Odds ratio (OR) of 90-day survival were assessed by logistic regression analyses. Cut-off values were calculated from area under the curve (AUC) via the Youden index. Results Fifty-six patients (25%) survived to hospital discharge, all were still alive after 90-days and 91% had a favorable neurological status at discharge. Factors independently associated with 90-day survival were: male sex, shockable presenting rhythm, low flow time, platelets, pH, lactate, C-reactive protein, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and creatine kinase MB (CK-MB) level. Comparing the ability of standard predictive variables (age, sex, shockable presenting rhythm, witnessed arrest, and low flow time) and selected biomarkers (from multivariate analyses) in predicting 90-day survival, biomarkers day 2 after OHCA were significantly better than standard variables (AUC 0.79 vs. 0.56, p=0.01). Conclusion Biomarkers of hypoperfusion (low lactate and high pH), inflammation (high platelets and CRP), and organ failure (low LDH, ALP, and CK-MB) were independently associated with 90-day survival. Biomarkers on day 2 after OHCA (d-dimer, ALP, and CK-MB) were more predictive of 90-day survival than standard predictive variables. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Odense University Hospital's and Rigshospitalet's Common Research Foundation

Clinical Study of Chemotherapy Combined with Antivirals for Adult T-cell Leukemia/Lymphoma

To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors. Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, β2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed. The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower β2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)％ and (40.9±2.1)％ (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)％ and (13.6±2.8)％ (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy ［HR=5.617 (95%CI 1.803-11.293), P=0.027］ were independent prognostic factors for the long-term efficacy. Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.

Diagnostic value of lactate dehydrogenase in COVID-19: A systematic review and meta-analysis.

BackgroundThis meta-analysis outlines the role of elevated lactate dehydrogenase (LDH) levels in assessing the severity of coronavirus disease 2019 (COVID-19).MethodsThe current study was designed as a systematic review and meta-analysis. Embase, Pub-Med, Web of Science, Scopus and Cochrane Central Register of Controlled Trials were searched to identify the usefulness of LDH as a marker of COVID-19 severity. All extracted data were analyzed using RevMan V.5.4 or STATA V.14 software.ResultsA total of 264 records were selected for this meta-analysis. Pooled analysis showed that LDH levels were statistically significantly lower in the group of survivors compared to patients who died in hospital (standardized mean differences [SMD] = −3.10; 95% confidence interval [CI]: −3.40 to −2.79; I2 = 99%; p < 0.001). Lower LDH levels were observed in non-severe groups compared to severe course of COVID-19 (SMD = −2.38; 95% CI: −2.61 to −2.14; I2 = 99%; p < 0.001). The level of LDH was statistically significantly lower in the severe group compared to the critical group (SMD = −1.48; 95% CI: −2.04 to −0.92; I2 = 98%; p < 0.001). Patients who did not require treatment in the intensive care unit (ICU) showed significantly lower levels of LDH compared to patients who required treatment in the ICU (SMD = −3.78; 95% CI: −4.48 to −3.08; I2 = 100%; p < 0.001).ConclusionsThis meta-analysis showed that elevated LDH was associated with a poor outcome in COVID-19.

Biomarkers predicting the 30‑day mortality of patients who underwent elective surgery and were infected with SARS‑CoV‑2 during the post‑operative period: A retrospective study.

The coronavirus disease 2019 (COVID-19) pandemic is a significant global concern that has had major implications for the healthcare system. Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) undergoing elective or emergency surgical procedures have a substantial risk of mortality and peri-operative complications. The present study aimed to describe the characteristics of patients who underwent elective surgery and developed nosocomial SARS-CoV-2 infection post-surgery. Patients who underwent thoracic, upper and lower abdominal or peripheral elective surgery with a polymerase chain reaction diagnosis of COVID-19, at 3-7 days after the surgery, were enrolled in the present retrospective study. Demographics, vaccination status against SARS-CoV-2, Charlson comorbidity index (CCI) and laboratory data were recorded upon admission to the hospital unit. In total, 116 subjects (80 males, 36 females; mean age, 67.31±16.83 years) fulfilling the inclusion criteria were identified. Among the 116 participants, 14 (12.1%) were intubated. From the 116 individuals analyzed, 84 were alive after 30 days (survivors), and 32 had succumbed to the disease (non-survivors). The mortality rate was 27.6% (32/116). The non-survivors had an older age and a higher CCI score. At the evaluation upon admission to the hospital unit, the survivors presented with higher serum albumin levels and a higher number of blood lymphocytes. In addition, the survivors exhibited lower levels of lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase (ALP) and C-reactive protein (CRP), as well as a higher neutrophil to lymphocyte ratio (NLR) and CRP to albumin ratio (CAR) (P<0.05). The patients that were intubated had higher levels of gamma glutamyl-transferase (GGT), ALP and ferritin, as well as a higher NLR and platelet to lymphocyte ratio upon admission to the hospital unit (P<0.05). According to the Cox proportional hazards multivariate regression analysis, the only independent predictors of mortality and intubation were ALP and GGT upon admission, respectively (P<0.05). On the whole, the findings of the present study suggest that more stringent guidelines are required in order to prevent infection during the post-operative period.

P833: CATEGORIZING HEMATOLOGICAL RESPONSE TO PEGCETACOPLAN IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A POST HOC ANALYSIS OF THE PHASE 3 PRINCE STUDY DATA

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare complement-mediated hematological disorder characterized by anemia, hemolysis, and bone marrow failure. Pegcetacoplan (PEG), an FDA/EMA-approved targeted C3 therapy for the treatment of PNH, can control intravascular and prevent extravascular hemolysis. A prior post hoc analysis of PEGASUS reported a higher proportion of patients presenting good or better hematologic responses to PEG versus eculizumab (Risitano A, et al., Blood, 2021;138 [Supplement 1]: 1104). The PRINCE study demonstrated efficacy/safety of PEG compared to control treatment (CTRL; supportive treatment of PNH without complement inhibitors) in complement-inhibitor naïve patients with PNH. Aims: This post hoc analysis categorized the hematologic response to PEG and CTRL at baseline and Week 26 in the PRINCE Trial (phase 3, multicenter, randomized, open-label, controlled trial [NCT04085601]). Methods: Adult complement-inhibitor naïve (no complement-inhibitor treatment within 3 months prior to screening) patients with PNH who had low hemoglobin (Hb) levels and high lactate dehydrogenase levels were included. Patients were randomized 2:1 to receive PEG or CTRL through Week 26. Hematologic response to PEG and CTRL was categorized as complete, good, partial, or minor at baseline and at Week 26 using the number of packed red blood cells transfusions needed in the last 6 months and Hb level at the specified timepoints (revised categorization criteria per Debureaux PE, et al. Bone Marrow Transplant. 2021; 56(10):2600-2602). Hematologic response categorization was performed according to the following criteria: Complete response: no transfusions, no anemia (≥12 g/dL); Good response: no transfusions, but with chronic mild anemia (10-12 g/dL); Partial response: no/occasional transfusions (≤2 units/6 months) and chronic moderate anemia (8-10 g/dL); Minor response: regular transfusions (≥3 units/6 months) and chronic moderate/severe anemia (<10 g/dL), or no/occasional transfusions (≤2 units/6 months) and chronic severe anemia (<8 g/dL). Any patients with missing data at Week 26 were evaluated using the most recent value within the 6 weeks prior. Statistical tests assessed significance for responses of ‘Good’ or ‘Complete’, collectively (Fisher’s Exact Test between PEG and CTRL groups at baseline; McNemar’s test within PEG group at baseline vs. Week 26). Results: In this study, 53 patients were randomized to PEG (n=35) or CTRL (n=18). At baseline, most patients had a partial or minor response to supportive therapy prior to randomization, with only 5.7% of patients in the PEG group and 0.0% in the CTRL group presenting a Good or Complete hematologic response (p= 0.5428). Hematologic response categorization for patients in the PEG group are shown for baseline and Week 26 (Figure). At Week 26, 80.0% of patients in the PEG group exhibited a Good or Complete response. The proportion of patients in the PEG group who demonstrated a Good or Complete response was significantly higher at Week 26 as compared to baseline (p<0.0001). One patient treated with PEG had missing data at Week 26 due to being lost to follow-up and was not evaluated. Image:Summary/Conclusion: This post hoc analysis of PRINCE trial data revealed that a substantial proportion of patients achieved good or complete hematologic response to PEG after 26 weeks. These findings further support the positive efficacy of PEG on hematologic parameters and provide evidence for the role of proximal complement inhibition on hematological and clinical improvements for patients with PNH.

Comparison of characteristics and laboratory tests of COVID-19 hematological patients from France and Brazil during the pre-vaccination period: identification of prognostic profiles for survival

IntroductionCOVID-19 disease presentation is heterogeneous, from asymptomatic up to severe life-threatening forms. Getting further insights into patients with specific diseases is of particular interest. We aimed to identify profiles of hematology patients hospitalized with COVID-19 that would be associated with survival and to assess the differences between cohorts MethodsA binational cohort of 263 patients with COVID-19 and hematological disease was studied in Paris, France and São Paulo, Brazil. Patient profiles were based on age, comorbidities, biological measurements, COVID-19 symptoms and hematological disease characteristics. A semi-supervised learning method with a survival endpoint was first used, following which, a classifier was identified to allow the classification of patients using only baseline information Main resultsTwo profiles of patients were identified, one being young patients with few comorbidities and low C-reactive protein (CRP), D-dimers, lactate dehydrogenase (LDH) and creatinine levels, and the other, older patients, with several comorbidities and high levels of the 4 biology markers. The profiles were strongly associated with survival (p < 0.0001), even after adjusting for age (p = 0.0002). The 30-day survival rate was 77.1% in the first profiles, versus 46.7% in the second. The Brazilian analysis emphasized the importance of age, while the French focused on the comorbidities ConclusionThis analysis showed the importance of CRP, LHD and creatinine in the COVID-19 presentation and prognosis, whatever the geographic origin of the patients.

Pearson’s patterns correlational of clinical risks at admissions with hospitalization outcomes during initial COVID-19 outbreak

SummaryCOVID-19 outbreaks have crushed our healthcare systems, which requires clinical guidance for the healthcare following the outbreaks. We conducted retrospective cohort studies with Pearson’s pattern-based analysis of clinical parameters of 248 hospitalized patients with COVID-19. We found that dysregulated neutrophil densities were correlated with hospitalization duration before death (p = 0.000066, r = −0.45 for % neutrophil; p = 0.0001, r = −0.47 for neutrophil count). As such, high neutrophil densities were associated with mortality (p = 4.23 × 10−31 for % neutrophil; p = 4.14 × 10−27 for neutrophil count). These findings were further illustrated by a representative “second week crash” pattern and validated by an independent cohort (p = 5.98 × 10−11 for % neutrophil; p = 1.65 × 10−7 for neutrophil count). By contrast, low aspartate aminotransferase (AST) or lactate dehydrogenase (LDH) levels were correlated with quick recovery (p ≤ 0.00005). Collectively, these correlational at-admission findings may provide healthcare guidance for patients with COVID-19 in the absence of targeted therapy.

Serological Biomarkers at Hospital Admission Are Not Related to Long-Term Post-COVID Fatigue and Dyspnea in COVID-19 Survivors

Objective: The aim of this study was to investigate the association between serological biomarkers at the acute phase of infection at hospital admission with the development of long-term post-COVID fatigue and dyspnea. Methods: A cohort study including patients hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the outbreak (from March 20 to June 30, 2020) was conducted. Hospitalization data, clinical data, and eleven serological biomarkers were systematically collected at hospital admission. Patients were scheduled for an individual telephone interview after hospital discharge for collecting data about the presence of post-COVID fatigue and dyspnea. Results: A total of 412 patients (age: 62 years, standard deviation: 15 years; 47.5% women) were assessed with a mean of 6.8 and 13.2 months after discharge. The prevalence of post-COVID fatigue and dyspnea was 72.8% and 17.2% at 6 months and 45.4% and 13.6% at 12 months after hospital discharge, respectively. Patients exhibiting post-COVID fatigue at 6 or 12 months exhibited a lower hemoglobin level, higher lymphocyte count, and lower neutrophil and platelets counts (all, p < 0.05), whereas those exhibiting post-COVID dyspnea at 6 or 12 months had a lower platelet count and lower alanine transaminase, aspartate transaminase, and lactate dehydrogenase (LDH) levels (all, p < 0.05) than those not developing post-COVID fatigue or dyspnea, respectively. The multivariate regression analyses revealed that a lower platelet count and lower LDH levels were associated but just explaining 4.5% of the variance, of suffering from post-COVID fatigue and dyspnea, respectively. Conclusion: Some serological biomarkers were slightly different in patients exhibiting post-COVID fatigue or dyspnea, but they could not explain the long-COVID problems in those patients.

The prognostic significance of immune checkpoint receptor expression in patients with lymphoma: Association with disease status and clinical outcomes.

Little is known about the expression of immune checkpoint receptors in the peripheral blood of lymphoma patients. Herein, we assessed the expression of inhibitory checkpoint receptors, including CTLA-4, PD-1/PDL-1, LAG-3, and TIM-3 in the peripheral blood of lymphoma patients and its correlation with the clinical outcomes of patients. Therefore, 47 classical Hodgkin lymphoma (cHL), 48 non-Hodgkin lymphoma patients with diffuse large B-cell lymphoma (DLBCL) subtype, and 30 healthy controls were recruited. The expression of inhibitory receptors was evaluated using SYBR Green real-time PCR method. CTLA-4, LAG-3, and TIM-3 genes were significantly upregulated in both cHL and DLBCL patients compared to the healthy controls. In addition, the level of these molecules was differentially expressed in cHL and DLBCL patients at different disease phases compared to the healthy controls. The CTLA-4 gene was highly expressed in newly diagnosed (ND) cHL patients compared to the relapsed ones. Relapsed DLBCL patients had significantly increased LAG-3 expression compared to patients at remission, as well as ND patients. Regarding cHL patients, high CTLA-4 expression was correlated with low lactate dehydrogenase level and better performance status, whereas the level of LAG-3 was significantly elevated in patients with poor performance status. Lower initial PD-1 expression was associated with improved disease-free survival in cHL patients. Inhibitory immune checkpoint receptors are aberrantly expressed in the peripheral blood of cHL and DLBCL patients in which high LAG-3 in DLBCL patients and PD-1/LAG-3 in cHL patients are associated with relapse occurrence and worse prognosis, respectively.