Abnormal Lactate Dehydrogenase Research Articles

Distinguishing Kikuchi-Fujimoto disease from lymphoma in patients by clinical and PET/CT features.

To develop a scheme for distinguishing Kikuchi-Fujimoto disease (KFD) from lymphoma in patients presenting enlarged lymph nodes (LNs) predominantly on the upper side of the diaphragm. From November 2015 to August 2023, 32 KFD patients and 38 lymphoma patients were pathologically confirmed and enrolled in this retrospectively study. Clinical and 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) features were collected. When comparing those PET/CT parameters, we set 5 models with different research objects: (1) all affected LNs; (2) the 5 largest affected LNs in terms of maximum diameter; (3) the 5 largest affected LNs in terms of maximum standard uptake values (SUVmax); (4) the largest affected LNs in terms of maximum diameter; (5) the largest affected LNs in terms of SUVmax. Compared to lymphoma patients, KFD patients were younger; and with higher incidence of fever, arthralgia, abnormal serum white blood cell, lactate dehydrogenase (LDH) and splenomegaly; lower incidence of affected LNs perinodal infiltration, necrosis and conglomeration; more affected LNs in Head and Neck nodes (particularly in level II) and Axillary in KFD (P ˂ .05). PET/CT parameters presented as various difference in each model. Finally, 11 clinical and PET/CT features (age ≤ 34, with fever, arthralgia, abnormal white blood cell, abnormal LDH, and without node necrosis and node conglomeration have a score of 2 each; splenomegaly, perinodal infiltration, median maximum diameter ≤ 20.5 and median SUVmax ≤ 7.1 of affected LNs in model 2 have score of 1 each) were selected as scheme items for distinguishing KFD from lymphoma. Individuals who have a total score > 8, meet the criteria for KFD. Sensitivity and specificity were high: 86.8% (95% CI: 71.9%, 95.5%) and 96.9% (95% CI: 83.7%, 99.5%), AUC = 0.975 (95% CI: 90.5%, 99.6%), respectively. It can effectively distinguish KFD from lymphoma by clinical and PET/CT parameters.

Real-world (RW) testing patterns of serum lactate dehydrogenase (LDH) and its prognostic value among patients (pts) with metastatic colorectal cancer (mCRC).

46 Background: LDH is a potential prognostic biomarker of outcomes for pts with mCRC. This retrospective, observational cohort study describes RW LDH testing patterns and assesses LDH as a prognostic factor for overall survival (OS) in pts receiving chemotherapy (CT) for mCRC in the USA. Methods: Pts with mCRC, ≥18 years (yrs) of age, who initiated first line (1L) CT (index date) between January 1, 2016, and November 30, 2022, were identified in the nationwide de-identified Flatiron Electronic Health Record-derived database. Practice patterns for LDH testing are described. Pts were categorized into normal vs abnormal LDH baseline (≤3 months prior to/at index date) value based on the lab reference range. Prognostic relationship between normal vs abnormal LDH baseline value and OS was assessed using Kaplan-Meier and multivariate Cox proportional-hazards model. Results: Of 15,329 eligible pts, 57% were male, 49% were ≥65 yrs of age and 66% had ECOG performance status 0–1; 59% had stage IV disease at initial diagnosis; 29% had a KRAS mutation (at any time ≤30 days post-index; 35% not tested). Median time from mCRC diagnosis to index was 35 days. Most common 1L regimens were FOLFOX ± bevacizumab (48%), FOLFIRI ± bevacizumab (15%), and capecitabine (13%). Median follow up from index date was 15.6 months (mos); 60% died. LDH testing was performed in 2,547 pts (17%) during baseline and 3,379 pts (22%) post-index. Among those with ≥1 LDH test during each line of therapy (LOT), median number of LDH tests per pt was 4–6 and median time from line initiation to first LDH test was 7–10 days across the first five LOTs (Table). Among LDH tested pts during follow-up (n=3,379), 21% and 40% had abnormal and normal LDH values at baseline, respectively (39% missing). Demographic characteristics of abnormal vs normal LDH pts were similar; abnormal LDH pts were more likely to be ≥65 years (52% vs 49%), African American or Black (12% vs 7%), and reside in the Northeast (30% vs 21%). Median OS (95% CI) in pts with normal vs abnormal baseline LDH was 29.9 (28.3, 31.7) mos vs 16.8 (14.8, 18.2) mos. In multivariate Cox proportional-hazards model, pts with abnormal baseline LDH values had higher risk of death (HR 1.91, p<0.0001) after adjustment for pt demographic and clinical characteristics. Conclusions: In RW clinical practice in the USA, only one-fifth of mCRC pts receiving CT undergo LDH testing even though LDH value has been found to be a prognostic factor of OS. Efforts to increase LDH testing may help guide treatment decisions in this setting. [Table: see text]

Serum Cell Division Cycle 42 before and after Programmed Death-1 Inhibitor Therapy in Advanced Melanoma Patients: Correlation with Tumor Features, Clinical Response, and Survival.

Cell division cycle 42 (CDC42) mediates immune escape in cancers. This study aimed to investigate linkages of CDC42 with tumor features, treatment response, and survival in advanced melanoma patients receiving programmed death-1 (PD-1) inhibitors. Pre-treatment and post-treatment (after 2 cycles) serum CDC42 of 35 advanced melanoma patients receiving PD-1 inhibitor was assessed by enzyme-linked immunosorbent assay. Patients with tumor-node-metastasis (TNM) stage IV (vs. III) (P = 0.050) and abnormal (vs. normal) lactate dehydrogenase (LDH) (P = 0.022) had higher pre-treatment CDC42. After 2-cycle therapy, CDC42 was declined (P < 0.001). Objective response and disease control rates were 34.3% and 62.9%, respectively. Additionally, pre-treatment and post-treatment CDC42 was reduced in patients with objective response and disease control than those without (all P < 0.050). Concerning survival, pre-treatment with CDC42 > 700 pg/mL was associated with shorter progression-free survival (PFS) (P = 0.013), but not overall survival (OS) (P = 0.060). Specifically, the 12-month PFS rate was 26.7% and 66.2%, and the 12-month OS rate was 61.1% and 82.5% in patients with pre-treatment with CDC42 > 700 pg/mL and ≤ 700 pg/mL, respectively. Post-treatment with CDC42 > 700 pg/mL was correlated with shortened PFS (P = 0.010) and OS (P = 0.006). The 12-month PFS rate was 12.5% and 62.0%, and the 12-month OS rate was 42.3% and 88.0% in patients with post-treatment with CDC42 > 700 pg/mL and ≤ 700 pg/mL, accordingly. Furthermore, post-treatment with CDC42 > 700 pg/mL was independently related to PFS [hazard ratio (HR): 2.704, P = 0.029 and OS (HR: 7.749, P = 0.005)]. Elevated CDC42 correlates with advanced TNM, abnormal LDH, worse clinical response, and dismal survival in advanced melanoma patients receiving PD-1 inhibitors.

CCT6A is associated with CDC20, Enneking stage and prognosis in osteosarcoma, and its knockdown suppresses osteosarcoma cell viability and invasion.

Chaperonin-containing tailless complex polypeptide 1 subunit 6A (CCT6A) regulates the proliferation, invasiveness and stemness of numerous types of cancer, and may interact with cell division cycle 20 (CDC20); however, its implication in osteosarcoma remains unclear. The present study aimed to investigate the relationship between CCT6A and CDC20, and their association with clinical features and prognosis. Subsequently, the present study explored the effects of their knockdown on osteosarcoma cell malignant behaviors. A total of 52 patients with osteosarcoma underwent tumor resection were retrospectively analyzed. CCT6A and CDC20 expression levels in tumor and nontumor tissues were detected by reverse transcription-quantitative PCR and immunohistochemistry. In addition, CCT6A and CDC20 small interfering RNA molecules were transfected into osteosarcoma cell lines. The results revealed that the mRNA (P<0.001) and protein (P<0.001) expression levels of CCT6A were elevated in tumor tissues compared with those in nontumor tissues. Tumor CCT6A mRNA expression was correlated with elevated CDC20 mRNA expression (P<0.001), higher Enneking stage (P=0.039), abnormal lactate dehydrogenase (LDH) level (>300 U/l) (P=0.048), lower pathological response (P=0.024) and worse disease-free survival (DFS) (P=0.015). Tumor CCT6A protein expression was also associated with increased CDC20 protein (P<0.001), elevated Enneking stage (P=0.005), abnormal LDH (P=0.019), decreased pathological response (P=0.014), shorter DFS (P=0.030) and overall survival (OS) (P=0.027). After adjustment by multivariate Cox analyses, tumor CCT6A mRNA expression was shown to independently predict lower pathological response (P=0.033) and poor DFS (P=0.028), but not OS. Regarding CDC20, it was associated with a higher Enneking stage and lower pathological response (both P<0.05), whereas it failed to estimate DFS or OS. In vitro experiments demonstrated that CCT6A and CDC20 knockdown inhibited proliferation and invasion, and enhanced apoptosis in U-2 OS and Saos-2 cells (all P<0.05). In conclusion, CCT6A is associated with CDC20, Enneking stage and prognosis of osteosarcoma, and its knockdown decreases the viability and invasion of osteosarcoma cells.

Association Between Pretreatment Skeletal Muscle and Outcomes After CAR T-Cell Therapy.

The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. The median age of the cohort was 63.1 years (range, 18.5-82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05-2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P<.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11-2.57) and worse survival (HR, 2.44; 95% CI, 1.49-4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P<.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97-9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81-19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.

Role of Initial and Follow-up LDH Titer in COVID-19 Pneumonia: A Single Center Experience of 2000 Cases in Tertiary Care Setting in India

Introduction: Robust data of LDH (Lactate dehydrogenase) is available in bacterial infection, and it can be utilized in this COVID-19 Pneumonia pandemic for initial assessment, planning of treatment in indoor setting in association with HRCT severity. Methods: Prospective, observational, 12 weeks follow up study, included 2000 COVID-19cases confirmed with RT PCR. All cases were assessed with lung involvement documented and categorized on HRCT thorax, oxygen saturation, LDH at entry point and follow up. Age, gender, comorbidity and BIPAP/NIV use and outcome as with or without lung fibrosis as per CT severity. Statistical analysis is done by Chi square test. Results: HRCT severity score at entry point has significant correlation with LDH titer [p&lt;0.00001] LDH titer has significant association with duration of illness (Doi) [p&lt;0.00001] Comorbidities has significant association with LDH titer. [p&lt;0.00001] LDH titer has significant association with oxygen saturation [p&lt;0.00001] BIPAP/NIV requirement during hospitalization has significant association with LDH titer. [p&lt;0.00001] Timing of BIPAP/NIV requirement has significant association with LDH titer. [p&lt;0.00001] Follow-up LDH titer during hospitalization as compared to entry point (initial) normal and abnormal LDH has significant association in post-covid lung fibrosis [p&lt;0.00001] Conclusion: LDH is easily available, and universally acceptable inflammatory marker in COVID-19 pandemic and documented very crucial role in covid-19 pneumonia in predicting severity of illness, assessing response to treatment and analyzing outcome during hospitalization. J MEDICINE 2023; 24: 10-17

Influence of diabetes mellitus on the biochemical parameters and outcomes of multiple myeloma

ABSTRACTObjective:The incidence of MM in most registries remains stable or showing only a slightly increase. However, prevalence of MM is increasing due to the increase in overall survival in the last two decades. The aim of this study was to observe changes in biochemical parameters during the diagnosis and treatment of MM.Methods:A retrospective analysis was made of the biochemical indicators, survival time, and related adverse events of 196 patients with MM.Results:Of the 196 patients with MM, 26 were diagnosed with DM (DM-MM group) at the first diagnosis, 31 with steroid-induced diabetes mellitus (SID-MM group) during treatment, and 139 without DM (MM group). There was no significant difference between the three groups in the mean age of onset, sex ratio, incidence of hypercalcemia, renal dysfunction, anemia, abnormal lactate dehydrogenase, and median value of D-dimer and fibrinogen during diagnosis and treatment. There was no significant difference in survival time between the SID-MM and MM groups, but there was a significant difference between the DM-MM and MM groups.Conclusion:There was no significant difference between the three groups in the incidence of hypercalcemia, anemia, and renal function impairment. The survival time of patients with DM was shorter than that of patients without DM.

A Study on Serum Lactate Dehydrogenase and Uric Acid in Preeclampsia and Eclampsia: Can they Predict Adverse Fetomaternal Outcome?

Hypertensive disorders of pregnancy affect 3%-5% of all pregnancies, contributing immensely to maternal morbidity and mortality. According to the WHO, the incidence of deaths due to preeclampsia and eclampsia in developing and developed countries is 2.8% and 0.4%, respectively. Lactate dehydrogenase (LDH) and uric acid are good predictors of disease severity. This study aims to determine the fetomaternal outcome in relation to abnormal serum levels of LDH and uric acid. A cross-sectional study was carried out in 1200 patients with preeclampsia and eclampsia at a tertiary care center over 2 years. Patients were divided into - Group A: patients with normal LDH (≤300 IU/L) and uric acid (<6 mg/dl) (n = 300). Group B: patients with abnormal LDH and uric acid (n = 900), who were further divided into mild and severe preeclampsia and eclampsia. Abnormal serum values were stratified into groups for easier comparison. The results were compared in terms of maternal and perinatal outcomes. The incidence of preeclampsia and eclampsia in our study is 3.14% and 1.57%, respectively. Significant changes in LDH and uric acid were associated with increased severity of the disease (LDH - 1116.94 ± 4.78; uric acid - 9.2 ± 2.89). Higher incidence of maternal and fetal complications was seen with severe preeclampsia and eclampsia with LDH >800 IU/L and uric acid >6 mg/dl. Standard antenatal follow-up should be carried out for early detection and prevention of preeclampsia, with strict monitoring of serum uric acid level and LDH. This may reduce the maternal and fetal complications due to preeclampsia.

Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation

Kaixin San (KXS) is one of the most famous traditional Chinese formulas prescribed by Sun Simiao in 652 Christian era. It is composed of Panax ginseng C.A.Mey, Polygala tenuifolia, Poria cocos and Acorus calamus var. angustatus Besser. KXS is widely used for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. However, whether KXS benefits hippocampal neurons and myocardial cells of mice impaired by paradoxical sleep deprivation (PSD) and its mechanism remains unclear. This study was aimed to investigate the effect of KXS on hippocampal neuron and cardiac ferroptosis in rapid-eye-movement (REM) sleep deprived mice and clarify its potential mechanism. PSD was induced by a modified multi-platform method. Morris water maze (MWM) was used to detect the ability of learning and memory. Cardiac morphological changes were assessed by hematoxylin and eosin (HE) staining. Heart rate was detected by a PowerLab multichannel physiological recorder. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of ferrotosis in hippocampus tissue and heart tissue of PSD mice. KXS administration improved the impaired learning and memory of PSD mice. It prevented the damage of mitochondria in the hippocampus and heart of PSD mice. KXS also alleviated the myocardial injury, such as morphological damage, abnormal heart rate, serum ANP, and serum LDH induced by PSD. Further study disclosed that KXS reversed the expressions of proteins involved in ferroptosis such as TFRC, SLC7A11/xCT, GPX-4, ACSL4, and FTH1 in hippocampus and heart tissues. KXS improved learning and memory of mice with REM sleep deprivation, which was closely associated with suppressed ferroptosis in hippocampal neurons and myocardiocytes.

Peripheral blood smear diagnosis of G6PD deficiency in an 83-year-old man.

An 83-year-old male was admitted to the emergency department for abrupt onset of jaundice and asthenia. Vital signs were in range, and physical examination was unremarkable except for jaundice and hyperchromic urine. Full blood count on admission showed his hemoglobin concentration to be 81 g/L with no alteration in white blood cell (WBC) or platelets count. Biochemical tests were significant for high bilirubin level 417.07 μmol/L (indirect bilirubin 369.53 μmol/L) and abnormal lactate dehydrogenase level 1520 μmol/L. The hypothesis of hemolytic anemia was confirmed by further laboratory tests, which showed undetectable haptoglobin and increased reticulocyte count 196 × 109/L. Direct and indirect Coombs tests were both negative, suggesting a Coombs-negative hemolytic anemia. A first blood smear did not show schistocytes and the coagulation profile was in order. Medical history was negative for oxidant drugs assumption, prosthetic heart valves, and liver and kidney diseases. Chest radiography was normal, and a complete abdominal echography did not show hepatomegaly or splenomegaly. Meanwhile, the patient clinical course was complicated by pain and tightness in the chest and dizziness and an electrocardiogram was compatible with a non-ST-segment elevation myocardial infarction. A new set of lab tests showed severe anemia with 66 g/L of hemoglobin, and the patient undergone blood transfusion. In the suspicion of a hemolytic crisis in the context of glucose-6-phosphate dehydrogenase (G6PD) deficiency, an accurate anamnesis was collected and the patient confirmed the assumption of fava beans 3 days earlier after a long time. G6PD levels could not be assessed overnight, but a second blood smear was significant for bite, blister, and ghost cells (Figure 1 A and B), which are findings compatible with G6PD deficiency. Testing for G6PD was performed as soon as available and it revealed a significant G6PD deficiency (2.7 U/g Hb, normal range 8–14 U/g Hb, overestimated because of low Hb concentration). This is a case of G6PD deficiency diagnosed in 83-yer-old patient with no previous similar event in an unfavorable setting (emergency department by night). It highlights the necessity of high clinical suspicion of G6PD deficiency in the context of Coombs-negative hemolytic anemia, even in elderly patients. It is worth noting that different species of fava beans have a different capacity in inducing oxidative stress. Lastly, blood smear can still provide useful morphological data in supporting the diagnosis, regardless the immediate availability of G6PD test. Fabio Giglio conceived the study; D. Sannipoli, D. T. Clerici, and Fabio Giglio provided all clinical and hematological data; A. Boletini and P. Ronchi performed and analyzed morphology; D. Sannipoli and Fabio Giglio wrote the paper. All authors approved the paper. The authors declare no conflict of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Nanohydroxyapatite Stimulates PD-L1 Expression to Boost Melanoma Combination Immunotherapy.

Although checkpoint-inhibitor immunotherapy held tremendous advances, improving immune response during treatment has always been an urgent clinical issue. With the help of mRNA microarray technology, it was found that short rod-like nanohydroxyapatite (nHA) promoted the upregulation of CD274 and PD-L1 related gene transcription, which was confirmed by the significantly enhanced PD-L1 expression level in B16, B16F10, and 4T1 cells in vitro. Hence, an injectable in situ responsive hydrogel reservoir embed with nHA and PD-1/PD-L1 inhibitor was engineered for a combination immunotherapy by peritumoral administration. The results confirmed that the combinational strategy effectively suppressed tumorigenesis and tumor growth, recovered the abnormal lactate dehydrogenase, aspartate transaminase, and alanine aminotransferase indicators, and significantly elongated the life span of a tumor-bearing mouse. The substantive progress mainly derived from nHA-induced T cell infiltration reinforcement in a tumor site and CD8+ T cell polarization in spleen, implying that nHA might function as an immunomodulator for melanoma immunotherapy.

Prognostic Factors in Patients with Advanced HER2-Positive Gastric Cancer Treated with Trastuzumab-Based Chemotherapy: a Cohort Study.

Prognostic factors for the survival of patients with advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy remain controversial. The aim of this study was to identify the clinical factors that predict prognosis in patients with advanced HER2-positive gastric cancer. We retrospectively reviewed the medical records of HER2-positive gastric cancer patients treated with trastuzumab-based chemotherapy at our institution. Clinical features and laboratory test results that considered prognostic factors were re-examined. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate analysis was performed with the log-rank test and multivariate analysis was performed using Cox's proportional hazard regression model. A total of 133 patients with advanced HER2-positive gastric cancer were enrolled. The median OS in this cohort was 18.7months. Four prognostic factors: visceral metastasis (lung or liver), levels of hemoglobin (Hb) (< 11.6g/dl), lactate dehydrogenase (LDH) (> 222mg/dl), and C-reactive protein (CRP) (> 0.14mg/dl), were identified as independent prognostic factors. The patients were placed into three groups according to their number of prognostic factors. These included low (0, 1), moderate (2, 3), and high (4) risk factors. The OS was separated into three categories with a median OS of 32.0, 18.7, and 10.1months, respectively. Compared to the low-risk group, hazard ratios for the moderate- and high-risk groups were 1.75 and 3.49, respectively. Visceral metastasis and abnormal Hb, LDH, and CRP levels were associated with unfavorable OS. These findings may be beneficial for the management of advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy.

Utility of Routine Serum LDH After HeartMate 3 Left Ventricular Assist Device Implantation

<h3>Purpose</h3> This study aims to evaluate the fluctuation of serum Lactate Dehydrogenase (LDH) in patients who are post-HeartMate 3 (HM3) Left Ventricular Assist Device (LVAD) implantation and to determine if routine monitoring of serum LDH values has changed management of patients, outcomes, or detected any pump thrombosis events. <h3>Methods</h3> This is a retrospective cohort study reviewing the electronic medical records of forty-eight HM3 LVAD patients at a tertiary care center in New Jersey, USA with implant dates ranging from 2017 to 2021. For each of these patients, serum LDH values were obtained including baseline values pre-implantation as well as fixed points in time post-operatively, specifically one week, one month, three months, six months, one year, one and a half years, and two years post-implantation as applicable for each patient. Each abnormal LDH value underwent further chart analysis to see if there was any change in clinical status, outcomes, management, or pump thrombosis event. An abnormal serum LDH value was defined as greater than 2.5 times the upper limit of normal, which has been standard practice to evaluate for pump thrombosis and/or hemolysis. <h3>Results</h3> Chart review of forty-eight HM3 LVAD patients showed that routine monitoring of serum LDH values did not change clinical outcomes or management of patients. Forty-six out of forty-eight patients did not have any recorded serum LDH value greater than 2.5 times the upper limit of normal post-implantation. The two patients with elevated serum LDH values post-operatively were never stable enough to be discharged from the hospital and expired shortly after implantation. There was also a 0% rate of pump thrombosis. <h3>Conclusion</h3> Routine monitoring of serum LDH in patients who are post-HM3 LVAD implantation does not change management or outcomes in asymptomatic patients. Therefore, ending routine monitoring of serum LDH eliminates unnecessary blood draws for patients and could represent a savings in healthcare costs as well as resources.

Evaluation of Liver Enzyme Levels in Patients with SARS-CoV-2 Infection

Background: Although coronavirus disease 2019 (COVID-19) is a respiratory disease, it seems that liver abnormalities are also prevalent in the patients. Objectives: The present study aimed to evaluate liver enzymes in COVID-19 patients. Methods: This descriptive, cross-sectional study was conducted on 111 COVID-19 patients admitted to Imam Reza Hospital in Kermanshah during September-November 2020. The required data were extracted from the hospital files, and data analysis was performed in the Excel software and SPSS version 21. Results: The mean age of the patients was 60.87 ± 15.85 years. 50.5% of patients were female. Among the patients, 38.7% had hypertension, 19.8% had diabetes, and 7.2% had cardiovascular diseases. Moreover, 34.2% of the patients had abnormal aspartate aminotransferase (AST), 17.1% had abnormal alanine aminotransferase (ALT), and 100% had abnormal lactate dehydrogenase (LDH). Conclusions: According to the results, hypertension, diabetes, and cardiovascular diseases were the most common comorbidities among the COVID-19 patients. AST, ALT, and LDH are important indicators of hepatic disorders, which were abnormal in these patients as well. Moreover, the patients aged less than 60 years, male patients, and those with renal disorders had a higher mean ALT.

Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients.

The lack of a randomized trial comparing carfilzomib (K) versus elotuzumab (Elo) associated with lenalidomide and dexamethasone (Rd) prompted us to assess the relative usefulness of one triplet over the other. Five independent retrospective cohorts of 883 relapsed/refractory multiple myeloma (RRMM) patients, including 300 EloRd and 583KRd cases, outside clinical trials, entered this non-randomized comparison. KRd cohort accounted for a higher incidence of younger patients, cases with ≥3lines of therapy, already exposed to lenalidomide, International Staging System (ISS) stage III, and abnormal lactic dehydrogenase (LDH) level compared with EloRd cohort. Moreover, cytogenetic risk categories, detected in roughly one-third of cases, were equally distributed between the two therapy arms. The probability of CR+VGPR response was significantly higher in KRd (n=314, 53.9%) than in EloRd patients (n=111, 37.0%). Likewise, the cumulative incidence function of CR+VGPR, taking into account the competitive risk of death, was significantly higher in KRd arm patients than those in the EloRd arm (p=.003). Moreover, KRd treatment significantly reduced the progression or death risk by 46% in an adjusted multivariate analysis (HR: 0.54, 95% CI 0.42-0.69, p<.0001). Finally, in an adjusted illness-progression/death model, the effect of KRd versus EloRd was of higher magnitude among those who achieved CR+VGPR (-39% hazard ratio reduction, p=.02) than among those who achieved<VGPR (-29% hazard ratio reduction, p=.007). With limitations characteristic to any retrospective analysis, this current clinical practice study's overall results demonstrated potential benefits of KRd therapy compared with EloRd. This observation may help the daily clinical practice.

Interim FDG 18-PET Δsuvmax Adds Prognostic Value to Deauville 5-Point Scale in the Identification of Patients with Very High-Risk Diffuse Large B Cell Lymphoma

IntroductionInterim response evaluation by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (iPET) in diffuse large B cell lymphoma (DLBCL) is encouraged to rule out disease progression and has been suggested to be predictive of survival. However, treatment guidance by iPET is not yet recommended for DLBCL in clinical practice.The aim of our study was to assess the predictive value of iPET in progression free survival (PFS) and overall survival (OS) in DLBCL patients (pts), interpreted according to visual and semiquantitative methods.MethodsSingle centre retrospective analysis of pts diagnosed with DLBCL from 2010 to 2019, uniformly treated with R-CHOP/R-CHOP-like protocols (6-8 cycles) and submitted to iPET assessment after 3-4 cycles of treatment, with no therapy change based on the latter. The iPET findings were interpreted using the visual Deauville 5-point scale (DS) and quantitative comparison of maximum standardized uptake value (SUVmax) before and during treatment. The percentage decrease in SUVmax between baseline PET (PET0) and iPET (ΔSUVmax) was calculated as follows: ΔSUVmax = (PET0 SUVmax-iPET SUVmax)/PET0 SUVmax × 100%. iPET with DS of 1-3 and ΔSUVmax ≥66% was defined as negative. Agreement between the 2 methods, DS and ΔSUVmax, was assessed by Cohen´s k computation. Cox regression model was used to estimate PFS and OS. Risk factors with p<0.1 in the univariate analysis were included in the multivariate model.ResultsA total of 335 pts were diagnosed with DLBCL. Forty-one percent (n=138) underwent iPET and SUVmax was available for 86 pts. Of these, 55.8% were male, with median age of 60 years old (24-84). At diagnosis, 72.1% presented with advanced stage disease, 55.8% with abnormal lactate dehydrogenase (LDH) and 49.4% with B symptoms. Bone marrow involvement and extranodal disease was present in 12% and 76.7%, respectively. According to International Prognostic Index (IPI) score, 44.7% of pts were intermediate-high/ high-risk.At interim evaluation, 26.7% (n=23) had an iPET positive by DS, while 17.4% (n=15) had a ΔSUVmax <66%. Nine patients (10.5%) had an iPET positive by DS and ΔSUVmax <66%. A fair agreement between DS and ΔSUVmax was observed (k=0.333).Primary refractoriness (PrR) and/or disease progression, defined according to Lugano criteria, was seen in 22.1% of the pts. iPET positivity, measured either by DS (OR 6.45 [95%CI: 1.68-24.82], p=0.007) or ΔSUVmax (OR 5.42, [95%CI: 1.39-21.12], p=0.015), showed predictive value of PrR, improved by combining the DS and the ΔSUVmax in iPET interpretation (OR 2.36 [95%CI: 1.35-4.13], p=0.003) (Figure 1).For a median follow-up of 50.1 months, median PFS was not reached (NR) and was higher in iPET negative pts, regardless of the interpretation by DS (84.3% versus 49.0% at 5 years; HR 4.27, p<0.001) or ΔSUVmax ≥66% (91.5% versus 60.4% at 5 years; HR 3.63, p=0.003). The impact of iPET negativity when assessed by DS became not significant after multivariate analysis (HR 2.86, p=0.07), however remained predictive of PFS when interpreted by ΔSUVmax ≥66% (HR 3.53, p=0.02).Median OS was NR and was higher in the iPET negative group, when assessed by DS (89.3% versus 62.2% at 5 years, HR 3.49, p=0.01). By contrast, ΔSUVmax ≥66% did not prove to be predictive of OS (85.8% versus 65.7% at 5 years, HR 2.63, p=0.06). The impact of iPET negativity on OS was not significant upon multivariate analysis, regardless scan measurement by DS or ΔSUVmax ≥66% (HR 4.01, p=0.07 for DS, and HR 1.06, p=0.94, for ΔSUVmax ≥66%).Interestingly, combined visual and semiquantitative analysis allowed to identify a very high-risk subgroup of patients in our cohort, with significantly inferior PFS and OS (PFS: HR 9.60, p<0.001, 81.3% vs 22.2% at 5 years; OS: HR 5.20, p<0.001, 86.7% vs 44.4% at 5 years) (Figure 2).ConclusionOur results showed that, in our cohort, ΔSUVmax semiquantitative method in iPET interpretation has an independent predictive value of PFS, but not of OS. iPET sub-analysis with combined DS and ΔSUVmax allowed to identify a very high-risk group of DLBCL pts with markedly inferior PFS and OS. In addition, both DS and ΔSUVmax are good predictors of primary refractoriness, particularly when both visual and semiquantitative methods are combined. [Display omitted] DisclosuresGomes: Takeda: Consultancy; Gilead: Consultancy; Janssen: Consultancy.

Cardioprotective Effect of Stem-Leaf Saponins From Panax notoginseng on Mice With Sleep Derivation by Inhibiting Abnormal Autophagy Through PI3K/Akt/mTOR Pathway.

Sleep deprivation (SD) may lead to serious myocardial injury in cardiovascular diseases. Saponins extracted from the roots of Panax notoginseng, a traditional Chinese medicine beneficial to blood circulation and hemostasis, are the main bioactive components exerting cardiovascular protection in the treatment of heart disorders, such as arrhythmia, ischemia and reperfusion injury, and cardiac hypertrophy. This study aimed to explore the protective effect of stem-leaf saponins from Panax notoginseng (SLSP) on myocardial injury in SD mice. SD was induced by a modified multi-platform method. Cardiac morphological changes were assessed by hematoxylin and eosin (H&E) staining. Heart rate and ejection fraction were detected by specific instruments. Serum levels of atrial natriuretic peptide (ANP) and lactate dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of autophagy and apoptosis in heart tissue of SD mice. In vitro, rat H9c2 cells pretreated with rapamycin and the effect of SLSP were explored by acridine orange staining, transient transfection, flow cytometry, and Western blotting analysis. SLSP prevented myocardial injury, such as morphological damage, accumulation of autophagosomes in heart tissue, abnormal high heart rate, serum ANP, and serum LDH induced by SD. In addition, it reversed the expressions of proteins involved in the autophagy and apoptosis and activated PI3K/Akt/mTOR signaling pathway that is disturbed by SD. On H9c2 cells induced by rapamycin, SLSP could markedly resume the abnormal autophagy and apoptosis. Collectively, SLSP attenuated excessive autophagy and apoptosis in myocardial cells in heart tissue induced by SD, which might be acted through activating PI3K/Akt/mTOR signaling pathway.

Type of tissue biopsy and outcomes in diffuse large B-cell lymphoma (DLBCL).

e13569 Background: Progress in understanding the molecular biology of DLBCL has led to development of complex molecular classifications that rely on sequencing methods. These molecular clusters are defined by activation of distinct pathways and may aid in selecting targeted therapy. In the molecular era, tissue requirements in clinical trials have increased to ensure sufficient tissue for molecular testing, potentially resulting in bias for enrollment of patients with larger excisional biopsies (EB). We examined the impact of tissue biopsy method on outcomes of DLBCL in a prospective observational study. Methods: Consecutive adult patients with DLBCL within 9 months from their initial diagnosis were enrolled into the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). Demographics, clinical variables, type of tissue biopsy (EB vs. core needle biopsy (CNB)) for initial diagnosis and initial treatment were recorded at baseline. Pts were contacted every 6 months from the date of diagnosis for first 3 years and then annually thereafter. Study objectives were event free survival (EFS) and overall survival (OS) by tissue biopsy method. Results: A total of 1061 patients with newly diagnosed DLBCL, from 2002 to 2015, were included. The table lists baseline characteristics of the cohort. 593 (56%) pts underwent EB and 468 (44%) underwent CNB for initial diagnosis. A significantly higher proportion of patients receiving CNB had performance status &gt;=2, advanced stage, high risk disease by international prognostic index (IPI), abnormal lactate dehydrogenase. Median time from diagnosis to treatment initiation (DTI) was significantly shorter in the CNB group (13 days) than EB group (19 days). 2-year EFS (60% vs 75%, HR 0.75 (0.6-0.9), p &lt;0.01) was significantly lower in CNB than EB group. There was a trend towards lower OS (75% vs 80%, HR: 0.8 (0.6-0.95), p =0.049) in CNB than EB group. Conclusions: Patients undergoing CNB are more likely to have higher risk disease, shorter DTI and survival compared to those undergoing EB. A need for large amount of diagnostic tissue in biomarker driven clinical trials may result in disproportional exclusion of high risk DLBCL pts who have inferior outcomes after standard treatment and could potentially benefit from novel agents, resulting in overperformance of the control arm. The need for tissue must be carefully balanced against resulting selection bias.[Table: see text]

Association of DNA repair gene XPC Ala499Val (rs2228000 C>T) and Lys939Gln (rs2228001 A>C) polymorphisms with the risk of chronic myeloid leukemia: A case-control study in a South Indian population.

Xeroderma pigmentosum complementation group C (XPC), a DNA repair protein, plays an important role in the maintenance of genomic integrity and is essential for the nucleotide excision repair pathway. Polymorphisms in the XPC gene may alter DNA repair leading to genetic instability and oncogenesis. The present study aimed to assess the relationship between the XPC Ala499Val (rs2228000 C>T) and Lys939Gln (rs2228001 A>C) non-synonymous polymorphisms and susceptibility to chronic myeloid leukemia (CML) pathogenesis, disease progression and the response to targeted therapeutic regimen, imatinib mesylate. This case-control study included 212 cases and 212 controls, and the genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism assays. Our results showed significant association of variant CT (odds ratio = 1.92, 95% confidence interval = 1.21-3.06, p =0.003) and TT (odds ratio = 2.84, 95% confidence interval = 1.22-6.71, p =0.007) genotypes in patients with the XPC Ala499Val polymorphism and CML risk. In addition, these genotypes were associated with CML progression to advanced phases (p =0.006), splenomegaly (p =0.017) and abnormal lactate dehydrogenase levels (p =0.03). XPC Lys939Gln was found to correlate with a poor response to therapy, showing borderline significant association with minor cytogenetic response (p =0.08) and a poor molecular response (p =0.06). Significant association of the Ala499Val and Lys939Gln polymorphisms with prognosis was observed (Hasford high risk, p = 0.031 and p = 0.019, respectively). Haplotype analysis showed a strong correlation of variant TC haplotype with poor therapy responses (minor cytogenetic response, p = 0.019; poor molecular response, p < 0.0001). In conclusion, our results suggest that XPC Ala499Val is a high-penetrance CML susceptibility polymorphism. Both polymorphisms studied are considered as genetic markers with respect to assessing disease progression, therapy response and prognosis in CML patients.

Preoperative MRI and LDH in women undergoing intra-abdominal surgery for fibroids: Effect on surgical route.

Our institution implemented a preoperative protocol to identify high-risk cases for which power morcellation should be avoided. In this retrospective cohort study, an institutional protocol requiring preoperative Magnetic Resonance Imaging with diffusion-weighted imaging and serum Lactate Dehydrogenase levels was implemented. Chart review was performed including all women who underwent intra-abdominal surgery for symptomatic fibroids from 4/23/2013 to 4/23/2015. A total of 1,085 women were included, 479 before and 606 after implementation of the Magnetic Resonance Imaging / Lactate Dehydrogenase protocol. The pre-protocol group had more post-menopausal women (4% vs. 2%, p = 0.022) and women using tamoxifen (2% vs. 0%, p = 0.022) than those in the post-protocol group, but baseline patient characteristics were otherwise similar between groups. Incidence of malignant pathological diagnoses did not change significantly over the time period in relation to protocol implementation. The rate of open surgery for both hysterectomy and myomectomy remained the same in the year preceding and the year following initiation of the protocol (open hysterectomy rate was 19% vs. 16% in pre- and post-protocol groups, respectively, P = 0.463, and open myomectomy rate was 10% vs. 9% rates in pre- and post-protocol groups, respectively, P = 0.776). There was a significant decrease in the use of power morcellation (66% in pre- and 50% in post-protocol cohorts, p<0.001) and an increased use of containment bags (1% in pre- and 19% in post-protocol cohort). When analyzing the subset of women who had abnormal Magnetic Resonance Imaging / and Lactate Dehydrogenase results, abnormal Magnetic Resonance Imaging results alone resulted in higher rates of open approach (65% for abnormal vs. 35% for normal). Similarly, a combination of abnormal Magnetic Resonance Imaging and Lactate Dehydrogenase tests resulted in higher rates of open approach (70% for abnormal and 17% for normal). Abnormal Lactate Dehydrogenase results alone did not influence route. Rates of MIS procedures were decreased for women with abnormal preoperative Magnetic Resonance Imaging results. False positive results appear to be one of the main drivers for the use of an open surgical route.