High Lactate Dehydrogenase Levels Research Articles

Silencing LncRNA SNHG7 alleviates hypoxia/reoxygenation-induced cardiomyocyte damage by regulating the expression of miR-181b-5p

To study the effect of silencing LncRNA SNHG7 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its targeted regulation on miR-181b-5p. Rat cardiomyocytes H9c2 were cultured in vitro and randomly divided into control group, H/R group, H/R + si-NC group, H/R + si-SNHG7 group, H/R + si-SNHG7 + anti-miR-NC group and H/R + si-SNHG7 + anti-miR-181b-5p group. The content of lactate dehydrogenase (LDH), malondialedhyde (MDA) and the activity of superoxide dismutase (SOD) were detected. Flow cytometry was carried out to detect the rate of apoptosis. qRT-PCR was used to detect the expression of SNHG7 and miR-181b-5p. Dual luciferase report experiment was used to verify the targeting relationship between SNHG7 and miR-181b-5p. Western blotting was used to detect the expression of Bax and Bcl-2. Compared with the control group, the H/R group showed significantly increased SNHG7 expression in cardiomyocytes, reduced miR-181b-5p expression, higher levels of LDH and MDA, reduced activity of SOD, increased cell apoptosis rate, higher level of Bax protein, and reduced level of Bcl-2 protein (all P< 0.05). Compared with the H/R and H/R + si-NC groups, the H/R + si-SNHG7 group had significantly reduced level of LDH and MDA, increased activity of SOD, reduced apoptosis rate, reduced level of Bax protein, increased level of Bcl-2 protein (all P< 0.05). The dual luciferase report experiment confirmed that SNHG7 could target miR-181b-5p. Interference with the expression of miR-181b-5p could reduce the effect of silencing SNHG7 on H/R-induced cardiomyocyte oxidative stress and apoptosis. Silencing SNHG7 may inhibit H/R-induced cardiomyocyte oxidative stress and apoptosis by up-regulating the expression of miR-181b-5p, thereby exerting a protective effect on cardiomyocytes.

Incidence of Venous Thromboembolism and Effect of Anticoagulant Dosing in Hospitalized COVID-19 Patients.

BackgroundCoronavirus disease 2019 (COVID-19) is characterized by coagulopathy and thrombotic events. We examined factors associated with development of venous thromboembolism (VTE) in COVID-19 and to discern if higher dose of anticoagulation was beneficial in these patients.MethodsThis study involves an observational study of prospectively collected data in the setting of a large community hospital in a rural setting in Northeast Georgia with COVID-19 between March 1, 2020 and February 5, 2021. Anticoagulation dose (none, standard, intermediate, and therapeutic dosages) was studied in adult patients (≥ 18 years). We constructed multivariable logistic regression model to examine the association of clinical characteristics with VTE. To examine the effect of dose of anticoagulation in preventing VTE, we used inverse probability weighted regression adjustment.ResultsOf the 4,645 patients with COVID-19, 251 (5.4%) patients were found to have VTE. Of these, 91 had pulmonary embolism, 148 had deep venous thrombosis (DVT) and 12 had both. A total of 129 of VTE cases were diagnosed at admission. Of all admissions, 12.9% did not receive any DVT prophylaxis, 70.4% received prophylactic dose, 1.3% received intermediate dose and 15.5% received therapeutic dose. Male gender (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.0 - 2.4, P = 0.04) and Black race (OR: 2.0, 95% CI: 1.2 - 3.4, P = 0.01), along with higher levels of lactate dehydrogenase (LDH) and D-dimer were associated with higher odds of developing VTE. Patients receiving steroids had lower rates of VTE (3.9% vs. 8.3%, P < 0.001). Use of intermediate or therapeutic anticoagulation was not associated with lower odds of developing VTE. However, patients on therapeutic anticoagulation had lower odds of in hospital mortality when compared to standard dose (OR: 0.47, 95% CI: 0.27 - 0.80, P = 0.006).ConclusionsIn COVID-19, D-dimer and LDH can be useful in predicting VTE. Steroids appear to have some protective role in development of VTE. Therapeutic anticoagulation did not result in lower rates of VTE but was associated with in-hospital mortality.

Prognostic Factors and Predictors of In-Hospital Mortality Among COVID-19 Patients Admitted to the Intensive Care Unit: An Aid for Triage, Counseling, and Resource Allocation.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains today a global health pandemic. Those with severe infection are at risk of rapid clinical deterioration; as a result, intensive care unit (ICU) admission is not uncommon in such patients. A number of determinants have been identified as predictors of poor prognosis and in-hospital mortality, ranging from demographic characteristics, laboratory and/or radiological findings.Aim: To identify determinants of in-hospital mortality and examine the accuracy of seven early warning scores in predicting in-hospital mortality.Methods: This is a retrospective study conducted in Kuwait from July 2020 to March 2021, and participants were adult patients with a positive test on the real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 and who met the criteria for ICU admission. Data collected included: demographics, clinical status on hospital arrival, laboratory test results, and ICU course. Furthermore, we calculated seven early warning scores for each of our patients.Results: A total of 133 patients were admitted to our COVID-19 ICU with a median age of 59 years. Arrival to ICU on mechanical ventilation (MV), developing in-hospital complications, having chronic kidney disease (CKD), having a high white blood count (WBC), lactate dehydrogenase (LDH), lactate, or urea levels were found to be significant predictors of in-hospital mortality. Furthermore, the 4C mortality score for COVID-19, VACO index for COVID-19 mortality, and the PRIEST COVID-19 clinical severity score proved to be the most superior in predicting in-hospital mortality.Conclusion: Identifying high-risk patients and those with a poor prognosis allows for efficient triaging and the delivery of high-standard care while minimizing the strain on the healthcare system.

Serum lactate dehydrogenase level as a possible predictor of treatment preference in psoriasis

BackgroundThe efficacy of small molecule inhibitors for intracellular signal mediators varies among the individuals, and their mechanism of action is broad. A phosphodiesterase 4 inhibitor apremilast shows a dramatic effect on a certain proportion of psoriatic patients by modulating the cellular metabolism and regulating the production of pro-inflammatory molecules. However, it is unclear to which disease subtype this drug benefits. While psoriasis is a Th17-mediated disease, how immune cells are affected by the modulation of cellular metabolism is not fully evaluated, either. ObjectiveThis study aims to identify the indices which predict the efficacy of apremilast in psoriasis, and to investigate the impact of metabolic activity in immune cells on the psoriatic pathogenesis. MethodsThe association of treatment efficacy with clinical and laboratory data of the 58 psoriatic patients was evaluated. The reflector of the associated index was also sought among the indices of cellular metabolic pathways by use of an extracellular flux analyzer. ResultsThere was a correlation between clinical improvement and the serum lactate dehydrogenase (LDH) level in the patients treated with apremilast but not in those with biologics. Serum LDH level did not correlate with the cutaneous disease severity but correlated with the oxygen consumption rate of blood T cells. ConclusionPsoriatic patients with high serum LDH level can be benefitted by apremilast. The serum LDH level reflects the augmented respiratory activity of T cells in psoriasis. Our results would highlight the importance of regarding metabolic skew in immune cells as a treatment target in psoriasis.

Lactate Dehydrogenase Is a Serum Prognostic Factor in Clinically Regional Lymph Node-positive Prostate Cancer.

Currently, there is no established prognostic serum parameter except PSA in clinically regional lymph node-positive prostate cancer. The aim of this study was to identify serum prognostic factors in clinically regional lymph node-positive prostate cancer. Patients diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017 were included. The prognostic value of serum parameters for progression-free survival (PFS) and overall survival (OS) was investigated. Univariate and multivariate analyses showed a statistically significant increased hazard risk for PFS and OS for men with lactate dehydrogenase (LDH) ≥230 IU/l at diagnosis. PFS at 5 years for patients with high and low LDH levels were 69.9% (95% CI=56.8-79.8%) and 18.9% (95% CI=1.23-53.2%), respectively (p=0.003). OS at 5 years for low and high LDH levels were 89.2% (95% CI=78.6-94.7%) and 46.3 (95% CI=11.2-76.2%), respectively (p=0.006). This study shows that LDH is an independent predictor of PFS and OS in patients with regional lymph node metastatic prostate cancer.

Clinical significance of prognostic nutrition index in hospitalized patients with COVID-19: Results from single-center experience with systematic review and meta-analysis.

BackgroundWe aimed to ascertain risk indicators of in‐hospital mortality and severity as well as to provide a comprehensive systematic review and meta‐analysis to investigate the prognostic significance of the prognostic nutrition index (PNI) as a predictor of adverse outcomes in hospitalized coronavirus disease 2019 (COVID‐19) patients.MethodsIn this cross‐sectional study, we studied patients with COVID‐19 who were referred to our hospital from February 16 to November 1, 2020. Patients with either a real‐time reverse‐transcriptase polymerase chain reaction test that was positive for COVID‐19 or high clinical suspicion based on the World Health Organization (WHO) interim guidance were enrolled. A parallel systematic review/meta‐analysis (in PubMed, Embase, and Web of Science) was performed.ResultsA total of 504 hospitalized COVID‐19 patients were included in this study, among which 101 (20.04%) patients died during hospitalization, and 372 (73.81%) patients were categorized as severe cases. At a multivariable level, lower PNI, higher lactate dehydrogenase (LDH), and higher D‐dimer levels were independent risk indicators of in‐hospital mortality. Additionally, patients with a history of diabetes, lower PNI, and higher LDH levels had a higher tendency to develop severe disease. The meta‐analysis indicated the PNI as an independent predictor of in‐hospital mortality (odds ratio [OR] = 0.80; P < .001) and disease severity (OR = 0.78; P = .009).ConclusionOur results emphasized the predictive value of the PNI in the prognosis of patients with COVID‐19, necessitating the implementation of a risk stratification index based on PNI values in hospitalized patients with COVID‐19.

Serum lactate dehydrogenase is a predictive biomarker in patients with oropharyngeal cancer undergoing radiotherapy: Retrospective study on predictive factors.

BackgroundThe present study aimed to evaluate the prognostic factors in human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal cancer (OPC) treated with definitive radiotherapy.MethodsWe retrospectively evaluated 101 patients with OPC who underwent definitive radiotherapy between 2008 and 2018.ResultsThe median follow‐up period of the surviving patients was 68 months (range, 8–164 months). The 5‐year overall survival rate was 69.8%. Univariate analyses revealed that poor survival was associated with male sex, smoking ≥30 pack‐years, Eastern Cooperative Oncology Group performance status ≥1, tumor‐node‐metastasis (TNM) stage III‐IV (8th edition), HPV‐negativity, serum lactate dehydrogenase (LDH) ≥202, C‐reactive protein/albumin ratio ≥0.15, and lymphocyte‐to‐monocyte ratio <2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack‐years (p < 0.01) and LDH ≥202 (p = 0.02).ConclusionsThe present study suggested that high LDH levels predicted poor survival after definitive radiotherapy for patients with both HPV‐positive and HPV‐negative OPC.

Analysis of characteristics and predictive factors of immune checkpoint inhibitor-related adverse events.

Objective:We aimed to retrospectively analyze the toxicity profiles and predictors of immune-related adverse events (irAEs) as well as the correlation between irAEs and the clinical efficacy of multi-type immune checkpoint inhibitors (ICIs) in patients with advanced pan-cancer in a real-world setting.Methods:We retrospectively analyzed data from 105 patients with advanced pan-cancer treated with multi-type ICIs at the First Hospital of Jilin University between January 1, 2016 and August 1, 2020. We used logistic regression analyses to investigate the associations of irAEs with clinical baseline characteristics, blood count parameters, and biochemical indicators during treatment. Receiver operating characteristic curves were used to determine cutoff values for parameters and area under the curve values. Kaplan–Meier and Cox multivariate regression analyses were performed to estimate the relationships of baseline characteristics and irAEs with progression-free survival (PFS) and overall survival (OS).Results:A lower relative lymphocyte count (cutoff = 28.5%), higher albumin level (cutoff = 39.05 g/L), and higher absolute eosinophil count (AEC) (cutoff = 0.175 × 109/L) were significantly associated with the occurrence of irAEs, among which a higher AEC (cutoff = 0.205 × 109/L) was strongly associated with skin-related irAEs [odds ratios (ORs) = 0.163, P = 0.004]. Moreover, a higher lactate dehydrogenase level (cutoff = 237.5 U/L) was an independent predictor of irAEs of grade ≥ 3 (OR = 0.083, P = 0.023). In immune cell subgroup analysis, a lower absolute count of CD8+CD28− suppressor T cells (OR = 0.806; 95% confidence interval: 0.643–1.011; P = 0.062), which are regulatory T lymphocytes, was associated with the occurrence of irAEs, although the difference was not statistically significant. Furthermore, a higher percentage of CD19+ B cells was associated with the occurrence of irAEs of grade ≥ 3 (P = 0.02) and grade ≥ 2 (P = 0.051). In addition, patients with any grade of irAE had a significantly high PFS (8.37 vs. 3.77 months, hazard ratios (HR) = 2.02, P = 0.0038) and OS (24.77 vs. 13.83 months, HR = 1.84; P = 0.024).Conclusions:This retrospective study reports clinical profile data for irAEs in unselected patients in a real-world setting and explored some parameters that may be potential predictive markers of the occurrence, type, or grade of irAEs in clinical practice. Evidence of a correlation between safety and efficacy may facilitate a complete assessment of the risk-benefit ratio for patients treated with ICIs.

A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients.

PurposeWe aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.Materials and MethodsIn this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.ResultsThe mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found six significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2), not undergoing chemotherapy, anorexia, a low lymphocyte level (< 12%), a high lactate dehydrogenase (LDH) level (≥ 300 IU/L), and a low mid-arm circumference (< 23 cm). We developed a prognostic model (score, 0–8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥ 4.0 points had a short survival of less than 3 months (p < 0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve was 0.88.ConclusionThe prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.

Multiple Extramedullary-Bone Related and/or Extramedullary Extraosseous Are Independent Poor Prognostic Factors in Patients With Newly Diagnosed Multiple Myeloma.

BackgroundExtramedullary (EM) lesions are common in multiple myeloma (MM) and are often related to the poor prognosis of MM but are scarcely understood.MethodsIn this retrospective study, the baseline characteristics of 357 newly diagnosed patients with extramedullary multiple myeloma (EMM) and their impact on the prognosis were analyzed. All patients received first-line treatment with bortezomib-based regimen.ResultsThe overall incidence rate of EM was 22.4%, and the detection rate of PET/CT was significantly higher than other imaging methods (P = 0.015). The cohorts consisted of 10 cases of extramedullary extraosseous (EME) and 70 cases of extramedullary-bone related (EMB), including 53 cases with single site involvement (one case with EME) and 27 cases with multiple sites (>1 site) involvement (nine cases with EME). EMM patients had high levels of hemoglobin (Hgb, ≥10 g/dl) and serum lactate dehydrogenase (LDH, >245u/L) and are inclined to early-stage revised international staging system (R-ISS). Compared to patients without EM, those with EMM had worse progression-free survival (PFS) (P = 0.014) and overall survival (OS) (P = 0.032). In addition, patients without EM and those with a single site of EMB had similar PFS and OS, while patients with multiple sites of EMB or EME and multiple sites of EMB with EME had poor PFS and OS. Multivariate analysis confirmed that multiple sites of EMB and/or EME were independent prognostic predictors affecting PFS and OS in newly diagnosed MM patients.ConclusionsThis study suggested that among patients treated with bortezomib-based regimens, multiple sites of EMB and/or EME are independent poor prognostic factors for newly diagnosed MM patients, while a single site of EMB does not affect the survival of newly diagnosed MM patients. Thus, these findings could be used as a reference for the study of EMM patients in the new drug era, but prospective clinical studies are needed to provide evidence-based data for the diagnosis and treatment of EMM.

Alkaline Phosphatase Serum Level at Time of Diagnosis Is a Prognostic Marker in Patients with Hodgkin Lymphoma

BackgroundHodgkin lymphoma (HL) is a potentially curable lymphoma with distinct histology, biologic behavior, and clinical characteristics. It is among the neoplastic diseases that has the best long-term outcome after treatment. Cure rates approach 80-90%; however, 15-20% of patients will be resistant to therapy or relapse after treatment. International Prognostic Score (IPS) is The most widely utilized clinical index to assign risk in HL patients. Alkaline Phosphatase (ALP) comprises a group of enzymes that catalyze the hydrolysis of phosphate esters in an alkaline environment, generating an organic radical and inorganic phosphate .ALP presents in all human tissues, but it's highest concentrations are found in the liver, bones, kidneys and placenta. Elevated ALP serum levels was shown to be a bad prognostic factor in patient with metastatic colorectal and breast cancers.AimTo study the prognostic role of ALP serum level at time of diagnosis in HL patients.Methods109 patients diagnosed with HL between January 2004 to December 2016 were retrospectively reviewed at King Abdullah University Hospital (KAUH) . Clinical and laboratory data at time of diagnosis including gender, age, presenting symptoms, ALP level, Complete Blood Count (CBC), Lactate Dehydrogenase (LDH) level, pathological subtypes, CT and PET/CT scans were studied. All IPS 7 variables including: male sex, age >45 years, stage IV disease, hemoglobin (Hb) <10.5g/dl, white blood count (WBC) ≥ 15 × 109/L, lymphocyte count < 0.6 × 109/L or <8% of total WBC, and albumin < 40g/dL were recorded at time of diagnosis. Extranodal involvement was confirmed by tissue diagnosis. All our patients received the same ABVD treatment regimen. The optimal cut-off value for ALP level was obtained using the Receiver Operating Curve (ROC) with a determination of the sensitivity and specificity . We analyzed for associations between ALP serum level and patient characteristics. Data were assessed using the Kaplan-Meier method, and the log-rank test was utilized to compare survival time between the groups.ResultsThe median age at diagnosis was 31 years (Range = 18-89 years). 55% were males and 45% were females. Patient characteristics are summarized in the table. Median ALP serum level was 250 U/L (range , 88-1234) and the optimal cutoff value of ALP serum level for predicting overall survival (OS) was 219 U/L (Sensitivity 86.4% , Specificity 46.50%; area under the curve [AUC] value: 0.668, 95% confidence interval [CI] 0.548-0.778, P= 0.019). In univariate analysis, elevated ALP level was significantly associated with poorer OS (HR=4.21, 95% CI: 1.24-14.26 , P-value=0.012). Mean survival time for patients with high ALP level was 11.68 years , compared to patients with low ALP level 10.96 years. In multivariate analysis ,there was significant association between high serum ALP level and IPS (P-value<.001), low Hb level (P-value=.002) , low Albumin level (P-value=.001) and high LDH level (.019). Involvement of more than one extra-nodal site was associated with poorer OS (HR=4.35 ,95% CI: 1.23-15.34 , P-value=0.022). There was no significant association between high ALP level and bone involvement (P-value=.072) ,liver involvement (P-value=.12) and HL subtype (P-value=.45).SummaryALP serum level may be a useful and un-expensive prognostic marker in patient with HL. The OS rate in patient with high ALP serum level at time of diagnosis is significantly lower than OS rate in patients with low serum levels. High ALP level is significantly associated with high IPS score , more than one EN site involvement , low Hb level , low albumin level and high LDH level. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of Full Inhalation of Sevoflurane and Total Intravenous Anesthesia on Hemodynamics, Serum Myocardial Enzymes, and Myocardial Markers in Elderly Patients Undergoing Hysterectomy.

Objective To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy. Methods Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia (T0), after anesthesia (T1), and after surgery (T2). Results Group A observed a longer extubation time and recovery time in PACU than group B (P < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of T1 by comparison with those of T0 (P < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR (P > 0.05), and there was no interaction effect of groups and time (P > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients (P > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all P < 0.05). Conclusion Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery.

"High Tumor Burden" in Metastatic Non-Small Cell Lung Cancer: Defining the Concept.

PurposeIdentifying patient characteristics that define a worse disease prognosis or “high tumor burden” (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice.Patients and MethodsA representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience.ResultsHTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively.ConclusionIn the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.

Diagnosis and prediction of COVID-19 severity: can biochemical tests and machine learning be used as prognostic indicators?

ObjectiveThis study aimed to implement and evaluate machine learning based-models to predict COVID-19’ diagnosis and disease severity. MethodsCOVID-19 test samples (positive or negative results) from patients who attended a single hospital were evaluated. Patients diagnosed with COVID-19 were categorised according to the severity of the disease. Data were submitted to exploratory analysis (principal component analysis, PCA) to detect outlier samples, recognise patterns, and identify important variables. Based on patients’ laboratory tests results, machine learning models were implemented to predict disease positivity and severity. Artificial neural networks (ANN), decision trees (DT), partial least squares discriminant analysis (PLS-DA), and K nearest neighbour algorithm (KNN) models were used. The four models were validated based on the accuracy (area under the ROC curve). ResultsThe first subset of data had 5,643 patient samples (5,086 negatives and 557 positives for COVID-19). The second subset included 557 COVID-19 positive patients. The ANN, DT, PLS-DA, and KNN models allowed the classification of negative and positive samples with >84% accuracy. It was also possible to classify patients with severe and non-severe disease with an accuracy >86%. The following were associated with the prediction of COVID-19 diagnosis and severity: hyperferritinaemia, hypocalcaemia, pulmonary hypoxia, hypoxemia, metabolic and respiratory acidosis, low urinary pH, and high levels of lactate dehydrogenase. ConclusionOur analysis shows that all the models could assist in the diagnosis and prediction of COVID-19 severity.

Factors affecting the mortality rate of patients with cancer hospitalized with COVID-19: a single center’s experience

The main objective is to define the mortality of patients with cancer admitted to our hospital, their clinical and demographic characteristics, investigate the risk of COVID-19 for patients with cancer, and determine factors that affect the mortality rates of patients with cancer dying of COVID-19. A total of 2401 patients were admitted to our hospital with the diagnosis of COVID-19 from March 11th, 2020, to May 31st, 2020. Ninety-two out of a total of 112 cancer patients were included in this study based on the planned inclusion/exclusion criteria. The clinical, demographic, and laboratory features and treatments provided were studied, and their effect on mortality rates was analyzed. In our study the median age of the patients was 67 years, and 55.4% were male. More than half (56.5%) of our patients had metastasis. The mortality rate was 6.2% in the overall population with COVID-19, whereas it was 23.9% in patients with cancer. The mortality rate in patients with metastasis was statistically significantly higher compared with those without metastasis (34.0% vs. 10.3% P = 0.008). The mortality rate in patients still smoking was statistically significantly higher than in non-smokers (37.5% vs. 12.5% P = 0.033). The mortality rates of patients with high average C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and D-dimer levels were statistically significantly higher than in those without, and the mortality rates of patients with lower average albumin and hemoglobin levels were statistically significantly higher than those without (P < 0.001, P = 0.006, P = 0.041, P < 0.001, P < 0.001, and P = 0.028, respectively). Having metastases concurrent with COVID-19 was a statistically significant factor predictive of prognosis. Also, high CRP, ferritin, LDH, and D-dimer, and low albumin and hemoglobin were related to increased mortality rates. The predictive and prognostic role of possible factors related to prognosis is still unknown and further large, multicenter prospective studies are needed to confirm these results.

Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma.

9507 Background: Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and OS and is standard of care for the treatment of advanced BRAF V600-mutant melanoma. Here we report a 5-year update from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450 mg QD + binimetinib 45 mg BID (COMBO450), encorafenib 300 mg QD (ENCO300), or vemurafenib 960 mg BID (VEM). An updated analysis including PFS, OS, objective response rate (ORR; by blinded independent central review), and safety was conducted after minimum follow-up of 65.2 months (mo). Data are as is; study is ongoing. Results: At data cut-off (Sep 15, 2020), there were 131 (68%), 117 (60%), and 145 (76%) deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. The median OS (95% CI) and 5-year OS rate (95% CI) with COMBO450 were 33.6 (24.4–39.2) mo and 34.7% (28.0–41.5), respectively (median follow-up: 70.4 mo). The 5-year OS rate (95% CI) in COMBO450 pts who had normal lactate dehydrogenase (LDH) levels at baseline was 45.1% (36.5–53.2). Median OS and 5-year OS rates for ENCO300 and VEM, as well as for pts with normal and high LDH levels and &gt; 3 organs involved at baseline, are shown in the table. For COMBO450, ENCO300, and VEM, the 5-year PFS rate was 22.9%, 19.3%, and 10.2%; ORR (95% CI) was 64.1% (56.8–70.8), 51.5% (44.3–58.8), and 40.8% (33.8–48.2); and the median duration of response (DOR) was 18.6, 15.5, and 12.3 mo, respectively. Safety results were consistent with the known tolerability profile of COMBO450. Additional efficacy and updated safety analyses will be presented. Following study drug discontinuation, the most common subsequent treatment in all arms was checkpoint inhibitors. Conclusions: Updated OS and DOR results with COMBO450 demonstrate continued long-term benefits in pts with BRAF V600-mutant melanoma. Clinical trial information: NCT01909453. [Table: see text]

Clinical characteristics and outcomes of adult patients with acquired thrombotic thrombocytopenic purpura: a single center retrospective study.

Thrombotic thrombocytopenic purpura (TTP) is a rare disease and a potentially life-threatening thrombotic microangiopathy. Although the diagnostic and therapeutic techniques have improved, it is still difficult for clinicians to identify early due to different initial clinical manifestations and the incidence and survival rate are reported inconsistently. This study investigated the clinical characteristics, treatment strategies, and treatment outcomes of adult patients with acquired TTP. A retrospective analysis of 55 patients (35 females and 20 males) treated for acquired TTP from January 1, 2013 to December 31, 2017 was conducted. The analysis included clinical manifestations at onset, treatment efficacy measures, survival, cause of death, and the APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (sequential organ failure assessment) scores. At onset, in addition to thrombocytopenia and hemolysis, 50 patients (90.91%) presented with neurological abnormalities, but only 19 (34.55%) showed the classic TTP pentad of symptoms. The overall mortality rate was 34.55%. Plasma exchange (PEX) was performed in 49 patients. The most effective treatment was PEX with a normal dose of corticosteroid and rituximab which showed a response rate of 81.25%. The main cause of death was cerebral hemorrhage. The APACHE II and SOFA scores were higher in non-survivors compared to survivors (APACHE II: 20.12±7.83 vs. 11.50±4.49, P<0.05; SOFA: 12.06±3.27 vs. 7.74±2.10, P<0.05). Non-survivors had higher levels of lactic dehydrogenase (LDH; 1,646.94±1,269.48 vs. 942.76±740.58 IU/L, P=0.015), and higher numbers of schistocytes (6.18%±4.69% vs. 3.44%±3.13%, P=0.035) compared to survivors. TTP progressed rapidly, and its clinical manifestations varied between patients. The diagnosis depended on the clinical features and laboratory tests. Combination therapy with PEX, immunosuppressive therapy, and rituximab may be useful. Higher APACHE II and SOFA scores, higher LDH levels, and a greater degree of schistocytosis were associated with the severity and outcome of TTP.

Diagnostic Delay of Pulmonary Embolism in COVID-19 Patients.

Pulmonary embolism (PE) is a frequent, life-threatening COVID-19 complication, whose diagnosis can be challenging because of its non-specific symptoms. There are no studies assessing the impact of diagnostic delay on COVID-19 related PE. The aim of our exploratory study was to assess the diagnostic delay of PE in COVID-19 patients, and to identify potential associations between patient- or physician-related variables and the delay. This is a single-center observational retrospective study that included 29 consecutive COVID-19 patients admitted to the San Matteo Hospital Foundation between February and May 2020, with a diagnosis of PE, and a control population of 23 non-COVID-19 patients admitted at our hospital during the same time lapse in 2019. We calculated the patient-related delay (i.e., the time between the onset of the symptoms and the first medical examination), and the physician-related delay (i.e., the time between the first medical examination and the diagnosis of PE). The overall diagnostic delay significantly correlated with the physician-related delay (p < 0.0001), with the tendency to a worse outcome in long physician-related diagnostic delay (p = 0.04). The delay was related to the presence of fever, respiratory symptoms and high levels of lactate dehydrogenase. It is important to rule out PE as soon as possible, in order to start the right therapy, to improve patient's outcome and to shorten the hospitalization.

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

Analysis in causes and risk factors of death in 53 children with acute leukemia

Objective To explore the causes and risk factors of death in children with acute leukemia (AL) in hospital. Methods Totally 53 dead children due to AL were divided into early death group (n=23) and non-early death group (n=30). The mortality, causes of death and risk factors of death were analyzed in both groups. Results Multiple organ dysfunction syndrome (MODS) and infection were the main causes of death in the early death group, while infection and bleeding were the main causes of death in the non-early death group. Bacterial septicemia was the main cause of death in both groups, and Gram-negative bacteria infection was the main cause. Age less than 1 year old, high white blood cell count and high serum lactate dehydrogenase level were the high risk factors of death in children with AL (P Conclusion For the high risk factors of death such as less than 1 year old, high white blood cell count and high serum lactate dehydrogenase level in children with AL, early implementation of active prevention and treatment measures may reduce the mortality of children.