Effect of serum lactate dehydrogenase-to-albumin ratio (LAR) on the short-term outcomes and long-term prognosis of colorectal cancer after radical surgery.

BACKGROUND: Whether serum lactate dehydrogenase-to-albumin ratio (LAR) influenced the outcomes of colorectal cancer (CRC) patients after radical surgery remained unclear. Therefore, this study sought to examine how LAR influences the short-term and long-term outcomes of CRC patients who have undergone radical surgery. METHODS: This study retrospectively included CRC patients who underwent radical resection between January 2011 and January 2020. We compared short-term outcomes, as well as overall survival (OS) and disease-free survival (DFS), among various groups. Both univariate and multivariate logistic regression analyses were utilized to pinpoint independent risk factors associated with overall complications and major complications. Moreover, Cox regression analysis were conducted for OS and DFS. Odds ratio (OR) and Hazard ratio (HR) were adjusted. RESULTS: This study encompassed a cohort of 3868 patients. 3440 patients were in the low LAR group and 428 patients constituted the high LAR group. In the high LAR group, patients experienced significantly longer operative times (p < 0.01), larger intraoperative blood loss (p < 0.01), and extended postoperative hospital stays (p < 0.01). Additionally, the incidence of both overall complications (p < 0.01) and major complications (p < 0.01) was higher in the high LAR group compared to the low LAR group. Furthermore, LAR was emerged as an independent prognostic factor for overall complications [OR/95% CI: (1.555/1.237 to 1.954), p < 0.01] and major complications [OR/95% CI: (2.178/1.279 to 3.707), p < 0.01]. As for long-term survival, the high LAR group had worse OS in stage II (p < 0.01) and stage III (p < 0.01). In both stage II (p < 0.01) and stage III (p < 0.01), the high LAR group exhibited poorer DFS. Additionally, according to Cox regression analysis, LAR was identified as an independent predictor for both OS [HR/95% CI: (1.930/1.554 to 2.398), p < 0.01] and DFS [HR/95% CI: (1.750/1.427 to 2.146), p < 0.01]. CONCLUSION: LAR emerged as an independent predictor not only for overall complications and major complications but also for both OS and DFS, highlighting its significance and deserving the attention of surgeons.

Serum lactate dehydrogenase is associated with impaired lung function: NHANES 2011-2012.

BACKGROUND: Serum lactate dehydrogenase levels reflect disease status in a variety of organs, but its role in indicating pulmonary function is not yet clear. Therefore, this study explored the correlation between pulmonary function and serum lactate dehydrogenase, and investigated thresholds for changes in pulmonary function indicators in the total population as well as in different strata of the population. METHODS: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 (n = 3453), univariate and stratified analyses were performed to investigate factors associated with pulmonary function, and multiple regression analysis was used to further investigate the specific relationship with serum lactate dehydrogenase. Smoothed curve fitting, threshold effect and saturation effect analysis were used to explore the threshold level of serum lactate dehydrogenase at the onset of changes in pulmonary function indicators. RESULTS: Adjusted smoothed curve fit plots showed a linear relationship between serum lactate dehydrogenase levels and forced vital capacity and forced expiratory volume in one second: for each 1 U/L increase in serum lactate dehydrogenase levels, forced vital capacity decreased by 1.24 mL (95% CI = -2.05, -0.42, P = 0.0030) and forced expiratory volume in one second by 1.11 mL (95% CI = -1.82, -0.39, P = 0.0025). CONCLUSIONS: Serum lactate dehydrogenase was negatively and linearly correlated with pulmonary function indices in the total population analyzed. Based on the total population and different population stratifications, this study determined the threshold values of serum lactate dehydrogenase at the onset of decline of pulmonary function in different populations. This provides a new serological monitoring indicator for patients suffering from respiratory diseases and has implications for patients with possible clinical impairment of pulmonary function. However, our cross-sectional study was not able to determine a causal relationship between these two factors, and further research is needed.

The Relationship between the SUVmax Value Obtained in Ga-68 PSMA PET/CT and Lactate Dehydrogenase and Alkaline Phosphatase in Prostate Cancer

Objectives: ALP and LDH are serum markers of prognostic importance in prostate cancer patients. PET/CT imaging with Ga-68 PSMA has played an important role in prostate cancer imaging in recent years. Our aim in this study was to evaluate the relationship and prognostic significance between SUVmax values obtained with Ga-68 PSMA PET/CT and LDH and ALP levels in prostate cancer patients. Methods: We retrospectively evaluated 61 prostate cancer patients who had Ga-68 PSMA PET/CT imaging and who did not have a prostatectomy between 2019 and 2020. PSA, ALP and LDH levels were measured in all patients before or after imaging within a maximum of 28 days. Results: The median age of the patients included in this study was 73 (range: 57–89) and all 61 patients were prostatic adenocarcinoma. 50 (82%) of the patients had distant metastasis in Ga-68 PSMA PET/CT. There was a significant positive correlation between serum LDH and PSA levels. There was a positive correlation between serum ALP and PSA levels. A negative correlation was found between ALP levels and prostate SUVmax. Conclusions: While negative correlation was found between SUVmax and ALP levels, no correlation was found between LDH levels and SUVmax. High ALP levels were found to be related to metastasis rates and severity and high serum PSA levels (AU)

Objetivos: ALP y LDH son marcadores séricos deimportancia pronóstica en pacientes con cáncer de próstata.Las imágenes de PET/CT con Ga-68 PSMA han jugado unpapel importante en las imágenes de cáncer de próstata enlos últimos años. Nuestro objetivo en este estudio fue evaluar la relación y la importancia pronóstica entre los valores de SUVmax obtenidos con Ga-68 PSMA PET/CT ylos niveles de LDH y ALP en pacientes con cáncer de próstata.Métodos: Evaluamos retrospectivamente a 61 pacientes con cáncer de próstata que se sometieron a imágenes de PET/CT con Ga-68 PSMA y que no se sometierona prostatectomía entre 2019 y 2020. Los niveles de PSA,ALP y LDH se midieron en todos los pacientes antes o después de la obtención de imágenes en un plazo máximo de28 días.Resultados: La mediana de edad de los pacientes incluidos en este estudio fue de 73 (rango: 57–89) y los 61pacientes eran adenocarcinoma de próstata. 50 (82%) delos pacientes tenían metástasis a distancia en Ga-68 PSMAPET/CT. Hubo una correlación positiva significativa entrelos niveles séricos de LDH y PSA. Hubo una correlaciónpositiva entre los niveles séricos de ALP y PSA. Se encontró una correlación negativa entre los niveles de ALP y elSUVmáx prostático.Conclusiones: Si bien se encontró una correlaciónnegativa entre los niveles de SUVmáx y ALP, no se encontró correlación entre los niveles de LDH y el SUVmáx. Seencontró que los niveles altos de ALP estaban relacionadoscon las tasas de metástasis y la gravedad y los niveles altosde PSA en suero. (AU)

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

Introduction: 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. Methods: 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). Results: 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. Conclusion: 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.

Changes in serum lactate dehydrogenase levels as markers of pathological response and prognosis in colorectal liver metastases patients receiving neoadjuvant chemotherapy followed by resection.

BACKGROUND: This study sought to evaluate the effects of pre-neoadjuvant chemotherapy lactate dehydrogenase (pre-NAC LDH) levels, preoperative LDH levels, and changes in LDH levels on the pathological response and outcomes of colorectal liver metastases (CRLM) patients treated with liver resection after NAC. METHODS: This study included 152 colorectal CRLM patients, who underwent NAC followed by liver resection. Patients were excluded if they were diagnosed with other malignancies or lacked follow-up and clinical data. Demographic and clinicopathological data were collected from hospital records. Pathological response and postoperative complications were measured according to the tumor regression grade (TRG) and Clavien-Dindo classification system, respectively. The optimal cutoff values were determined by the receiver operating characteristic curve and the X-tile analysis. Changes in LDH levels were graded as 0, 1, and 2. A logistic regression analysis was conducted to identify the independent predictors of pathological response and postoperative major complications. Univariate and multivariate Cox regression analyses were used to identify the independent risk factors of progression-free survival (PFS) and overall survival (OS). RESULTS: The multivariate analysis indicated that a grade 2 LDH level change was a risk factor of an unfavorable histological response [odds ratio (OR) 0.249, 95% confidence interval (CI): 0.066-0.942; P=0.041] and major postoperative complications (OR 2.523, 95% CI: 1.179-10.530; P=0.024), which were independent of other clinical covariates. A pre-NAC LDH level ≥145 IU/L [hazards ratio (HR) 0.584, 95% CI: 0.359-0.950; P=0.030], a grade 1 LDH level change (HR 0.584, 95% CI: 0.359-0.950; P=0.030) and a grade 2 LDH level change (HR 0.447, 95% CI: 0.231-0.864; P=0.017) were independent prognostic predictors of PFS. A preoperative a LDH level ≥231 IU/L (HR 0.405, 95% CI: 0.192-0.852; P=0.017) and a grade 2 LDH level change (HR 0.362, 95% CI: 0.157-0.834; P=0.017) were independent prognostic factors of OS, which were independent of other clinical covariates. CONCLUSIONS: LDH levels and changes in LDH levels are potentially useful biomarkers for predicting the pathological response and prognosis of CRLM patients receiving NAC followed by liver resection.

Association between serum lactate dehydrogenase and frailty among individuals with metabolic syndrome.

While metabolic syndrome (MetS) is associated with frailty, the correlation of serum lactate dehydrogenase (sLDH) and frailty with MetS remain uncertain. To investigate the relationship between sLDH and frail components in the US with MetS. A total of 4,066 participants aged 40-90 years were assessed from the database of the third National Health and Nutrition Examination Survey, 1988-1994. The participants were classified into MetS and non-MetS groups. Multivariate logistic regression analysis with four models were performed to assess the odds ratio (OR) of the divided tertiles of sLDH levels with frailty, and frail components including slow walking (SW), weakness, exhaustion, low physical activity (LPA), and low body weight (LBW). Higher sLDH levels were positively associated with frailty in the MetS group (p = 0.024) but not in non-MetS group (p = 0.102). After covariate adjustments, the OR of frailty in the upper two tertiles compared to the lowest tertile and revealed statistical significance (p < 0.05). Frail components of SW, weakness, exhaustion, and LPA were associated with higher sLDH (p < 0.05) except for LBW in MetS and non-MetS groups. The results demonstrated the strong association of higher sLDH levels and frailty among US individuals with MetS.

The relationship between serum lactate dehydrogenase level and mortality in critically ill patients.

Background: To assess the association between serum lactate dehydrogenase (LDH) levels and mortality in intensive care unit patients. Materials & methods: A total of 1981 patients in the eICU Collaborative Research Database were divided into four groups according to quartiles of LDH levels. Logistic regressions were performed. Results: Elevated LDH levels were significantly associated with higher mortality (intensive care unit mortality: Q2 vs Q1: 1.046 [0.622-1.758]; Q3 vs Q1: 1.667 [1.029-2.699]; and Q4 vs Q1: 1.760 [1.092-2.839]). Similar results persisted in patients with different acute physiology and chronic health evaluation IV scores, and with or without sepsis. Conclusion: The serum LDH level may aid in the early identification of mortality risk in critically ill patients.

Blood biomarkers of bone metastasis in digestive tract malignant tumors.

Aim: To evaluate the role of clinical features and blood markers in patients with malignant digestive tract tumors bone metastasis. Materials & methods: A total of 267 patients were included in this trial. Age, gender, primary tumor site, metastatic sites, T/N stage, high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, alkaline phosphatase, LDH, Ca levels, platelet, neutrophils to absolute value of lymphocytes (NLR), ratio of platelets to absolute values of lymphocytes (PLR) were analyzed. Results: T stage, lymph node metastasis, N stage and liver and lung metastasis were independent risk factors. LDH + alkaline phosphatase + NLR + PLR and LDH + NLR, respectively have higher predictive value for bone metastasis compared with patients with early-stage malignant digestive tract tumor and patients with advanced malignant digestive tract tumor without bone metastasis. Conclusion: Some clinical features or blood markers have the potential to detect bone metastasis early to avoid skeletal complications.

Serum lactate dehydrogenase level is associated with in-hospital mortality in critically Ill patients with acute kidney injury.

OBJECTIVE: Sixty percent of critically ill patients suffer from acute kidney injury (AKI) and 12% of them require renal replacement therapy during their ICU stay. However, we lack effective biomarkers to predict the mortality of critically ill patients with AKI. Few studies have investigated the association between lactate dehydrogenase levels and mortality in patients with AKI. METHODS: We conducted a retrospective cohort study with large samples, using a large database, the Multi parameter Intelligent Monitoring in Intensive Care III project. Clinical and demographic data were collected from the database by structure query language. Multiple models were constructed by stepwise methods to examine the association between lactate dehydrogenase (LDH) and in-hospital mortality. The predictive performance of LDH was assessed by ROC analysis and p values were calculated for trends. RESULTS: In the final analysis, 8436 patients met the inclusion criteria, and 1519 patients died during their hospital stay. The mortality rate increased with increasing LDH levels. The association between LDH and in-hospital mortality was almost linear (p < 0.001). A multiple logistic regression model indicated that LDH level was an independent predictor of in-hospital mortality (OR = 1.56, 95% CI (1.39-1.73), p < 0.001) and this effect remained stable in the subgroup analysis. Moreover, the combined AUC of LDH and SAPSII was 0.83. CONCLUSIONS: The LDH level, which can be easily assessed, is significantly and independently associated with in-hospital mortality, and could increase the predictive ability of SAPSII for in-hospital mortality in our study.

Lactate dehydrogenase, COVID-19 and mortality / Lactato deshidrogenasa, COVID-19 y mortalidad

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Specificity of the lactate dehydrogenase isoenzyme index as a preoperative screen for uterine sarcoma before myomectomy.

OBJECTIVE: To evaluate the applicability of the Uterine mass Magna Graecia (UMG) risk index (elevation defined by a lactate dehydrogenase isoenzyme index >29) in women undergoing surgery for benign fibroids and to determine whether other factors were associated with an elevated index. An elevated UMG index has been reported to be associated with an increased risk of uterine sarcoma in Italian women. DESIGN: Retrospective cohort study. SETTING: University fibroid center. PATIENTS: All women presenting from July 1, 2013, through June 30, 2019, with fibroids who had lactate dehydrogenase isoenzymes collected and surgery performed. INTERVENTIONS: Calculation of UMG index. MAIN OUTCOME MEASURE: Applicability of UMG index. RESULTS: Of 272 patients initially identified, 179 met inclusion criteria, 163 with UMG index ≤29 and 16 with UMG index >29. There were no cases of uterine sarcoma. Race, age, and presence of endometriosis, adenomyosis, or degenerating fibroids were not predictors of elevated UMG index. Body mass index (BMI) was positively associated with elevated UMG index. Specificity of UMG index to exclude uterine sarcoma was 91.1% (163/179) and higher in non-obese (BMI<30; 95.1%) than obese women (85.5%). CONCLUSION: A previously reported UMG index cutoff of 29 had a specificity of 91.1% (higher with normal BMI and lower when obese) in our patient population. Although lower than previously reported, the index could be a useful initial method of preoperative screening of women with symptomatic fibroids. Higher BMI appears to be associated with elevated UMG indices, increasing the false-positive rate in obese women.

Dynamics of clinical biomarkers as predictors of immunotherapy benefit in metastatic melanoma patients.

PURPOSE: Baseline LDH, derived neutrophil-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) are associated with outcomes of patients with metastatic melanoma (MM). We hypothesized whether dynamic shifts in LDH, dNLR and incidence of irAEs may impact the prognosis of MM patients treated with anti-CTLA4 or anti-PD1 as single agents. METHODS: Retrospective analysis of medical charts from MM patients with prospective monitoring of dNLR, LDH values and irAE incidence. Primary endpoint was overall survival (OS). RESULTS: Patients switching from either high dNLR (≥2.5) to low dNLR (HR: 0.14; 0.03-0.74; p = 0.02) or high LDH (≥1.5 × ULN) to low LDH levels (HR: 0.08; 0.01-0.68; p = 0.02) had significantly better OS than those with high dNLR or LDH scores at the end of cycle 2. Longer OS was also observed in patients developing irAEs ≥ grade 2 as compared to no irAEs (HR: 0.2; 0.05-0.89; p = 0.03). CONCLUSIONS: We found that major shifts in dNLR and LDH measures from baseline to cycle 2 measures and shifts from baseline to cycle 2 are significantly associated with OS in MM patients receiving single agent anti-PD1 therapy. Laboratory changes and clinical variables may help optimize prognostic estimates.

Expansion of the LabBM Score: Is the LabPS the Best Tool Predicting Survival in Patients With Brain Metastases?

OBJECTIVES: The objective of this study were to improve the 3-tiered, purely biomarker-based LabBM score, which predicts the survival of patients with brain metastases, by adding the well-established prognostic factor performance status (PS), and to define its role in comparison with the recently proposed Extracranial-Graded Prognostic Assessment score, which is based on the well-known Diagnosis-specific Graded Prognostic Assessment and 2 of the same biomarkers. MATERIALS AND METHODS: This was a retrospective single-institution analysis of 212 patients, managed with upfront brain irradiation. Survival was stratified by LabBM and LabPS score. Each included serum hemoglobin, platelets, albumin, C-reactive protein, and lactate dehydrogenase (plus PS for the LabPS). Zero, 0.5, or 1 point was assigned and the final point sum calculated. A higher point sum indicates shorter survival. RESULTS: The new LabPS score predicted overall survival very well (median: 12.1 to 0.7 mo, 1-y rate: 52% to 0%), P=0.0001. However, the group with the poorest prognosis (3 or 3.5 points) was very small (4%). Most patients with comparably short survival had a lower point sum. The LabPS score failed to outperform the recently proposed Extracranial-Graded Prognostic Assessment score. CONCLUSIONS: Integration of blood biomarkers should be considered when attempting to develop improved scores. Additional research is needed to improve the tools which predict short survival, because many of these patients continue to go undetected with all available scores.

Pretreatment age and serum lactate dehydrogenase as predictors of synchronous second primary cancer in patients with nasopharyngeal carcinoma.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) is a common cancer and is treated primarily by chemotherapy and radiotherapy. However, NPC with synchronous second primary cancer (SSPC) is very rare and its risk factors, treatment and prognosis remain unclear. In this study, we aimed to analyze patients with NPC and SSPC, and attempt to find potential predictors for these patients. MATERIALS AND METHODS: We retrospectively collected 681 patients with NPC from 2006 to 2018. Patients in this study were divided into two groups: those patients with SSPC and those without SSPC. We then analyzed the demographic data and survival of these two groups. Independent predictors of SSPC were determined by multivariate regression analysis. A comprehensive review of the literature was also performed. RESULTS: We identified 17 NPC patients with SSPC in our case series and 13 cases in the literatures, and the most common SSPC is lung (16.1%). In univariate analysis, NPC patients with SSPC had older age (P < 0.001) and higher serum lactate dehydrogenase (LDH) (P = 0.008), compared with those without SSPC. In multivariate analysis, old age (P = 0.001) and high serum LDH (P = 0.023) remained independent predictors of SSPC, and a predictive equation model was established. NPC patients with SSPC had a significantly lower 5-year disease-specific survival rate compared with patients without SSPC (34.0% vs. 77.6%, P < 0.001) CONCLUSION: This study demonstrated that pretreatment age and serum LDH were independent predictors for SSPC in NPC patients. These independent factors can be used for early detection, and better facilitate the design of more appropriate treatment by medical professionals.

Aberrant Expression of Prohibitin Is Related to Prognosis of Nasal Extranodal Natural Killer/T Cell Lymphoma, Nasal Type.

INTRODUCTION: Nasal extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) is a high-grade Epstein-Barr virus (EBV)-associated malignancy with poor outcomes. There are few biomarkers for the accurate diagnosis and prognostic prediction of the disease. The aim of this study was to investigate the clinicopathological significance of prohibitin (PHB) expression in nasal ENKTCL. METHODS: The expression level of PHB was detected via immunohistochemical staining in 49 nasal ENKTCL tissues and age- and sex-matched controls of 30 nasal mucosa-reactive lymphoid hyperplasia (NRLH) tissues. The correlations between the PHB expression and clinicopathological features of patients with nasal ENKTCL were evaluated. RESULTS: The results indicated a significantly decreased expression of PHB in nasal ENKTCL tissues compared with in NRLH tissues. Low-level PHB expression was significantly associated with younger age and fever (p = 0.008 and 0.018, respectively). The Kaplan-Meier analysis showed that the cytoplasm expression level of PHB in nasal ENKTCL was inversely related to overall survival (p = 0.046). CONCLUSIONS: PHB may be a potential diagnostic marker and prognostic predictor of nasal ENKTCL.

Elevated Lactate Dehydrogenase (LDH) level as an independent risk factor for the severity and mortality of COVID-19.

Early identification of severe patients with coronavirus disease 2019 (COVID-19) is very important for individual treatment. We included 203 patients with COVID-19 by propensity score matching in this retrospective, case-control study. The effects of serum lactate dehydrogenase (LDH) at admission on patients with COVID-19 were evaluated. We found that serum LDH levels had a 58.7% sensitivity and 82.0% specificity, based on a best cut-off of 277.00 U/L, for predicting severe COVID-19. And a cut-off of 359.50 U/L of the serum LDH levels resulted in a 93.8% sensitivity, 88.2% specificity for predicting death of COVID-19. Additionally, logistic regression analysis and Cox proportional hazards model respectively indicated that elevated LDH level was an independent risk factor for the severity (HR: 2.73, 95% CI: 1.25-5.97; P=0.012) and mortality (HR: 40.50, 95% CI: 3.65-449.28; P=0.003) of COVID-19. Therefore, elevated LDH level at admission is an independent risk factor for the severity and mortality of COVID-19. LDH can assist in the early evaluating of COVID-19. Clinicians should pay attention to the serum LDH level at admission for patients with COVID-19.

Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer.

BACKGROUND: To investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa). PATIENTS AND METHODS: A cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). RESULTS: After a median 34.2 (22.9-45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524-6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008-10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125-3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis. CONCLUSIONS: Preoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion.

BACKGROUND: Incomplete fracture healing may lead to chronic nonunion; thus, determining fracture healing is the primary issue in the clinical treatment. However, there are no validated early diagnostic biomarkers for assessing chronic nonunion. In this study, bioinformatics analysis combined with an experimental verification strategy was used to identify blood biomarkers for chronic nonunion. METHODS: First, differentially expressed genes in chronic nonunion were identified by microarray data analysis. Second, Dipsaci Radix (DR), a traditional Chinese medicine for fracture treatment, was used to screen the drug target genes. Third, the drug-disease network was determined, and biomarker genes were obtained. Finally, the potential blood biomarkers were verified by ELISA and qPCR methods. RESULTS: Fifty-five patients with open long bone fractures (39 healed and 16 nonunion) were enrolled in this study, and urgent surgical debridement and the severity of soft tissue injury had a significant effect on the prognosis of fracture. After the systems pharmacology analysis, six genes, including QPCT, CA1, LDHB, MMP9, UGCG, and HCAR2, were chosen for experimental validation. We found that all six genes in peripheral blood mononuclear cells (PBMCs) and serum were differentially expressed after injury, and five genes (QPCT, CA1, MMP9, UGCG, and HCAR2) were significantly lower in nonunion patients. Further, CA1, MMP9, and QPCT were markedly increased after DR treatment. CONCLUSION: CA1, MMP9, and QPCT are biomarkers of nonunion patients and DR treatment targets. However, HCAR2 and UGCG are biomarkers of nonunion patients but not DR treatment targets. Therefore, our findings may provide valuable information for nonunion diagnosis and DR treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN13271153. Registered 05 April 2020-Retrospectively registered.