Analysis of risk factors, pathogenic bacteria characteristics, and drug resistance of postoperative surgical site infection in adults with limb fractures.

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.

More Efficient Approach: Independent Diagnostic Value of Audiovisual Sexual Stimulation for Psychogenic Erectile Dysfunction.

The diagnostic value of audiovisual sexual stimulation (AVSS) for psychogenic erectile dysfunction (ED) is still unclear. We investigated the independent diagnostic value and optimal cut-off parameter of AVSS for psychogenic ED. All participants had received the AVSS test and nocturnal penile tumescence and rigidity (NPTR) monitoring at least twice. ED patients were divided into psychogenic ED and organic ED according to NPTR examination. The diagnostic accuracy of AVSS parameters was evaluated with the receiver operating characteristic (ROC) curve, and the Youden index was employed to determine the optimal diagnostic cut-off values. A total of 346 patients with ED and 60 healthy men were included in this study, among which 162 and 184 cases of psychogenic and organic ED were identified based on NPTR, respectively. When comparing the two ED groups, the area under the curve (AUC) of AVSS parameters was 0.85-0.89. Six-selected AVSS parameters could precisely diagnose psychogenic ED, exhibiting increased diagnostic specificity compared with corresponding sensitivity. When comparing psychogenic ED with the control group, the AUC of the tumescence of the tip was superior to the AUC other parameters (0.81 vs. 0.58, 0.66, 0.59, 0.53, 0.68), and the best determined diagnostic cut-off value was the tumescence of the tip < 29.87%. Independent AVSS could diagnose psychogenic ED objectively and effectively, and its diagnostic value was highest when 1.50% ≤ tumescence of the tip < 29.87%.

Prophylactic inguinal lymphadenectomy for high-risk cN0 penile cancer: The optimal surgical timing.

Background: Few reports have investigated the oncologically safe timing of prophylactic inguinal lymphadenectomy for penile cancer patients with clinically normal inguinal lymph nodes (cN0), particularly those who received delayed surgical treatment. Methods: The study included pT1aG2, pT1b-3G1-3 cN0M0 patients with penile cancer who received prophylactic bilateral inguinal lymph nodes dissection (ILND) at the Department of Urology of Tangdu Hospital between October 2002 and August 2019. Patients who received simultaneous resection of primary tumor and inguinal lymph nodes were assigned to the immediate group, while the rest were assigned to the delayed group. The optimal timing of lymphadenectomy was determined based on the time-dependent ROC curves. The disease-specific survival (DSS) was estimated based on the Kaplan-Meier curve. Cox regression analysis was used to evaluate the associations between DSS and the timing of lymphadenectomy and tumor characteristics. The analyses were repeated after stabilized inverse probability of treatment weighting adjustment. Results: A total of 87 patients were enrolled in the study, 35 of them in the immediate group and 52 in the delayed group. The median (range) interval time between primary tumor resection and ILND of the delayed group was 85 (29-225) days. Multivariable Cox analysis demonstrated that immediate lymphadenectomy was associated with a significant survival benefit (HR, 0.11; 95% CI, 0.02-0.57; p = 0.009). An index of 3.5 months was determined as the optimal cut-point for dichotomization in the delayed group. In high-risk patients who received delayed surgical treatment, prophylactic inguinal lymphadenectomy within 3.5 months was associated with a significantly better DSS compared to dissection after 3.5months (77.8% and 0%, respectively; log-rank p<0.001). Conclusions: Immediate and prophylactic inguinal lymphadenectomy in high-risk cN0 patients (pT1bG3 and all higher stage tumours) with penile cancer improves survival. For those patients at high risk who received delayed surgical treatment for any reason, within 3.5 months after resection of the primary tumor seems to be an oncologically safe window for prophylactic inguinal lymphadenectomy.

An enhancer RNA-based risk model for prediction of bladder cancer prognosis.

Background: Bladder cancer patients have a high recurrence and poor survival rates worldwide. Early diagnosis and intervention are the cornerstones for favorable prognosis. However, commonly used predictive tools cannot meet clinical needs because of their insufficient accuracy. Methods: We have developed an enhancer RNA (eRNA)-based signature to improve the prediction for bladder cancer prognosis. First, we analyzed differentially expressed eRNAs in gene expression profiles and clinical data for bladder cancer from The Cancer Genome Atlas database. Then, we constructed a risk model for prognosis of bladder cancer patients, and analyzed the correlation between this model and tumor microenvironment (TME). Finally, regulatory network of downstream genes of eRNA in the model was constructed by WGCNA and enrichment analysis, then Real-time quantitative PCR verified the differentiation of related genes between tumor and adjacent tissue. Results: We first constructed a risk model composed of eight eRNAs, and found the risk model could be an independent risk factor to predict the prognosis of bladder cancer. Then, the log-rank test and time-dependent ROC curve analysis shown the model has a favorable ability to predict prognosis. The eight risk eRNAs may participate in disease progression by regulating cell adhesion and invasion, and up-regulating immune checkpoints to suppress the immunity in TME. mRNA level change in related genes further validated regulatory roles of eRNAs in bladder cancer. In summary, we constructed an eRNA-based risk model and confirmed that the model could predict the prognosis of bladder cancer patients.

Selecting an Individualized Treatment Approach: The Predictive Value of Erotic Stimulation and Nocturnal Erections for Efficacy of Tadalafil and Cure in Patients With Erectile Dysfunction.

Purpose: This study aimed to evaluate two modes of Rigiscan for predicting tadalafil response, and to identify which Rigiscan variables are the most efficient at making these predictions. Methods: All patients received at least two rounds of nocturnal penile tumescence and rigidity (NPTR) testing and/or audiovisual sexual stimulation (AVSS), then completed the International Index of Erectile Function-5 (IIEF-5) questionnaire, followed by oral 5 mg tadalafil daily for 4 weeks. After a 4-week washout period, all respondents underwent an the IIEF-5 questionnaire again. ED patients were then categorized into tadalafil responders and tadalafil non-responders, who were then further divided into cured patients and uncured patients. Results: When predicting tadalafil responders, the area under the curve (AUC) of NPTR was superior to that of AVSS (0.68~0.84 VS 0.69~0.73), and the predicted optimal cut-off values were DOEE60≥17.75 min in NPTR, compared to other parameters regardless of AVSS or NPTR (P<0.05). When predicting which patients would be cured, the AUC of AVSS was superior to NPTR parameters (0.77~0.81 vs 0.61~0.76), and the determined best diagnostic cut-off values were DOEE≥4.125min in AVSS, compared to other parameters regardless of AVSS or NPTR (P < 0.05). Conclusion: Rigiscan was able to predict the efficacy of daily tadalafil accurately and efficiently. Its diagnostic value was at maximum when DOEE60 ≥17.75 min of NPTR in tadalafil responders and DOEE ≥ 4.125 min of AVSS in cured patients.

Should we support prophylactic intervention for asymptomatic kidney stones? A retrospective cohort study with long-term follow-up.

The purpose of this study was to evaluate the long-term outcomes of patients undergoing prophylactic intervention or active surveillance for asymptomatic kidney stones and identify factors influencing the outcomes. In this retrospective cohort study, we reviewed the medical records of patients with asymptomatic kidney stones in two institutes between November 2014 and November 2019. Standardized questions were asked via phone calls to supplement the outcomes. Pain, hydronephrosis, stone growth, serious infection, gross hematuria, and spontaneous passage were defined as stone-related events. Future intervention was also recorded to evaluate management. A total of 101 patients with 120 kidney units were enrolled in this study. The median follow-up time was 63 months. The patients were classified into the control group (79 cases) or exposure group (41 cases) according to whether they underwent prophylactic intervention before any stone-related events. Generally, the rates of stone-related events and future intervention were significantly different between the two groups (57.0 vs. 12.2%, p < 0.001; and 31.6 vs. 4.9%, p = 0.002, respectively). After applying stabilized inverse probability of treatment weighted, Cox regression suggested that patients who underwent prophylactic intervention were less likely to experience stone-related events and future intervention (HR = 0.175, and HR = 0.028, respectively). In conclusion, patients who underwent prophylactic intervention had a lower risk of stone-related events and future intervention, although they had some slight complications.

Prognostic value and underlying mechanism of autophagy-related genes in bladder cancer.

Bladder cancer (BLCA) is the most common malignancy whose early diagnosis can ensure a better prognosis. However, the predictive accuracy of commonly used predictors, including patients' general condition, histological grade, and pathological stage, is insufficient to identify the patients who need invasive treatment. Autophagy is regarded as a vital factor in maintaining mitochondrial function and energy homeostasis in cancer cells. Whether autophagy-related genes (ARGs) can predict the prognosis of BLCA patients deserves to be investigated. Based on BLCA data retrieved from the Cancer Genome Atlas and ARGs list obtained from the Human Autophagy Database website, we identified prognosis-related differentially expressed ARGs (PDEARGs) through Wilcox text and constructed a PDEARGs-based prognostic model through multivariate Cox regression analysis. The predictive accuracy, independent forecasting capability, and the correlation between present model and clinical variables or tumor microenvironment were evaluated through R software. Enrichment analysis of PDEARGs was performed to explore the underlying mechanism, and a systematic prognostic signature with nomogram was constructed by integrating clinical variables and the aforementioned PDEARGs-based model. We found that the risk score generated by PDEARGs-based model could effectively reflect deteriorated clinical variables and tumor-promoting microenvironment. Additionally, several immune-related gene ontology terms were significantly enriched by PDEARGs, which might provide insights for present model and propose potential therapeutic targets for BLCA patients. Finally, a systematic prognostic signature with promoted clinical utility and predictive accuracy was constructed to assist clinician decision. PDEARGs are valuable prognostic predictors and potential therapeutic targets for BLCA patients.

Bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer: A retrospective study.

OBJECTIVE: To assess the feasibility, safety, and efficiency of bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer. MATERIALS AND METHODS: We reviewed retrospectively the records of 65 patients who underwent inguinal lymph nodes dissection (ILND) for penile cancer from January 2012 to May 2019. Treatments included open ILND (OILND, 19 patients), video-endoscopic inguinal lymphadenectomy (VEIL) using single laparoscopy (S-VEIL, 24 patients), and VEIL using double laparoscopies (D-VEIL, 22 patients). We evaluated the peri-operative and short-term oncological outcomes of the three groups. RESULTS: The mean operative time of D-VEIL (105.91 ± 10.87 minutes) was significantly shorter than the other two groups, OILND shorter than S-VEIL (160.47 ± 13.74 minutes, 191.67 ± 17.80 minutes, respectively) (P < 0.001). Intraoperative blood loss in the S-VEIL and D-VEIL groups were 53.54 ± 8.78 and 48.41 ± 13.22 ml, respectively; they were significantly lower than that of the OILND group (99.74 ± 9.64 ml; P < 0.001). The numbers of unilateral and total lymph nodes harvested were similar in all groups. The complication rates in the S-VEIL group (4.2%) and the D-VEIL group (4.5%) were significantly lower than that in the OILND group (63.2%; P < 0.001). Compared with open surgery (13.53 ± 1.74 days for hospitalization; 11.37 ± 1.92 days for the left side of drain, 11.95 ± 1.84 days for the right side), the two VEIL groups had significantly shorter drainage tube residence time (7.42 ± 2.02 and 7.32 ± 1.52 days, respectively for the left side; 7.63 ± 1.81 and 7.27 ± 1.58 days, respectively for the right side), shorter postoperative hospitalization (9.46 ± 1.64 and 9.00 ± 1.83 days, respectively) (P < 0.001). There were no statistically significant differences in rates of regional recurrence and short-term survival among the three groups. CONCLUSION: Bilateral inguinal lymphadenectomy using double laparoscopies simultaneously can provide adequate oncological outcomes safely and efficiently, and carry significantly lower morbidity than OILND, at a median follow-up of 33.5 months. It is a more time-saving surgical approach for penile cancer patients who need bilateral ILND.

CD248+ Cancer-Associated Fibroblasts: A Novel Prognostic and Therapeutic Target for Renal Cell Carcinoma.

BACKGROUND: The tumor microenvironment (TME) plays an important role in the progression of renal cell carcinoma (RCC). Cancer-associated fibroblasts (CAFs) are considered to constitute a major component of the TME and participate in various tumor-promoting molecular events. We have previously confirmed that CD248 represents a promising biomarker of CAFs, which may provide insight into CAF-based tumor-promoting effects. However, CAF-mediated tumor progression and the potential mechanism of CD248 remain largely unknown in RCC patients. METHODS: Expression profiling and clinical data of RCC patients were obtained from The Cancer Genome Atlas (TCGA) database. An MCP-counter algorithm and Kaplan-Meier survival analysis were performed to explore the prognostic value of CAFs and CD248, respectively. A Pearson correlation coefficient test and Student's t-test were employed to evaluate the relationship between immunosuppressive TME and CD248 or CAFs. Immunohistochemistry and immunofluorescence staining were performed to confirm CD248 expression within CAFs. CD248-specific siRNA was used to investigate the potential function of CD248 in CAF tumor promotion. Differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and enrichment analysis were conducted to clarify the function of CD248+ CAFs in RCC progression and the associated regulatory mechanism. RESULTS: CD248 overexpression and CAF infiltration could predict poor RCC prognosis, which may involve the immunosuppressive TME. CD248 may serve as a promising CAFs biomarker and be involved with the tumor-promoting effect of CAFs. Moreover, CD248+ CAF infiltration may contribute to RCC progression and an immunosuppressive TME through cell-extracellular matrix (ECM) interactions and metabolism regulation. CONCLUSION: CD248+ CAFs participate in the regulation of RCC progression and immunosuppressive TME, which may represent a novel prognostic and therapeutic target for RCC.

The Diagnostic and Immunotherapeutic Value of CD248 in Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) is the most common malignancy in the urinary system. Despite substantial improvements in available treatment options, the survival outcome of advanced RCC is unsatisfactory. Identifying novel biomarkers to assist in early diagnosis and to screen patients who are sensitive to immunotherapy would be beneficial. CD248 is a promising candidate that deserves to be investigated. Methods: The Cancer Genome Atlas (TCGA) data set and clinical specimens were adopted to analyze the expression of CD248 between normal and tumor tissues. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors and construct a CD248-based prognostic signature. The correlation among the present signature, tumor-infiltrating immune cells (TIICs), the tumor mutation burden (TMB), and immunomodulatory molecules was evaluated. The weighted gene co-expression network analysis (WGCNA), the enrichment analysis, and the miRNA correlation analysis were performed to explore the underlying mechanism of CD248 in the progression of RCC. Results: The overexpression of CD248 in RCC was related to a poor prognosis, and a CD248-based prognostic signature could precisely stratify patients with RCC with different survival outcomes regardless of the training or testing cohort. The present signature could reflect the immunosuppressive landscape of RCC (i.e., increased infiltration of regulatory T cells and upregulated immune checkpoints), accompanied by deteriorated clinicopathologic indexes. The TMB and immunostimulatory molecules expression also increased with the risk score generated from the present signature. CD248 co-expressed gene sets were identified through the WGCNA algorithm, and several immunosuppressive Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched. The result of CD248-correlated miRNA further emphasized the importance of CD248 in RCC. Conclusion: CD248 is a valuable biomarker to improve the diagnostic and therapeutic efficiency of RCC. The immunosuppressive effect of CD248 co-expressed genes may provide insight for the present study, and miRNA would help to reveal the mechanism of the expressive regulation of CD248.

CD248 as a bridge between angiogenesis and immunosuppression: a promising prognostic and therapeutic target for renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is characterized by significant vascularization and immunogenicity, which contributes to drug resistance and immune escape. CD248, a pericytes marker in tumor vasculature, might help explain tumor microenvironment (TME) remodeling and serve as a novel therapeutic target. METHODS: Transcriptome data and clinical information of RCC patients were obtained from The Cancer Genome Atlas (TCGA) database. ESTIMATE and microenvironment cell population (MCP)-counter algorithms were adopted to calculate immune and stromal contents. The prognostic value of TME was evaluated via Kaplan-Meier and Wilcoxon signed rank test. Pearson's correlation coefficient was employed to explore the correlation between angiogenesis and TME, and the relationship between CD248 and TME or RCC progression. CD248 overexpression and vascular colocalization in RCC were confirmed via histology staining. The weighted gene coexpression network analysis (WGCNA) and enrichment analysis were performed to explore CD248-mediated regulatory mechanism in angiogenesis and TME remodeling. CD248-based drug response was predicted through CellMiner database. RESULTS: Tumor angiogenesis contributed to deteriorated RCC progression, which might be involved with immunosuppression. More specifically, upregulated immune checkpoints exhausted infiltrated T cells. CD248 overexpressed in RCC vessels correlated with TME and predicted a bad survival outcome. CD248 and coexpressed genes participated in angiogenesis and TME remodeling. Several clinical approved drugs that might inhibit CD248-mediated tumor promoting effects were selected. CONCLUSIONS: CD248 appears to contribute to angiogenesis and immunosuppressive TME, and may thus be a promising prognostic and therapeutic target for RCC. CD248-based medication guidance might benefit RCC patients.

miR-144-3p inhibits proliferation and invasion of bladder cancer T24 cells through targeted regulation of E2F3 / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression of miR144-3p in bladder cancer tissues and cells and its effect on the proliferation and invasion of T24 cells. Methods: A total of 36 cases of bladder cancer tissue specimens and 10 cases of normal bladder epithelial tissue specimens were collected from Tangdu Hospital of Air Force Medical University during February 2018 and December 2018. In addition, bladder cancer T24 cell line and normal urothelial cell line SV-HUC-1 were also collected for this study. The levels of miR144-3p in bladder cancer tissues and cells were detected by qPCR methods. The miR-144-3p mimics and miR-NC were transfected into T24 cells by LipofectamineTM 2000, respectively. The proliferation, cell cycle distribution and invasion abilities were detected by MTT, Flow cytometry and Transwell chamber methods, respectively. TargetScan software was used to predict the binding site between miR-144-3p and E2F3 (E2F transcription factor 3); Dual luciferase reporter gene assay was used to verify the relationship between miR-144-3p and E2F3; and WB was used to detect the expression levels of miR-144-3p and E2F3 in cells. Results: The expression of miR-144-3p was downregulated in bladder cancer tissues and cells (all P<0.01). In addition, the expression level of miR-144-3p in muscular invasive bladder cancer tissues was significantly lower than that in non-muscular invasive bladder cancer tissues (P<0.05). Dual luciferase reporter gene assay confirmed that there was a targeted relationship between miR-144-3p and E2F3. Overexpression of miR-144-3p inhibited the proliferation and invasion of T24 cells (all P<0.01) and downregulated the expression of E2F3 (P<0.01); upregulation of E2F3 could reverse the inhibitory effect of miR-144-3p overexpression on proliferation and invasion of T24 cells. Conclusion: miR-144-3p has low expression level in bladder cancer tissues. It inhibits proliferation and invasion of bladder cancer cells by downregulating E2F3.

MIR22HG regulates miR-486/PTEN axis in bladder cancer to promote cell proliferation.

The tumor suppressive role of MIR22HG has been studied in several types of cancer. We analyzed the TCGA dataset and found the down-regulation of MIR22HG in bladder cancer (BC). Bioinformatics analysis predicted the interaction between MIR22HG and miR-486. The direct interaction between MIR22HG and miR-486 was also confirmed by dual luciferase assay. However, overexpression of these two factors did not significantly affect the expression of each other. Interestingly, overexpression of MIR22HG led to up-regulated phosphatase and tensin homolog (PTEN), which is a target of miR-486. In cell proliferation assay, overexpression of MIR22HG and PTEN led to decreased rates of BC cell proliferation. Moreover, overexpression of miR-486 played an opposite role and attenuated the effects of overexpression of MIR22HG and PTEN. Therefore, MIR22HG regulates miR-486/PTEN axis to promote cell proliferation in BC.