Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures.

Background: Autophagy is involved in the pathophysiological process of sepsis. This study was designed to identify autophagy-related key genes in sepsis, analyze their correlation with immune cell signatures, and search for new diagnostic and prognostic biomarkers. Methods: Whole blood RNA datasets GSE65682, GSE134347, and GSE134358 were downloaded and processed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify autophagy-related key genes in sepsis. Then, key genes were analyzed by functional enrichment, protein-protein interaction (PPI), transcription factor (TF)-gene and competing endogenous RNA (ceRNA) network analysis. Subsequently, key genes with diagnostic efficiency and prognostic value were identified by receiver operating characteristic (ROC) curves and survival analysis respectively. The signatures of immune cells were estimated using CIBERSORT algorithm. The correlation between significantly different immune cell signatures and key genes was assessed by correlation analysis. Finally, key genes with both diagnostic and prognostic value were verified by RT-qPCR. Results: 14 autophagy-related key genes were identified and their TF-gene and ceRNA regulatory networks were constructed. Among the key genes, 11 genes (ATIC, BCL2, EEF2, EIF2AK3, HSPA8, IKBKB, NLRC4, PARP1, PRKCQ, SH3GLB1, and WIPI1) had diagnostic efficiency (AUC > 0.90) and 5 genes (CAPN2, IKBKB, PRKCQ, SH3GLB1 and WIPI1) were associated with survival prognosis (p-value < 0.05). IKBKB, PRKCQ, SH3GLB1 and WIPI1 had both diagnostic and prognostic value, and their expression were verified by RT-qPCR. Analysis of immune cell signatures showed that the abundance of neutrophil, monocyte, M0 macrophage, gamma delta T cell, activated mast cell and M1 macrophage subtypes increased in the sepsis group, while the abundance of resting NK cell, resting memory CD4+ T cell, CD8+ T cell, naive B cell and resting dendritic cell subtypes decreased. Most of the key genes correlated with the predicted frequencies of CD8+ T cells, resting memory CD4+ T cells, M1 macrophages and naive B cells. Conclusion: We identified autophagy-related key genes with diagnostic and prognostic value in sepsis and discovered associations between key genes and immune cell signatures. This work may provide new directions for the discovery of promising biomarkers for sepsis.

The effects of external diaphragmatic pacing on diaphragm function and weaning outcomes of critically ill patients with mechanical ventilation: a prospective randomized study.

Background: Diaphragmatic pacing can improve diaphragm function, which is beneficial for the prognosis of patients treated with prolonged mechanical ventilation (MV). While most previous studies have focused on the role of implanted diaphragm pacing (IDP), our study is the first to examine the effects of external diaphragmatic pacing (EDP) in mechanically ventilated patients. Specifically, the effect of EDP on diaphragm function, the success rate of weaning, the duration of MV (DMV), and the intensive care unit (ICU) length of stay (ILOS) were assessed. Methods: From September 2019 to December 2020, a total of 51 mechanically ventilated patients in the ICU of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University were enrolled and randomly divided into an EDP group of 27 patients and a control group of 24 patients. The control group received routine treatment, and the EDP group received EDP treatment in addition to routine treatment. The diaphragm excursion (DE), diaphragm thickening fraction (DTF), DMV, ILOS, and average survival time were recorded to evaluate efficacy. Results: Patients treated with EDP had increased DE [exp(B) =1.86, 95% CI: 1.39 to 2.50, P<0.001] and DTF [exp(B) =1.35, 95% CI: 1.05 to 1.76, P=0.022], shortened weaning time (P=0.026) and prolonged average survival time (P<0.001) compared to patients who did not receive EDP therapy. Especially in cases with difficult weaning, the improvement of DE and DTF in the EDP treatment group was more obvious than that in the control group (P=0.013 and P=0.032). Moreover, the DTF upon attempted spontaneous breathing trial (SBT) was negatively correlated with the fraction of inspired oxygen (FiO2) [r=-0.54; 95% confidence interval (CI): -0.77 to -0.19; P=0.004], the arterial partial pressure of oxygen (PaO2) (r=-0.58; 95% CI: -0.79 to -0.25; P=0.001), the PaO2/FiO2 ratio (r=-0.52; 95% CI: -0.75 to -0.16; P=0.006), and the serum lactate concentration (Lac) (r=-0.39; 95% CI: -0.68 to 0.003; P=0.046). Conclusions: EDP treatment can effectively reduce the DMV and prolong the average survival time of mechanically ventilated patients. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900024096.

High level of neutrophil to lymphocyte ratio increases the risk of deep venous thrombosis in intensive care unit patients after oral cancer surgery: a retrospective study.

Background: The incidence of deep venous thrombosis (DVT) is higher in surgical patients, but there have been few studies on the risk factors of DVT in intensive care unit (ICU) patients after oral cancer surgery, particularly in relation to the inflammatory and nutritional scores, and intervene with these risk factors early may decrease the occurrence of DVT. Methods: We performed a retrospective study of adult patients who were admitted to ICU after undergoing radical resection of oral cancer and performed ultrasound detection for DVT within 1 week after surgery from April 2019 to July 2021. DVT was diagnosed by venous ultrasonography of the lower extremities. Preoperative inflammatory and nutritional scores, including neutrophil to lymphocyte ratio (NLR), plate to lymphocyte ratio (PLR), prognostic nutritional index (PNI) were retrospectively calculated according to test results before surgery. Clinical characteristics, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Caprini Risk Score (CRS), Charlson comorbidity index, anticoagulation therapy, and mechanical ventilation time (MVT) after admitted to ICU were obtained. The risk factors affecting DVT occurrence were analyzed by logistic regression, and the receiver operating characteristic (ROC) curve was used to analyze the value of the relevant indicators in evaluating DVT. Results: Among the 128 patients, 43 patients (33.6%) developed DVT. Compared with the non-DVT group, the preoperative glucose (GLU), postoperative D-dimer (P<0.05), and postoperative NLR (P<0.001) were higher in the DVT group than in the non-DVT group. In multivariate logistic analysis, NLR (P=0.001), postoperative D-dimer >5.57 µg/mL (P=0.002), GLU >5.15 mmol/L (P=0.025) was associated with DVT, and the areas under the curve (AUCs) of NLR in predicting DVT was 0.729. We also found that the DVT group had longer MVT and length of stay (LOS) than the non-DVT group, and correlation analysis indicated that NLR level was positively related with MVT (r=0.36; P<0.0001) and LOS (r=0.452; P<0.0001). Conclusions: A high level of NLR, indicative of a poor immunity and nutrition status, increases the risk of DVT in patients after oral cancer surgery, and improvement of immunity and nutrition status may help decrease the occurrence of postoperative DVT.

Identification of differentially expressed genes, transcription factors, microRNAs and pathways in neutrophils of sepsis patients through bioinformatics analysis.

Sepsis has been recognized to be a life-threatening organ dysfunction caused by the dysregulation of the host response to infections. Our work aims to screen key biomarkers related to neutrophils in sepsis using bioinformatics analysis. For this purpose, the microarray datasets related to neutrophils in sepsis patients were downloaded from the Gene Expression Omnibus (GEO) database. According to the Bayesian test, the Limma package in R was used to screen differentially expressed genes (DEGs). Then, DEGs were uploaded to the DAVID online diagnostic tool for subsequent Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on the selected DEGs. Next, protein-protein interaction (PPI) network was established based on the selected DEGs using the STRING website and the Cytoscape software. Furthermore, according to the function of the iRegulon plug-in in Cytoscape, our study further predicts and established regulatory networks related to transcription factors and regulatory genes. In addition, the miRWalk2.0 database was used to search for miRNA-DEG pairs, associated with the conduction of intersections of miRNAs predicted by TargetScan, Miranda, miRDB and RNA22 databases. Then, these miRNA-DEG pairs were also displayed in the form of a regulatory network through Cytoscape. Finally, two datasets were selected to verify the screened genes, regulatory factors, and miRNAs, to plot receiver operating characteristics (ROC) curves and compute the area under the curve (AUC) values. The results showed that AKT1, MMP9, ARG1, ETS1 targeting AKT1, and has-miR-124-3p targeting RPS6KA5 may have diagnostic value for patients with sepsis and septic shock. While further experimental studies are required to confirm their role in septic neutrophils.

[Impact of hypophosphatemia on weaning from mechanical ventilation].

OBJECTIVE: To explore the influence of hypophosphatemia on weaning from mechanical ventilation. METHODS: An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1:2 case-control matching based on gender, age, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis. RESULTS: Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE (r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). CONCLUSIONS: Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.

Silencing of LncRNA-PVT1 ameliorates lipopolysaccharide-induced inflammation in THP-1-derived macrophages via inhibition of the p38 MAPK signaling pathway.

BACKGROUND: Sepsis is common in intensive care units and has a high mortality rate; yet, its pathogenesis and treatment remain unclear. Recent studies have shown that long non-coding RNA plasmacytoma variant translocation 1 (lncRNA-PVT1) plays a pro-inflammatory role in immune-related inflammatory diseases. Therefore, we investigated whether lncRNA-PVT1 plays an important pro-inflammatory effect in the inflammatory response of sepsis. METHODS: Quantitative real-time PCR (RT-qPCR) was employed for the detection of lncRNA-PVT1, interleukin 1ß (IL-1ß), and tumor necrosis factor α (TNF-α) mRNA, and the correlations between their expressions were analyzed. After lncRNA-PVT1 knockdown by lncRNA Smart Silencer, abnormal expressions of lncRNA-PVT1, and IL-1ß and TNF-α mRNA were detected. The expressions of total and phosphorylated protein of p38 were detected by western blotting. The effect of silencing lncRNA-PVT1 on p38 mitogen-activated protein kinase (MAPK) signaling pathway during lipopolysaccharide (LPS)-induced inflammation was subsequently analyzed. The MAPK selective inhibitor, SB202190, was used to block this signaling pathway, and the expressions of lncRNA-PVT1 and TNF-α were detected by RT-qPCR. Furthermore, the effect of partial blockade of the p38 MAPK signaling pathway by SB202190 on the levels of lncRNA-PVT1 was explored. RESULTS: Following treatment of THP-1-derived macrophages with different concentrations of LPS, the levels of lncRNA-PVT1 and IL-1ß, TNF-α mRNA were increased in a dose-dependent manner. Silencing of lncRNA-PVT1 reduced the expressions of IL-1ß and TNF-α mRNA via inhibition of the p38 MAPK signaling pathway. Specifically, inhibiting the p38 MAPK pathway significantly decreased the LPS-induced lncRNA-PVT1 elevation. CONCLUSIONS: Our observations suggest that lncRNA-PVT1 can be silenced to ameliorate LPS-induced inflammation in macrophages via inhibition of the p38 MAPK pathway. Further, the p38 MAPK pathway can regulate the expression of lncRNA-PVT1 via a positive feedback loop.

Caspofungin pharmacokinetics and probability of target attainment in ICU patients in China.

OBJECTIVES: Effective antifungal therapy is important to reduce mortality in patients with invasive fungal infections (IFIs). Numerous factors affect pharmacokinetic/pharmacodynamic (PK/PD) parameters in critically-ill patients. To guide individualised administration in critically-ill patients, it is of great significance to determine the population pharmacokinetics of caspofungin. METHODS: A prospective study in 42 ICU patients with IFIs was conducted in China. A population pharmacokinetic model of caspofungin was established using a non-linear mixed-effects model, which was utilised to investigate the effects of demographic indices, liver function and kidney function on pharmacokinetics. Additionally, appropriate dosages of caspofungin under various scenarios were determined based on MICs and probability of target attainment (PTA) at specific dosages. RESULTS: In critically-ill Chinese patients, clearance (CL), volume of distribution (V) and area under the curve at steady-state (AUCss) of caspofungin were 0.32 L/h, 6.77 L and 135.47 mg•h/L, respectively. Blood albumin and total bilirubin levels were factors affecting CL, while body weight was the only factor affecting V among Chinese people with relatively low weight compared with other populations. A maintenance dose of 50 mg caspofungin achieved a high PTA for treating IFIs caused by Candida albicans (MIC ≤ 0.06 mg/L) and Candida glabrata (MIC ≤ 0.125 mg/L). The maintenance dose of caspofungin should be adjusted to 70-200 mg for IFIs caused by C. albicans (MIC, 0.06-0.125 mg/L). For IFIs caused by Candida parapsilosis, an MIC > 0.03 mg/L is associated with a very low PTA, but higher doses of caspofungin or alternative antifungals need to be further studied. CONCLUSION: The population pharmacokinetic model established here described well the PK/PD characteristics of caspofungin in critically-ill Chinese patients. These results could guide the formulation of individualised caspofungin dosing regimens for critically-ill patients.

Clinical significance of prognostic nutritional index in renal cell carcinomas.

ABSTRACT: Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study. The prognostic correlation between PNI and overall survival (OS) and recurrence-free survival (RFS) was analyzed respectively using Kaplan-Meier method and univariate and multivariate Cox model. Studies about the association between pretreatment or preoperative PNI and prognosis of RCC were systemically reviewed and a meta-analysis method was performed to further evaluate the pooled prognostic value of PNI in RCC.267 (38.47%) RCC patients had low PNI according to the cut off value (49.08). Low PNI was associated with poor OS (P < .001) and RFS (P < .001), respectively. In the multivariate Cox analysis, PNI was identified to be an independent prognostic factor for OS (hazard ratio [HR] = 2.13, 95%CI: 1.25-3.62, P = .005). Compared to other nutritional indexes, this risk correlation of PNI is better than that of geriatric nutritional risk index (GNRI; HR = 1.19; P = .531), while is no better than that of neutrophil-lymphocyte ratio (NLR; 1/HR = 2.56; P < .001) and platelet-lymphocyte ratio (PLR; 1/HR = 2.85; P < .001) respectively. Meanwhile, additional 4785 patients from 6 studies were included into pooled analysis. For RCC patients who underwent surgery, low preoperative PNI was significantly associated with worse OS (pooled HR = 1.57, 95%CI: 1.37-1.80, P < .001) and worse RFS (pooled HR = 1.69, 95%CI: 1.45-1.96, P < .001). Furthermore, low PNI (<41-51) was also significantly associated with poor OS (HR = 1.78, 95%CI: 1.26-2.53 P < .05) and poor RFS (HR = 2.03, 95%CI: 1.40-2.95, P < .05) in advanced cases treated with targeted therapies.The present evidences show that PNI is an independent prognostic factor in RCC. Low PNI is significant associated with poor prognosis of RCC patients.

Mutation analysis of the cystic fibrosis transmembrane conductance regulator gene in Chinese congenital absence of vas deferens patients.

To find the variant spectrum of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and evaluate its frequent variants in Chinese congenital absence of vas deferens (CAVD) patients. A total of 276 patients with azoospermia and CAVD (aged from 21 to 44 years old) were investigated from May 2013 to September 2019 in the Third Affiliated Hospital of Sun Yat-sen University. Additionally, 50 healthy, unrelated volunteers were recruited as controls (aged from 21 to 46 years old). The 5'-UTR, exons and their flanking side of the CFTR gene were sequenced by high-throughput sequencing technology. The results were compared with those retrieved from the Ensembl Genome Browser. In addition, all 13 novel variants were further confirmed independently by Sanger sequencing and evaluated in the bioinformatics web servers. A schematic of the variant spectrum of the CFTR gene, including 13 novel variants (12 in CAVD patients, one in the control group), is shown, and the frequent variants in Chinese CAVD patients were 5 T (27.54%), c.-8G > C (7.25%), p.Q1352H (5.98%), and p.I556V (3.08%). 5 T was found to be the most frequent variant. p.Q1352H had a significantly high allelic frequency in CAVD patients (P < 0.05). c.-8G > C and p.I556V had high allelic frequencies but showed no difference between patients and controls (P > 0.05). p.Q1352H is the most common and important missense variant in Chinese patients with CAVD, while the pathological effects of C.-8G > C and p.I556V may be weak after evaluation.

Protective effects of P2X7R antagonist in sepsis-induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression.

BACKGROUND: Sepsis induces pulmonary P2X7 receptor (P2X7 R) expression and P2X7 R-knockout reduced lung inflammation in mice. The present study investigated the expression of circular RNA (circRNA) and mRNA in sepsis-induced acute lung injury (ALI) treated with a P2X7 R antagonist. METHODS: Sepsis was induced by tracheal administration of lipopolysaccharide (LPS), and the mice were then divided into two groups: without [sepsis + dimethyl sulfoxide (DMSO)] or with P2X7 R antagonist treatment (sepsis + P2X7 A). Sham mice were administrated sterile normal saline. Serum levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, pathological changes, cell apoptosis and P2X7 R expression in lung were assessed, followed by RNA sequencing (RNA-seq) and bioinformatics analyses. A quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate circRNAs and mRNAs. RESULTS: Compared to the sham group, LPS-induced sepsis produced obvious pathological changes in lung tissue, as well as increased apoptotic lung cells, serum TNF-α and IL-1ß levels, and P2X7 R expression; P2X7 R antagonism significantly ameliorated these changes. RNA-seq identified many dysregulated circRNAs and mRNAs during sepsis, whereas this changed with P2X7 R antagonism. RT-qPCR confirmed that Mus musculus (mmu)_circ_0001679, mmu_circ_0001212, phospholamban (Pln), cadherin-2 (Cdh2) and nitrogen permease regulator 3-like (Nprl3) expression were significantly increased in the sepsis + DMSO group compared to that in the sham group but were decreased in the sepsis + P2X7 A group compared to that in the sepsis + DMSO group. The circRNA-microRNA-mRNA coexpression network indicated that mmu_circ_0001679 may regulate Nprl3 and that mmu_circ_0001212 may similarly regulate Pln, Cdh2 and Nprl3 as a competing endogenous RNA. CONCLUSIONS: P2X7 R antagonism attenuates sepsis-induced ALI by inhibiting dysregulated expression of circRNA (circ_0001679, circ_0001212) and mRNA (Pln, Cdh2 and Nprl3).

Consecutive nightly measurements are needed for accurate evaluation of nocturnal erectile capacity when the first-night laboratory recording is abnormal.

Multiple measurements of nocturnal penile tumescence and rigidity (NPTR) are widely accepted as a method to differentiate psychogenic erectile dysfunction (ED) from organic ED. However, direct evidence remains limited regarding the first-night effect on NPTR measurement using the RigiScan. Here, we evaluated the first-night effect on the results of NPTR measurement to validate the necessity of NPTR measurement for two consecutive nights, particularly when abnormal first-night measurements are recorded in a laboratory setting. We retrospectively reviewed 105 patients with a complaint of ED, who underwent NPTR measurement using the RigiScan in the Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), for two consecutive nights, during the period from November 2015 to May 2016. NPTR parameters were collected and analyzed. We found that more effective nocturnal erections were detected during the second night than during the first night (P <0.001). Twenty percent of all patients had no effective erection during the first night, but exhibited at least one effective erection during the second night. The negative predictive value of NPTR measurement during the first night was 43.2%; this was significantly lower than that on the second night (84.2%; P = 0.003). Most NPTR parameters were better on the second night than on the first night. The first-night effect might be greater among patients younger than 40 years of age. In conclusion, two consecutive nightly measurements of NPTR can avoid a false-abnormal result caused by the first-night effect; moreover, these measurements more accurately reflect erectile capacity, especially when the first-night record is abnormal in a laboratory setting.

Increased expression of miR-155 correlates with abnormal allograft status in solid organ transplant patients and rat kidney transplantation model.

AIMS: Increasing evidence has shown the diagnostic value of miR-155 in organ transplantation. The dysregulation of miR-155 is reported to be associated with development of acute or chronic complications in solid organ transplant recipients. Here, we summarized related evidence to explore the correlation between the dysregulation of miR-155 and various allograft dysfunction in transplant recipients, and verified the dynamic change of miR-155 level in acute rejection (AR) using a rat renal transplantation model. MAIN METHODS: Eligible studies were retrieved from PubMed, Embase, and Cochrane Library databases. A meta-analysis method was performed to evaluate the diagnostic value of miR-155 in transplant recipients. Furthermore, the F344-Lewis rat renal transplantation model was established to validate the dynamic change of miR-155 expression during AR. KEY FINDINGS: A total of 275 transplant patients, including renal, heart, and lung transplantation from 6 studies were analysed. The pooled SEN of miR-155 was 0.87 (95% CI, 0.78-0.93), the pooled SPE was 0.76 (95% CI, 0.63-0.85), the pooled PLR was 3.6 (95% CI, 2.2-5.8), the pooled NLR was 0.17 (95% CI, 0.09-0.31), the pooled DOR was 17.31 (95% CI, 7.20-41.65) and pooled AUC was 0.89 (95% CI, 0.86-0.92). The rat renal transplantation model (n = 24) and control model (n = 15) were successfully established. Expression of miR-155 in plasma was significantly increased in 7 d and 9 d post-transplantation compared to the control group (P < 0.05), and was consistent with the dynamic change of AR degree. SIGNIFICANCE: miR-155 is a potential biomarker for monitoring the abnormal allograft status in solid organ transplantation.

The Role of Nocturnal Penile Tumescence and Rigidity (NPTR) Monitoring in the Diagnosis of Psychogenic Erectile Dysfunction: A Review.

INTRODUCTION: Nocturnal penile tumescence and rigidity (NPTR) monitoring with RigiScan was considered one of the most reliable methods to differentiate psychogenic erectile dysfunction (pED) from organic ED. However, its reliability has been questioned because of some limitations in the practice. AIM: To present contemporary views on the role of NPTR monitoring in the diagnosis of pED. METHOD: We performed a comprehensive review of English-language literature on NPTR and pED by a PubMed search. MAIN OUTCOME MEASURES: Studies were included if the mechanisms of pED and nocturnal erection and the practice of NPTR monitoring in ED were the main research contents. RESULTS: The pED results from not only psychosocial factors but also physiological changes containing central nervous abnormality. NPTR monitoring with RigiScan is still considered a useful method for the diagnosis of pED. A normal NPTR recording in a man with ED complaints probably suggests pED, whereas an abnormal recording may represent organic ED. Radial rigidity of no more than 60% is correlated well with axial rigidity, but, when it is more than 60%, the correlation between them is questioned. The consistency between NPTR and sex-stimulated erection is questionable, and the correlation of NPTR with different patient-reported outcome scoring systems is different. A normal NPTR recording in patients with ED does not necessarily mean pED, especially in patients with spinal cord injury. NPTR recordings can be influenced by depression, smoking, aging, negative dream content, and sleep disorders. CONCLUSION: NPTR monitoring with the RigiScan is still considered a useful diagnostic tool for pED at the present stage. However, there are some disputes regarding the correlation between penile radial rigidity and axial rigidity and between NPTR and sex-related erection, as well as normative evaluation criteria for ED and the possibility of a false NPTR result, that need to be further studied. Zou Z, Lin H, Zhang Y, et al. The Role of Nocturnal Penile Tumescence and Rigidity (NPTR) Monitoring in the Diagnosis of Psychogenic Erectile Dysfunction: A Review. Sex Med Rev 2019;7:442-454.

Knockdown of ribosomal protein S15A inhibits human kidney cancer cell growth in vitro and in vivo.

Ribosomal protein S15A (RPS15A), a member of the ribosomal protein gene family, was demonstrated to be closely associated with tumorigenesis in multiple human malignancies. Nevertheless, the role of RPS15A in the progression of renal cell carcinoma (RCC) remains unknown. In the present study, by comparing the publicly available data from RCC tissues and reverse transcription­quantitative polymerase chain reaction results, it was identified that RPS15A was upregulated in RCC tissues and cell lines (P<0.001). Notably, knockdown of RPS15A suppressed 786­O cell proliferation (P<0.001) and promoted its apoptosis/necrotic (P=0.0001) in vitro. Additionally, tumour formation and growth of transfected 786­O cells were observed to be restrained in a mouse model (P<0.05). Subsequent to analysing the microarray data, 747 genes were differentially expressed in the RPS15A­knockdown 786­O cells. The enriched canonical pathways, diseases and functions of differentially expressed genes, and the interactive network of RPS15A in RCC were successfully constructed by ingenuity pathway analysis. Overall, the present results provided a preliminary experimental basis for RPS15A as a novel oncogene and potential therapeutic target in RCC.

Early post-operative serum albumin level predicts survival after curative nephrectomy for kidney cancer: a retrospective study.

BACKGROUND: Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7 days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer. METHODS: We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed. RESULTS: A total of 329 patients were included. The median duration of follow-up was 54.8 months. Patients with an early post-operative serum albumin level < 32 g/L had a significantly shorter median recurrence-free survival (RFS; 49.1 versus 56.5 months, P = 0.001) and median overall survival (OS; 52.2 versus 57.0 months, P = 0.049) than patients with an early post-operative serum albumin level ≥ 32 g/L. After adjusting for age, BMI, tumor stage, post-operative hemoglobin concentration, and pre-operative albumin, globulin, and hemoglobin levels, multivariate Cox regression showed that an early post-operative serum albumin level < 32 g/L was an independent prognostic factor associated with a decreased RFS (HR = 3.60; 95% CI,1.05-12.42 [months], P = 0.042) and decreased OS (HR = 9.95; 95% CI, 1.81-54.80 [months], P = 0.008). CONCLUSION: An early post-operative serum albumin level < 32 g/L is an independent prognostic factor leading to an unfavorable RFS and OS. Prospective trials and further studies involving additional patients are warranted.

A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer.

BACKGROUND: The 8th American Joint Committee on Cancer tumor-node-metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer. METHODS: A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation. RESULTS: A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort. CONCLUSIONS: T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.

A Risk Prediction Model for Invasive Fungal Disease in Critically Ill Patients in the Intensive Care Unit.

PURPOSE: Developing a risk prediction model for invasive fungal disease based on an analysis of the disease-related risk factors in critically ill patients in the intensive care unit (ICU) to diagnose the invasive fungal disease in the early stages and determine the time of initiating early antifungal treatment. METHODS: Data were collected retrospectively from 141 critically ill adult patients with at least 4 days of general ICU stay at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during the period from February 2015 to February 2016. Logistic regression was used to develop the risk prediction model. Discriminative power was evaluated by the area under the receiver operating characteristics (ROC) curve (AUC). RESULTS: Sequential organ failure assessment (SOFA) score, antibiotic treatment period, and positive culture of Candida albicans other than normally sterile sites are the three predictors of invasive fungal disease in critically ill patients in the ICU. The model performs well with an ROC-AUC of .73. CONCLUSION: The risk prediction model performs well to discriminate between critically ill patients with or without invasive fungal disease. Physicians could use this prediction model for early diagnosis of invasive fungal disease and determination of the time to start early antifungal treatment of critically ill patients in the ICU.

Laparoscopic versus open adrenalectomy for localized (stage 1/2) adrenocortical carcinoma: Experience at a single, high-volumecenter.

BACKGROUND: Open adrenalectomy is considered a standard operative approach for adrenocortical carcinoma, and laparoscopic adrenalectomy remains controversial. We analyzed our outcomes of laparoscopic adrenalectomy and open adrenalectomy for localized (stage 1/2) adrenocortical carcinoma in our hospital. METHODS: This study retrospectively reviewed all patients with stage 1/2 adrenocortical carcinoma and a tumor size < 10 cm who underwent radical resection in our hospital between 2009 and 2017. These patients were divided into laparoscopic adrenalectomy and open adrenalectomy groups. Demographics, operative data, and follow-up outcomes were collected. The 5-year overall survival and recurrence-free survival were calculated with the Kaplan-Meier method and compared between laparoscopic adrenalectomy and open adrenalectomy group. RESULTS: A total of 23 patients operated by an open adrenalectomy and 21 patients operated with a laparoscopic adrenalectomy were included. Baseline patient characteristics (age, sex, tumor size, hormonal secretion) were similar between 2 groups. The mean postoperative stay was less in the laparoscopic adrenalectomy group (P = .003). The mean follow-up time was similar for the two groups (33 ± 24 vs 35 ± 25 months; P = NS). The local and peritoneal recurrence rates were 42% for laparoscopic adrenalectomy and 22% for open adrenalectomy (P = .035). Time to local and peritoneal recurrence was less in the laparoscopic adrenalectomy than in the open adrenalectomy (P = .048). The 5-year overall survival and recurrence-free survival for open adrenalectomy versus laparoscopic adrenalectomy were 43% vs 47% (P = .635) and 36% vs 39% (P = .802), respectively. CONCLUSION: We believe that open adrenalectomy should still be considered the standard operative management of adrenocortical carcinoma. Laparoscopic adrenalectomy may not provide patients with localized adrenocortical carcinoma with an equivalent oncologic outcome based on site and timing of initial tumor recurrence.

Benefits of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The adjuvant use of mitotane on adrenocortical carcinoma (ACC) has always been in controversy. We aimed to assess the prognostic benefits of adjuvant mitotane after resection of ACC in patients without distant metastasis. METHODS: The PubMed, WoS, Embase, and Cochrane Library databases were systematically searched. Recurrence-free survival (RFS) and overall survival (OS) were adopted as measurements. A meta-analysis was conducted based on hazard ratio (HR) with 95% confidence interval (CI). A study was included only if the enrolled patients underwent resection of ACC without adjuvant chemotherapy except mitotane. RESULTS: A total of 5 retrospective studies reporting on 1249 patients were included for this meta-analysis. The meta-analysis showed that adjuvant mitotane was significantly associated with prolonged RFS (HR = 0.62; 95%CI, 0.42-0.94; P < 0.05) and prolonged OS (HR = 0.69; 95%CI, 0.55-0.88, P < 0.05). CONCLUSION: After comprehensive review, current evidence suggests that adjuvant mitotane significantly decreases the recurrence rate and mortality after resection of ACC in patients without distant metastasis, but these findings need further demonstration from prospective controlled trials.