Preoperative renal insufficiency predicts postoperative adverse outcomes in a mixed surgical population: a retrospective matched cohort study using the NSQIP database.

BACKGROUND: The incidence of chronic kidney disease is increasing, but most cases are not diagnosed until the accidental finding of abnormal laboratory data or the presentation of severe symptoms. Patients with chronic kidney disease are reported to have an increased risk of postoperative mortality and morbidities, but previous studies mainly targeted populations undergoing cardiovascular surgery. The authors aimed to evaluate the risk of postoperative mortality and complications in a surgical population with preoperative renal insufficiency (RI). MATERIALS AND METHODS: This retrospective cohort study used data from the National Surgical Quality Improvement Program database between 2013 and 2018 to evaluate the risk of postoperative morbidity and mortality in the surgical population. Patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m 2 were defined as the RI group. Propensity score matching methods and multivariate logistic regression were used to calculate the risk of postoperative morbidity and mortality. RESULTS: After propensity score matching, 502 281 patients were included in the RI and non-RI groups. The RI group had a higher risk of 30-day in-hospital mortality (odds ratio: 1.54, 95% CI: 1.49-1.58) than the non-RI group. The RI group was associated with a higher risk of postoperative complications, including myocardial infarction, stroke, pneumonia, septic shock, and postoperative bleeding. The RI group was also associated with an increased risk of prolonged ventilator use for over 48 h, readmission, and reoperation. CONCLUSION: Patients with preoperative RI have an increased risk of postoperative 30-day mortality and complications. RI group patients with current dialysis, estimated glomerular filtration rate less than or equal to 30 ml/min/1.73 m 2 or concomitant anemia had an elevated risk of postoperative mortality.

Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer.

BACKGROUND: Prostate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prostate cancer remain ambiguous. METHODS: The tumor immune contexture score (TICS) involving eight immune contexture-related signatures was developed using seven cohorts of 1120 patients treated with radical prostatectomy (training: GSE46602, GSE54460, GSE70769, and GSE94767; validation: GSE70768, DKFZ2018, and TCGA). The association between the TICS and treatment efficacy was investigated in GSE111177 (androgen deprivation therapy [ADT]) and EGAS00001004050 (ipilimumab). RESULTS: A high TICS was associated with prolonged BCRFS after radical prostatectomy in the training (HR = 0.32, 95% CI 0.24-0.45, P < 0.001) and the validation cohorts (HR = 0.45, 95% CI 0.32-0.62, P < 0.001). The TICS showed stable prognostic power independent of tumor stage, surgical margin, pre-treatment prostatic specific antigen (PSA), and Gleason score (multivariable HR = 0.50, 95% CI 0.39-0.63, P < 0.001). Adding the TICS into the prognostic model constructed using clinicopathological features significantly improved its 1/2/3/4/5-year area under curve (P < 0.05). A low TICS was associated with high homologous recombination deficiency scores, abnormally activated pathways concerning DNA replication, cell cycle, steroid hormone biosynthesis, and drug metabolism, and fewer tumor-infiltrating immune cells (P < 0.05). The patients with a high TICS had favorable BCRFS with ADT (HR = 0.25, 95% CI 0.06-0.99, P = 0.034) or ipilimumab monotherapy (HR = 0.23, 95% CI 0.06-0.81, P = 0.012). CONCLUSIONS: Our study delineates the associations of tumor immune contexture with molecular features, recurrence after radical prostatectomy, and the efficacy of ADT and immunotherapy. The TICS may improve the existing risk stratification systems and serve as a patient-selection tool for ADT and immunotherapy in prostate cancer.

Plasma cfDNA methylation markers for the detection and prognosis of ovarian cancer.

BACKGROUND: Plasma cell-free DNA (cfDNA) methylation has shown the potential in the detection and prognostic testing in multiple cancers. Herein, we thoroughly investigate the performance of cfDNA methylation in the detection and prognosis of ovarian cancer (OC). METHODS: The OC-specific differentially methylated regions (DMRs) were identified by sequencing ovarian tissue samples from OC (n = 61), benign ovarian disease (BOD, n = 49) and healthy controls (HC, n = 37). Based on 1,272 DMRs, a cfDNA OC detection model (OC-D model) was trained and validated in plasma samples from patients of OC (n = 104), BOD (n = 56) and HC (n = 56) and a prognostic testing model (OC-P model) was developed in plasma samples in patients with high-grade serous OC (HG-SOC) in the training cohort and then tested the rationality of this model with International Cancer Genome Consortium (ICGC) tissue methylation data. Mechanisms were investigated in the TCGA-OC cohort. FINDINGS: In the validation cohort, the cfDNA OC-D model consisting of 18 DMRs achieved a sensitivity of 94.7% (95% CI: 85.4%‒98.9%) at a specificity of 88.7% (95% CI: 78.7%‒94.9%), which outperformed CA 125 (AUC: 0.967 vs 0.905, P = 0.03). Then the cfDNA OC-P model consisting of 15 DMRs was constructed and associated with a better prognosis of HG-SOC in multivariable Cox regression analysis (HR: 0.29, 95% CI, 0.11‒0.78, P = 0.01) in the training cohort, which was also observed in the ICGC cohort using tissue methylation (HR: 0.56, 95% CI, 0.32‒0.98, P = 0.04). Investigation into mechanisms revealed that the low-risk group had higher homologous recombination deficiency and immune cell infiltration (P < 0.05). INTERPRETATION: Our study demonstrated the potential utility of cfDNA methylation in the detection and prognostic testing in OC. Future studies with a larger population are warranted. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sector.

DNA Damage Response Gene-Based Subtypes Associated With Clinical Outcomes in Early-Stage Lung Adenocarcinoma.

DNA damage response (DDR) pathways play a crucial role in lung cancer. In this retrospective analysis, we aimed to develop a prognostic model and molecular subtype based on the expression profiles of DDR-related genes in early-stage lung adenocarcinoma (LUAD). A total of 1,785 lung adenocarcinoma samples from one RNA-seq dataset of The Cancer Genome Atlas (TCGA) and six microarray datasets of Gene Expression Omnibus (GEO) were included in the analysis. In the TCGA dataset, a DNA damage response gene (DRG)-based signature consisting of 16 genes was constructed to predict the clinical outcomes of LUAD patients. Patients in the low-DRG score group had better outcomes and lower genomic instability. Then, the same 16 genes were used to develop DRG-based molecular subtypes in the TCGA dataset to stratify early-stage LUAD into two subtypes (DRG1 and DRG2) which had significant differences in clinical outcomes. The Kappa test showed good consistency between molecular subtype and DRG (K = 0.61, p < 0.001). The DRG subtypes were significantly associated with prognosis in the six GEO datasets (pooled estimates of hazard ratio, OS: 0.48 (0.41-0.57), p < 0.01; DFS: 0.50 (0.41-0.62), p < 0.01). Furthermore, patients in the DRG2 group benefited more from adjuvant therapy than standard-of-care, which was not observed in the DRG1 group. In summary, we constructed a DRG-based molecular subtype that had the potential to predict the prognosis of early-stage LUAD and guide the selection of adjuvant therapy for early-stage LUAD patients.

Identification of a Ten-Gene Signature of DNA Damage Response Pathways with Prognostic Value in Esophageal Squamous Cell Carcinoma.

Molecular prognostic signatures are critical for treatment decision-making in esophageal squamous cell cancer (ESCC), but the robustness of these signatures is limited. The aberrant DNA damage response (DDR) pathway may lead to the accumulation of mutations and thus accelerate tumor progression in ESCC. Given this, we applied the LASSO Cox regression to the transcriptomic data of DDR genes, and a prognostic DDR-related gene expression signature (DRGS) consisting of ten genes was constructed, including PARP3, POLB, XRCC5, MLH1, DMC1, GTF2H3, PER1, SMC5, TCEA1, and HERC2. The DRGS was independently associated with overall survival in both training and validation cohorts. The DRGS achieved higher accuracy than six previously reported multigene signatures for the prediction of prognosis in comparable cohorts. Furtherly, a nomogram incorporating DRGS and clinicopathological features showed improved predicting performance. Taken together, the DRGS was identified as a novel, robust, and effective prognostic indicator, which may refine the scheme of risk stratification and management in ESCC patients.

Ultrasound-guided superior laryngeal nerve block assists in anesthesia for bronchoscopic surgical procedure: A case report of anesthesia for rigid bronchoscopy.

INTRODUCTION: Evolving techniques in the field of therapeutic bronchoscopy have led to the return of rigid bronchoscopy in the treatment of complex central airway disease. Rigid bronchoscopy is typically performed under general anesthesia because of the strong stimulation caused by metal instruments. Anesthesia for rigid bronchoscopy is challenging to administer because anesthesiologists and interventionists share the same working channel: the airway. Previously reviewed anesthetic methods are used primarily for short procedures. Balanced anesthesia with ultrasound-guided superior laryngeal nerve (SLN) block and total intravenous anesthesia might provide anesthesia for a prolonged procedure and facilitate patient recovery. PATIENT CONCERNS: A patient with obstructed endobronchial stent was referred for therapeutic rigid bronchoscopy, which requires deeper anesthesia than flexible bronchoscopy. There were concerns of the stronger stimulation of the rigid bronchoscopy, lengthy duration of the procedure, higher risk of hypoxemia, and the difficulty of mechanical ventilation weaning after anesthesia due to the patients co-morbidities. DIAGNOSIS: A 66-year-old female patient presented with a history of breast cancer with lung metastases. Right main bronchus obstruction due to external compression of lung metastases was relieved through insertion of an endobronchial stent, but obstructive granulation developed after 4 months. Presence of the malfunctioning stent caused severe cough and discomfort. Removal of the stent by using a flexible bronchoscope was attempted twice but failed. INTERVENTIONS: Regional anesthesia of the upper airway through ultrasound-guided SLN block combined with intratracheal 2% lidocaine spray was performed to assist in total intravenous anesthesia (TIVA) during rigid bronchoscopy. OUTCOMES: The patient maintained steady spontaneous breathing throughout the procedure without laryngospasm, bucking, or desaturation. Emergence from anesthesia was smooth and rapid after propofol infusion was discontinued. The surgery lasted 2.5 hours without discontinuity, and no perioperative pulmonary or cardiovascular complications were noted. CONCLUSION: Ultrasound-guided SLN block is a simple technique with a high success rate and low complication rate. Application of SLN block to assist TIVA provides sufficient anesthesia for lengthened therapeutic rigid bronchoscopy without interruption and facilitates patient recovery.

Agrobacterium-produced and exogenous cytokinin-modulated Agrobacterium-mediated plant transformation.

Agrobacterium tumefaciens is a plant pathogenic bacterium that causes neoplastic growths, called 'crown gall', via the transfer and integration of transferred DNA (T-DNA) from the bacterium into the plant genome. We characterized an acetosyringone (AS)-induced tumour-inducing (Ti) plasmid gene, tzs (trans-zeatin synthesizing), that is responsible for the synthesis of the plant hormone cytokinin in nopaline-type A. tumefaciens strains. The loss of Tzs protein expression and trans-zeatin secretions by the tzs frameshift (tzs-fs) mutant is associated with reduced tumorigenesis efficiency on white radish stems and reduced transformation efficiencies on Arabidopsis roots. Complementation of the tzs-fs mutant with a wild-type tzs gene restored wild-type levels of trans-zeatin secretions and transformation efficiencies. Exogenous application of cytokinin during infection increased the transient transformation efficiency of Arabidopsis roots infected by strains lacking Tzs, which suggests that the lower transformation efficiency resulted from the lack of Agrobacterium-produced cytokinin. Interestingly, although the tzs-fs mutant displayed reduced tumorigenesis efficiency on several tested plants, the loss of Tzs enhanced tumorigenesis efficiencies on green pepper and cowpea. These data strongly suggest that Tzs, by synthesizing trans-zeatin at early stage(s) of the infection process, modulates plant transformation efficiency by A. tumefaciens.