Prognostic Model and Immune Response of Clear Cell Renal Cell Carcinoma Based on Co-Expression Genes Signature.

BACKGROUND: The identification of reliable prognostic markers is crucial for optimizing patient management and improving clinical outcomes in clear cell renal cell carcinoma (ccRCC). METHODS: We used the GSE89563 dataset from the GEO database and the Kidney Clear Cell Carcinoma (KIRC) dataset from the TCGA database to develop a prognostic model based on weighted gene co-expression network analysis (WGCNA) and non-negative matrix factorization (NMF) to predict disease progression and prognosis in ccRCC. RESULT: We utilized WGCNA to identify risk genes and applied NMF to stratify high-risk populations in ccRCC. We characterized the immune gene features of these high-risk groups and ultimately developed a risk prediction model for ccRCC patients using a Lasso regression approach. The risk score was calculated as follows: Risk score = SUM (-0.136394797 ANK3 + 0.004238138 BIVM_ERCC5 - 0.046248451 C4orf19 - 0.036013206 F2RL3 - 0.125531316 GNG7 - 0.012698109 METTL7A + 0.078462369 MSTO1 - 0.050450656 PINK1 - 0.059446590 SLC16A12 - 0.039883686 SLC2A9 + 0.083310722 TLCD1 - 0.059801739 WDR72 + 0.071430088 ZNF117). CONCLUSION: We develop a prognostic model for clear cell renal cell carcinoma and analyzed immune response in subgroups and confirmed protein-level expression concordance.

Translocation of probiotics via gut-lung axis enhanced pulmonary immunity of weaned piglets exposed to low concentrations of ammonia.

OBJECTIVE: Lactobacillus salivarius is a probiotic bacteria strain in human and animal diets. The administration of probiotics to weaned piglets may improve their growth by optimizing the gastrointestinal bacterial composition. To further investigate the effect of bacterial communication between the gastrointestinal tract and lungs on bodily immunity, we reared weaned piglets in a low-ammonia gas environment. L. salivarius was supplemented to explore its effects on pulmonary immunity and its potential for bacterial translocation. RESULTS: One hundred sixty weaned piglets were allocated to four groups: L. salivarius-supplemented, L. reuteri-supplemented, control, and antibiotic drug (aureomycin)-supplemented. The feeding duration was 28 d. The body weights of piglets administered a strain of Lactobacillus were better than those of the control (P < 0.01). The transcription level of immune factors interleukin 2 (IL-2), IL-4, interferon α (IFN-α), and tumor necrosis factor α (TNF-α) in cells of the ileum and lung was significantly higher (P < 0.01). Lung and ileal mucus tissues were isolated to sequence the bacterial composition, which suggested a higher richness in the lungs at the phylum level, which was not significant in the ileum. Functional bacteria were more abundant in the ileum and lungs. The proportion of the genera of Lactobacillus, Prevotella, Actinobacillus, and Prevotellaceae_ NK3B31_group increased in two tissues, and a lower ratio of Streptococcus, Escherichia-Shigella, and mycoplasma was detected. The correlation between the microbial genus composition and the levels of immune factors suggests that the abundance of Lactobacillus plays the same positive role in the lungs and ileum. Mycoplasmas play a negative role in ileal and pulmonary immunity. More Lactobacillus reuteri and anaerobic probiotic bacteria were detected in the lungs. CONCLUSION: The colonization of Lactobacillus salivarius and Lactobacillus reuteri in the membrane of the ileum optimized the ileal microbial composition, enrolled other probiotic bacteria translating to the lung, improved the abundance of pulmonary microbiota, and enhanced immunity after exposure to low concentrations of ammonia.

Metabolomic and lipidomic profiling of the spinal cord in type 2 diabetes mellitus rats with painful neuropathy.

In this paper we investigated lipid and metabolite changes in diabetic neuropathy, using untargeted lipidomics and metabolomics analyses of the spinal cords from streptozotocin-treated diabetic rats.170 metabolites and 45 lipids were dysregulated in the painful diabetic neuropathy (PDN) phase. Pathway enrichment analysis revealed perturbations in starch and sucrose, tryptophan, pyrimidine, cysteine and methionine, thiamine, tyrosine, and nucleotides. The disturbance of tyrosine, tryptophan, methionine, triacylglycerol, and phosphatidylethanolamine metabolism indicated that pathological mechanisms in the PDN involved energy metabolism, oxidative stress, and neural reparative regeneration. These revelations offered potential biomarkers for PDN and enriched the comprehension of the complex molecular mechanisms characterizing PDN, establishing a solid foundation for subsequent inquiries into neural convalescence and recovery after PDN.

SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a-PINK1-Parkin signaling pathway to activate mitophagy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.

Modeling the complexity of drug-drug interactions: A physiologically-based pharmacokinetic study of Lenvatinib with Schisantherin A/Schisandrin A.

BACKGROUND: Lenvatinib's efficacy as a frontline targeted therapy for radioactive iodine-refractory thyroid carcinoma and advanced hepatocellular carcinoma owes to its inhibition of multiple tyrosine kinases. However, as a CYP3A4 substrate, lenvatinib bears susceptibility to pharmacokinetic modulation by co-administered agents. Schisantherin A (STA) and schisandrin A (SIA) - bioactive lignans abundant in the traditional Chinese medicinal Wuzhi Capsule - act as CYP3A4 inhibitors, engendering the potential for drug-drug interactions (DDIs) with lenvatinib. METHODS: To explore potential DDIs between lenvatinib and STA/SIA, we developed a physiologically-based pharmacokinetic (PBPK) model for lenvatinib and used it to construct a DDI model for lenvatinib and STA/SIA. The model was validated with clinical trial data and used to predict changes in lenvatinib exposure with combined treatment. RESULTS: Following single-dose administration, the predicted area under the plasma concentration-time curve (AUC) and maximum plasma concentrations (Cmax) of lenvatinib increased 1.00- to 1.03-fold and 1.00- to 1.01-fold, respectively, in the presence of STA/SIA. Simulations of multiple-dose regimens revealed slightly greater interactions, with lenvatinib AUC0-t and Cmax increasing up to 1.09-fold and 1.02-fold, respectively. CONCLUSION: Our study developed the first PBPK and DDI models for lenvatinib as a victim drug. STA and SIA slightly increased lenvatinib exposure in simulations, providing clinically valuable information on the safety of concurrent use. Given the minimal pharmacokinetic changes, STA/SIA are unlikely to interact with lenvatinib through pharmacokinetic alterations synergistically but rather may enhance efficacy through inherent anti-cancer efficacy of STA/ SIA.

Selective removal behavior of lead and cadmium from calcium-rich solution by MgO loaded soybean straw biochars and mechanism analysis.

Modified biochars has great potential for removing heavy metals from aquatic environments, but the removal of heavy metals by biochars is usually significantly affected by the co-presence of the macro amount of metal ions, such as Ca. Enhancing the ion exchange capacity of biochar by increasing its alkali metal content is a very prospective method to improve its selectivity. In this paper, MgO loaded biochar (MBC) was synthesized by co-pyrolysis of soybean straw and MgCl2·6H2O for selective remove Pb and Cd from calcium-rich wastewater. MBC exhibited excellent selective adsorption performance for Pb and Cd in calcium-rich wastewater due to the successful loading of MgO. The adsorption capacities of MBC for Pb and Cd were 582.57 and 167.40 mg/g, and the removal efficiency of Ca below 2.5% with an initial concentration of 800 mg/L. The ion exchange capacities of Pb and Cd enhanced almost 27 and 23 times than BC. By analyzing the results of BET, XRD, SEM-EDS, XPS and FTIR, the adsorption mechanisms of MBC were mainly including ion exchange, precipitation with minerals, and interaction with oxygen-containing functional groups. The easy preparation method and high selective adsorption capacity makes MBC an ideal alternative for efficiently selective removal Pb and Cd from calcium-rich wastewater.

Correction: Wang et al. Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma. Molecules 2019, 24, 3540.

When reviewing our publications, an error in article [...].

The Chemical Profiling and Anticancer Potential of Functional Polysaccharides from Flos Sophorae Immaturus.

Polysaccharides from Flos Sophorae Immaturus (FSI) are one of its pharmacological compounds that can perform effective activities. Aiming to extract the most effective polysaccharides against hepatocellular carcinoma (HCC), the polysaccharides were separated from FSI through ultrasonic microwave extraction, and the first comparison was carried out on the characterization of the structure and its cytotoxic properties on HCC SMMC 7721 cells of undeproteinized purified polysaccharides (PFSI-1) and papain-deproteinized polysaccharides (PFSI-2) from FSI. The findings indicated that PFSI-1 and PFSI-2 had characteristic absorption peaks of polysaccharides; PFSI-1 contained three monosaccharides and PFSI-2 contained ten; and SEM, AFM, and NMR were consistent with the verification of IR polysaccharide characteristics, suggesting probable additional latent activities. The pharmacotoxic effects of both PFSI-1 and PFSI-2 on SMMC 7721 cells (p < 0.05), attenuated the migration ability of SMMC 7721 cells (p < 0.05) and promoted apoptosis (p < 0.05), with an increase in G0/G1-phase cells and decrease in S-phase cells in the PFSI-1 as well as a decrease in G0/G1-phase cells, increase in S-phase cells, and decrease in apoptosis in the PFSI-2 (p < 0.05). The significant cytotoxic effect of PFSI-2 on SMMC 7721 cells (p < 0.05) and its protective effect on human hepatic L02 cells (HL-7702) at low concentrations (p > 0.05) could indicate its potential as a new drug for the treatment of HCC.

Intraoperative Hypotension and Myocardial Injury After Noncardiac Surgery in Adults With or Without Chronic Hypertension: A Retrospective Cohort Analysis.

BACKGROUND: The risk of myocardial injury progressively increases at intraoperative mean arterial pressures (MAPs) ≤65 mm Hg. Higher pressures might be required in chronically hypertensive patients. We aimed to test the hypothesis that the harm threshold is higher in patients with chronic hypertension than in normotensive patients. METHODS: We conducted a single-center retrospective cohort analysis of adults >45 years old who had noncardiac surgery between 2010 and 2018 and scheduled, rather than symptom-driven, postoperative troponin measurements. The MAP thresholds under which risk started to increase were compared between patients with chronic hypertension (baseline MAP ≥110 mm Hg) and normotensive patients (baseline MAP <110 mm Hg). The primary outcome was a composite of in-hospital mortality and myocardial injury within 30 days, defined by any postoperative 4th-generation troponin T measurement ≥0.03 ng/mL apparently due to cardiac ischemia. Multivariable logistic regression and moving average smoothing methods were used to evaluate confounder-adjusted associations between the composite outcome and the lowest intraoperative MAP sustained for either 5 or 10 cumulative minutes, and whether the relationship depended on baseline pressure (normotensive versus hypertensive). RESULTS: Among 4576 eligible surgeries, 2066 were assigned to the normotensive group with mean (standard deviation [SD]) baseline MAP of 100 (7) mm Hg, and 2510 were assigned to the hypertensive group with mean baseline MAP of 122 (10) mm Hg. The overall incidence of the composite outcome was 5.6% in normotensive and 6.0% in hypertensive patients ( P = .55). The relationship between intraoperative hypotension and the composite outcome was not found to depend on baseline MAP in a multivariable mixed effects logistic regression model. Furthermore, no statistical change points were found for either baseline MAP group. CONCLUSIONS: Baseline blood pressure of the hypertensive patients was only moderately increased on average, and the event rate was low. Nonetheless, we were not able to demonstrate a difference in the harm threshold between normotensive and chronically hypertensive patients. Our results do not support the theory that hypertensive patients should be kept at higher intraoperative pressures than normotensive patients.

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects.

BACKGROUND: Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. METHODS: We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. RESULTS: Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. CONCLUSIONS: The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.

Intra-operative hypertension and myocardial injury and/or mortality and acute kidney injury after noncardiac surgery: A retrospective cohort analysis.

BACKGROUND: Whether intra-operative hypertension causes postoperative complications remains unclear. OBJECTIVE: We sought to assess whether there is an absolute systolic hypertensive threshold associated with increased odds of a composite of postoperative myocardial injury and mortality, and acute kidney injury. DESIGN: A retrospective cohort analysis using an electronic medical record registry. SETTING: The Cleveland Clinic Main Campus, Cleveland, Ohio, USA, between January 2005 and December 2018. PATIENTS: A total of 76 042 adults who had inpatient noncardiac surgery lasting at least an hour, creatinine recorded preoperatively and postoperatively, and had an available clinic blood pressure within 6 months before surgery. MAIN OUTCOME MEASURES: Univariable smoothing and multivariable logistic regression were used to estimate the probability of each outcome as a function of the highest intra-operative pressure for a cumulative 5, 10, or 30 min. We further assessed whether the relationships between intra-operative hypertension and each outcome depended on baseline systolic blood pressure. RESULTS: The composite of myocardial injury and mortality was observed in 1.9%, and acute kidney injury in 4.5% of patients. After adjustment for confounders, there was little or no relationship between systolic pressure and either outcome over the range from 120 to 200 mmHg. There were also no obvious change points or thresholds above which odds of each outcome increased. And finally, there was no interaction with preoperative clinic blood pressure. CONCLUSIONS: There was no clinically meaningful relationship between intra-operative systolic pressure and the composite of myocardial injury and mortality, or acute kidney injury, over the range from 120 and 200 mmHg.

Postoperative Outcomes Associated With Procedural Sedation Conducted by Physician and Nonphysician Anesthesia Providers: Findings From the Prospective, Observational African Surgical Outcomes Study.

BACKGROUND: There is an unmet need for essential surgical services in Africa. Limited anesthesia services are a contributing factor. Nonphysician anesthesia providers are utilized to assist with providing anesthesia and procedural sedation to make essential surgeries available. There is a paucity of data on outcomes following procedural sedation for surgery in Africa. We investigated the postoperative outcomes following procedural sedation by nonphysicians and physicians in Africa. We hypothesized that the level of training of the sedation provider may be associated with the incidence of severe postoperative complications and death. METHODS: A secondary analysis of a prospective cohort of inhospital adult surgical patients representing 25 African countries was performed. The primary outcome was a collapsed composite of inhospital severe postoperative complications and death. We assessed the association between receiving procedural sedation conducted by a nonphysician (versus physician) and the composite outcome using logistic regression. We used the inverse probability of treatment weighting propensity score method to adjust for potential confounding variables including patient age, hemoglobin level, American Society of Anesthesiologists (ASA) physiological status, diabetes mellitus, urgency of surgery, severity of surgery, indication for surgery, surgical discipline, seniority of the surgical team, hospital level of specialization, and hospital funding system using public or private funding. All patients who only received procedural sedation for surgery were included. RESULTS: Three hundred thirty-six patients met the inclusion criteria, of which 98 (29.2%) received sedation from a nonphysician provider. The incidence of severe postoperative complications and death was 10 of 98 (10.2%) in the nonphysician group and 5 of 238 (2.1%) in the physician group. The estimated association between procedural sedation conducted by a nonphysician provider and inhospital outcomes was an 8-fold increase in the odds of severe complications and/or death, with an odds ratio (95% confidence interval [CI]) of 8.3 (2.7-25.6). CONCLUSIONS: The modest number of observations in this secondary data analysis suggests that shifting the task of procedural sedation from physicians to nonphysicians to increase access to care may be associated with severe postoperative complications and death in Africa. Research focusing on identifying factors contributing to adverse outcomes associated with procedural sedation is necessary to make this practice safer.

Intraoperative Hypotension and Acute Kidney Injury after Noncardiac Surgery in Infants and Children: A Retrospective Cohort Analysis.

BACKGROUND: Age- and sex-specific reference nomograms for intraoperative blood pressure have been published, but they do not identify harm thresholds. The authors therefore assessed the relationship between various absolute and relative characterizations of hypotension and acute kidney injury in children having noncardiac surgery. METHODS: The authors conducted a retrospective cohort study using electronic data from two tertiary care centers. They included inpatients 18 yr or younger who had noncardiac surgery with general anesthesia. Postoperative renal injury was defined using the Kidney Disease Improving Global Outcomes definitions, based on serum creatinine concentrations. The authors evaluated potential renal harm thresholds for absolute lowest intraoperative mean arterial pressure (MAP) or largest MAP reduction from baseline maintained for a cumulative period of 5 min. Separate analyses were performed in children aged 2 yr or younger, 2 to 6 yr, 6 to 12 yr, and 12 to 18 yr. RESULTS: Among 64,412 children who had noncardiac surgery, 4,506 had creatinine assessed preoperatively and postoperatively. The incidence of acute kidney injury in this population was 11% (499 of 4,506): 17% in children under 6 yr old, 11% in children 6 to 12 yr old, and 6% in adolescents, which is similar to the incidence reported in adults. There was no association between lowest cumulative MAP sustained for 5 min and postoperative kidney injury. Similarly, there was no association between largest cumulative percentage MAP reduction and postoperative kidney injury. The adjusted estimated odds for kidney injury was 0.99 (95% CI, 0.94 to 1.05) for each 5-mmHg decrease in lowest MAP and 1.00 (95% CI, 0.97 to 1.03) for each 5% decrease in largest MAP reduction from baseline. CONCLUSIONS: In distinct contrast to adults, the authors did not find any association between intraoperative hypotension and postoperative renal injury. Avoiding short periods of hypotension should not be the clinician's primary concern when trying to prevent intraoperative renal injury in pediatric patients.

Mechanisms contributing to hypotension after anesthetic induction with sufentanil, propofol, and rocuronium: a prospective observational study.

It remains unclear whether reduced myocardial contractility, venous dilation with decreased venous return, or arterial dilation with reduced systemic vascular resistance contribute most to hypotension after induction of general anesthesia. We sought to assess the relative contribution of various hemodynamic mechanisms to hypotension after induction of general anesthesia with sufentanil, propofol, and rocuronium. In this prospective observational study, we continuously recorded hemodynamic variables during anesthetic induction using a finger-cuff method in 92 non-cardiac surgery patients. After sufentanil administration, there was no clinically important change in arterial pressure, but heart rate increased from baseline by 11 (99.89% confidence interval: 7 to 16) bpm (P < 0.001). After administration of propofol, mean arterial pressure decreased by 23 (17 to 28) mmHg and systemic vascular resistance index decreased by 565 (419 to 712) dyn*s*cm-5*m2 (P values < 0.001). Mean arterial pressure was < 65 mmHg in 27 patients (29%). After propofol administration, heart rate returned to baseline, and stroke volume index and cardiac index remained stable. After tracheal intubation, there were no clinically important differences compared to baseline in heart rate, stroke volume index, and cardiac index, but arterial pressure and systemic vascular resistance index remained markedly decreased. Anesthetic induction with sufentanil, propofol, and rocuronium reduced arterial pressure and systemic vascular resistance index. Heart rate, stroke volume index, and cardiac index remained stable. Post-induction hypotension therefore appears to result from arterial dilation with reduced systemic vascular resistance rather than venous dilation or reduced myocardial contractility.

Failure to detect ward hypoxaemia and hypotension: contributions of insufficient assessment frequency and patient arousal during nursing assessments.

BACKGROUND: Postoperative hypotension and hypoxaemia are common and often unrecognised. With intermittent nursing vital signs, hypotensive or hypoxaemic episodes might be missed because they occur between scheduled measurements, or because the process of taking vital signs arouses patients and temporarily improves arterial blood pressure and ventilation. We therefore estimated the fraction of desaturation and hypotension episodes that did not overlap nursing assessments and would therefore usually be missed. We also evaluated the effect of taking vital signs on blood pressure and oxygen saturation. METHODS: We estimated the fraction of desaturated episodes (arterial oxygen saturation <90% for at least 90% of the time within 30 continuous minutes) and hypotensive episodes (MAP <70 mm Hg for 15 continuous minutes) that did not overlap nursing assessments in patients recovering from noncardiac surgery. We also evaluated changes over time before and after nursing visits. RESULTS: Among 782 patients, we identified 878 hypotensive episodes and 2893 desaturation episodes, of which 79% of the hypotensive episodes and 82% of the desaturation episodes did not occur within 10 min of a nursing assessment and would therefore usually be missed. Mean BP and oxygen saturation did not improve by clinically meaningful amounts during nursing vital sign assessments. CONCLUSIONS: Hypotensive and desaturation episodes are mostly missed because vital sign assessments on surgical wards are sparse, rather than being falsely negative because the assessment process itself increases blood pressure and oxygen saturation. Continuous vital sign monitoring will detect more disturbances, potentially giving clinicians time to intervene before critical events occur.

Acute pain after serratus anterior plane or thoracic paravertebral blocks for video-assisted thoracoscopic surgery: A noninferiority randomised trial.

BACKGROUND: Serratus anterior plane blocks (SAPBs) and thoracic paravertebral blocks (TPVBs) can both be used for video-assisted thoracic surgery. However, it remains unknown whether the analgesic efficacy of a SAPB is comparable to that of a TPVB. OBJECTIVE: We tested the primary hypothesis that SAPBs provide noninferior analgesia compared with TPVBs for video-assisted thoracic surgery. DESIGN: A noninferiority randomised trial. SETTING: Shanghai Chest Hospital, between August 2018 and November 2018. PATIENTS: Ninety patients scheduled for video-assisted thoracic lobectomy or segmentectomy were randomised. Patients were excluded if they were unable to perform the visual analogue pain scale, or surgery was converted to thoracotomy. INTERVENTIONS: Blocks were performed after induction of general anaesthesia. The three groups were paravertebral blocks (n = 30); serratus anterior plane blocks (n = 29); and general anaesthesia alone (n = 30). PRIMARY OUTCOME MEASURES: Visual analogue pain scores (0 to 10 cm) at rest and while coughing, and Prince-Henry pain scores (0 to 4 points) were used to assess postoperative analgesia at 2, 24 and 48 h after surgery. We assessed the noninferiority of SAPBs with TPVBs on all three primary pain outcomes using a delta of 1 cm or one point as appropriate. RESULTS: The mean difference (95% confidence intervals) in visual analogue scores between the SAPBs and TPVBs was -0.04 (-0.10 to 0.03) cm at rest, -0.22 (-0.43 to -0.01) cm during coughing and -0.10 (-0.25 to 0.05) for Prince-Henry pain scores. As the upper limit of the confidence intervals were less than 1 (all P < 0.001), noninferiority was claimed for all three primary outcomes. Compared with general anaesthesia alone, the VAS scores at rest and while coughing, and the Prince-Henry pain scores for the two blocks were significantly lower during the initial 2 h after surgery. CONCLUSIONS: Serratus anterior plane blocks are quicker and easier to perform than paravertebral blocks and provide comparable analgesia in patients having video-assisted thoracic surgery. Both blocks provided analgesia that was superior to general anaesthesia alone during the initial 2 h after surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR1800017671.

Percutaneous Peripheral Nerve Stimulation (Neuromodulation) for Postoperative Pain: A Randomized, Sham-controlled Pilot Study.

BACKGROUND: Percutaneous peripheral nerve stimulation is an analgesic technique involving the percutaneous implantation of a lead followed by the delivery of electric current using an external pulse generator. Percutaneous peripheral nerve stimulation has been used extensively for chronic pain, but only uncontrolled series have been published for acute postoperative pain. The current multicenter study was undertaken to (1) determine the feasibility and optimize the protocol for a subsequent clinical trial and (2) estimate the treatment effect of percutaneous peripheral nerve stimulation on postoperative pain and opioid consumption. METHODS: Preoperatively, an electrical lead was percutaneously implanted to target the sciatic nerve for major foot/ankle surgery (e.g., hallux valgus correction), the femoral nerve for anterior cruciate ligament reconstruction, or the brachial plexus for rotator cuff repair, followed by a single injection of long-acting local anesthetic along the same nerve/plexus. Postoperatively, participants were randomized to 14 days of either electrical stimulation (n = 32) or sham stimulation (n = 34) using an external pulse generator in a double-masked fashion. The dual primary treatment effect outcome measures were (1) cumulative opioid consumption (in oral morphine equivalents) and (2) mean values of the "average" daily pain scores measured on the 0 to 10 Numeric Rating Scale within the first 7 postoperative days. RESULTS: During the first 7 postoperative days, opioid consumption in participants given active stimulation was a median (interquartile range) of 5 mg (0 to 30) versus 48 mg (25 to 90) in patients given sham treatment (ratio of geometric means, 0.20 [97.5% CI, 0.07 to 0.57]; P < 0.001). During this same period, the average pain intensity in patients given active stimulation was a mean ± SD of 1.1 ± 1.1 versus 3.1 ± 1.7 in those given sham (difference, -1.8 [97.5% CI, -2.6 to -0.9]; P < 0.001). CONCLUSIONS: Percutaneous peripheral nerve stimulation reduced pain scores and opioid requirements free of systemic side effects during at least the initial week after ambulatory orthopedic surgery.

Supplemental Intraoperative Oxygen and Long-term Mortality: Subanalysis of a Multiple Crossover Cluster Trial.

BACKGROUND: Whether supplemental oxygen worsens long-term mortality remains unclear, with contradictory trial results. The authors therefore tested the hypothesis that supplemental oxygen (80% vs. 30%) increases the hazard for long-term mortality. METHODS: The authors conducted a post hoc analysis of a large multiple crossover cluster trial in which more than 5,000 colorectal surgeries on 4,088 adults were allocated to receive either 30% or 80% inspired oxygen during general anesthesia. The authors assessed the effect of 80% versus 30% target-inspired oxygen on long-term mortality and calculated Kaplan-Meier survival estimates. Analysis was restricted to patients with a home address in Ohio because the authors could obtain reliable vital status information from the Ohio Department of Health (Columbus, Ohio) for them. RESULTS: A total of 3,471 qualifying colorectal surgeries performed in 2,801 patients were analyzed, including 1,753 (51%) surgeries in 1,577 patients given 80% oxygen and 1,718 surgeries in 1,551 patients given 30% oxygen. The observed incidence of death after a median of 3 yr was 13% (234 of 1,753) in the 80% oxygen group and 14% (245 of 1,718) in the 30% oxygen group. The estimated hazard ratio for mortality was 0.94 (95% CI, 0.78 to 1.13; P = 0.493). CONCLUSIONS: In this post hoc analysis of a large, controlled trial, supplemental oxygen did not increase postoperative mortality.

Whole-exome Sequencing of Prostate Cancer in Sardinian Identify Recurrent UDP-glucuronosyltransferase Amplifications.

Globally, prostate cancer is the third most common cancer in the world, and the second most common cancer in men. However, rates for incidence and mortality vary considerably with race, ethnicity, and geography. Over 97 significantly mutated genes that have been identified in prostate cancer; however, a lack of genomic prostate cancer studies focusing on different racial and ethnic groups and racial mixing pose a serious challenge to universalize these findings. The Sardinian population is an isolated Mediterranean population that has a high frequency of centenarians and a much lower incidence of prostate cancer than found in males in mainland Europe. Here, we conducted a genomic prostate cancer study on a Sardinian cohort diagnosed with local prostate cancer. Our data reveals a low rate of ERG fusion in Sardinian prostate cancer. Interestingly, we identified a novel BTBD7-SLC2A5 fusion that occurred in 13% of the patients. We also found that the UGT2B4 on 4q13.2 was amplified in 20% of the Sardinian patients but rarely amplified in patients of other population. These observations underscore the importance of the inter-population molecular heterogeneity of prostate cancer. In addition, we examined the expression of UGT2B4 in 497 prostate cancer patients derived from The Cancer Genome Atlas database. We found that high expression of UGT2B4 was associated with low-grade prostate cancer and upregulation of UGT2B4 in tumors was associated with upregulation of metabolism pathways such as 'de novo' IMP biosynthetic process, glutamine and monocarboxylic acid metabolism. These data provide insight into clinical relevance and functional mechanism of UGT2B4. Further understanding functional mechanism of UGT2B4 amplification and BTBD7-SLC2A5 fusion will aid in developing drugs to benefit the prostate cancer patients.

Ethnic Differences in Analgesic Efficacy and Safety of Liposomal Bupivacaine Among Asian and Caucasian Surgical Patients: A Retrospective Matched-Cohort Analysis.

BACKGROUND: Extended-release local anesthetics allow for prolonged analgesia after a single administration. Although Asians demonstrate different pain thresholds than Caucasians, whether they have different postoperative local anesthetic analgesic effects has not been elucidated. OBJECTIVE: We aimed to compare the postoperative analgesic efficacy of liposomal bupivacaine on Asian and Caucasian adults, and the incidence of local anesthetic systemic toxicity (LAST) syndrome. METHODS: We conducted a retrospective, assessor-blinded cohort study of adult patients who received liposomal bupivacaine for surgery between 2012 and 2018. Asians and Caucasians were matched in a 1:1 ratio by clinical characteristics and surgery type. The primary outcome was pain management, defined as average pain score and opioid consumption during the initial 72 postoperative hours. The secondary outcome was the incidence of LAST syndrome. Reviewers were blinded to the ethnicity of the patient. RESULTS: After 1:1 propensity score matching, 130 Asians and 129 Caucasians were analyzed. All confounding variables were balanced, except for higher body mass index in the Asian group. Pain scores were lower (adjusted mean difference of -0.50 [97.5% CI, -0.98, -0.01]; superiority p = 0.011) and opioid consumption was not greater (geometric means ratio, 0.61 [97.5% CI, 0.36, 1.04]; non-inferiority p ＜ 0.001) in Asian patients compared to Caucasian patients. Only one Caucasian patient was judged as having a potential case of LAST syndrome. The length of hospital stay and the incidence of additional complications were not different between the groups. CONCLUSION: Asian adults receiving liposomal bupivacaine as part of multimodal perioperative analgesia demonstrated lower pain scores compared to matching Caucasians, despite not having greater opioid consumption.