Perioperative morbidity and 3-year survival in non-intubated thoracoscopic surgery: a propensity matched analysis.

Background: Non-intubated thoracoscopic surgery with spontaneous breathing is rarely utilized, but may have several advantages over standard intubation, especially in those with significant cardiopulmonary comorbidities. In this study we evaluate the safety, feasibility, and 3-year survival of thoracoscopic surgery without endotracheal intubation for oncologic and non-oncologic indications. Methods: All consecutive patients [2018-2022] selected for lung resection or other pleural space intervention under local anesthesia and sedation were compared to a cohort undergoing elective thoracoscopic procedures with endotracheal intubation. A propensity-score matched cohort was used to compare perioperative outcomes and 3-year overall survival. Results: A total of 72 patients underwent thoracoscopic surgery without intubation compared to 1,741 who were intubated. Non-intubated procedures included 19 lobectomies (26.4%), 9 segmentectomies (12.5%), 25 wedge resections (34.7%), and 19 pleural or mediastinal resections (26.4%). Non-intubated patients had a lower average body mass index (BMI; 24.6 vs. 27.1 kg/m2, P<0.001) and a higher comorbidity burden. Primary lung cancer was the indication in 30 (41.7%) non-intubated patients. The non-intubated cohort had no operative or 30-day mortality. After propensity-score matching, there was no significant difference in pre-operative factors. In propensity-score matched analysis, non-intubated patients had shorter median total operating room time (109 vs. 159 min, P<0.001) and procedure time (69 vs. 119 min, P<0.001). Peri-operative morbidity was rare and did not differ between intubated and non-intubated patients. There was no significant difference in 3-year survival associated with non-intubation in the propensity-score matched cohorts (95% vs. 89%, P=0.10) or in a Cox proportional hazard model [hazard ratio (HR), 1.15; 95% confidence interval (CI): 0.36-3.67; P=0.81]. Conclusions: Non-intubated thoracoscopic surgery is safe and feasible in carefully selected patients for both benign and oncologic indications.

AcumenTM hypotension prediction index guidance for prevention and treatment of hypotension in noncardiac surgery: a prospective, single-arm, multicenter trial.

BACKGROUND: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. METHODS: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. MEASUREMENTS: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. RESULTS: Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: - 0.35 (95%CI - 0.43, - 0.27); p < 0.001]. CONCLUSIONS: The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. TRIAL REGISTRATION: Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

Predictors of Venous Thromboembolism After Lung Cancer Resection.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients undergoing oncologic operations. We sought to identify risk factors for postoperative VTE to define high-risk groups that may benefit from enhanced prophylactic measures. METHODS: A retrospective cohort analysis using The Society of Thoracic Surgeons General Thoracic Surgery Database was conducted on patients who underwent lung cancer resection between 2009 and 2021. Baseline characteristics and postoperative outcomes were compared between patients who did and did not develop a postoperative pulmonary embolism (PE) or deep venous thrombosis. Multivariable regression models identified risk factors associated with VTE. RESULTS: Of 57,531 patients who underwent lung cancer resection, a postoperative PE developed in 758 (1.3%). Patients with PE were more likely to be Black (12% vs 7%, P < .001), have interstitial fibrosis (3% vs 2%, P = .016), and prior VTE (12% vs 6%, P < .001). Postoperative PE was most likely to develop in patients with locally advanced disease who underwent bilobectomy (6% vs 4%, P < .001) or pneumonectomy (8% vs 5%, P < .001). Patients with postoperative PE had increased 30-day mortality (14% vs 3%, P < .001), reintubation (25% vs 8%, P < .001), and readmission (49% vs 15%, P < .001). On multivariable analysis, Black race (odds ratio, 1.74; 95% CI, 1.39-2.16; P < .001), interstitial fibrosis (odds ratio, 1.77; 95% CI, 1.15-2.72; P = .009), extent of resection, and increased operative duration were independently predictive of postoperative PE. A minimally invasive approach compared with thoracotomy was protective. CONCLUSIONS: Because nonmodifiable risk factors (Black race, interstitial fibrosis, and advanced-stage disease) predominate in postoperative PE and VTE-associated mortality is increased, enhanced perioperative prophylactic measures should be considered in high-risk cohorts.

Stable SERS Detection of Lactobacillus fermentum Using Optical Tweezers in a Microfluidic Environment.

Rapid identification of fermented lactic acid bacteria has long been a challenge in the brewing industry. This study combined label-free surface-enhanced Raman scattering (SERS) and optical tweezer technology to construct a test platform within a microfluidic environment. Six kinds of lactic acid bacteria common in industry were tested to prove the stability of the SERS spectra. The results demonstrated that the utilization of optical tweezers to securely hold the bacteria significantly enhanced the stability of the SERS spectra. Furthermore, SVM and XGBoost machine learning algorithms were utilized to analyze the obtained Raman spectra for identification, and the identification accuracies exceeded 95% for all tested lactic acid bacteria. The findings of this study highlight the crucial role of optical tweezers in improving the stability of SERS spectra by capturing bacteria in a microfluidic environment, prove that this technology could be used in the rapid identification of lactic acid bacteria, and show great significance in expanding the applicability of the SERS technique for other bacterial testing purposes.

Discovery of Highly Selective and Orally Bioavailable PI3Kδ Inhibitors with Anti-Inflammatory Activity for Treatment of Acute Lung Injury.

PI3Kδ is a promising target for the treatment of inflammatory disease; however, the application of PI3Kδ inhibitors in acute respiratory inflammatory diseases is rarely investigated. In this study, through scaffold hopping design, we report a new series of 1H-pyrazolo[3,4-d]pyrimidin-4-amine-tethered 3-methyl-1-aryl-1H-indazoles as highly selective and potent PI3Kδ inhibitors with significant anti-inflammatory activities for treatment of acute lung injury (ALI). There were 29 compounds designed, prepared, and subjected to PI3Kδ inhibitory activity evaluation and anti-inflammatory activity evaluation in macrophages. (S)-29 was identified as a candidate with high PI3Kδ inhibitory activity, isoform selectivity, and high oral bioavailability. The in vivo administration of (S)-29 at 10 mg/kg dosage could significantly ameliorate histopathological changes and attenuate lung inflammation in lung tissues of LPS-challenged mice. Molecular docking demonstrated the success of scaffold hopping design. Overall, (S)-29 is a potent PI3Kδ inhibitor which might be a promising candidate for the treatment of ALI.

The underlying mechanisms of cisplatin-induced nephrotoxicity and its therapeutic intervention using natural compounds.

Cisplatin is an effective chemotherapeutic drug widely used for the treatment of various solid tumors; however, its clinical use and efficacy are limited by its inherent nephrotoxicity. The pathogenesis of cisplatin-induced nephrotoxicity is complex and has not been fully elucidated. Cellular uptake and transport, DNA damage, apoptosis, oxidative stress, inflammatory response, and autophagy are involved in the development of cisplatin-induced nephrotoxicity. Currently, despite some deficiencies, hydration regimens remain the major protective measures against cisplatin-induced nephrotoxicity. Therefore, effective drugs must be explored and developed to prevent and treat cisplatin-induced kidney injury. In recent years, many natural compounds with high efficiency and low toxicity have been identified for the treatment of cisplatin-induced nephrotoxicity, including quercetin, saikosaponin D, berberine, resveratrol, and curcumin. These natural agents have multiple targets, multiple effects, and low drug resistance; therefore, they can be safely used as a supplementary regimen or combination therapy for cisplatin-induced nephrotoxicity. This review aimed to comprehensively describe the molecular mechanisms underlying cisplatin-induced nephrotoxicity and summarize natural kidney-protecting compounds to provide new ideas for the development of better therapeutic agents.

Discovery and Optimization of N-Acyl-6-sulfonamide-tetrahydroquinoline Derivatives as Novel Non-Steroidal Selective Glucocorticoid Receptor Modulators.

Selective glucocorticoid receptor modulators (SGRMs), which can dissociate the transactivation from the transrepression of the glucocorticoid receptor (GR), are regarded as very promising therapeutics for inflammatory and autoimmune diseases. We previously discovered a SGRM HP-19 based on the passive antagonistic conformation of GR and bioassays. In this study, we further analyzed the dynamic changes of the passive antagonistic state upon the binding of HP-19 and designed and synthesized 62 N-acyl-6-sulfonamide-tetrahydroquinoline derivatives by structural optimization of HP-19. Therein, compound B53 exhibits the best transrepression activity (IC50 NF-κB = 0.009 ± 0.001 µM) comparable with dexamethasone (IC50 NF-κB = 0.005 ± 0.001 µM) and no transactivation activity. B53 can efficiently reduce the expression of inflammatory factors IL-6, IL-1ß, TNF-α, and so on and makes a milder adverse effect and is highly specific to GR. Furthermore, B53 is able to significantly relieve dermatitis on a mouse model via oral drug intervention.

Regional anesthesia and acute perioperative pain management in thoracic surgery: a narrative review.

Background and Objective: Thoracic surgery causes significant pain which can negatively affect pulmonary function and increase risk of postoperative complications. Effective analgesia is important to reduce splinting and atelectasis. Systemic opioids and thoracic epidural analgesia (TEA) have been used for decades and are effective at treating acute post-thoracotomy pain, although both have risks and adverse effects. The advancement of thoracoscopic surgery, a focus on multimodal and opioid-sparing analgesics, and the development of ultrasound-guided regional anesthesia techniques have greatly expanded the options for acute pain management after thoracic surgery. Despite the expansion of surgical techniques and analgesic approaches, there is no clear optimal approach to pain management. This review aims to summarize the body of literature regarding systemic and regional anesthetic techniques for thoracic surgery in both thoracotomy and minimally invasive approaches, with a goal of providing a foundation for providers to make individualized decisions for patients depending on surgical approach and patient factors, and to discuss avenues for future research. Methods: We searched PubMed and Google Scholar databases from inception to May 2021 using the terms "thoracic surgery", "thoracic surgery AND pain management", "thoracic surgery AND analgesia", "thoracic surgery AND regional anesthesia", "thoracic surgery AND epidural". We considered articles written in English and available to the reader. Key Content and Findings: There is a wide variety of strategies for treating acute pain after thoracic surgery, including multimodal opioid and non-opioid systemic analgesics, regional anesthesia including TEA and paravertebral blocks (PVB), and a recent expansion in the use of novel fascial plane blocks especially for thoracoscopy. The body of literature on the effectiveness of different approaches for thoracotomy and thoracoscopy is a rapidly expanding field and area of active debate. Conclusions: The optimal analgesic approach for thoracic surgery may depend on patient factors, surgical factors, and institutional factors. Although TEA may provide optimal analgesia after thoracotomy, PVB and emerging fascial plane blocks may offer effective alternatives. A tailored approach using multimodal systemic therapies and regional anesthesia is important, and future studies comparing techniques are necessary to further investigate the optimal approach to improve patient outcomes.

Facile Synthesis of γ-Butenolides and Maleic Anhydrides via Annulation of α-Keto Acids and Triazenyl Alkynes.

A facile synthesis of γ-butenolides and maleic anhydrides via annulation of α-keto acids and triazenyl alkynes is described. In this process, α-keto acids and triazenyl alkynes could undergo a self-catalyzed annulation at room temperature to deliver γ-butenolides efficiently, while the further addition of BF3-Et2O furnished maleic anhydrides. Overall, these processes have mild reaction conditions, broad scope, and high efficiency.

Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery.

STUDY OBJECTIVE: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery. DESIGN: Randomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526). SETTING: 3 academic institutions in the United States. PATIENTS: 60 patients undergoing laparoscopic colorectal surgery. INTERVENTIONS: A continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia. MEASUREMENTS: The outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids. MAIN RESULTS: Postoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group. CONCLUSIONS: VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526.

Construction and Validation of a Novel Ferroptosis-Related lncRNA Signature to Predict Prognosis in Colorectal Cancer Patients.

Background: Colorectal cancer (CRC) ranks as the third most common malignancy worldwide but a reliable prognostic biomarker of CRC is still lack. Thus, the purpose of our study was to explore whether ferroptosis - related lncRNAs could predict the prognosis of CRC. Methods: The mRNA expression profiling of colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) patients in The Cancer Genome Atlas (TCGA) database were downloaded. Univariate Cox and multivariate Cox regression analyses was used to obtain prognostic differently expressed ferroptosis-related lncRNAs (DE-FLs) and a risk signature was developed. Quantitative polymerase chain reaction (q-PCR) was used to validated the different expressions of DE-FLs. The calibration curves, C-index and the receiver operating characteristic (ROC) curves were applied to evaluate the accuracy of nomogram. Gene set enrichment analyses (GSEA) were carried out to explore the biological mechanism between high- and low-risk group and the potential regulated pathway of prognostic DE-FLs in CRC. Results: Forty-nine DE-FLs were identified between CRC and normal tissue. Then, a 4-DE-FLs (AC016027.1, AC099850.3, ELFN1-AS1, and VPS9D1-AS1) prognostic signature model was generated. AC016027.1 was downregulated in CRC tissue; VPS9D1-AS1 and ELFN1-AS1 were upregulated by q-PCR. The model had a better accuracy presenting by 1-, 3-, and 5-years ROC curve (AUC ≥0.6), and identified survival probability (p < 0.05) well. Moreover, the risk signature could play as an independent factor of CRC (p < 0.05). Further, a nomogram including age, pathologic stage, T stage, and risk score with good prognostic capability (C-index = 0.789) was constructed. In addition, we found biological pathways mainly related to metabolism and apoptosis were down-regulated in high-risk group who with poor outcome. Finally, the functional enrichment showed prognostic DE-FLs may significantly impact bile secretion in CRC. Conclusion: A risk model and nomogram based on ferroptosis-related lncRNAs were created to predict 1-, 3-, and 5-years survival probability of CRC patients. Our data suggested that the prognostic lncRNAs could serve as valuable prognostic marker.

Randomized trial of transversus abdominis plane block with liposomal bupivacaine after cesarean delivery with or without intrathecal morphine.

STUDY OBJECTIVE: To investigate efficacy and safety of liposomal bupivacaine (LB) transversus abdominis plane (TAP) block with or without intrathecal morphine (ITM) compared with ITM alone for postsurgical analgesia after cesarean delivery (CD). DESIGN: Multicenter, open-label, randomized trial (NCT03853694). SETTING: Operating room. PATIENTS: Women with term pregnancy of 37 to 42 weeks scheduled for elective CD under spinal anesthesia. INTERVENTION: Patients were randomized 1:1:1 to LB 266 mg TAP block alone (LB group), ITM 50 µg followed by LB 266 mg TAP block (LB + ITM group), or ITM 150 µg alone (ITM group). All groups received the same postsurgical multimodal analgesic regimen. MEASUREMENTS: The LB and LB + ITM groups were compared with the ITM group for all efficacy outcomes. Postsurgical opioid consumption in morphine milligram equivalents (MMEs) through 72 h was compared by assessing noninferiority before testing superiority. Postsurgical pruritus severity was assessed on an 11-point numerical rating scale. MAIN RESULTS: Between March 4, 2019, and January 10, 2020, 153 patients (LB, n = 52; LB + ITM, n = 48; ITM, n = 53) were enrolled. Baseline characteristics were comparable across groups. The LB group had statistically noninferior postsurgical opioid consumption through 72 h compared with the ITM group (least squares mean [LSM], 19.2 vs 16.4 MMEs; LSM treatment ratio, 1.17 [95% confidence interval (CI), 0.74-1.86]; noninferiority P < 0.0034) as did the LB + ITM group (LSM, 14.6 vs 16.4 MMEs; LSM treatment ratio, 0.89 [95% CI, 0.55-1.44]; noninferiority P < 0.0001). The LB and LB + ITM groups had significantly reduced pruritus severity scores through 12, 24, 48, and 72 h compared with the ITM group (P ≤ 0.0121). Adverse events occurred in 58%, 85%, and 81% of the LB, LB + ITM, and ITM groups, respectively. CONCLUSIONS: LB TAP block with or without ITM resulted in statistically noninferior postsurgical opioid consumption through 72 h, reduced pruritus, and favorable safety compared with ITM in women undergoing CD.

Anesthetic Management for Pulmonary Resection: Current Concepts and Improving Safety of Anesthesia.

Increasingly complex procedures are routinely performed using minimally invasive approaches, allowing cancers to be resected with short hospital stays, minimal postsurgical discomfort, and improved odds of cancer-free survival. Along with these changes, the focus of anesthetic management for lung resection surgery has expanded from the provision of ideal surgical conditions and safe intraoperative patient care to include preoperative patient training and optimization and postoperative pain management techniques that can impact pulmonary outcomes as well as patient lengths of stay.

Albuca Bracteate Polysaccharides Synergistically Enhance the Anti-Tumor Efficacy of 5-Fluorouracil Against Colorectal Cancer by Modulating ß-Catenin Signaling and Intestinal Flora.

The first-line treatment for colorectal cancer (CRC) is 5-fluorouracil (5-FU). However, the efficacy of this treatment is sometimes limited owing to chemoresistance as well as treatment-associated intestinal mucositis and other adverse events. Growing evidence suggests that certain phytochemicals have therapeutic and cancer-preventing properties. Further, the synergistic interactions between many such plant-derived products and chemotherapeutic drugs have been linked to improved therapeutic efficacy. Polysaccharides extracted from Albuca bracteata (Thunb.) J.C.Manning and Goldblatt (ABP) have been reported to exhibit anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, murine CRC cells (CT26) and a murine model of CRC were used to examine the anti-tumor properties of ABP and explore the mechanism underlying the synergistic interactions between ABP and 5-FU. Our results revealed that ABP could inhibit tumor cell proliferation, invasion, and migratory activity in vitro and inhibited tumor progression in vivo by suppressing ß-catenin signaling. Additionally, treatment with a combination of ABP and 5-FU resulted in better outcomes than treatment with either agent alone. Moreover, this combination therapy resulted in the specific enrichment of Ruminococcus, Anaerostipes, and Oscillospira in the intestinal microbiota and increased fecal short-chain fatty acid (SCFA) levels (acetic acid, propionic acid, and butyric acid). The improvement in the intestinal microbiota and the increase in beneficial SCFAs contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Together, these data suggest that ABP exhibits anti-neoplastic activity and can effectively enhance the efficacy of 5-FU in CRC treatment. Therefore, further research on the application of ABP in the development of novel anti-tumor drugs and adjuvant compounds is warranted and could improve the outcomes of CRC patients.

Assisted Fluid Management Software Guidance for Intraoperative Fluid Administration.

BACKGROUND: Excessive or inadequate fluid administration causes complications, but despite this, fluid administration during noncardiac surgery is highly variable. Goal-directed management helps optimize the amount and timing of fluid administration; however, implementation is difficult because algorithms are complex. The authors therefore tested the performance of the Acumen Assisted Fluid Management software (Edwards Lifesciences, USA), which is designed to guide optimal intravenous fluid administration during surgery. METHODS: In this multicenter, prospective, single-arm cohort evaluation, the authors enrolled 330 adults scheduled for moderate- to high-risk noncardiac surgery that required arterial catheter insertion and mechanical ventilation. Clinicians chose a fluid strategy based on a desired 10%, 15%, or 20% increase in stroke volume (SV) in response to a fluid bolus. Dedicated fluid management software prompted "test" or "recommended" boluses, and clinicians were free to initiate a "user" bolus of 100 to 500 ml of crystalloid or colloid. Clinicians were free to accept or decline the software prompts. The authors primarily compared the fraction of software-recommended boluses that produced suitable increases in SV to a 30% reference rate. On an exploratory basis, we compared responses to software-recommended and clinician-initiated boluses. RESULTS: Four hundred twenty-four of 479 (89%) software-recommended fluid boluses and 508 of 592 (86%) clinician-initiated fluid boluses were analyzed per protocol. Of those, 66% (95% CI, 62 to 70%) of delivered fluid boluses recommended by the software resulted in desired increases in SV, compared with the 30% reference rate, whereas only 41% (95% CI, 38 to 44%) of clinician-initiated boluses did (P < 0.0001). The mean ± SD increase in SV after boluses recommended by the software was 14.2 ± 13.9% versus 8.3 ± 12.1% (P < 0.0001) for those initiated by clinicians. CONCLUSIONS: Fluid boluses recommended by the software resulted in desired SV increases more often, and with greater absolute SV increase, than clinician-initiated boluses. Automated assessment of fluid responsiveness may help clinicians optimize intraoperative fluid management during noncardiac surgery.

A Powerful Nomogram Based on the Novel D-Index to Predict Prognosis After Surgical Resection of Hepatocellular Carcinoma.

PURPOSE: Conventional staging and scoring systems such as the Tumor, Node, and Metastasis; Cancer of the Liver Italian Program; Barcelona Clinic Liver Cancer; and Okuda have failed to predict overall survival (OS) in patients with resected primary hepatocellular carcinoma. Thus, we aimed to establish a novel D-index and nomogram to improve prognostic accuracy. PATIENTS AND METHODS: We selected 396 patients who underwent liver resection between January 2007 and February 2015 at the First Affiliated Hospital of Wenzhou Medical University. These patients were randomly divided into the training and validation groups in a ratio of 7:3. RESULTS: We generated a nomogram using five independent risk factors, including the D-index (calculated by total bilirubin × tumor size/the ratio of fat-to-muscle area 0.5) in the training set. The predictive performance of the nomogram was similar in both the training and validation cohorts according to the concordance index. The nomogram demonstrated the strongest predictive power for 1-year, 3-year, and 5-year OS, with the area under the receiving operating characteristic curve being 0.8486, 0.7785, and 0.752, respectively. The calibration curves exhibited stable capabilities in both cohorts. The stratification of the Kaplan-Meier curve was significant (P < 0.001). CONCLUSION: The associated nomogram of the D-index demonstrated a powerful and accurate predictive ability for OS in patients with primary hepatocellular carcinoma.

Airway management and anesthesia for airway surgery: a narrative review.

OBJECTIVE: To discuss and summarize the literature for airway and anesthetic management tools the anesthesiologist can use for airway surgery to both successfully manage the patient's physiological needs and provide the surgeon the optimal surgical conditions with which to perform the surgery safely. BACKGROUND: The airway and anesthetic management of patients presenting for thoracic surgery poses the anesthesiologist with a unique set of challenges, but also a unique set of opportunities to artfully utilize and adapt a variety of management options that has developed over several decades of innovation. Sixty years ago, airway surgery was initially performed with the patient spontaneously breathing and providing anesthesia with halogenated agents and airway topicalization. As medicine entered the latter half of the twentieth century with its development of new airway devices and modern anesthetic agents, most airway surgeries could be safely performed under general anesthesia with secured airways. Today, with continued technological advancements in surgical techniques and an expanding population of challenging patients, the application of nonintubated anesthetic techniques and extracorporeal support is on the rise. METHODS: We conduct a narrative review of the literature on the history of airway and anesthetic management for thoracic surgery, the current management methods and evidence for each modality, and discuss future directions for the field. CONCLUSIONS: While the airway and anesthetic management for airway surgery is challenging, the anesthesiologist has a variety of options including cross-field ventilation, jet ventilation, nonintubated techniques, and extracorporeal support to safely care for the patient. Whichever methods are chosen for the patient and surgery, thoracic surgery remains uniquely positioned in its need for close sharing and collaboration of all airway and anesthetic management decisions between the anesthesiologist and the surgeon.

Transversus Abdominis Plane Block With Liposomal Bupivacaine for Pain After Cesarean Delivery in a Multicenter, Randomized, Double-Blind, Controlled Trial.

BACKGROUND: In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone. METHODS: Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14. RESULTS: Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups). CONCLUSIONS: TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).

Prediction of overall survival time in patients with colon adenocarcinoma using DNA methylation profiling of long non-coding RNAs.

Long non-coding RNAs (lncRNAs) are a subgroup of RNAs able to regulate gene expression at the epigenetic level, and are therefore central to the regulation of numerous biological processes and the progression of multiple cancer types. However, lncRNAs have not been identified to considerably influence overall survival (OS) outcome in numerous different types of cancer. The majority of studies investigating the association between lncRNAs and epigenetic regulation have focused on their altered expression levels in cancerous cells, and few studies have focused on determining the correlation between lncRNAs and OS time. In the present study, comprehensive lncRNA expression analysis was performed on a cohort of patients diagnosed with colon adenocarcinoma (COAD) using the least absolute shrinkage and selection operator method (LASSO). Subsequently, the construction of a prognostic methylation-based predictive system was performed based on the results of LASSO analysis. Functional enrichment analysis of lncRNA co-expression genes was also performed. According to the results of the present study, the classifier was able to significantly predict the prognosis of patients with COAD, and the investigation of the relevant elucidated genes further revealed the mechanism of COAD pathogenesis.