Predictive Factors for Delayed Recovery From Anesthesia in Patients Receiving Free Vascularized Flap Reconstruction for Head and Neck Defects: A Retrospective Cohort Study.

OBJECTIVE: Free flap reconstruction for head and neck defects is currently a common procedure. This study aimed to create and validate a predictive model for identifying patients at risk of delayed recovery from anesthesia after free flap reconstruction for head and neck defect. METHODS: Electronic medical records from all patients were retrospectively collected. The primary outcome variable was delayed recovery from anesthesia. The least absolute shrinkage and selection operator regression model was employed to identify the most relevant features, followed by the construction of a nomogram model using multivariable logistic regression analysis. The discriminatory power, calibration, and clinical utility of the nomogram model were assessed using receiver operating characteristic curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: This novel nomogram model incorporated 4 predictors for delayed recovery from anesthesia: preoperative albumin, intraoperative fresh frozen plasma infusion, preoperative platelet-to-lymphocyte ratio, and duration of intraoperative hypotension. The area under the receiver operating characteristic curve (area under the curve) for the nomogram model was determined to be 0.821 (95% CI: 0.803-0.836). After internal validation, the corrected area under the curve was found to be 0.768 (95% CI: 0.639-0.812). In addition, the model exhibited well-fitted calibration curves and demonstrated favorable clinical usability as indicated by the calibration curve and decision curve analysis curve. CONCLUSION: The authors created and validated a novel predictive model utilizing a limited number of 4 predictors, yet exhibiting commendable predictive performance. This innovative tool holds the potential to mitigate delayed recovery from anesthesia and enhance the efficient allocation of medical resources.

Development and validation of a novel nomogram model for identifying risk of prolonged length of stay among patients receiving free vascularized flap reconstruction of head and neck cancer.

Background: The aim of the present study was to build and internally validate a nomogram model for predicting prolonged length of stay (PLOS) among patients receiving free vascularized flap reconstruction of head and neck cancer (HNC). Methods: A retrospective clinical study was performed at a single center, examining patients receiving free vascularized flap reconstruction of HNC from January 2011 to January 2019. The variables were obtained from the electronic information system. The primary outcome measure was PLOS. Univariate and multivariate analyses were used to find risk factors for predicting PLOS. A model was then built according to multivariate results. Internal validation was implemented via 1000 bootstrap samples. Results: The study included 1047 patients, and the median length of stay (LOS) was 13.00 (11.00, 16.00) days. Multivariate analysis showed that flap types ((radial forearm free flap (odds ratio [OR] = 2.238; 95% CI, 1.403-3.569; P = 0.001), free fibula flap (OR = 3.319; 95% CI, 2.019-4.882; P < 0.001)), duration of surgery (OR = 1.002; 95% CI, 1.001-1.003; P = 0.004), postoperative complications (OR = 0.205; 95% CI, 0.129-0.325; P = P < 0.001) and unplanned reoperation (OR = 0.303; 95% CI, 0.140-0.653; P = 0.002) were associated with PLOS. In addition to these variables, blood transfusion was comprised in the model. The AUC of the model was 0.78 (95% CI, 0.711-0.849) and 0.725 (95% CI, 0.605-0.845) in the primary and internal validation cohorts, respectively. The DCA revealed the clinical utility of the current model when making intervention decisions within the PLOS possibility threshold range of 0.2-0.8. Conclusions: Our study developed a nomogram that exhibits a commendable level of accuracy, thereby aiding clinicians in assessing the risk of PLOS among patients receiving free vascularized flap reconstruction for HNC.

A Potent SOS1 PROTAC Degrader with Synergistic Efficacy in Combination with KRASG12C Inhibitor.

AMG510, as the first approved inhibitor for KRASG12C mutation, has shown promising efficacy in nonsmall-cell lung cancer and colorectal cancer harboring KRASG12C mutation. However, the moderate response rate and the rapid emergence of acquired resistance limit the therapeutic potential of AMG510, highlighting the need for the development of combination strategies. Here, we observed the suppression of RAS-MAPK signaling induced by AMG510 was prolonged and enhanced by SOS1 knockdown. Thus, we design, synthesize, and characterize a potent and specific SOS1 degrader 23. Compound 23 showed efficient SOS1 degradation in KRAS-driven cancer cells and achieved significant antiproliferative potency. Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRASG12C mutant cells in vitro and in vivo. Our findings demonstrated that KRASG12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRASG12C inhibitor.

Valsa mali PR1-like protein modulates an apple valine-glutamine protein to suppress JA signaling-mediated immunity.

Apple Valsa canker (AVC) is a devastating disease of apple (Malus × domestica), caused by Valsa mali (Vm). The Cysteine-rich secretory protein, Antigen 5, and Pathogenesis-related protein 1 (CAP) superfamily protein PATHOGENESIS-RELATED PROTEIN 1-LIKE PROTEIN c (VmPR1c) plays an important role in the pathogenicity of Vm. However, the mechanisms through which it exerts its virulence function in Vm-apple interactions remain unclear. In this study, we identified an apple valine-glutamine (VQ)-motif-containing protein, MdVQ29, as a VmPR1c target protein. MdVQ29-overexpressing transgenic apple plants showed substantially enhanced AVC resistance as compared with the wild type. MdVQ29 interacted with the transcription factor MdWRKY23, which was further shown to bind to the promoter of the jasmonic acid (JA) signaling-related gene CORONATINE INSENSITIVE 1 (MdCOI1) and activate its expression to activate the JA signaling pathway. Disease evaluation in lesion areas on infected leaves showed that MdVQ29 positively modulated apple resistance in a MdWRKY23-dependent manner. Furthermore, MdVQ29 promoted the transcriptional activity of MdWRKY23 toward MdCOI1. In addition, VmPR1c suppressed the MdVQ29-enhanced transcriptional activation activity of MdWRKY23 by promoting the degradation of MdVQ29 and inhibiting MdVQ29 expression and the MdVQ29-MdWRKY23 interaction, thereby interfering with the JA signaling pathway and facilitating Vm infection. Overall, our results demonstrate that VmPR1c targets MdVQ29 to manipulate the JA signaling pathway to regulate immunity. Thus, this study provides an important theoretical basis and guidance for mining and utilizing disease-resistance genetic resources for genetically improving apples.

Preoperative flurbiprofen diminishes the rate of reoperation after free flap reconstruction: A retrospective study.

This study aimed to evaluate the association between preoperative flurbiprofen, a non-selective COX inhibitor, and reoperation for flap crisis after free flap reconstruction. In this retrospective study, patients who underwent head and neck surgery with free flap reconstructions were collected. To identify risk factors for reoperation from demographic features and perioperative variables, univariate and multivariate logistic analyses were conducted. After propensity score matching (PSM), univariate and adjusted multivariate analyses were employed to explore the impact of preoperative flurbiprofen on reoperation after free flap reconstruction. This study comprised 437 patients, 33 of whom underwent reoperations for flap crisis. After multivariate analysis, radiotherapy history (P = 0.005; odds ratio [OR] = 0.225; 95% CI, 0.080-0.636) and preoperative flurbiprofen (P = 0.038; OR = 5.059; 95% CI, 1.094-23.386) were identified as independent factors for reoperation. PSM was achieved, and preoperative flurbiprofen was found to diminish the reoperation rate (P = 0.046; OR = 4.765; 95% CI, 1.029-22.202) without increasing bleeding complications. Within the limitations of the study, flurbiprofen should be administered preoperatively to reduce the rate of reoperations for flap crisis whenever appropriate.

Nomogram incorporating potent inflammatory indicators for overall survival estimation of patients with primary oral squamous cell carcinoma.

Background: Inflammation has been recognized to be a factor that substantially influences tumorigenesis and tumor prognosis. Hence, this study was aimed to investigate an inflammatory marker with the most potent prognostic ability and to evaluate the survival estimation capability of dynamic change in this marker for patients suffered from oral squamous cell carcinoma (OSCC). Methods: 469 patients' inflammatory indicators including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory response index (SIRI), were calculated. Their predictive abilities for overall survival (OS) were evaluated by Kaplan-Meier curves to screen for the one with the most potent prognostic value. The predictive ability of dynamic changes in this marker was verified and a predictive nomogram incorporating inflammatory indicators was developed. Results: A high LMR was identified to be an indicator of a satisfactory survival rate. Compared with that of other inflammatory markers, area under the receiver operating characteristics (ROC) curve (AUC) of LMR for 1-year and 3-year OS was significantly larger (P<0.001). Dynamic LMR change remained an significant parameter for predicting OS (OR: 2.492, 95% CI: 1.246-4.981, p = 0.010). The nomogram incorporating LMR exhibited a superior prognostic significance than the TNM system, as suggested by the C-index (0.776 vs 0.651 in primary cohort; 0.800 vs 0.707 in validation cohort, P<0.001) and AUC. Conclusions: LMR was demonstrated to possess a more potent survival estimation capability than the other three inflammatory parameters. Dynamic changes in LMR serves as a significant parameter for overall survival estimation of primary OSCC patients. The established nomogram incorporating inflammatory markers showed more accuracy and sensitivity for survival estimation of primary OSCC patients.

Perioperative Risk Factors Associated With Unplanned Reoperation Following Vascularized Free Flaps Reconstruction of the Oral Squamous Cell Carcinoma.

OBJECTIVES: To find out the occurrence rate and risk factors of unplanned reoperation (any unscheduled surgery within 30 d after the initial surgery) in patients who have received oral squamous cell carcinoma (OSCC) surgery and vascularized free flap reconstruction. PATIENTS AND METHODS: We organized a retrospective study of 1058 patients who underwent OSCC resection and reconstruction with vascularized free flaps from 2011 to 2019. Clinical characteristics, reasons for unplanned reoperation, flap types, and previous treatment were compared between the unplanned reoperation group and the control group. Univariate and multivariate analyses were performed to identify perioperative risk factors for unplanned reoperation. The related perioperative factors that may influence perioperative infusion were included in propensity score matching to investigate the independent contribution of intraoperative colloid infusion on unplanned reoperation. RESULTS: The overall rate of unplanned reoperation in OSCC patients was 11% (n=115). Flap necrosis and bleeding were the most common causes. Higher American Society of Anesthesiologists (ASA) grade [odds ratio (OR)=1.709, P=0.009], postoperative anemia (OR=0.983, P=0.011) and excessive intraoperative colloid input (OR=1.55, P=0.037) were identified as risk factors for unplanned reoperation. Propensity score matching was applied, and the difference of unplanned reoperation incidence between the matched groups was statistically significant (14.59% versus 8.54%; P=0.025). The multivariate analyses after propensity score matching confirmed that the intraoperative rate of colloid infusion of more than 2.3 mL/kg/h (OR=1.756, P=0.042) and prior radiotherapy (OR=2.78, P=0.001) are independent risk factors for unplanned reoperation. CONCLUSION: High intraoperative colloid infusion rate and prior radiotherapy may increase the risk of unplanned reoperation in patients who underwent OSCC surgery and vascularized free flap reconstruction.

Dietary thiamine modulates carbohydrate metabolism, antioxidant status, and alleviates hypoxia stress in oriental river prawn Macrobrachium nipponense (de Haan).

Hypoxia is one of the challenges in prawns aquaculture. However, the role of thiamine, which is a coenzyme in carbohydrate metabolism with antioxidant properties, in reducing hypoxia in prawns aquaculture is currently unknown. We investigated the effects of thiamine on antioxidant status, carbohydrate metabolism and acute hypoxia in oriental river prawn, Macrobrachium nipponense. One thousand eight hundred prawns (0.123 ± 0.003 g) were fed five diets (60 prawns each tank, six replicates per diet) supplemented with graded thiamine levels (5.69, 70.70, 133.67, 268.33 and 532.00 mg/kg dry mater) for eight weeks and then exposed to hypoxia stress for 12 h followed by reoxyegnation for 12 h. The results showed that, under normoxia, prawns fed the 133.67 or 268.33 mg/kg thiamine diet had significantly lower glucose 6-phosphatedehydrogenase, succinate dehydrogenase and phosphoenolpyruvate carboxykinase activities than those fed the other diets. Moreover, total antioxidant capacity (T-AOC) increased significantly when prawns were fed the 133.67 mg/kg thiamine diet. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) content also increased significantly when prawns were fed the 268.33 or 532.00 mg/kg thiamine diet under hypoxia. And the significantly increased SOD activity and MDA level also observed in prawns fed 532.00 mg/kg thiamine under reoxygenation. Under normoxia, prawns fed the 70.70 or 133.67 mg/kg thiamine diet decreased the mRNA expressions of AMP-activated protein kinase-alpha (AMPK-α), pyruvate dehydrogenase-E1-α subunit (PDH-E1-α) and hypoxia-inducible factor-1s (HIF-1α, HIF-1ß), but increased the mRNA expressions of phosphofructokinase (PFK) significantly. After 12 h of hypoxia, the energy metabolism related genes (AMPK-ß, AMPK-γ, PFK, PDH-E1-α), hypoxia-inducible factor related genes (HIF-1α, HIF-1ß) and thiamine transporter gene (SLC19A2) were up-regulated significantly in prawns fed the 133.67 or 268.33 mg/kg thiamine diets. After 12 h of reoxygenation, prawns fed the 133.67 or 268.33 mg/kg diet significantly decreased the SOD activity, MDA level and SLC19A2 mRNA expression compared with other diets. The optimum thiamine was 161.20 mg/kg for minimum MDA content and 143.17 mg/kg for maximum T-AOC activity based on cubic regression analysis. In summary, supplementing 143.17 to 161.20 mg/kg thiamine in the diets for M. nipponense improves the antioxidant capacity under normoxia and reduces the oxidative damage under hypoxia stress.

MafG-like contribute to copper and cadmium induced antioxidant response by regulating antioxidant enzyme in Procambarus clarkii.

Avian musculoaponeurotic fibrosarcoma (Maf) proteins play an important role in Nrf2/Keap1 signaling pathway, which mainly resist the oxidant stress. The members of sMaf have a high homology basic leucine zipper (bZIP) and lack trans activation domain, and could interact with other transcriptional regulatory factors as a molecular chaperone. In this study, a full-length MafG-like gene was cloned from Procambarus Clarkii, designated as PcMafG-like, which consisted of an ORF length of 246 bp encoding 82 amino acids, a 5' untranslated region (UTR) of 483 bp, and a 3' UTR of 111 bp. The domain of PcMafG-like had a bZIP-Maf domain that binds to DNA. The cDNA sequence of PcMafG-like was 99 % similar to that of Penaeus vannamei. The mRNA of PcMafG-like was expressed in all tested tissues, and the highest expression was in muscle tissue. Under stimulation of Cu2+ and Cd2+, PcMafG-like was significantly up-regulated in hepatopancreas and gill, and the same result was testified by situ hybridization. The representative antioxidant genes, CAT, GPx and CZ-SOD, were significantly induced by Cu2+; CAT and GPx was induced by Cd2+. PcMafG-dsRNA significantly inhibited the expression of these up-regulated genes, but also inhibited the expression of other detected genes CZ-SOD, GST-θ and GST-1like. The antioxidant effect of PcMafG-like was further verified by oxidative stress markers (T-SOD, CuZnSOD, GPx, CAT, GSH and MDA) kits. Cu2+ and Cd2+ could induce the contents of these oxidative stress markers (MDA, GSH, CZ-SOD, CAT in Cu2+/Cd2+ treated group, and GSH-Px in Cd2+ group), while interference of PcMafG-like significantly inhibited the up-regulation. Furthermore, hematoxylin-eosin staining experiments showed that the degree of pathological damage was dose-dependent and time-dependent, and the pathological damage was more serious after dsRNA interfered with PcMafG-like. In addition, subcellular localization showed that PcMafG-like gene existed in nucleus. The recombinant protein PcMafG-like was expressed and purified in prokaryotic expression. The affinity analysis of promoter by agarose gel electrophoresis suggested that PcMafG-like could bind with CAT promoter in vitro. This indicated that PcMafG-like could activate antioxidant genes.

Infusion management associated with prolonged length of stay following free flap reconstruction of head and neck defects: A propensity score matching study.

BACKGROUND: Surgical resection of the primary lesion and reconstruction of the defects with free flaps are common treatments for head and neck cancer (HNC). However, various variables can lead to prolonged length of stay (LOS). The aim of this study is to investigate risk factors correlated with prolonged LOS following free flap reconstruction of head and neck defects. METHODS: A retrospective study of patients with all types of free flaps reconstruction of HNC between January 2011 and January 2019 at Sun Yat-sen Memorial Hospital was performed. We recorded predictive variables and divided them into: personal and clinical, hemodynamic, anesthetic and surgical. The primary endpoint was prolonged length of stay. Univariate and multivariate analyses were applied to identify risk factors that associated with prolonged LOS. Propensity score matching was performed with the identified risk variables and other perioperative factors that may impact transfusion decision to explore the independent influence of intraoperative blood transfusion on prolonged LOS. RESULTS: A total of 1047 patients were included in this study. The median LOS was 13.00 (11.00, 16.00) days. Multivariate analysis suggested that blood transfusion, duration of surgery, postoperative complications and unplanned reoperation were associated with prolonged LOS. After propensity score matching, unnecessary blood transfusion and inadequate fluid rate over 24 h, postoperative complications and unplanned reoperation were identified risk factors that led to prolonged LOS. CONCLUSION: Unnecessary blood transfusion and inadequate fluid infusion rate over 24 h were independent risk factors associated with prolonged LOS in HNC patients who underwent free flap reconstruction. Our results indicated consideration of restrictive blood transfusion and adequate fluid infusion over postoperative 24 h in these patients.

Risk factors associated with postoperative complications following free flap reconstruction of head and neck defects.

BACKGROUND: Free flap reconstruction of head and neck defects is routinely performed with a high success rate nowadays. However, postoperative complications are still commonly observed. The aim of this study is to investigate risk factors correlated with postoperative complications following free flap reconstruction of head and neck defects. METHODS: A retrospective study of all patients undergoing free flap reconstruction of head and neck defects between January 2018 and January 2020 at Sun Yat-sen Memorial Hospita, Guangzhou, China was performed. Preoperative, intraoperative, and postoperative data were collected retrospectively. The primary outcome variables were postoperative complications, which were divided into medical and surgical complications. All patients were grouped by either complications or no complications. Univariate and multivariate logistic regression models were used to identify risk factors predicting complications. RESULTS: 850 patients underwent free flap reconstruction of head and neck defects during the study period (Male: 65.29%; Mean [SD] age: 54.90 [13.78] years). Postoperative complications developed in 125 (14.71%) patients, among which, 101 (11.88%) patients developed surgical complications, 29 (3.41%) patients developed medical complications and 5 (0.59%) patients developed both surgical and medical complications. Total flap necrosis was observed in 11 (1.29%) patients. After multivariate analysis, several risk factors incluing postoperative ICU admission, coronary heart disease, post radiotherapy surgery and flap types were identified correlated with postoperative complications. CONCLUSIONS: Our study identified related variables for a higher risk of postoperative complications development following free flap reconstruction of head and neck defects. Early detection of these risk factors will improve prognosis.

Continuous infusion of lidocaine in pediatric colonoscopy: A randomized double-blind placebo-controlled study.

BACKGROUND: Propofol is commonly used for providing procedural sedation during pediatric colonoscopy. Intravenous (i.v.) lidocaine can mitigate visceral pain and reduce propofol requirements during surgery. The aim of this study is to investigate the effect of i.v. lidocaine on perioperative propofol and sufentanil dose, pulse oxygen saturation, postoperative pain score, and recovery time during pediatric colonoscopy. METHODS: We designed a randomized, double-blind, placebo-controlled study and enrolled 40 children aged from 3 to 10 years who underwent colonoscopy. After titration of propofol to achieve unconsciousness, the patients were given i.v. lidocaine (1.5 mg/kg later 2 mg/kg/hour) or the same volume of saline. Sedation was standardized and combined propofol with sufentanil. The primary outcome variables were intraoperative propofol and sufentanil requirements, and the number of oxygen desaturation episodes. Secondary outcome variables were recovery time after colonoscopy and post-colonoscopy pain. RESULTS: Lidocaine infusion resulted in a significant reduction in propofol requirements: (median (quartile) 1.8 (1.5-2.0) vs. 3.0 (2.8-3.3) mg/kg respectively; P < 0.001) and sufentanil requirements: (median (quartile) 0.06 (0.05-0.08) vs. 0.1 (0.1-0.1) µg/kg respectively; P < 0.001). The number of subjects who experienced oxygen desaturation below 95% in the lidocaine group was also significantly less than that in the control group: 1 vs. 6 (P = 0.04). The mean (SD) recovery time was significantly shorter in the lidocaine group: (19.2 (2.6) vs. 13.3 (2.6) min respectively; P < 0.001). There was no significant difference in post-colonoscopy pain. CONCLUSION: Continuous infusion of lidocaine resulted in reduction of propofol and sufentanil requirements, recovery time, and risk of hypoxemia during pediatric colonoscopy.

Comparative analysis of bile culture and blood culture in patients with malignant biliary obstruction complicated with biliary infection.

OBJECTIVE: This study is aimed to provide a clinical basis for the identification and treatment of patients with malignant biliary obstruction (MBO) complicated with biliary infection by comparing pathogenic bacteria detected in bile and blood cultures from these patients. MATERIALS AND METHODS: A total of 380 patients with MBO who received percutaneous transhepatic cholangic drainage from January 2004 to January 2019 were included in the study. A total of 90 patients were diagnosed with having MBO complicated with biliary infection, and bile and blood culture were simultaneously performed on these patients. The patients included 58 men and 32 women, ranging in age from 33 to 86 years old, with a mean age of 60.69 years. RESULTS: The detection rate using bile bacterial culture in patients with MBO complicated with biliary infection was significantly higher than that using blood culture, and there were significant differences in the two kinds of bacterial culture found positive bile and blood cultures from the same patients. Gram-positive cocci were dominant in the bile cultures and Gram-negative bacilli were dominant in the blood cultures. Therefore, it is necessary to conduct simultaneous bile bacterial culture and blood culture for patients with MBO complicated with biliary infection, especially those with severe or critical diseases. CONCLUSIONS: It is vital to enable simultaneous bile bacterial culture and blood culture in patients with MBO complicated with biliary infection. Existing guidelines for the diagnosis and treatment of benign biliary infection are not applicable to patients with MBO complicated with biliary infection.

Nomogram based on albumin and neutrophil-to-lymphocyte ratio for predicting postoperative complications after pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to identify a preoperative inflammatory marker with the most predictive value for postoperative complications after pancreaticoduodenectomy (PD). We then combined it with other perioperative variables to construct and validate a nomogram for complications after PD. METHODS: A total of 223 patients who received PD from January 2014 to July 2019 at a high-volume (>60 PDs/year) pancreatic centers in China were included in this retrospective study. All of the PDs were performed by the same surgeon who is beyond the learning curve with more than 100 PDs over the previous 3 years before 2014. 15 preoperative inflammatory markers were collected, including neutrophils, lymphocytes, high-sensitivity C-reactive protein and lactic dehydrogenase. The inflammatory markers' predicting abilities for complications were analyzed by calculating the values of an area under the curve (AUC). The complications included surgical complications (such as pancreatic fistula, delayed gastric emptying and bile leakage) and medical complications (such as sepsis, pneumonia, urinary tract infection, acute heart failure and acute liver failure) in this study. Univariable and multivariable logistic regression analyses were performed to investigate the perioperative features for independent risk factors for complications after PD. Nomograms with or without the most predictive inflammatory for complications were subsequently developed based on multivariable logistic regression using Akaike information criterion. Nomograms' performance was quantified and compared in terms of calibration and discrimination. We studied the utility of the nomograms using decision curve analysis. RESULTS: The albumin/ NLR score (ANS) exhibited the highest AUC value (0.616) for predicting postoperative complications. ANS and approach method were identified as independent risk factors for complications. The nomogram with ANS had higher C-index (0.725) and better calibration. The NRI compared between nomograms was 0.160 (95% CI: 0.023-0.296; P=0.022). By decision curve analysis, the model with ANS had higher clinical value. CONCLUSIONS: The ANS is a useful predictor and an independent risk factor for postoperative complications after PD. The nomogram with ANS was constructed with better performance and more clinical benefit for predicting postoperative complications.

Safety and efficacy of vaginal laser therapy for stress urinary incontinence: a meta-analysis.

BACKGROUND: Laser therapy has recently been proposed as a novel treatment for stress urinary incontinence (SUI) due to offering several advantages. This study aimed to evaluate the safety and efficacy of laser treatment of SUI by a meta-analysis. METHODS: The systematic review registration number is INPLASY202080001. A comprehensive search to identify relevant studies was conducted using the PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases with a cutoff date of 1 November, 2020. Outcome measures were extracted based on subjective and objective indexes, including International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), and objective measurements "1-hour pad test" (1-hour test under standardized conditions). Score changes before and after treatment were evaluated through meta-analysis. Subgroup analysis was performed according to geographic region, type of urinary incontinence (UI), severity of UI, age, and body mass index (BMI). RESULTS: Sixteen published clinical research studies, involving 899 patients with SUI, were included in this study. After laser treatment, the change in the ICIQ-SF score at 1, 2, and 6 months was -5.49 (95% CI: -6.74--4.24; I2=91%, P<0.01), -4.97 (95% CI: -6.24--3.71), and -5.48 (95% CI: -6.15--4.81), respectively. The improvement in 1-hour pad weight test results at 1, 3, and 12 months post treatment was -5.59 (95% CI: -6.93--4.25), -4.96 (95% CI: -6.73--3.20), and -5.82 (95% CI: -6.77--4.87), respectively. The PISQ-12 score increased by 5.39 (95% CI: 1.20-9.58) following treatment. Subgroup analysis identified the type and severity of UI as the potential source of heterogeneity. Adverse effects were reported in 6 of the 16 trials and affected only a small number of patients. Most adverse events were mild or moderate and required no medical intervention or resolved in a few days. CONCLUSIONS: Vaginal laser therapy appears to be a safe, effective, and minimally invasive treatment option for SUI that can be well tolerated by patients.

Unnecessary Blood Transfusion Prolongs Length of Hospital Stay of Patients Who Undergo Free Fibular Flap Reconstruction of Mandibulofacial Defects: A Propensity Score-Matched Study.

PURPOSE: Blood transfusion is usually a common clinical practice in flap transfer surgery because of its invasive hemorrhagic nature. Although intraoperative restrictive transfusion policy was suggested in vascularized fibular flap reconstruction, its clinical evidence was still insufficient. Therefore, our study aimed to investigate the influence of intraoperative blood transfusion on length of stay (LOS) after vascularized fibular flap reconstruction. PATIENTS AND METHODS: Patients who underwent vascularized fibular flap reconstruction of mandibulofacial defects between 2012 and 2018 were reviewed. Univariate and multivariate analyses were performed to identify factors that influenced LOS. The identified factors and other perioperative factors that may influence transfusion decision were included in propensity score matching to explore the independent impact of intraoperative blood transfusion on LOS. RESULTS: About 375 patients were included, and the median LOS was 14.00 (12.00, 19.00) days in our study. Multivariate analysis suggested that duration of surgery, fluid infusion speed for more than 24 hours on operative day, intraoperative blood transfusion, and postoperative complication were associated with prolonged LOS (P < .05). Propensity score matching was performed, and the difference of LOS between the matched transfused and nontransfused group was statistically significant (15.00 [12.75, 20.00] vs 14.00 [11.75, 16.25]; P < .001). The comparison between the matched and unmatched transfused patients indicated that the former has less radiotherapy history, blood loss, and higher preoperative hemoglobin (P ≤ .001). CONCLUSIONS: Intraoperative blood transfusion is independently associated with prolonged LOS in patients without preoperative anemia, radiotherapy history, or intraoperative massive hemorrhage who undergo vascularized fibular flap reconstruction. Efforts should be made to avoid unnecessary intraoperative blood transfusion, and our results support consideration of a restrictive transfusion policy in these patients.

Postoperative administration of ketorolac averts morphine-induced angiogenesis and metastasis in triple-negative breast cancer.

AIMS: Opioids (i.e. morphine) were found to induce triple negative breast cancer (TNBC) metastasis while nonsteroidal anti-inflammatory drugs (i.e. ketolorac) were associated with decreased metastasis in TNBC. These contradictory findings demand clarification on the effect of postoperative morphine and ketorolac on TNBC metastasis. MATERIALS AND METHODS: TNBC xenograft mice were established using MDA-MB-231 cells. When tumors reached ~100 mm3, the primary tumor was resected. Mice were then randomly assigned to four groups (n = 14): (i) saline, (ii) morphine (10 mg kg-1) (iii) morphine + ketorolac (10 mg kg-1 of morphine and 20 mg kg-1 of ketorolac) (iv) ketorolac (20 mg kg-1); administrated for three consecutive days after resection. Three weeks after resection, the number of lung metastases was measured. Microvessel density, thrombospondin-1 (TSP-1) and c-Myc expression in recurrent tumors were determined. To elucidate the above phenomenon in vitro, MDA-MB-231 cells were treated according to the regiment above; with or without supplementation of an AKT inhibitor to determine the activation of PI3K/AKT/c-Myc pathway. KEY FINDINGS: In mice, morphine promoted TNBC metastasis and angiogenesis, decreased TSP-1 expression and increased c-Myc expression, while co-administration of ketorolac significantly reversed the phenotypes above (p < .05). Mechanistically, morphine inhibited TSP-1 secretion by activating PI3K/AKT/c-Myc pathway (p < .05), while ketorolac promoted TSP-1 secretion (p < .05) by suppressing PI3K/AKT/c-Myc pathway. SIGNIFICANCE: Our study indicated that morphine enhanced TNBC metastasis and angiogenesis while ketorolac suppressed this effect. Mechanistically, this may be related to the enhancement of TSP-1 synthesis after ketorolac administration which further de-activated PI3K/AKT/c-Myc pathway.

A general strategy for highly sensitive analysis of genetic biomarkers at single-base resolution with ligase-based isothermally exponential amplification.

Robust, reliable, and sensitively quantitative detection of genetic biomarkers at single-base resolution has the potential to revolutionize medical diagnostics, especially for precision medicine. Here, taking the advantages of the high specificity of ligase reaction and the powerful amplification features of the isothermally exponential amplification, we have demonstrated a novel methodology to sensitively quantify genetic biomarkers at one-base resolution. The methodology is based on the ligase reaction of two stem-loop DNA probes templated by the nucleic acid targets to form a double stem-loop DNA, which subsequently initiates the isothermally exponential amplification reaction with high amplification efficiency. With the proposed method, high sensitivity to determine as low as 0.01 fM DNA or 0.1 fM RNA targets and high specificity to detect single-base changes can be achieved. The new methodology is robust to be performed by using a pair of universal primers under isothermal conditions, which should be employed to quantitatively detect any genetic biomarkers because all DNA/RNA targets can be directly used as the templates to ligate the stem-loop DNA probes with single-base resolution.

Perioperative Risk Factors for Radial Forearm-Free Flap Complications.

PURPOSE: To determine perioperative risk factors predicted complications in elderly Chinese patients undergoing oral and maxillofacial reconstruction with radial forearm free flaps (RFFF). PATIENTS AND METHODS: The authors implemented a retrospective study and enrolled a sample of patients at least 65-year old who underwent resection of oral and maxillofacial tumors and RFFF reconstruction from January 2011 to June 2018. Predictor variables were divided into: demographic variables (gender, age, weight, comorbidities, history of smoking, radiotherapy history, primary lesions); hemodynamic (preoperative and postoperative hemoglobin and albumin level, blood loss, blood transfusion, urine output (mL), and rate (mL/kg/h), and infusion rates for crystalloids and colloids (mL/kg/h, and volumes given intraoperatively and postoperatively for 24 hours); anesthetic and surgical (American Society of Anesthesiologists classification, visual analogue score, duration of tourniquet, and operation). The primary outcome was the presence of postoperative complications (yes/no), and secondary outcome was types of complications (medical and surgical). All the variables were analyzed by univariate and multivariable analysis and statistical significance was set at a P < 0.05 RESULTS:: The study sample was composed of 118 patients with a mean age of 72 years. There were 15 complications, of which 9 were surgical and 6 medical. Risk factors were: postoperative hypoproteinemia, crystal in 24 hours, and hypertension combined with diabetes. CONCLUSIONS: Although reconstruction with a RFFF is a common and safe treatment for elderly patients with oral and maxillofacial tumors, postoperative hypoproteinemia, crystal in 24 hours, and hypertension combined with diabetes are potential predictors of postoperative complications.

Morphine Promotes the Angiogenesis of Postoperative Recurrent Tumors and Metastasis of Dormant Breast Cancer Cells.

BACKGROUND: Surgery plays a significant role in the comprehensive treatment of breast cancer, and opioids are often the first-choice analgesics in the perioperative period. However, recent studies showed that opioids may enhance the angiogenesis of breast cancer and the recurrence and metastasis of tumor cells. OBJECTIVES: We aim to investigate the influence of opioids on recurrence and metastasis of breast cancer in nude mice. METHODS: Forty female nude mice with breast tumor were randomly divided into 4 groups (n = 10). They were treated with (i) normal saline (10 mL/kg), (ii) morphine (10 mg/kg), (iii) morphine plus naloxone (10 + 4 mg/kg), and (iv) naloxone (4 mg/kg) for 2 weeks. Four groups of MDA-MB-231 cells were administered (i) Dulbecco's Modified Eagle's Medium, (ii) morphine (10 µmol/mL), (iii) morphine plus naloxone (10 + 10 µmol/mL), and (iv) naloxone (10 µmol/mL). The influence of morphine in each treated group was evaluated by immunocytochemistry and Western blotting. RESULTS: Mice in the morphine group had higher rates of Ki67-positive cells, lower rates of apoptotic index, and a significant increase in the microvessels density of the tumor as evidenced by CD31 staining (p < 0.05). Furthermore, the MDA-MB-231 cells in the morphine group showed an increase in p-Akt, c-Myc, and thrombosponin-1 expression. CONCLUSION: In the current study, we found that morphine promotes the angiogenesis of the recurrent postoperative tumors of nude mice with breast cancer and the proliferation of tumor cells and such promotion may be related to the PI3K-c-Myc signaling pathway.