Association between Preoperative Blood Pressures and Postoperative Adverse Events.

BACKGROUND: The relationship between postoperative adverse events and blood pressures in the preoperative period remains poorly understood. This study tested the hypothesis that day-of-surgery preoperative blood pressures are associated with postoperative adverse events. METHODS: The authors conducted a retrospective, observational study of adult patients having elective procedures requiring an inpatient stay between November 2017 and July 2021 at Vanderbilt University Medical Center to examine the independent associations between preoperative systolic and diastolic blood pressures (SBP, DBP) recorded immediately before anesthesia care and number of postoperative adverse events-myocardial injury, stroke, acute kidney injury, and mortality-while adjusting for potential confounders. The study used multivariable ordinal logistic regression to model the relationship. RESULTS: The analysis included 57,389 cases. The overall incidence of myocardial injury, stroke, acute kidney injury, and mortality within 30 days of surgery was 3.4% (1,967 events), 0.4% (223), 10.2% (5,871), and 2.1% (1,223), respectively. The independent associations between both SBP and DBP measurements and number of postoperative adverse events were found to be U-shaped, with greater risk both above and less than SBP 143 mmHg and DBP 86 mmHg-the troughs of the curves. The associations were strongest at SBP 173 mmHg (adjusted odds ratio, 1.212 vs. 143 mmHg; 95% CI, 1.021 to 1.439; P = 0.028), SBP 93 mmHg (adjusted odds ratio, 1.339 vs. 143 mmHg; 95% CI, 1.211 to 1.479; P < 0.001), DBP 106 mmHg (adjusted odds ratio, 1.294 vs. 86 mmHg; 95% CI, 1.003 to 1.17671; P = 0.048), and DBP 46 mmHg (adjusted odds ratio, 1.399 vs. 86 mmHg; 95% CI, 1.244 to 1.558; P < 0.001). CONCLUSIONS: Preoperative blood pressures both less than and above a specific threshold were independently associated with a higher number of postoperative adverse events, but the data do not support specific strategies for managing patients with low or high blood pressure on the day of surgery.

Effectiveness of Oral Iron Therapy in Anemic Inpatient Pregnant Women: A Single Center Retrospective Cohort Study.

Background and aim Oral iron therapy is effective in treating iron deficiency anemia in outpatient pregnant women but has not been studied in inpatient pregnant women. We aimed to evaluate the effect of oral iron therapy versus no therapy during hospitalization on maternal and neonatal outcomes in women with anemia who are hospitalized for pregnancy-related morbidities (i.e., preterm premature rupture of membranes, preterm labor, pre-eclampsia, abnormal placentation, or fetal monitoring). Methods A retrospective, single-center study was conducted in hospitalized pregnant women (2018 to 2020) with inpatient stays of more than three days. The primary outcome was a change in hemoglobin level from admission to delivery in women treated with oral iron compared with those left untreated. Secondary outcomes included the total amount of iron administered before delivery, the time interval from admission to delivery, and neonatal effects. Results Two hundred sixty-three women were admitted, 79 women had anemia, and 29 (36.7%) received at least one dose of oral iron. Baseline patient characteristics were similar between groups. The median (interquartile range) dose of iron in the oral iron group was 1185.0 (477.0, 1874.0) mg. Neither absolute hemoglobin before delivery (control group: 10.0±1.2 g/dL; iron group: 10.1±1.1 g/dL; p=0.774) nor change in hemoglobin from admission to delivery (control group: -0.1±1.1 g/dL vs. iron group: 0.4±1.1 g/dL; p=0.232) differed between groups. Women in the control group had shorter length of stay (LOS) median (IQR) than women in the iron group (control group: 7.1 (5.0, 13.7) days; iron group: 11.4 (7.4, 25.9) days; p=0.03). There were no differences in maternal mode of delivery, though each group had high rates of cesarean delivery (control group: 53.7%; iron group: 72.4%; p=0.181). There were no differences in estimated blood loss at delivery (control group: 559±401; iron group: 662.1±337.4;p=0.264) in either group. Neonatal birthweight (control group: 1.9±0.7 kg; iron group: 1.9±0.7 kg; p=0.901), birth hemoglobin (control group: 16.3±2.2 g/dL; iron group: 16±2.2 g/dL; p=0.569), neonatal intensive care unit (NICU) admission (control group: 93.3%; iron group: 84.8%;p=0.272 ), or neonatal death (control group: 8.9%; iron group: 3%; p=0.394) were not different between groups. Conclusions Oral iron administered to anemic inpatient pregnant women was not associated with higher hemoglobin concentrations before delivery. Lack of standardized iron regimens and short hospital stays may contribute to the inefficacy of oral iron for this inpatient pregnant population. The small sample size and retrospective nature of this study are limiting factors in drawing conclusive evidence from this study.

Candidate Kidney Protective Strategies for Patients Undergoing Major Abdominal Surgery: A Secondary Analysis of the RELIEF Trial Cohort.

BACKGROUND: Acute kidney injury (AKI) is common after major abdominal surgery. Selection of candidate kidney protective strategies for testing in large trials should be based on robust preliminary evidence. METHODS: A secondary analysis of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted in adult patients undergoing major abdominal surgery and randomly assigned to a restrictive or liberal perioperative fluid regimen. The primary outcome was maximum AKI stage before hospital discharge. Two multivariable ordinal regression models were developed to test the primary hypothesis that modifiable risk factors associated with increased maximum stage of postoperative AKI could be identified. Each model used a separate approach to variable selection to assess the sensitivity of the findings to modeling approach. For model 1, variable selection was informed by investigator opinion; for model 2, the Least Absolute Shrinkage and Selection Operator (LASSO) technique was used to develop a data-driven model from available variables. RESULTS: Of 2,444 patients analyzed, stage 1, 2, and 3 AKI occurred in 223 (9.1%), 59 (2.4%), and 36 (1.5%) patients, respectively. In multivariable modeling by model 1, administration of a nonsteroidal anti-inflammatory drug or cyclooxygenase-2 inhibitor, intraoperatively only (odds ratio, 1.77 [99% CI, 1.11 to 2.82]), and preoperative day-of-surgery administration of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker compared to no regular use (odds ratio, 1.84 [99% CI, 1.15 to 2.94]) were associated with increased odds for greater maximum stage AKI. These results were unchanged in model 2, with the additional finding of an inverse association between nadir hemoglobin concentration on postoperative day 1 and greater maximum stage AKI. CONCLUSIONS: Avoiding intraoperative nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors is a potential strategy to mitigate the risk for postoperative AKI. The findings strengthen the rationale for a clinical trial comprehensively testing the risk-benefit ratio of these drugs in the perioperative period.

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis.

BACKGROUND: Anti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients. METHODS: Plasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM. CONCLUSION: This study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.

Red Blood Cell Transfusion and Pulmonary Complications: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis.

BACKGROUND: Intraoperative packed red blood cell (PRBC) transfusion during cardiac surgery is associated with increased postoperative morbidity and mortality; however, data on the association between PRBC transfusion and postoperative pulmonary complications (PPCs) are somewhat conflicting. Using The Society of Thoracic Surgeons Adult Cardiac Surgery Database, we sought to determine whether intraoperative PRBC transfusion was associated with PPCs as well as with longer intensive care unit (ICU) stay after isolated coronary artery bypass grafting (CABG) surgery. METHODS: A registry-based cohort study was performed on 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of PPCs (hospital-acquired pneumonia [HAP], mechanical ventilation for >24 hours, or reintubation), ICU length of stay, and ICU readmission. RESULTS: Transfusion of 1, 2, 3, and ≥4 units of PRBCs was associated with increased odds for HAP (odds ratios [ORs], 1.24 [95% CI, 1.21-1.26], 1.28 [95% CI, 1.26-1.32], 1.36 [95% CI, 1.33-1.39], 1.31 [95% CI, 1.28-1.34]), reintubation (ORs, 1.23 [95% CI, 1.21-1.25], 1.38 [95% CI, 1.35-1.40], 1.57 [95% CI, 1.55-1.60], 1.70 [95% CI, 1.67-1.73]), prolonged ventilation (ORs, 1.34 [95% CI, 1.33-1.36], 1.56 [95% CI, 1.53-1.58], 1.97 [95% CI, 1.94-2.00], 2.27 [95% CI, 2.24-2.30]), initial ICU length of stay (mean difference in hours, 6.79 [95% CI, 6.00-7.58], 9.55 [95% CI, 8.71-10.38], 17.26 [95% CI, 16.38-18.15], 22.14 [95% CI, 21.22-23.06]), readmission to ICU (ORs, 1.14 [95% CI, 1.12-1.64], 1.15 [95% CI, 1.12-1.17], 1.15 [95% CI, 1.13-1.18], 1.32 [95% CI, 1.29-1.35]), and additional ICU length of stay (mean difference in hours, 0.55 [95% CI, 0.18-0.92], 0.38 [95% CI, 0.00-0.77], 1.02 [95% CI, 0.61-1.43], 1.83 [95% CI, 1.40-2.26]), respectively. CONCLUSIONS: Intraoperative PRBC transfusion was associated with increased incidence of PPCs, prolonged ICU stay, and ICU readmissions after isolated CABG surgery.

Randomized Controlled Trial Comparing Liposomal to Plain Bupivacaine in the Transversus Abdominis Plane for DIEP Flap Breast Reconstruction.

BACKGROUND: Pain control after autologous breast reconstruction is important for patient satisfaction and early recovery. Transversus abdominis plane (TAP) blocks are commonly used as part of an enhanced recovery after surgery (ERAS) pathway for breast reconstruction. It is uncertain whether liposomal bupivacaine used in TAP blocks offers additional advantages. This study aimed to compare the efficacy of liposomal bupivacaine versus plain bupivacaine for patients undergoing deep inferior epigastric perforator flap reconstruction. METHODS: This double-blinded randomized controlled trial studied patients undergoing abdominally based autologous breast reconstruction between June of 2019 and August of 2020. Subjects were randomly assigned liposomal or plain bupivacaine, performed using ultrasound-guided TAP block technique. All patients were managed according to an ERAS protocol. Primary outcomes were postoperative narcotic analgesia required, measured in oral morphine equivalents from postoperative days 1 to 7. Secondary outcomes included numeric pain scale score on postoperative days 1 to 7, nonnarcotic pain medication use, time to first narcotic use, return of bowel function, and length of stay. RESULTS: Sixty patients were enrolled: 30 received liposomal bupivacaine and 30 received plain bupivacaine. There were no significant differences in demographics, daily oral morphine equivalent narcotic use, nonnarcotic pain medication use, time to narcotic use, numeric pain scale score, time to bowel function, or length of stay. CONCLUSION: Liposomal bupivacaine does not confer advantages over plain bupivacaine when used in TAP blocks for abdominally based microvascular breast reconstruction in patients under ERAS protocols and multimodal approaches for pain control. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery.

OBJECTIVE: We determined whether intraoperative packed red blood cell (PRBC) transfusion was associated with a higher incidence of hospital-acquired venous thromboembolic (HA-VTE) complications and adverse outcomes after isolated coronary artery bypass grafting (CABG) surgery. BACKGROUND: Intraoperative PRBC has been associated with increased risk for postoperative deep venous thrombosis after cardiac surgery, but validation of these findings in a large, multi-institutional, national cohort of cardiac surgery patients has been lacking. METHODS: A registry-based cohort study of 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of HA-VTE and adverse outcomes. RESULTS: Administration of 1, 2, 3, and ≥4 units of PRBC transfusion was associated with increased odds for HA-VTE [odds ratios (ORs): 1.27 (1.22-1.32), 1.21 (1.16-1.26), 1.93 (1.85-2.00), 1.82 (1.75-1.89)], deep venous thrombosis [ORs: 1.39 (1.33-1.46), 1.38 (1.32-1.44), 2.18 (2.09-2.28), 1.82 (1.74-1.91], operative mortality [ORs: 1.11 (1.08-1.14), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], readmission within 30 days [ORs: 1.05 (1.04-1.06), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], and a prolonged postoperative length of stay [mean difference in days, 0.23 (0.19-0.27), 0.34 (0.30-0.39), 0.69 (0.64-0.74), 0.77 (0.72-0.820]. The odds of pulmonary venous thromboembolism were lower for patients transfused with 1 or 2 units [ORs: 0.98 (0.91-1.06), 0.75 (0.68-0.81)] of PRBC but remained significantly elevated for those receiving 3 and ≥4 units [ORs: 1.19 (1.09-1.29), 1.35 (1.25-1.48)]. CONCLUSIONS: Intraoperative PRBC transfusion was associated with HA-VTE and adverse outcomes after isolated CABG surgery.

Developing a risk stratification tool for predicting opioid-related respiratory depression after non-cardiac surgery: a retrospective study.

OBJECTIVES: Accurately assessing the probability of significant respiratory depression following opioid administration can potentially enhance perioperative risk assessment and pain management. We developed and validated a risk prediction tool to estimate the probability of significant respiratory depression (indexed by naloxone administration) in patients undergoing noncardiac surgery. DESIGN: Retrospective cohort study. SETTING: Single academic centre. PARTICIPANTS: We studied n=63 084 patients (mean age 47.1±18.2 years; 50% men) who underwent emergency or elective non-cardiac surgery between 1 January 2007 and 30 October 2017. INTERVENTIONS: A derivation subsample reflecting two-thirds of available patients (n=42 082) was randomly selected for model development, and associations were identified between predictor variables and naloxone administration occurring within 5 days following surgery. The resulting probability model for predicting naloxone administration was then cross-validated in a separate validation cohort reflecting the remaining one-third of patients (n=21 002). RESULTS: The rate of naloxone administration was identical in the derivation (n=2720 (6.5%)) and validation (n=1360 (6.5%)) cohorts. The risk prediction model identified female sex (OR: 3.01; 95% CI: 2.73 to 3.32), high-risk surgical procedures (OR: 4.16; 95% CI: 3.78 to 4.58), history of drug abuse (OR: 1.81; 95% CI: 1.52 to 2.16) and any opioids being administered on a scheduled rather than as-needed basis (OR: 8.31; 95% CI: 7.26 to 9.51) as risk factors for naloxone administration. Advanced age (OR: 0.971; 95% CI: 0.968 to 0.973), opioids administered via patient-controlled analgesia pump (OR: 0.55; 95% CI: 0.49 to 0.62) and any scheduled non-opioids (OR: 0.63; 95% CI: 0.58 to 0.69) were associated with decreased risk of naloxone administration. An overall risk prediction model incorporating the common clinically available variables above displayed excellent discriminative ability in both the derivation and validation cohorts (c-index=0.820 and 0.814, respectively). CONCLUSION: Our cross-validated clinical predictive model accurately estimates the risk of serious opioid-related respiratory depression requiring naloxone administration in postoperative patients.

Cellular and Molecular Mechanism of Cell Proliferation in Human Gastric Cancer Drug-Resistant Cells After Hyperthermia and Cisplatin: Role of mRNAs and Long-Non-coding RNAs.

BACKGROUND: Since thermo-chemotherapy was suggested as an effective treatment for gastric cancer, we aimed to evaluate the effects of hyperthermia combined with cisplatin (DDP) on the inhibition of human gastric cancer drug-resistant cells in vitro and explore its possible mechanisms. METHODS: SGC-7901/DDP cells were cultured and divided into control, cisplatin, hyperthermia, and hyperthermia combined with cispla- tin groups. Hyperthermia was done at 42°C, 44°C, 46°C, 48°C, and 50°C for 12 h, 24 h, 36 h; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay detected the proliferation of SGC-7901/DDP at different time and temperature, and the apoptotic rate of SGC-7901/DDP cells was evaluated by using Annexin staining assay. High-throughput Chromatin immunoprecipitation (ChIP)- seq was applied to test long non-coding RNA expression in SGC-7901/DDP cells. Then, real-time fluorescence quantitative polymerase chain reaction was used to verify the expression of long non-coding RNA in all groups. RESULTS: Double staining showed that hyperthermia combined with cisplatin increased the rate of early apoptosis of SGC-7901/DDP cells. Long non-coding RNA high-throughput ChIP-seq showed a significantly larger amount of long non-coding RNAs and mRNAs in the cells treated with hyperthermia combined cisplatin group in comparison with the control group. We observed that the upregulated mRNAs and long non-coding RNAs were highly related to immune system response and CD95 signaling pathway in nucleus, and down- regulated mRNAs and long non-coding RNA were highly related to Mammalian target of rapamycin (mTOR) and Tumor necrosis factor (TNF) receptor signaling pathway in cytoplasm. CONCLUSION: Hyperthermia combined with cisplatin reversed the expression of a large number of mRNAs and long non-coding RNAs in human gastric cancer drug-resistant cells. The molecular mechanism of inhibiting the proliferation of human gastric cancer drug- resistant cells may be related to the upregulation of long non-coding RNAs and mRNAs contributed in CD95, mTOR, and TNF receptor signaling pathway.

Alamandine, a new member of the renin-angiotensin system (RAS), attenuates collagen-induced arthritis in mice via inhibiting cytokine secretion in synovial fibroblasts.

Alamandine is a novel component of the renin-angiotensin system (RAS) as well as an important biologically active peptide. It has predominantly been studied in cardiovascular context. However, its role in rheumatoid arthritis (RA) remains unknown. Here we illustrated its effects on inflammatory cytokines production by synovial fibroblasts from RA and pathological changes in collagen-induced arthritis (CIA) mice. Alamandine (0.1, 1 and 10 µg/ml) did not affect the survival of the synovial fibroblasts, but decreased the migration and proinflammatory cytokines expression in TNF-α (10 ng/ml) stimulated cells in vitro. Additionally, alamandine selectively decreased phosphorylated-JNK expression induced by TNF-a stimulation in RA FLS. DBA/1 J mice were induced arthritis by a primary injection with an emulsion of bovine type II collagen (CII) and complete Freund's adjuvant (day 0) and a booster injection of CII in incomplete Freund's adjuvant (day 21). Mice were then given alamandine intraperitoneally in saline (50 µg/kg/day) from days 21-42. Histology and multiplex immunobead assay showed that alamandine treatment inhibited the development of arthritis and reduced the joint damage. This effect was accompanied by the reduced inflammatory cytokines (IL-6, IL-23, IFN-γ) mRNA expression in local joints, the decreased TNF-α, IL-6, IL-17 and the increased IL-10 levels in the serum from alamandine administrated CIA mice. In conclusion, alamandine attenuates the development of arthritis by suppressing inflammatory cytokines expression in RA synovial fibroblasts via MAPK signaling pathway, suggesting a potential therapeutic role for RA.

Processed Electroencephalographic Use During Anesthesia and Outcomes: Analysis of The Society of Thoracic Surgeons Adult Cardiac Surgery Database.

BACKGROUND: This study assessed associations between processed electroencephalographic (pEEG) use during anesthesia, surgery- and anesthesia-related risk factors, and neurologic outcomes and mortality after cardiac surgery. METHODS: Drawing from The Society of Thoracic Surgeons Adult Cardiac Surgery Database and its Adult Cardiac Anesthesiology Section, we identified 42 932 records for elective, urgent, and emergency cardiac surgical procedures between July 1, 2017 and December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the associations between pEEG use during anesthesia on the primary outcome, postoperative delirium (POD), and secondary outcomes of stroke, encephalopathy, coma, and operative mortality. RESULTS: The rate of pEEG use during anesthesia use was 32.8% (n = 14 086), and its use was not associated with decreased odds for POD (odds ratio [OR], 0.88; 95% CI, 0.78-1.02) or encephalopathy (OR, 0.85; 95% CI, 0.70-1.03). Intraoperative pEEG monitoring use was also not associated with increased odds for stroke (OR, 1.17; 95% CI, 0.97-1.42) or coma (OR, 1.44; 95% CI, 0.82-2.52). In contrast, pEEG use during anesthesia was associated with higher odds for operative mortality (OR, 1.23; 95% CI, 1.05-1.44). This association remained significant after adjusting for POD (OR, 1.21; 95% CI, 1.03-1.41), stroke (OR, 1.21; 95% CI, 1.04-1.42), and encephalopathy (OR, 1.28; 95% CI, 1.07-1.52). CONCLUSIONS: This large retrospective database study found no association between pEEG use during cardiac surgery and postoperative neurologic outcomes such as POD, stroke, encephalopathy, or coma. However, patients who underwent pEEG monitoring during anesthesia experienced higher mortality, even after adjustment for neurologic outcomes.

Prognostic and immunological role of Ras-related protein Rap1b in pan-cancer.

Ras-related Protein Rap1b, a GTP-binding protein belonging to the proximal RAS, which affects tumor progression through regulating tumor cell proliferation, invasion and participates in the functions of various immune cells. However, the potential roles and mechanisms of Rap1b in tumor progression and immunology remains unclear. In this study, we systematically analyzed the pan-cancer expression and prognostic correlation of Rap1b based on GTEX, CCLE, Oncomine, PrognoScan, Kaplan-Meier plotters and TCGA databases. The potential correlations of Rap1b with immune infiltration were revealed via TIMER and TCGA database. SangerBox database was used to analyzed the correlations between Rap1b expression and immune checkpoint (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repairs (MMRs) and DNA methylation. The results indicated that the expression level of Rap1b varies in different tumors. Meanwhile, the expression level of Rap1b strongly correlated with prognosis in patients with tumors, higher expression of Rap1b usually was linked to poor prognosis in different datasets. Rap1b was correlated closely with tumor immunity and interacted with various immune cells in different types of cancers. In addition, there were significant positive correlations between Rap1b expression and ICP, TMB, MSI, MMRs and DNA methylation. In conclusion, the results of pan-cancer analysis showed that the abnormal Rap1b expression was related to poor prognosis and tumor immune infiltration in different cancers. Furthermore, Rap1b gene may be used as a potential biomarker of clinical tumor prognosis.

CFP is a prognostic biomarker and correlated with immune infiltrates in Gastric Cancer and Lung Cancer.

Complement factor properdin (CFP), encodes plasma glycoprotein, is a critical gene that regulates the complement pathway of the innate immune system. However, correlations of CFP in cancers remain unclear. In this study, the expression pattern and prognostic value of CFP in pan-cancer were analyzed via the Oncomine, PrognoScan, GEPIA and Kaplan-Meier plotters. In addition, we used immunohistochemical staining to validate CFP expression in clinical tissue samples. Finally, we evaluated the correlations between CFP and cancer immune infiltrates particularly in stomach adenocarcinoma (STAD) and lung adenocarcinoma (LUAD) by using GEPIA and TIMER databases. The results of database analysis and immunohistochemistry showed that the expression level of CFP in STAD and LUAD was lower than that in normal tissues. Low expression level of CFP was associated with poorer overall survival (OS), first progression (FP), post progression survival (PPS) and was detrimental to the prognosis of STAD and LUAD, specifically in stage 3, stage T3, stage N2 and N3 of STAD (P<0.05). Moreover, expression of CFP had significant positive correlations with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (DCs) in STAD and LUAD. Furthermore, gene markers of infiltrating immune cells exhibited different CFP-related immune infiltration patterns such as tumor-associated-macrophages (TAMs). These results suggest that CFP can serve as a prognostic biomarker for determining prognosis and immune infiltration in STAD and LUAD.

Dexmedetomidine, Delirium, and Adverse Outcomes: Analysis of the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

BACKGROUND: We tested the hypothesis that dexmedetomidine was associated with a reduced incidence of postoperative delirium (POD) and adverse outcomes in cardiac surgery patients from The Society of Thoracic Surgeons Adult Cardiac Surgery Database including the Adult Cardiac Anesthesiology subsection. METHODS: We identified 55,905 patients in The Society of Thoracic Surgeons Adult Cardiac Surgery Database who underwent cardiac surgery between July 2014 and December 2018. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative dexmedetomidine on the primary (POD) and secondary outcomes (highest pain score on day 3 and at discharge, stroke, prolonged ventilation, postoperative intubation/reintubation, additional postoperative hours ventilated, renal failure, atrial fibrillation, and 30-day mortality). In separate propensity score-weighted analyses, we examined the effect of postoperative dexmedetomidine on the highest postoperative pain score at discharge and 30-day mortality. RESULTS: The rate of intraoperative dexmedetomidine use was 25.5% (n = 13,963), and its administration was associated with increased odds for POD (odds ratio, 1.85; 95% confidence interval [CI], 1.60-2.13), a small higher average pain score on day 3 (mean difference, 0.08; 95% CI, 0.02-0.14), increased odds for postoperative intubation/reintubation (odds ratio, 1.29; 95% CI, 1.12-1.48), and a small lower average pain score at discharge (mean difference, -0.31; 95% CI, -0.21 to-0.41). Postoperative dexmedetomidine was associated with a small higher average pain score at discharge (mean difference, 0.27; 95% CI, 0.21-0.34) and higher odds for 30-day mortality (odds ratio, 1.25, 95% CI, 1.07-1.46). CONCLUSIONS: In this registry of cardiac surgical patients dexmedetomidine administration was associated with POD and adverse outcomes.

Modulatory effect of Tagetes erecta flowers essential oils via Nrf2/HO-1/NF-κB/p65 axis mediated suppression of N-methyl-N'nitro-N-nitroguanidine (MNNG) induced gastric cancer in rats.

Protective effect of Tagetes erecta flowers essential oils was investigated on oxidative stress, immune response, inflammation, and apoptosis against N-methyl-N'nitro-N-nitroguanidine (MNNG) induced gastric cancer in rats. Essential oil were extracted from Tagetes erecta flowers and analyzed using gas chromatography-mass spectrometry (GC-MS). For observing a protective effect against MNNG induced gastric cancer, we divided rats into 4 groups (group A to D) having 10 rats in each group. Performed various experiments and measured a different parameters to investigate antioxidant activity, immune response, anti-inflammatory and anti-apoptotic activity. The levels of malondialdehyde were markedly increased in the presence of N-methyl-N'nitro-N-nitroguanidine, whereas, the antioxidant activities of superoxide dismutase, and catalase were lowered in the treated rats in contrast with the control. Intervention with TEEO to gastric cancer-induced rats upregulated the redox status and the activity of the immune system to decrease cancer risk. The proinflammatory cytokines (IL-6 and TNF-α) secretions that were induced by MNNG were markedly inhibited by TEEO. Administration of TEEO also significantly reduced terminal deoxynucleotidyl transferase dUTP nick end labeling positive gastric cancer cells, expression of mRNA of caspase-3, and Bax. Whereas, the expression of Bcl-2 was increased. Additionally, downregulation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) and IκBα degradation and the nuclear factor-κB (NF-κB) p65 expression in tissues of the stomach of MNNG-induced-rats were markedly elevated due to TEEO. This suggested possession of TEEO with a protective shield against MNNG induced gastric cancer by the exertion of antioxidative stress, anti-apoptotic response, the anti-inflammatory response through Nrf2/HO-1, and NF-κB signaling pathways.

Effects of an anesthesia perioperative surgical home for total knee and hip arthroplasty at a Veterans Affairs Hospital: a quality improvement before-and-after cohort study.

BACKGROUND: A perioperative surgical home, the Anesthesia Perioperative Care Service (APCS), was created to execute enhanced recovery after surgery pathways for total knee and total hip arthroplasty patients at the Tennessee Valley Health System Nashville VA Medical Center. We hypothesized that the APCS would be associated with reduced length of stay, in-hospital and post-discharge opioid exposure, costs, and hospital readmissions. METHODS: Data were collected for all patients admitted to the Nashville VA Medical Center following their respective surgery, for 400 days after the initiation of the APCS and for a 400-day period prior. This cohort study was based on a quality improvement project set up at the initiation of the service. The adjusted effect on each quantitative outcome was evaluated using proportional odds logistic regression methods. In addition, each regression analysis was performed in segmented regression fashion to identify changes in the outcomes over time. RESULTS: We included 282 patients in our cohort-96 prior and 186 post-implementation. Median hospital length of stay, intravenous (IV) and per os (PO) inpatient opioid administration, outpatient opioid quantity, and total days of supply were all reduced in the cohort cared for by the APCS. After adjusting for potential cofounders and evaluated outcome over time, the APCS remained independently associated with a reduction of hospital length of stay of one day (95% confidence interval, 0.09 to 1.97; P = 0.05) and with decreased IV and PO inpatient opioid administration, while continuing to show no increase in hospital readmissions. CONCLUSIONS: This cohort study showed significant improvements in important post-surgical outcomes after total knee and hip arthroplasty that were associated with the implementation of an APCS.

RéSUMé: CONTEXTE: Un centre de soins chirurgicaux périopératoires (perioperative surgical home), le Service de soins périopératoires en anesthésie (SSPA), a été créé pour mettre en œuvre des trajectoires de soins de récupération rapide après la chirurgie pour les patients ayant subi une arthroplastie totale du genou ou de la hanche au centre médical Tennessee Valley Health System Nashville VA Medical Center. Nous avons émis l'hypothèse que le SSPA serait associé à une réduction de la durée du séjour, de l'exposition aux opioïdes à l'hôpital et après le congé, ainsi qu'à une diminution des coûts et des réadmissions à l'hôpital. MéTHODE: Les données ont été recueillies pour tous les patients admis au centre médical Nashville VA Medical Center après leur chirurgie respective, pendant 400 jours avant et après la création du SSPA. Cette étude de cohorte se fondait sur un projet d'amélioration de la qualité mis en place lors de l'inauguration du service. L'effet ajusté sur chaque résultat quantitatif a été évalué à l'aide de méthodes de régression logistique proportionnelles. De plus, chaque analyse de régression a été effectuée de façon segmentée afin d'identifier l'évolution des résultats au fil du temps. RéSULTATS: Nous avons inclus 282 patients dans notre cohorte ­ 96 avant et 186 après la mise en œuvre. La durée médiane du séjour à l'hôpital, l'administration d'opioïdes par voie intraveineuse (IV) et per os (PO) pendant le séjour hospitalier, la quantité d'opioïdes en ambulatoire et sa durée en jours ont tous été réduites dans la cohorte prise en charge par le SSPA. Après avoir procédé à des ajustements pour tenir compte des facteurs de confusion potentiels et évalué l'évolution des résultats au fil du temps, le SSPA est demeuré indépendamment associé à une réduction de la durée de séjour à l'hôpital d'un jour (intervalle de confiance 95 %, 0,09 à 1,97; P = 0,05), à une réduction de l'administration d'opioïdes IV et PO durant le séjour, et il n'y a eu aucune augmentation des réadmissions à l'hôpital. CONCLUSION: Cette étude de cohorte a montré des améliorations significatives en matière de résultats post-chirurgicaux importants après une arthroplastie totale du genou et de la hanche associés à la mise en œuvre d'un SSPA.

MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLSs) are key effector cells in the pathogenesis of rheumatoid arthritis (RA) and display a unique aggressive tumor-like phenotype with remarkable hyperplasia, increased cell migration and invasion. How FLSs undergo these changes in RA remains unknown. We previously reported a novel function of transcription factor SOX5 in RA-FLSs that promote cell migration and invasion. In this study, we found that miR-15a/16 directly targets the SOX5 3'UTR and suppresses SOX5 expression. Moreover, miR-15a/16 is significantly down-regulated in RA-FLSs, which negatively correlates with SOX5 expression. Transfection with miR-15a/16 mimics in RA-FLSs inhibits cell migration, invasion, IL-1ß and TNFα expression. Overexpression SOX5 in RA-FLSs decreases miR-15a/16 expression and rescues miR-15a/16-mediated inhibitory effect. Furthermore, RA patients with the lower baseline serum miR-15a/16 level present poor response of 3 months disease-modifying antirheumatic drugs (DMARDs) therapy. Collectively, this study reveals that miR-15a/16/SOX5 axis functions as a key driver of RA-FLSs invasion, migration and inflammatory response in a mutual negative feedback loop and correlates with DMARDs treatment response in RA.

Polyporus Polysaccharide Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing Myofibroblast Differentiation via TGF-ß/Smad2/3 Pathway.

Pulmonary fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc) with no effective medication. Polyporus polysaccharide (PPS), extracted from Chinese herbs, has immune regulation, anticancer, antioxidant and antiinflammatory activities. This study aims to investigate antifibrotic effects of PPS. We show that PPS markedly ameliorates bleomycin-induced lung fibrosis in mice. Myofibroblasts are the effector cells responsible for excessive deposition of extracellular matrix (ECM) proteins in fibrotic diseases. In vitro evidence reveals that PPS exerts potent antifibrotic effects by inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, and repressing lung fibroblast proliferation and migration. We also find that PPS inhibits TGF-ß1-induced Smad2/3 activating. This study is the first to demonstrate an antifibrotic role of PPS in lungs, thus warranting further therapeutic evaluation.

Three-Dimensionally-Printed Polyether-Ether-Ketone Implant with a Cross-Linked Structure and Acid-Etched Microporous Surface Promotes Integration with Soft Tissue.

Polyether-ether-ketone (peek) is one of the most common materials used for load-bearing orthopedic devices owing to its radiolucency and favorable mechanical properties. However, current smooth-surfaced peek implants can lead to fibrous capsule formation. To overcome this issue, here, peek specimens with well-defined internal cross-linked structures (macropore diameters of 1.0-2.0 mm) were fabricated using a three-dimensional (3D) printer, and an acid-etched microporous surface was achieved using injection-molding technology. The cell adhesion properties of smooth and microporous peek specimens was compared in vitro through a scanning electron microscope (SEM), and the soft tissue responses to the both microporous and cross-linked structure of different groups were determined in vivo using a New Zealand white rabbit model, and examined through histologic staining and separating test. The results showed that the acid-etched microporous surface promoted human skin fibroblasts (HSF) adherence, while internal cross-linked structure improved the ability of the peek specimen to form a mechanical combination with soft tissue, especially with the 1.5 mm porous specimen. The peek specimens with both the internal cross-linked structure and external acid-etched microporous surface could effectively promote the close integration of soft tissue and prevent formation of fibrous capsules, demonstrating the potential for clinical application in surgical repair.