Analysis of outcomes and prognostic factor in acute type A aortic dissection complicated with preoperative shock: A single-center study.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency that requires prompt surgical intervention for preserving life, particularly in patients with critical preoperative status. This retrospective study aimed to investigate the clinical features, early and late outcomes, and prognostic factors in patients undergoing aortic repair surgery for ATAAD complicated with preoperative shock. METHODS: Between April 2007 and July 2020, 694 consecutive patients underwent emergency ATAAD repair at our institution, including 162 (23.3%) presenting with preoperative shock (systolic blood pressure <90 mm Hg), who were classified into the survivor (n = 125) and non-survivor (n = 37) groups according to whether they survived to hospital discharge. The clinical demographics, surgical information, and postoperative complications were compared. Five-year survival and freedom from reoperation rates of survivors were analyzed using the Kaplan-Meier actuarial method. Multivariate logistic regression analysis was used to identify independent risk factors for in-hospital mortality. RESULTS: The in-hospital surgical mortality rate in patients with ATAAD and shock was 22.8%. The non-survivor group showed higher rates of preoperative cardiopulmonary resuscitation, acute myocardial infarction, and cerebral infarction, and was associated with longer cardiopulmonary bypass time, higher rates of total arch replacement and intraoperative extracorporeal membrane oxygenation implementation. The non-survivor group had higher blood transfusion volumes and rates of malperfusion-related complications. Multivariate analysis revealed that preoperative cardiopulmonary resuscitation, prolonged cardiopulmonary bypass time, and total arch replacement were risk factors for in-hospital mortality. For patients who survived to discharge, the 5-year cumulative survival and freedom from aortic reoperation rates were 75.6% (95% confidence interval, 67.6%-83.6%) and 82.6% (95% confidence interval, 74.2%-91.1%), respectively. CONCLUSIONS: Preoperative shock in ATAAD is associated with a high risk of in-hospital mortality, particularly in patients who undergo cardiopulmonary resuscitation and complex aortic repair procedures with extended cardiopulmonary bypass. However, late outcomes are acceptable for patients who were stabilized through surgical treatment and survived to discharge.

Acute type a aortic intramural hematoma complicated with preoperative hemopericardium: early and late surgical outcome analyses.

BACKGROUND: Acute type A aortic intramural hematoma (ATAIMH) is a variant of acute type A aortic dissection (ATAAD), exhibiting an increased risk of hemopericardium and cardiac tamponade. It can be life-threatening without emergency treatment. However, comprehensive studies of the clinical features and surgical outcomes of preoperative hemopericardium in patients with ATAIMH remain scarce. This retrospective study aims to investigate the clinical features and early and late outcomes of patients who underwent aortic repair surgery for ATAIMH complicated with preoperative hemopericardium. METHODS: We investigated 132 consecutive patients who underwent emergency ATAIMH repair at this institution between February 2007 and August 2020. These patients were dichotomized into the hemopericardium (n = 58; 43.9%) and non-hemopericardium groups (n = 74; 56.1%). We compared the clinical demographics, surgical information, postoperative complications, 5-year cumulative survival rates, and freedom from reoperation rates. Furthermore, multivariable logistic regression analysis was utilized to identify independent risk factors for patients who underwent re-exploration for bleeding. RESULTS: In the hemopericardium group, 36.2% of patients presented with cardiac tamponade before surgery. Moreover, the hemopericardium group showed higher rates of preoperative shock and endotracheal intubation and was associated with an elevated incidence of intractable perioperative bleeding, necessitating delayed sternal closure for hemostasis. The hemopericardium group exhibited higher blood transfusion volumes and rates of re-exploration for bleeding following surgery. However, the 5-year survival (59.5% vs. 75.0%; P = 0.077) and freedom from reoperation rates (93.3% vs. 85.5%; P = 0.416) were comparable between both groups. Multivariable analysis revealed that hemopericardium, cardiopulmonary bypass time, and delayed sternal closure were the risk factors for bleeding re-exploration. CONCLUSIONS: The presence of hemopericardium in patients with ATAIMH is associated with an elevated incidence of cardiac tamponade and unstable preoperative hemodynamics, which could lead to perioperative bleeding tendencies and high complication rates. However, patients of ATAIMH complicated with hemopericardium undergoing aggressive surgical intervention exhibited long-term surgical outcomes comparable to those without hemopericardium.

Validation of cardiac output estimation using the fourth-generation FloTrac/EV1000™ system in patients undergoing robotic-assisted off-pump coronary artery bypass surgery.

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (COFT) compared to that measured with PAC using the thermodilution method (COPAC) during robotic-assisted off-pump coronary artery bypass (OPCAB) surgery. COFT and COPAC were obtained simultaneously at 4 predefined time points during robotic-assisted OPCAB: 5 min after the induction of general anesthesia (T1), after starting one-lung ventilation (T2), after capnothorax (T3), and after mini-thoracotomy was performed (T4). The agreement of data was investigated by Bland-Altman analysis. Thirty-four patients were initially enrolled. After exclusion, 32 patients and a total of 128 paired CO measurements were obtained. The overall bias was 1.46 L/min, the 95% limits of agreements were - 3.40 to 6.33 L/min, and the percentage error was 72.98%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between COPAC and COFT showed that the bias was moderately correlated with the SVRI (r2 = 0.43; p < 0.0001). Despite a software upgrade, the reliability of the fourth-generation FloTrac/EV1000™ system during robotic-assisted OPCAB to estimate CO was not acceptable, especially in patients with low SVRI.

Novel application of rhein and its prodrug diacerein for reversing cancer-related multidrug resistance through the dual inhibition of P-glycoprotein efflux and STAT3-mediated P-glycoprotein expression.

Multidrug resistance (MDR) is a multifactorial issue in cancer treatment. Drug efflux transporters, particularly P-glycoprotein (P-gp), are major contributors to such resistance. In the present study, we evaluated the P-gp-inhibiting and MDR-reversing effects of two compounds, namely rhein, an anthraquinone, and diacerein, the acetylated prodrug of rhein. ABCB1/Flp-In-293 was used as a model for investigating the related molecular mechanisms, and the multi-drug-resistant cancer cell line KB/VIN was used as a platform for evaluating the reversal of MDR0. The results indicated that at a concentration of 2.5 µM, both diacerein and rhein significantly inhibited P-gp efflux function. They also downregulated P-gp expression by interacting with the signal transducer and activator of transcription 3. Further investigation of the inhibitory mechanism of these compounds revealed that both stimulated P-gp ATPase activity dose dependently and engaged in the noncompetitive inhibition of rhodamine 123 efflux. Furthermore, rhein was revealed to be a potent reverser of MDR in cancer, and the combination of 30 µM rhein and 1000 nM vincristine exerted a strong synergistic effect, achieving a high combination index (CI) of 0.092. Diacerein demonstrated potential applications as a selective cytotoxic agent against multi-drug-resistant cancer cells at a concentration of > 18.92 µM and as a mild MDR reverser at doses of < 10 µM. In conclusion, diacerein and rhein are potential candidates for P-gp inhibition and MDR reversal in cancer cells.

Pre-operative proteinuria, postoperative acute kidney injury and mortality: A systematic review and meta-analysis.

OBJECTIVE: To investigate the association of pre-operative proteinuria with postoperative acute kidney injury (AKI) development as well as the requirement for a renal replacement therapy (RRT) and mortality at short-term and long-term follow-up. BACKGROUND: Postoperative AKI is associated with surgical morbidity and mortality. Pre-operative proteinuria is potentially a risk factor for postoperative AKI and mortality. However, the results in literature are conflicting. METHODS: We searched PubMed, Embase, Scopus, Web of Science and Cochrane Library from the inception through to 3 June 2020. Observational cohort studies investigating the association of pre-operative proteinuria with postoperative AKI development, requirement for RRT, and all-cause mortality at short-term and long-term follow-up were considered eligible. Using inverse variance method with a random-effects model, the pooled effect estimates and 95% confidence interval (CI) were calculated. RESULTS: Twenty-eight studies were included. Pre-operative proteinuria was associated with postoperative AKI development [odds ratio (OR) 1.74, 95% CI, 1.45 to 2.09], in-hospital RRT (OR 1.70, 95% CI, 1.25 to 2.32), requirement for RRT at long-term follow-up [hazard ratio (HR) 3.72, 95% CI, 2.03 to 6.82], and long-term all-cause mortality (hazard ratio 1.50, 95% CI, 1.30 to 1.73). In the subgroup analysis, pre-operative proteinuria was associated with increased odds of postoperative AKI in both cardiovascular (OR 1.77, 95% CI, 1.47 to 2.14) and noncardiovascular surgery (OR 1.63, 95% CI, 1.01 to 2.63). Moreover, there is a stepwise increase in OR of postoperative AKI development when the quantity of proteinuria increases from trace to 3+. CONCLUSION: Pre-operative proteinuria is significantly associated with postoperative AKI and long-term mortality. Pre-operative anaesthetic assessment should take into account the presence of proteinuria to identify high-risk patients. PROSPERO REGISTRATION: CRD42020190065.

Submental Ultrasound Is Effective in Predicting Difficult Mask Ventilation but Not in Difficult Laryngoscopy.

The goal of this study was to determine the utility of submental ultrasound parameters in distinguishing difficult airway management from easy airway management. Forty-one adult patients who underwent elective surgery under general anesthesia with endotracheal intubation from March to December 2018 were included. We used submental ultrasound to measure tongue base thickness (TBT) in the midsagittal plane and the distance between lingual arteries (DLA) in the transverse dimension. The primary outcome was difficult laryngoscopy, and the secondary outcome was difficult mask ventilation. Receiver operating characteristic curve analysis and logistic regression revealed no correlation between difficult laryngoscopy and SMUS measurements. Nevertheless, patients with difficult mask ventilation had significantly higher TBT (p = 0.009) and longer DLA (p = 0.010). After adjustment of confounding factors, increased TBT (>69.6 mm) was the sole independent predictor of difficult mask ventilation. The results indicated that SMUS is effective in predicting difficult mask ventilation but not difficult laryngoscopy.

Anesthesia and Long-term Oncological Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND: Whether propofol elicits a survival benefit over volatile anesthetics during cancer surgery remains inconclusive. The primary aim of this systematic review and meta-analysis is to compare the effects of propofol-based total intravenous anesthesia (TIVA) with any volatile anesthesia on long-term oncological outcomes. The secondary aim is to compare propofol-based TIVA with specific volatile agents on long-term oncological outcomes. METHODS: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library from inception through March 3, 2020. Randomized control trials and observational studies that compared the effects of propofol-based TIVA and volatile anesthesia on long-term oncological outcomes, which also reported hazard ratios (HR) as effect estimates, were considered eligible for inclusion. Using the inverse variance method with a random-effects model, HR and 95% confidence intervals (CI) were calculated. Trial sequential analysis was incorporated to test if the results were subject to a type I or type II error. RESULTS: Nineteen retrospective observational studies were included. Patients who received propofol-based TIVA during cancer surgery were associated with significantly better overall survival than those who received volatile anesthesia (HR = 0.79, 95% CI, 0.66-0.94, P = .008, I2 = 82%). In contrast, no statistically significant difference was observed in recurrence-free survival between patients who received propofol-based TIVA and volatile anesthesia during cancer surgery (HR = 0.81, 95% CI, 0.61-1.07, P = .137, I2 = 85%). In the subgroup analysis by different volatile anesthetics, patients who received propofol-based TIVA were associated with better overall survival than those who received desflurane (HR = 0.54, 95% CI, 0.36-0.80, P = .003, I2 = 80%). In contrast, there was no statistically significant difference in overall survival between patients who received propofol-based TIVA and those who received sevoflurane (HR = 0.92, 95% CI, 0.74-1.14, P = .439, I2 = 70%). In the trial sequential analysis of overall survival, the cumulative Z curve reached the required heterogeneity-adjusted information size and crossed the traditional significance boundary. In contrast, in the trial sequential analysis of recurrence-free survival, the cumulative Z curve did not cross the traditional significance boundary. However, the required heterogeneity-adjusted information size has not yet been reached. CONCLUSIONS: Propofol-based TIVA is generally associated with better overall survival than volatile anesthesia during cancer surgery. Further large-scaled, high-quality randomized control trials are warranted to confirm our findings.

Hyperlipidemia patients with long-term statin treatment are associated with a reduced risk of progression of benign prostatic enlargement.

OBJECTIVE: To evaluate the impacts of statin treatment on the risk of benign prostatic enlargement (BPE) progression in hyperlipidemia patients. METHODS: Newly diagnosed hyperlipidemia patients (n = 7961), identified from Taiwan's National Health Insurance Research Database, were divided into four statin cohorts (statin use >365 days, n = 1604; statin use 181-365 days, n = 813; statin use 91-180 days, n = 739; and statin use 31-90 days, n = 713) and one control cohort (cohort that used no statins, n = 4092). Study endpoint was occurrence of BPE progression (BPE diagnosis plus receiving BPE-related medications or surgery). Relative risks of BPE progression in the statin cohorts compared to the control cohort were analyzed. RESULTS: Multivariable Cox proportional hazards regression analyses demonstrated that BPE progression risk in the cohort used statins for >365 days was significantly lower than the control cohort (adjusted hazard ratio: 0.70, 95% confidence interval: 0.58 ∼ 0.85, p < .001). However, BPE progression risks of the other three statin cohorts did not significantly differ from the control cohort. Trend analysis revealed that the effects of statin treatment on decreasing BPE progression risk were significantly related to statin treatment duration (p = .001). CONCLUSIONS: Hyperlipidemia patients with long-term statin treatment (more than 365 days) are associated with a reduced risk of BPE progression.

Optimal measuring timing of cystatin C for early detection of contrast-induced acute kidney injury: A systematic review and meta-analysis.

OBJECTIVE: The optimal measuring timing of serum/plasma Cystatin C (CysC) for early detection of contrast-induced acute kidney injury (CIAKI) remains un-studied. We elucidated further on this issue. METHODS: We searched PubMed, MEDLINE, and Embase from inception until March 2018 for studies evaluating diagnostic accuracy of CysC for detecting CIAKI in patients exposed to contrast agents during diagnostic examinations or cardiac/peripheral catheterizations. RESULTS: A total of 10 relevant studies, comprising 2554 patients, were included and divided into the <24 -h and 24 -h groups based on CysC measuring timing (i.e., hours after contrast agent exposure). Compared with creatinine, pooled diagnostic odds ratio of CysC for detecting CIAKI of the <24 -h and 24 -h groups was 7.59 (95 % confidence interval [CI]: 1.31-44.08) and 53.81 (95 % CI: 13.57-213.26). Pooled sensitivity of the <24 -h and 24 -h groups was 0.81 and 0.88. Pooled specificity of the <24 -h and 24 -h groups was 0.64 and 0.88, respectively. Area under the hierarchical summary receiver operating characteristic curve of the <24 -h and 24 -h groups was 0.75 and 0.93. CONCLUSIONS: Measuring CysC at 24 h after contrast agent exposure shows higher diagnostic accuracy for early detection of CIAKI than measuring CysC at <24 h after contrast agent exposure.

Resveratrol alleviates nuclear factor-κB-mediated neuroinflammation in vasculitic peripheral neuropathy induced by ischaemia-reperfusion via suppressing endoplasmic reticulum stress.

Vasculitic peripheral neuropathy (VPN) arises from an inflammatory obstruction in the blood vessels supplying peripheral nerves and subsequent ischaemic insults, which exhibits the clinical features of neuropathic pain and impaired peripheral nerve function. VPN induced by ischaemia-reperfusion (IR) has been reported to involve nuclear factor-κB (NF-κB)-mediated neuroinflammation. Recent studies have suggested that endoplasmic reticulum (ER) stress has been implicated in the development of peripheral neuropathies. Resveratrol possesses a potent anti-inflammatory capacity. We hypothesized that resveratrol may exert a protective effect against VPN through modulating the interrelated ER stress and NF-κB pathways. Male Sprague-Dawley rats were allocated into five groups: sham, sham + resveratrol 40 mg/kg (R40), IR, IR + R20 and IR + R40. VPN was induced by occluding the right femoral artery for 4 hours followed by reperfusion. Our data have shown that VPN induced by IR led to hind paw mechanical allodynia, heat hyperalgaesia, and impaired motor nerve conduction velocity (MNCV). With resveratrol intervention, the behavioural parameters were improved in a dose-dependent manner and the MNCV levels were increased as well. The molecular data revealed that VPN induced by IR significantly increased the expression of NF-κB as well as the ER stress sensor proteins, protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 and activating transcription factor 6 in the sciatic nerves. More importantly, resveratrol significantly attenuated the expression of NF-κB and the ER stress sensor proteins after IR. In conclusion, resveratrol alleviates VPN induced by IR. The mechanisms may involve modulating NF-κB-mediated neuroinflammation via suppressing ER stress.

Magnesium sulfate inhibits binding of lipopolysaccharide to THP-1 cells by reducing expression of cluster of differentiation 14.

We investigated effects of magnesium sulfate (MgSO4) on modulating lipopolysaccharide (LPS)-macrophage binding and cluster of differentiation 14 (CD14) expression. Flow cytometry data revealed that the mean levels of LPS-macrophage binding and membrane-bound CD14 expression (mCD14) in differentiated THP-1 cells (a human monocytic cell line) treated with LPS plus MgSO4 (the LPS + M group) decreased by 28.2% and 25.3% compared with those THP-1 cells treated with LPS only (the LPS group) (P < 0.001 and P = 0.037), indicating that MgSO4 significantly inhibits LPS-macrophage binding and mCD14 expression. Notably, these effects of MgSO4 were counteracted by L-type calcium channel activation. Moreover, the mean level of soluble CD14 (sCD14; proteolytic cleavage product of CD14) in the LPS + M group was 25.6% higher than in the LPS group (P < 0.001), indicating that MgSO4 significantly enhances CD14 proteolytic cleavage. Of note, serine protease inhibition mitigated effects of MgSO4 on both decreasing mCD14 and increasing sCD14. In conclusion, MgSO4 inhibits LPS-macrophage binding through reducing CD14 expression. The mechanisms may involve antagonizing L-type calcium channels and activating serine proteases.

Vidian Neurectomy for Management of Chronic Cluster Headache.

BACKGROUND: Management of chronic cluster headache (CCH) remains a challenging endeavor, and the optimal surgical approach for medically refractory CCH remains controversial. OBJECTIVE: To conduct a preliminary evaluation of the efficacy and safety of vidian neurectomy (VN) in patients with medically refractory CCH. METHODS: Between March 2013 and December 2015, 9 CCH patients, all of whom had failed to respond to conservative therapy, underwent VN with a precise nerve cut and maximal preservation of the sphenopalatine ganglion. Data included demographic variables, cluster headache onset and duration, mean attack frequency, mean attack intensity, and pain disability index measures pre- and through 12-mo postsurgery. RESULTS: Seven of the 9 cases (77.8%) showed immediate improvement. Improvement was delayed by 1 mo in 1 patient, after which the surgical effects of pain relief were maintained throughout the follow-up period. One patient (11.1%) did not improve after surgery. One year after VN, patients' mean attack frequency, mean attack intensity, and pain disability index decreased by 54.5%, 52.9%, and 56.4%, respectively. No patient experienced treatment-related side effects or complications. CONCLUSION: VN is an effective treatment method for CCH patients. Precise Vidian nerve identification and maximal preservation of the sphenopalatine ganglion may achieve good surgical outcomes and dramatically improve quality of life among patients, without significant adverse events.

Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium.

BACKGROUND: Nod-like receptor protein 3 (NLRP3) inflammasome is a multiprotein complex composed of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain. Activation of NLRP3 inflammasome leads to interleukin-1ß (IL-1ß) upregulation and pyroptosis, a proinflammatory cell death characterized by increased cell size. Of note, calcium signaling is crucial for NLRP3 inflammasome activation. This study elucidated the effects of magnesium sulfate (MgSO4), a potent calcium antagonist, on modulating NLRP3 inflammasome. MATERIALS AND METHODS: THP-1 cells, the human monocytic leukemia cell line, were treated with lipopolysaccharide (LPS, 1 µg/ml) plus nigericin (5 µM) (the LPS + Nig group) and LPS plus nigericin plus MgSO4 (20 mM) [the LPS + Nig + M(20)] to facilitate investigations. Levels of IL-1ß, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed. RESULTS: IL-1ß concentration of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.001). Cell size of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P < 0.001). Level of pyroptotic cell death of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.004). NLRP3 mRNA and protein concentrations of the LPS + Nig + M(20) group were also significantly lower than the LPS + Nig group (P = 0.021 and P < 0.001). Similarly, apoptosis-associated speck-like protein containing a caspase recruitment domain speck formation ratio and caspase-1 concentration of the LPS + Nig + M(20) group were significantly lower than the LPS + Nig group (both P < 0.001). The change in intracellular calcium level of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P = 0.001). CONCLUSIONS: MgSO4 inhibits NLRP3 inflammasome, IL-1ß upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels.

The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

PURPOSE: The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). METHODS: A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. RESULTS: A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test; P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis. CONCLUSIONS: By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

Hyperlipidemia is associated with an increased risk of clinical benign prostatic hyperplasia.

BACKGROUND: A high fat diet is associated with risk of benign prostatic hyperplasia (BPH). However, whether hyperlipidemia is associated with BPH remains unclear. This population-based cohort study elucidated whether hyperlipidemia is associated with an increased risk of BPH. METHODS: We used a new-exposure design and analyzed data retrieved from the Taiwan National Health Insurance Database between January 1, 2000 and December 31, 2013. The cohort of men with newly diagnosed hyperlipidemia and the age- and index-date-matched (1:3) nonhyperlipidemia cohort were tracked for incidence of BPH during a 1- to 14-year follow-up. Diagnosis of BPH using the International Classification of Diseases, Ninth Revision, Clinical Modification codes, and the occurrence of BPH diagnosis plus the use of alpha-blockers or 5-alpha reductase inhibitors or receipt of transurethral resection of the prostate were the primary and secondary endpoints, respectively. The confounders in this study were diabetes mellitus, hypertension, coronary heart disease, obesity, liver cirrhosis, nonsteroidal anti-inflammatory drugs, metformin, aspirin, and number of urologist visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a multivariate Cox proportional hazards regression model adjusted for the propensity score. RESULTS: A total of 35 860 subjects (aged 40-99 years)-including the hyperlipidemia cohort (n = 8,965) and nonhyperlipidemia cohort (n = 26 895)-were identified. Our data revealed that the hyperlipidemia cohort had significantly higher incidences of developing BPH (24.6% vs 12.3%, P < 0.001) and treated BPH (13% vs 5.7%, P < 0.001) compared with the nonhyperlipidemia cohort. The risk of developing BPH in the hyperlipidemia cohort was significantly higher than that in the nonhyperlipidemia cohort (HR = 1.73, 95% CI = 1.63-1.83, P < 0.001) after adjustment for the propensity score. CONCLUSIONS: Hyperlipidemia is associated with an increased risk of clinical BPH.

Naloxone inhibits nod-like receptor protein 3 inflammasome.

BACKGROUND: Naloxone, an opioid receptor antagonist, possesses potent anti-inflammation effects. We previously confirmed the effects of naloxone on inhibiting upregulation of inflammatory cytokine interleukin-1ß (IL-1ß). Production of mature form IL-1ß is mediated by the nod-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex composed of NLRP3, and the adaptor protein apoptosis-associated speck-like protein contains a caspase recruitment domain (ASC). We elucidated whether naloxone could inhibit the activation of NLRP3 inflammasome. MATERIAL AND METHODS: To induce IL-1ß production and NLRP3 inflammasome activation, the human monocytic leukemia cell line THP-1 cells were first primed with lipopolysaccharide (LPS, 1 µg/mL) and then activated with adenosine triphosphate (ATP, 1 mM). For NLRP3 transcription, THP-1 cells were only treated with LPS priming. RESULTS: Enzyme-link immunosorbent assay data revealed that the concentration of IL-1ß in THP-1 cells treated with LPS plus ATP was significantly higher than that in THP-1 cells treated with LPS plus ATP plus naloxone (0.1 µM) (P < 0.001). Real-time quantitative reverse transcription and polymerase chain reaction data also revealed that NLRP3 mRNA concentration in THP-1 cells treated with LPS was significantly higher than that in THP-1 cells treated with LPS plus naloxone (P = 0.001). ASC speck formation, that is, ASC assembles into a large protein complex, is an indicator for NLRP3 inflammasome activation. Our data revealed that the percentage of cells containing ASC specks in THP-1 cells treated with LPS plus ATP was also significantly higher than that in THP-1 cells treated with LPS plus ATP plus naloxone (P < 0.001). CONCLUSIONS: Naloxone inhibits NLRP3 inflammasome activation.

Esmolol pretreatment attenuates heart rate increase and parasympathetic inhibition during rapid increases in desflurane concentration: A preliminary randomized study.

BACKGROUND: Rapid increases in desflurane concentration can transiently increase the heart rate (HR). Esmolol possesses a high ß1-adrenoceptor selectivity and a short duration of action. This preliminary study aimed at investigating the effects of esmolol on the HR and autonomic modulation during a desflurane-induced HR increase. METHODS: American Society of Anesthesiologists physical status I female subjects, aged 20 to 50 years, who were undergoing minor breast surgery were randomly assigned to 2 groups. Rapid increases in desflurane concentration were commenced after induction of anesthesia. Each subject received either i.v. saline (control group) or esmolol 0.5 mg/kg (esmolol group) before desflurane inhalation. Using time-frequency spectral analysis of HR variability, the HR indices were studied at baseline, postinduction, posttreatment, as well as at minimal alveolar concentrations of desflurane reaching 1.0, 1.3, and 1.5. The low frequency (LF) power is influenced by both the sympathetic and parasympathetic activity, whereas the high frequency (HF) power reflects the parasympathetic activity. The LF/HF ratio is thought to reflect either sympathovagal balance or sympathetic modulation. RESULTS: Electrocardiograms for data analysis were obtained from 8 subjects in each group. Rapid increases in desflurane concentration after induction caused a HR increase. Both the corresponding LF and HF powers were low and the LF/HF ratio remained unchanged. This indicates that the desflurane-induced HR increase may be attributed to parasympathetic inhibition and may be independent of sympathetic activation. Esmolol pretreatment effectively attenuated desflurane-induced HR increase. Moreover, subjects receiving esmolol pretreatment had increased LF and HF powers, but did not have changes in their LF/HF ratios, as compared to those without esmolol. CONCLUSION: Esmolol pretreatment attenuates HR increase and parasympathetic inhibition during rapid increases in desflurane concentration.

Vasculitic peripheral neuropathy induced by ischemia-reperfusion in the rat femoral artery involves activation of proinflammatory signaling pathway in the sciatic nerve.

Ischemia-reperfusion (IR) in the rat femoral artery has been proposed as an experimental model of vasculitic peripheral neuropathy (VPN) which presents neuropathic pain and peripheral nerve injury patterns observed clinically. This study investigates the involvement of the proinflammatory signaling pathway underlying the peripheral mechanisms of VPN. Male Sprague-Dawley rats were allocated to receive either a sham operation or IR. IR was induced by occluding the right femoral artery for 4h followed by reperfusion periods from 0 to 72h. The behavioral parameters were assessed at baseline as well as at days 1, 2 and 3 after reperfusion. The time-course analyses of proinflammatory mediators in the sciatic nerves were also performed on rats of the sham group or IR groups with reperfusion periods of 0, 2, 4, 24 and 72h, respectively. The behavioral data confirmed that this VPN model induced hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength. The molecular data revealed that IR in the femoral artery activated the expression of nuclear factor-κB (NF-κB) in the sciatic nerve indicating a neuroinflammatory response. Moreover, IR in the femoral artery increased the expression of proinflammatory cytokines TNF-α and IL-1ß in the sciatic nerve. This study elucidated the novel time-course expression profiles of NF-κB and proinflammatory cytokines in VPN induced by IR which may be involved in the development of neuropathic pain. Since NF-κB is a key element during neuroinflammation, strategies targeting the NF-κB signaling pathway may provide therapeutic potential against VPN induced by IR.

Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin.

Vasopressin possesses potent anti-inflammatory capacity. Phosphoinositide 3-kinase (PI3K) and its downstream activator Akt contribute to endogenous anti-inflammation capacity. We sought to elucidate whether PI3K is involved in mediating the anti-inflammation effects of vasopressin. Macrophages (RAW264.7 cells) were randomized to receive endotoxin, endotoxin plus vasopressin, or endotoxin plus vasopressin plus the nonselective PI3K inhibitor (LY294002) or the selective isoform inhibitor of PI3Kα (PIK-75), PI3Kß (TGX-221), PI3Kδ (IC-87114), or PI3Kγ (AS-252424). Compared to macrophages treated with endotoxin, the concentrations of cytokines (tumor necrosis factor-α, interleukin-6) and chemokine (macrophage inflammatory protein-2) in macrophages treated with endotoxin plus vasopressin were significantly lower (all P < 0.05). The concentrations of phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in nuclear extracts and phosphorylated inhibitor-κBα (p-I-κBα) in cytosolic extracts as well as NF-κB-DNA binding activity were also lower (all P < 0.05). Of note, except for macrophages treated with endotoxin plus vasopressin plus PIK-75, the concentrations of cytokines, chemokine, p-NF-κB p65, and p-I-κBα as well as NF-κB-DNA binding activity in macrophages treated with endotoxin plus vasopressin plus LY294002, TGX-221, IC-87114, or AS-252424 were significantly higher than those in macrophages treated with endotoxin plus vasopressin (all P < 0.05). In contrast, the phosphorylated Akt concentration in macrophages treated with endotoxin plus vasopressin was significantly higher than that in macrophages treated with endotoxin or in macrophages treated with endotoxin plus vasopressin plus LY294002, TGX-221, IC-87114, or AS-252424, but not PIK-75. These data confirmed that PI3K, especially the isoforms of PI3Kß, PI3Kδ, and PI3Kγ, is involved in mediating the anti-inflammatory effects of vasopressin.