Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1β (IL-1β) 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 (MgSO 4 ), 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 MgSO 4 (20 mM) [the LPS + Nig + M(20)] to facilitate investigations. Levels of IL-1β, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed. Results IL-1β 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 MgSO 4 inhibits NLRP3 inflammasome, IL-1β upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels. [ABSTRACT FROM AUTHOR]

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), PI3Kβ (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 PI3Kβ, PI3Kδ, and PI3Kγ, is involved in mediating the anti-inflammatory effects of vasopressin. [ABSTRACT FROM AUTHOR]

Background Oxidation and inflammation caused by lower limb ischemia–reperfusion (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent antioxidative and anti-inflammatory drug, can mitigate lung injury induced by lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated. Materials and methods Adult male Sprague–Dawley rats were randomized to receive I/R, I/R plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 24 h. Results Rats receiving I/R had significant increases in concentrations of nitric oxide, malondialdehyde (lipid peroxidation marker), and inflammatory molecules (including interleukin 6, macrophage inflammatory protein 2, and prostaglandin E 2 ) in plasma, and the lungs, indicating that I/R caused significant oxidation and inflammation in rats. Rats receiving I/R also had significant increases in concentration of phosphorylated inhibitor-κB, indicating that I/R caused significant nuclear factor κB activation. Assays of arterial blood gas, biochemistry, and histopathology confirmed that I/R-induced significant lung injury in rats. Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor κB activation, and lung injury induced by I/R. Of note, cepharanthine significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these previously mentioned effects of cepharanthine were partially reversed by inhibiting the activity of HO-1. Conclusions Cepharanthine mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve its effects on reducing oxidation and inflammation. The mechanisms may also involve enhancing HO-1 expression. [ABSTRACT FROM AUTHOR]

Background Cepharanthine possesses strong anti-inflammation capacity. We sought to clarify whether cepharanthine could mitigate pro-inflammatory cytokine production in acute lung injury induced by hemorrhagic shock/resuscitation (HS/RES). The involvement of heme oxygenase-1 (HO-1) was also investigated. Methods Male Sprague Dawley rats were allocated to receive HS/RES, HS/RES plus iv cepharanthine or HS/RES plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP) and denoted as the HS/RES, HS/RES + CEP, and HS/RES + CEP + SnPP group, respectively. HS/RES was achieved by blood drawing to lower mean arterial pressure (40–45 mmHg for 60 min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5 h before sacrifice. Results Arterial blood gas, lung permeability and histologic assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced significant lung injury. Significant increases in pulmonary levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, prostaglandin E 2 and cyclooxygenase-2 confirmed that HS/RES induced a significant inflammatory response in the lungs. Cepharanthine significantly attenuated the pulmonary pro-inflammatory cytokine production and lung injury induced by HS/RES. However, the protective effects of cepharanthine were blocked by SnPP, the potent HO-1 activity inhibitor. Conclusion Cepharanthine significantly mitigates pro-inflammatory cytokine response in acute lung injury induced by HS/RES in rats. The mechanism may involve the HO-1 pathway. [ABSTRACT FROM AUTHOR]

Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR) of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group), sham-operation (Sham), or sham plus caffeine (n=12 in each group). To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection) was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001 and P=0.008, resp.). Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2) and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P<0.05). These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs. [ABSTRACT FROM AUTHOR]

Limb ischemia/reperfusion (I/R) causes oxidation and inflammation and subsequently induces muscle and kidney injuries. Cepharanthine, a natural plant alkaloid, possesses anti-inflammatory and antioxidative properties. We elucidated the salutary effects of cepharanthine against muscle and kidney injuries following limb I/R. Adult male rats were randomized to receive I/R or I/R plus cepharanthine. I/R was achieved by applying tourniquet high around each thigh for 3 hours followed by reperfusion for 24 hours. Cepharanthine (10 mg/kg, intraperitoneal) was injected immediately before reperfusion. After euthanization, degrees of tissue injury, inflammation, and oxidation were examined. Our data revealed that the I/R group had significant increases in injury biomarker concentrations of muscle (creatine kinase and lactate dehydrogenase) and kidney (creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1). Histological assays revealed moderate muscle and kidney injury characteristics in the I/R group. The I/R group also had significant increases in concentrations of inflammatory molecules (interleukin-6, macrophage inflammatory protein-2, and prostaglandin E2) and reactive nitrogen species (nitric oxide) as well as lipid peroxidation (malondialdehyde). Of note, these effects of limb I/R could be mitigated by cepharanthine. These data confirmed that cepharanthine attenuated muscle and kidney injuries induced by limb I/R. The mechanisms may involve its anti-inflammatory and antioxidative capacities. [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1β (IL-1β). Production of mature form IL-1β 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-1β 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-1β 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO4) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO4 could mitigate I/R-induced lung injury. As MgSO4 is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated. Materials and Methods: Adult male rats were allocated to receive I/R, I/R plus MgSO4 (10, 50, or 100 mg/kg), or I/R plus MgSO4 (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined. Results: Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E2 concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO4, at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO4. Conclusions: MgSO4 mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels. [Copyright &y& Elsevier]

Objective To elucidate the effectiveness of ultrasound-guided genicular nerve radiofrequency ablation in alleviating pain as well as its effects on functional outcomes, quality of life and physical performance in knee osteoarthritis patients. Design Prospective observational study. Setting Patients were recruited within one community hospital. Subjects Patients with knee osteoarthritis. Methods The subjects underwent ultrasound-guided radiofrequency ablation of genicular nerves after showing a positive response to a diagnostic block. Outcome assessments were performed at baseline and at 2 and 12 weeks posttreatments using the 36-item Short Form Health Survey (SF-36), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a physical performance evaluation including balance tests, quadriceps muscle strength test, two-minute walking test and knee joint proprioception test. Results Thirteen out of 38 patients were eligible for genicular nerve radiofrequency ablation. There were significant improvements from baseline to posttreatment in the numeric rating scale score, physical health domain score of SF-36, and pain and stiffness domain scores of the WOMAC. Regarding physical performance, the step test result significantly improved over the 12 weeks of follow-up. On the other hand, no significant deteriorations in the single leg stance test, isokinetic quadriceps muscle strength test, knee joint proprioception test or two-minute walking test results were observed after radiofrequency ablation of genicular nerves. Conclusions Radiofrequency ablation of genicular nerves may significantly alleviate pain and improve functional outcomes in knee osteoarthritis patients. More importantly, static balance control and quadriceps muscle strength were preserved and there was a change of proprioception in the good direction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Cystatin C (CysC) is a superior biomarker to serum creatinine for early detection of contrast-induced acute kidney injury (CIAKI). • The optimal CysC measuring timing for early detecting CIAKI is at 24 h after contrast agent exposure. • Positive findings on the diagnostic accuracy of CysC for early detecting CIAKI can be made based on absolute CysC values or increased magnitudes from baseline. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia–reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN. [ABSTRACT FROM AUTHOR]

Background: Impacts of delivery modes on the subsequent risk of coronary heart disease (CHD) in pregnant women have not been elucidated. Materials and Methods: Data of women who had undergone cesarean delivery (CD cohort) or vaginal delivery (VD cohort) between January 2000 and December 2012 from Taiwan Health Insurance Database were analyzed. All subjects were tracked until December 31, 2013. For women with multiple deliveries, only the first delivery data were included. Study end point was the diagnosis of new-onset CHD after delivery. Results: In total, 51,765 subjects (CD cohort: n = 17,839; VD cohort: n = 33,926) were included. During 1–14 years of follow-up, the incidence rate of new-onset CHD in the CD cohort was significantly higher than in the VD cohort (1.3% [231/17,839] vs. 0.8% [257/33,926], p < 0.001; effect size: 0.30). Analysis revealed that the subsequent risk of CHD in the CD cohort was significantly higher than in the VD cohort (adjusted hazard ratio [HR] = 1.28, 95% confidence intervals [CI]: 1.06–1.55, p = 0.012). We performed sensitivity tests by excluding subjects who had undergone CD due to nonmedical reasons from the CD cohort. The remaining subjects were named as the *CD cohort. Analysis also revealed a higher subsequent risk of CHD in the *CD cohort than in the VD cohort (adjusted HR = 1.32, 95% CI: 1.08–1.60, p = 0.006). Conclusions: Women who had undergone primary CD, especially those who had undergone CD due to medical reasons, were associated with an ∼30% higher risk of CHD than those who had undergone VD. [ABSTRACT FROM AUTHOR]

Background Vascular hyporeactivity contributes to hemodynamic alterations and circulatory failure in severe sepsis. Among the identified mechanisms, inflammation and oxidative stress are the most crucial ones in mediating the development of vascular hyporeactivity induced by sepsis. Platonin, a photosensitive dye and an antioxidant, possesses potent antiinflammation effects. We elucidated whether platonin could mitigate vascular hyporeactivity of thoracic aorta in septic rats. Material and methods Adult male Sprague–Dawley rats were randomized to receive sham operation (Sham), Sham plus platonin (100 μg/kg), cecal ligation and puncture (CLP), or CLP plus platonin (10, 50, or 100 μg/kg) and designated as the Sham, P, CLP, CLP + P(10), CLP + P(50), and CLP + P(100) group, respectively ( n = 6 in each group). After maintaining for 12 hours, surviving rats were euthanized and thoracic aorta was isolated and vascular reactivity of aortic rings was determined. Results Vascular reactivity induced by vasoconstrictors phenylephrine and angiotensin II of the Sham and the P groups ( n = 6 in both groups) were similar, whereas vascular reactivity of the CLP group ( n = 5) were significantly lower than those of the Sham group (both P < 0.001). Of note, vascular reactivity induced by phenylephrine and angiotensin II of the CLP + P(10) group ( n = 5) and the CLP group were not significantly different. In contrast, vascular reactivity induced by phenylephrine and angiotensin II of the CLP + P(50) and the CLP + P(100) groups ( n = 6 in both groups) were significantly higher than those of the CLP group (phenylephrine: P = 0.024 and 0.017; angiotensin II: P = 0.031 and 0.036). Conclusion Platonin could mitigate vascular hyporeactivity of thoracic aorta in septic rats. [ABSTRACT FROM AUTHOR]

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 4 h followed by reperfusion periods from 0 to 72 h. 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 72 h, 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-1β 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. [ABSTRACT FROM AUTHOR]

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively ( n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression. [ABSTRACT FROM AUTHOR]

Unfortunately, Fig. 5 was incorrectly published in the original publication. The complete corrected Fig. 5 is given below. [ABSTRACT FROM AUTHOR]