Postoperative Analgesic Effects of Serratus Anterior Plane Block for Thoracic and Breast Surgery: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Postoperative pain is a concern after thoracic and breast surgeries. Recent studies have demonstrated that ultrasound-guided serratus anterior plane block (SAPB) could provide postoperative analgesia. OBJECTIVE: The objective of this systematic review and meta-analysis was to examine the effects of SAPB on postoperative analgesia in thoracic and breast surgery. STUDY DESIGN: A systematic review and meta-analysis of randomized control trials (RCTs). METHODS: We systematically queried the PubMed, Embase, Web of Science, and Cochrane Library online databases from their establishment through Mar 31, 2022. Eligible RCTs were selected for the purpose of conducting the meta-analysis. The risk of bias of the included trials was assessed by Cochrane Review Manager. The level of certainty was examined utilizing the GRADE (Grade of Recommendations Assessment, Development, and Evaluation) scale to determine whether the evidence was of high quality or not. RESULTS: During the process of the meta-analysis, a total of 27 pieces of literature was included in the present research. SAPB significantly reduced the intraoperative opioid consumption (mean difference [MD] = -9.52 mg of morphine equivalent, 95% CI, -15.50 to -3.54; P < 0.01, I2 = 98%) and postoperative pain opioid consumption (MD = -23.12 mg of morphine equivalent, 95% CI, -30.59 to -15.65; P < 0.01, I2 = 100%. Also, patients in the SAPB group had lower pain scores during the first postoperative 24 hours. Furthermore, SAPB attenuated the occurrence of postsurgical nausea and vomiting, as well as chronic postsurgical pain. LIMITATIONS: Double-blinding was not performed in some trials, also some assessors were not blinded; the included sample sizes of eligible trials which reported the incidence of chronic postsurgical pain were relatively small; the comparisons between SAPB and other types of blocks were not performed in our meta-analysis. CONCLUSION: Our findings suggest that SAPB not only relieves acute pain after thoracic and breast surgery, but also reduces the incidence of chronic postsurgical pain.

Comparing the Clinical Outcomes Observed with Rivaroxaban Versus Warfarin for the Management of Obese Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is an irregular heart rhythm which is becoming more and more common in this new era. Obesity is a risk factor for cardiovascular events, and obese patients are more at risk for stroke. The Framingham Heart Study demonstrated an increase in the developmental risk of AF by 4% for every unit (kg/m2) increase in body mass index (BMI). An anticoagulant is often required for the management of such patients. In this analysis, we aimed to systematically compare the clinical outcomes which were associated with rivaroxaban versus warfarin for the treatment of obese patients with non-valvular AF. METHODS: PubMed, EMBASE, Web of Science, http://www. CLINICALTRIALS: gov , Google Scholar, and Cochrane Central were the searched databases. Clinical outcomes including stroke, systemic embolism, and major bleeding were the endpoints. In this study, dichotomous data were analyzed by the RevMan software version 5.4. Risk ratio (RR) with 95% confidence interval (CI) was used for result interpretation. RESULTS: Ten studies consisting of a total number of 168,081 obese participants were included whereby 81,332 participants were treated with rivaroxaban and 86,749 participants were treated with warfarin. The risks of ischemic (RR: 0.79, 95% CI: 0.74-0.84; P = 0.00001) and hemorrhagic stroke (RR: 0.61, 95% CI: 0.48-0.76; P = 0.0001) as well as systemic embolism (RR: 0.73, 95% CI: 0.62-0.87; P = 0.0004) were significantly lower with rivaroxaban compared to warfarin for the management of these obese patients with non-valvular AF. Rivaroxaban was also associated with a significantly lower risk of major bleeding (RR: 0.75, 95% CI: 0.65-0.87; P = 0.0001). CONCLUSION: Based on this analysis, rivaroxaban seemed to be a better option in comparison to warfarin, due to its association with significantly lower risks of stroke and bleeding outcomes in obese patients with non-valvular AF. However, this hypothesis should further be confirmed in larger clinical trials.

Increased bleeding events with the addition of apixaban to the dual anti-platelet regimen for the treatment of patients with acute coronary syndrome: A meta-analysis.

BACKGROUND: Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel has been the mainstay of treatment for patients with acute coronary syndrome (ACS). However, the recurrence of thrombotic events, potential aspirin and clopidogrel hypo-responsiveness, and other limitations of DAPT have led to the development of newer oral anti-thrombotic drugs. Apixaban, a new non-vitamin K antagonist, has been approved for use. In this meta-analysis, we aimed to compare the bleeding outcomes observed with the addition of apixaban to DAPT for the treatment of patients with ACS. METHODS: Online databases including EMBASE, Cochrane Central, http://www.ClinicalTrials.gov, MEDLINE and Web of Science were searched for English based publications comparing the use of apixaban added to DAPT for the treatment of patients with ACS. Different categories of bleeding events and cardiovascular outcomes were assessed. The analysis was carried out by the RevMan software version 5.4. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the data following analysis. RESULTS: This research analysis consisted of 4 trials with a total number of 9010 participants. Thrombolysis in myocardial infarction (TIMI) defined major bleeding (OR: 2.45, 95% CI: 1.45-4.12; P = .0008), TIMI defined minor bleeding (OR: 3.12, 95% CI: 1.71-5.70; P = .0002), International society of thrombosis and hemostasis (ISTH) major bleeding (OR: 2.49, 95% CI: 1.80-3.45; P = .00001) and Global Use of Strategies to Open Occluded Arteries (GUSTO) defined severe bleeding (OR: 3.00, 95% CI: 1.56-5.78; P = .01) were significantly increased with the addition of apixaban to DAPT versus DAPT alone in these patients with ACS. However fatal bleeding (OR: 10.96, 95% CI: 0.61-198.3; P = .11) was not significantly different. CONCLUSIONS: Addition of the novel oral anticoagulant apixaban to the DAPT regimen significantly increased bleeding and therefore did not show any beneficial effect in these patients with ACS. However, due to the extremely limited data, we apparently have to rely on future larger studies to confirm this hypothesis.

In-hospital, short-term and long-term adverse clinical outcomes observed in patients with type 2 diabetes mellitus vs non-diabetes mellitus following percutaneous coronary intervention: A meta-analysis including 139,774 patients.

BACKGROUND: Several studies have shown that patients with type 2 diabetes mellitus (T2DM) have worse clinical outcomes in comparison to patients without diabetes mellitus (DM) following Percutaneous Coronary Intervention (PCI). However, the adverse clinical outcomes were not similarly reported in all the studies. Therefore, in order to standardize this issue, a meta-analysis including 139,774 patients was carried out to compare the in-hospital, short-term (<1 year) and long-term (≥1 year) adverse clinical outcomes in patients with and without T2DM following PCI. METHODS: Electronic databases including MEDLINE, EMBASE, and the Cochrane Library were searched for Randomized Controlled Trials (RCTs) and observational studies. The adverse clinical outcomes which were analyzed included mortality, myocardial infarction (MI), major adverse cardiac events (MACEs), stroke, bleeding, target vessel revascularization (TVR), target lesion revascularization (TLR), and stent thrombosis. Risk Ratios (RR) with 95% confidence intervals (CI) were used to express the pooled effect on discontinuous variables and the analysis was carried out by RevMan 5.3 software. RESULTS: A total number of 139,774 participants were assessed. Results of this analysis showed that in-hospital mortality and MACEs were significantly higher in patients with T2DM (RR 2.57; 95% CI: 1.95-3.38; P = .00001) and (RR: 1.38; 95% CI: 1.10-1.73; P = .005) respectively. In addition, majority of the short and long-term adverse clinical outcomes were also significantly higher in the DM group as compared to the non-DM group. Stent thrombosis was significantly higher in the DM compared to the non-DM group during the short term follow-up period (RR 1.59; 95% CI: 1.16-2.18;P = .004). However, long-term stent thrombosis was similarly manifested. CONCLUSION: According to this meta-analysis including a total number of 139,774 patients, following PCI, those patients with T2DM suffered more in-hospital, short as well as long-term adverse outcomes as reported by most of the Randomized Controlled Trials and Observational studies, compared to those patients without diabetes mellitus.

Adverse clinical outcomes associated with double dose clopidogrel compared to the other antiplatelet regimens in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: Recently, several newer antiplatelet treatment strategies have been used in patients with coronary artery disease (CAD). Apart from the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel, double dose clopidogrel (DDC), triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol and other newer antiplatelet agents have shown to be effective in different ways. In this analysis, we aimed to systematically compare the adverse clinical outcomes and the bleeding events which were observed when DDC was compared to the other antiplatelet regimens in patients with CAD. METHODS: English publications comparing DDC with other antiplatelet regimens were searched from MEDLARS/MEDLINE, EMBASE, www.ClinicalTrials.gov and Google Scholar. Adverse cardiovascular outcomes and bleeding events were the study endpoints. Statistical analysis was carried out by the RevMan 5.3 software whereby odds ratios (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total number of 23,065 participants were included. Results of this analysis showed major adverse cardiac events (MACEs), all-cause mortality, cardiac death, stroke, stent thrombosis, revascularization and myocardial infarction (MI) to have been similarly manifested in patients who were treated with DDC versus the control group with OR: 0.98, 95% CI: 0.78-1.22; p = 0.83, OR: 0.95, 95% CI: 0.77-1.17; p = 0.62, OR: 0.97, 95% CI: 0.79-1.20; p = 0.81, OR: 0.98, 95% CI: 0.65-1.48; p = 0.94, OR: 0.84, 95% CI: 0.40-1.75; p = 0.64, OR: 0.88, 95% CI: 0.52-1.49; p = 0.63, and OR: 0.89, 95% CI: 0.65-1.21; p = 0.45 respectively. Any minor and major bleedings were also similarly manifested. When DDC was compared to DAPT, no significant difference was observed in any bleeding event with OR: 1.58, 95% CI: 0.86-2.91; p = 0.14. Even when DDC was compared with either ticagrelor or prasugrel or TAPT, still no significant difference was observed in terms of bleeding outcomes. CONCLUSIONS: In patients with CAD, adverse clinical outcomes were not significantly different when DDC was compared to the other antiplatelet regimens. In addition, bleeding events were also similarly manifested when DDC was compared to DAPT, TAPT or ticagrelor/prasugrel.

Protectin DX increases alveolar fluid clearance in rats with lipopolysaccharide-induced acute lung injury.

Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/kg) administration, and alveolar fluid clearance was measured in live rats (n = 8). In primary rat ATII epithelial cells, protectin DX (3.605 × 10-3 mg/l) was added to the culture medium with LPS for 6 h. Protectin DX improved alveolar fluid clearance (9.65 ± 1.60 vs. 15.85 ± 1.49, p < 0.0001) and decreased pulmonary edema and lung injury in LPS-induced lung injury in rats. Protectin DX markedly regulated alveolar fluid clearance by upregulating sodium channel and Na, K-ATPase protein expression levels in vivo and in vitro. Protectin DX also increased the activity of Na, K-ATPase and upregulated P-Akt via inhibiting Nedd4-2 in vivo. In addition, protectin DX enhanced the subcellular distribution of sodium channels and Na, K-ATPase, which were specifically localized to the apical and basal membranes of primary rat ATII cells. Furthermore, BOC-2, Rp-cAMP, and LY294002 blocked the increased alveolar fluid clearance in response to protectin DX. Protectin DX stimulates alveolar fluid clearance through a mechanism partly dependent on alveolar epithelial sodium channel and Na, K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway.

Maresin1 stimulates alveolar fluid clearance through the alveolar epithelial sodium channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 pathway.

Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.

PD98059 Protects Brain against Cells Death Resulting from ROS/ERK Activation in a Cardiac Arrest Rat Model.

The clinical and experimental postcardiac arrest treatment has not reached therapeutic success. The present study investigated the effect of PD98059 (PD) in rats subjected to cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Experimental rats were divided randomly into 3 groups: sham, CA, and PD. The rats except for sham group were subjected to CA for 5 min followed by CPR operation. Once spontaneous circulation was restored, saline and PD were injected in CA and PD groups, respectively. The survival rates and neurologic deficit scores (NDS) were observed, and the following indices of brain tissue were evaluated: ROS, MDA, SOD, p-ERK1/2/ERK1/2, caspase-3, Bax, Bcl-2, TUNEL positive cells, and double fluorescent staining of p-ERK/TUNEL. Our results indicated that PD treatment significantly reduced apoptotic neurons and improved the survival rates and NDS. Moreover, PD markedly downregulated the ROS, MDA, p-ERK, and caspase-3, Bax and upregulated SOD and Bcl-2 levels. Double staining p-ERK/TUNEL in choroid plexus and cortex showed that cell death is dependent on ERK activation. The findings in present study demonstrated that PD provides neuroprotection via antioxidant activity and antiapoptosis in rats subjected to CA/CPR.

The benefits of respective and combined use of green tea polyphenols and ERK inhibitor on the survival and neurologic outcomes in cardiac arrest rats induced by ventricular fibrillation.

BACKGROUND: Cerebral injury is a main factor contributing to a high mortality after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). OBJECTIVE: We sought to evaluate the effect of green tea polyphenols (GTPs) and ERK1/2 inhibitor PD98059 (PD) on the survival and neurologic outcomes after CA/CPR in rats. METHODS: First, rats were subjected to CA after CPR. The rats that restored spontaneous circulation were blindly allocated to the saline group (saline, IV, n = 12), the GTP group (GTPs, 10 mg/kg, IV, n = 12), the PD group (PD, 0.3 mg/kg, IV, n = 12), and the GTPs + PD group (GTPs, 10 mg/kg; PD, 0.3 mg/kg, IV, n = 12). Another 12 rats without experiencing CA and CPR were served as a sham group. Survival and the neurologic deficit score were observed for 72 hours after restoration of spontaneous circulation. Second, same experimental procedures were performed, and in 1 of 5 groups, animals were divided into 4 subgroups further according to the different time points (12, 24, 48, and 72 hours after restoration of spontaneous circulation [ROSC], n = 6/group). Brain tissues were harvested at relative time points for the morphologic evaluation as well as reactive oxygen species (ROS), malonylaldehyde, and superoxide dismutase (SOD) measurement. RESULTS: Green tea polyphenols, PD, and a combination of GTPs and PD used after ROSC alleviated the morphologic changes of the cerebrum. These 3 treatments also decreased the productions of ROS and malonylaldehyde, increased SOD activities in cerebral tissues, and improved the neurologic deficit and survival rates at 12, 24, 48, and 72 hours after ROSC. CONCLUSIONS: Administration of GTPs and PD after ROSC can alleviate cerebral injury, improve the survival and neurologic outcomes via reduction of ROS, and increase of SOD activity in a rat CA/CPR model.