Real-World Experience of Angiotensin Receptor-Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease.

OBJECTIVE: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m2), which have been excluded from the landmark trials. PATIENTS AND METHODS: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints. RESULTS: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m2) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m2 vs 21.4±17.5 mL/min per 1.73 m2; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users. CONCLUSION: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.

Mono or Dual Antiplatelet Therapy for Treating Patients with Peripheral Artery Disease after Lower Extremity Revascularization: A Systematic Review and Meta-Analysis.

The efficacy of dual antiplatelet therapy (DAPT) for patients with peripheral artery disease (PAD) after lower-limb intervention remains controversial. Currently, the prescription of DAPT after an intervention is not fully recommended in guidelines due to limited evidence. This study compares and analyzes the prognosis for symptomatic PAD patients receiving DAPT versus monotherapy after lower-limb revascularization. Up to November 2021, PubMed/MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting the efficacy, duration, and bleeding complications when either DAPT or monotherapy were used to treat PAD patients after revascularization. Three randomized controlled trials and seven nonrandomized controlled trials were included in our study. In total, 74,651 patients made up these ten studies. DAPT in PAD patients after intervention was associated with lower rates of all-cause mortality (HR = 0.86; 95% CI, 0.79−0.94; p < 0.01), major adverse limb events (HR = 0.60; 95% CI, 0.47−0.78; p < 0.01), and major amputation (HR = 0.78; 95% CI, 0.64−0.96) when follow-up was for more than 1-year. DAPT was not associated with major bleeding events when compared with monotherapy (OR = 1.22; 95% CI, 0.69−2.18; p = 0.50) but was associated with a higher rate of minor bleeding as a complication (OR = 2.54; 95% CI, 1.59−4.08; p < 0.01). More prospective randomized studies are needed to provide further solid evidence regarding the important issue of prescribing DAPT.

Characteristics, prognostic factors, and chronological trends of out-of-hospital cardiac arrests with shockable rhythms in Taiwan - A 7-year observational study.

BACKGROUND: The study aimed to explore the characteristics, predictors, and chronological trends of outcomes for adult out-of-hospital cardiac arrests (OHCAs) with shockable rhythms. METHODS: A 7-year, community-wide observational study using an Utstein-style registry was conducted. Patients who were not transported, those who experienced trauma and those who lacked electronic electrocardiography data were excluded; those with initial shockable rhythms of ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) were included. Outcomes were survival of discharge (SOD) and favorable neurological status (CPC 1-2). The outcome predictors, chronological trends, and their relationship with system interventions were analyzed. RESULTS: Of the 1544 shockable OHCAs (incidence 12.6%) included, 97.6% had VF and 2.4% had pVT. VF showed better outcomes than pVT. Predictors for both outcomes (SOD; CPC 1-2) were chronological change (adjusted odds ratio [aOR]: 1.133; 1.176), younger age (aOR: 0.973; 0.967), shorter response time (aOR: 0.998; 0.999), shorter scene time (aOR: 0.999; 0.999), witnessed collapse (aOR: 1.668; 1.670), and bystander cardiopulmonary resuscitation (BCPR) (aOR: 1.448; 1.576). Predictors for only SOD were public location (aOR: 1.450) and successful prehospital defibrillation (aOR: 3.374). The use of the supraglottic airway was associated with adverse outcomes. Chronologically with system interventions, BCPR rate, the proportion of shockable OHCA, and improved neurological outcomes increased over time. CONCLUSION: The incidence of shockable OHCA remained low in Asian community. VF showed better outcomes than pVT. Over time, the incidence of shockable rhythm, BCPR rate and patient outcomes did improve with health system interventions. The number of prehospital defibrillations did not predict outcomes.

Differential Diagnosis of Thoracoacromial Artery Pseudoaneurysm from Shoulder Inflammatory Pseudotumor: A Case Report.

Diagnosing shoulder tumors is a challenge because the joint is very complex, and a static examination can misdiagnose some tumors. However, we found that a pseudoaneurysm provides a differential diagnosis of a tumor, and to that end, we present a case that mimics shoulder infection. The patient was an 80-year-old female who had a history of coronary artery disease and end-stage renal disease under regular hemodialysis and complained of right shoulder swelling and progression. A magnetic resonance imaging (MRI) scan revealed an abscess, inflammatory pseudotumor (IPT), and osteomyelitis of the humerus. Computed tomography (CT)-guided pigtail drainage was performed twice without significant improvement. An angiogram revealed a right shoulder pseudoaneurysm fed by the acromial branch of the thoracoacromial artery. After endovascular coiling, the patient was discharged and outpatient follow-up was arranged. If aspiration of the abscess leads to only mild improvement in shoulder swelling, further evaluation should be arranged. An angiogram examination is a good method for diagnosing and designing operations, and endovascular treatment is good for preventing injury to the muscle, tendon, nerve, or blood vessels.

Percutaneous Coronary Intervention for Very Small Vessels With the Use of a Newer-Generation 2.0 mm Drug-Eluting Stent.

OBJECTIVES: The outcomes of treating coronary artery disease (CAD) in very small vessels <2.25 mm are sparse. The present study aimed to compare the safety and efficacy of the Resolute Onyx 2.0 mm drug-eluting stent (DES) (Medtronic) with the Onyx 2.25 mm DES for the treatment of CAD. METHODS: We retrospectively evaluated patients who underwent percutaneous coronary intervention (PCI) for CAD involving Onyx 2.0 mm DES (Onyx 2.0 group) and Onyx 2.25 mm DES (Onyx 2.25 group) in the 2 consecutive years from November 2016 to November 2018. Major adverse cardiac and cerebral event (MACCE) rate, defined as all-cause mortality, non-fatal myocardial infarction, stroke, and repeat revascularization for target-lesion failure, was reported. RESULTS: A total of 152 subjects with 160 lesions were enrolled. The baseline demographics, lesion characteristics, and procedural results between the two groups were similar. The lesions were significantly shorter (P<.01), fewer stents were consequently deployed (P=.04), and the total stent length was shorter (P<.01) in the Onyx 2.0 group vs the Onyx 2.25 group. At a median follow-up of 673 days, MACCE rate did not differ significantly between the two groups. Multivariate analysis identified the presence of atrial fibrillation, chronic kidney disease, and the use of statins to be independently associated with MACCE. CONCLUSIONS: Our data suggest that the use of the Onyx 2.0 mm DES to treat CAD in very small vessels (<2.25 mm) is feasible and safe, and the clinical outcomes were similar to those of the Onyx 2.25 mm group.

Progressing left-side sciatica revealing a common iliac artery mycotic aneurysm in an elderly patient: A CARE-compliant case report.

RATIONALE: Sciatica is usually caused by lumbar spine disease; the incidence of sciatica from extra-spinal causes is noted to be only about 0.09%. PATIENT CONCERNS: We report a case of a 92-year-old man who came to the neurologist outpatient department due to left buttock pain and numbness that radiated to the left lower leg in the recent 6 months and progressed rapidly over 10 days. DIAGNOSIS: We arranged magnetic resonance imaging for lumbar nerve lesion. Magnetic resonance imaging showed a common iliac artery mycotic aneurysm, at about 6.3 cm in diameter, which compressed the psoas muscle, nerve plexus, and vein. INTERVENTIONS: We used a left-side iliac bifurcation stent graft of 12 mm in diameter for aneurysm repair. An internal iliac artery with a stent graft of 10 mm x 5 cm. An abdomen aortic aneurysm stent was inserted, 1 cm beneath the right renal artery from the right side femoral artery. OUTCOMES: After endovascular repair and 4 weeks of antibiotic treatment, he could walk again, and no sciatica was noted. We repeated computed tomography 5 months after the operation and noted that the size of the iliac artery aneurysm decreased without stent graft migration or extravasation. Our patient recovered from sciatic and left leg weakness; above all, he could walk again. LESSONS: We suggest practitioners check for common iliac artery aneurysms in the diagnosis of symptoms mimicking spinal cord origin sciatica, especially in elder patients.

Radial artery harvesting in coronary artery bypass grafting surgery-Endoscopic or open method? A meta-analysis.

We analyzed the clinical outcomes of open radial artery harvesting (OAH) and endoscopic radial artery harvesting (EAH) undergoing coronary artery bypass grafting (CABG). We designed this meta-analysis conducted using Pubmed, Medline, the Cochrane Library, and EMBASE. Articles with comparisons of OAH and EAH undergoing CABG were included. Primary outcomes included the wound infection rate, the wound complication rate, neurological complications of the forearm, in-hospital mortality, long-term survival, and the patency rate. The results of our study included six randomized controlled trials (RCTs), two non-randomized controlled trials (NRCTs) with matching, and 10 NRCTs. In total, 2919 patients were included in 18 studies, while 1187 (40.7%) and 1732 (59.3%) patients received EAH and OAH, respectively. EAH was associated with a lower incidence of wound infection (RR = 0.29, 95% confidence interval (CI) = 0.14 to 0.60, p = 0.03), and neurological complications over the harvesting site (RR = 0.41, 95% CI = 0.27 to 0.62, p < 0.0001). There was no significant difference in 30-day mortality, long-term survival (over one year), and the graft patency rate. According to our analysis, endoscopic radial artery harvesting can improve the outcome of the harvesting site, without affecting the mortality, long-term survival, and graft patency.

Using an incentive spirometer reduces pulmonary complications in patients with traumatic rib fractures: a randomized controlled trial.

BACKGROUND: An incentive spirometer (IS) is a mechanical device that promotes lung expansion. It is commonly used to prevent postoperative lung atelectasis and decrease pulmonary complications after cardiac, lung, or abdominal surgery. This study explored its effect on lung function and pulmonary complication rates in patients with rib fractures. METHODS: Between June 2014 and May 2017, 50 adult patients with traumatic rib fractures were prospectively investigated. Patients who were unconscious, had a history of chronic obstructive pulmonary disease or asthma, or an Injury Severity Score (ISS) ≥ 16 were excluded. Patients were randomly divided into a study group (n = 24), who underwent IS therapy, and a control group (n = 26). All patients received the same analgesic protocol. Chest X-rays and pulmonary function tests (PFTs) were performed on the 5th and 7th days after trauma. RESULTS: The groups were considered demographically homogeneous. The mean age was 55.2 years and 68% were male. Mean pretreatment ISSs and mean number of ribs fractured were not significantly different (8.23 vs. 8.08 and 4 vs. 4, respectively). Of 50 patients, 28 (56%) developed pulmonary complications, which were more prevalent in the control group (80.7% vs. 29.2%; p = 0.001). Altogether, 25 patients had delayed hemothorax, which was more prevalent in the control group (69.2% vs. 29.2%; p = 0.005). Two patients in the control group developed atelectasis, one patient developed pneumothorax, and five patients required thoracostomy. PFT results showed decreased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in the control group. Comparing pre- and posttreatment FVC and FEV1, the study group had significantly greater improvements (p < 0.001). CONCLUSIONS: In conclusion, the use of an IS reduced pulmonary complications and improved PFT results in patients with rib fractures. The IS is a cost-effective device for patients with rib fractures and its use has clinical benefits without harmful effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04006587. Registered on 3 July 2019.

Initiation of antiplatelet medication after surgical thrombectomy jeopardized arteriovenous graft longevity.

INTRODUCTION: The efficacy of antiplatelet agents in preventing thrombosis in newly formed arteriovenous graft (AVG) in hemodialysis (HD) patients has been extensively examined. The aim of this study was to investigate the possible effect of initiation of antiplatelet medications on preventing AVG thrombosis recurrence after surgical thrombectomy for acute occlusion in HD patients. Whether post-operatively antiplatelet medications have protective effects on the patency or longevity of AVG after surgical thrombectomy in HD patients has not been investigated. METHODS: We conducted a 4-year quasi-randomized study of the unassisted patency and AVG longevity for 213 HD patients with or without initiating antiplatelet drugs after receiving surgical thrombectomy for first episode of acute AVG thrombosis. RESULTS: From the propensity-score-matched quasi-randomized study, initiation of antiplatelet drugs after first surgical thrombectomy in HD patients did not prevent the recurrence of surgical thrombectomy (log-rank p = 0.81), but significantly decreased the longevity of the access (log-rank p = 0.034). Multivariate Cox model demonstrated that prescription of antiplatelet drugs significantly increased the risk of graft failure (adjusted hazard ratio 2.13, p = 0.025). CONCLUSIONS: Adjunctive prescription with antiplatelet medications in HD patients after surgical thrombectomy did not prevent recurrent thrombosis of AV access, but significantly jeopardized the longevity of AVG after surgical thrombectomy.

The risk of diabetic renal function impairment in the first decade after diagnosed of diabetes mellitus is correlated with high variability of visit-to-visit systolic and diastolic blood pressure: a case control study.

BACKGROUND: The variability of visit-to-visit (VVV) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is proved as a predictor of renal function deterioration in patients with non-diabetic chronic kidney disease. The purpose of this study was to investigate the relationship of the variability in SBP and the magnitude of renal function impairment for normal renal function patients in the first 10-years diagnosed with type II diabetes mellitus (DM). METHODS: We retrospectively reviewed the electronic medical records of 789 patients who were first diagnosed with diabetes mellitus during 2000-2002 and regularly followed for 10 years with a total of 53,284 clinic visits. The stages of Chronic Kidney Disease (CKD) of every patient were determined using estimated glomerular filtration rate. The occurrence of nephropathy was defined in those patients whose CKD stages elevated equal or larger than three. RESULTS: Patients were categorized according to the VVV of systolic and diastolic BP into three groups. Patients with high VVV of both SBP and DBP had a 2.44 fold (95% CI: 1.88-3.17, p < 0.001) increased risk of renal function impairment compared with patients with low VVV of both SBP and DBP. Risk of renal function impairment for patients with high VVV of either SBP or DBP had a 1.43-fold increase (95% CI: 1.08-1.89, p = 0.012) compared with patients with low VVV of both SBP and DBP. Cox regression analysis also demonstrated that every 1-year increase of DM diagnosed age significantly raised the risk of renal function impairment with a hazard ration of 1.05 (95% CI: 1.04-1.06, p < 0.001). CONCLUSIONS: Not only VVV of SBP but also VVV in DBP is correlated with diabetic nephropathy in the first decade for patients diagnosed with type 2 DM.

Skin autofluorescence is associated with inappropriate left ventricular mass and diastolic dysfunction in subjects at risk for cardiovascular disease.

BACKGROUND: Enhanced advanced glycation end products deposition within myocardial tissue may cause diastolic dysfunction. However, whether this is related to left ventricular hypertrophy or inappropriate left ventricular mass remains unclear. METHODS: We prospectively enrolled 139 subjects at risk for cardiovascular diseases. We used echocardiography for measurements of left ventricular mass and cardiac systolic and diastolic functional parameters. An advanced glycation end product reader was applied for measurements of skin autofluorescence values. Comparisons of left ventricular mass and echocardiographic parameters between the higher and lower skin autofluorescence groups were analyzed. RESULTS: Compared with the lower skin autofluorescence group, left ventricular mass index and the ratio of observed left ventricular mass/predicted left ventricular mass (oLVM/pLVM) was significantly higher in the higher skin autofluorescence group (61.22 ± 17.76 vs. 47.72 ± 11.62, P < 0.01, 1.62 ± 0.38 vs. 1.21 ± 0.21, P < 0.01). After adjustment for potential confounding factors, skin autofluorescence was an independent factor for left ventricular mass index (ß = 0.32, P < 0.01) and the ratio of oLVM/pLVM (ß = 0.41, P < 0.01). Skin autofluorescence ≥2.35 arbitrary unit predicted left ventricular hypertrophy at a sensitivity of 58.8%, and a specificity of 73.0% (P < 0.01). Skin autofluorescence ≥2.25 arbitrary unit predicted inappropriate left ventricular mass at a sensitivity of 71.1%, and a specificity of 83.9% (P < 0.01). Skin autofluorescence was positively correlated with E/E', an indicator for diastolic dysfunction (r = 0.21, P = 0.01). CONCLUSIONS: Skin autofluorescence is a useful tool for detecting left ventricular hypertrophy, inappropriate left ventricular mass and diastolic dysfunction.

High Systolic and Diastolic Blood Pressure Variability Is Correlated with the Occurrence of Peripheral Arterial Disease in the First Decade following a Diagnosis of Type 2 Diabetes Mellitus: A New Biomarker from Old Measurement.

Background. To assess whether the visit-to-visit variability in blood pressure (BP) is a risk factor of peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM) 10 years after diagnosis. Methods. The electronic medical records of 825 patients, who were diagnosed with type 2 diabetes mellitus (T2DM) during 2000-2002 and regularly followed for 10 years, were retrospectively reviewed. A total of 53,284 clinic visit records, including analysis of BP, BMI, serum glycohemoglobin, and lipid profile, were analyzed. Results. Patients were categorized into two groups according to their visit-to-visit variability in systolic and diastolic BP (SBP and DBP, resp.). The high-risk group included patients with high SBP and DBP visit-to-visit variability; this group had a 1.679-fold (95% CI: 1.141-2.472, P = 0.009) increased risk of PAD compared with patients in the low-risk group. Cox regression analysis also demonstrated that the age at which the patients were diagnosed with T2DM, smoking status, and mean creatinine level was significantly associated with increased risk of PAD with a hazard ration of 1.064 (95% CI: 1.043-1.084, P < 0.001), 1.803 (95% CI: 1.160-2.804, P = 0.009), and 1.208 (95% CI: 1.042-1.401, P = 0.012), respectively. Conclusions. High SBP and DBP visit-to-visit variability is correlated with PAD in the first decade following a diagnosis of T2DM.

Effects of Antiplatelet Medication on Arteriovenous Fistula Patency After Surgical Thrombectomy.

OBJECTIVES: To study the effect of antiplatelet agents on preventing arteriovenous (AV) fistulae thrombosis in hemodialysis (HD) patients after surgical thrombectomy (ST) for acute AV fistulae occlusion. Whether post-operative antiplatelet drugs have similar effects on the patency of AV fistula after surgical thrombectomy in patients with end-stage renal disease who undergo HD has not been investigated. DESIGN, MATERIALS AND METHODS: We employed the Taiwan National Health Insurance Research Database (NHIRD) from 1999 to 2010 to assess the recurrent occlusion requiring ST and longevity of AV fistula after ST in 1049 patients on regular HD, with or without antiplatelet drugs. RESULTS: From the propensity-score (PS)-matched NHIRD, Multivariate Cox model demonstrated that concomitant antiplatelet medication in the HD patients who received the first ST significantly reduced the duration of recurrent ST (adjusted hazard ratio (HR) 1.69; 95% confidence interval (CI) 1.22-2.35, p=0.002) and the longevity of the fistula (adjusted HR 1.79; 95% CI 1.31-2.46, p<0.001). CONCLUSION: Treatment with antiplatelet drugs in HD patients did not prevent recurrent thrombosis requiring further ST, but significantly jeopardized the longevity of AV fistula after ST.

Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis.

BACKGROUND: Elevated levels of advanced glycation end products (AGEs) within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis. METHODS AND RESULTS: One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD) were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD). An AGE reader measured skin autoflurorescence (AF). We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01) and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01) than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01). CONCLUSIONS: Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.

A simple weighted scoring system to guide surgical decision-making in patients with parapneumonic pleural effusion.

BACKGROUND: The selection of ideal candidates for surgical intervention among patients with parapneumonic pleural effusion remains challenging. In this retrospective study, we sought to identify the main predictors of surgical treatment and devise a simple scoring system to guide surgical decision-making. METHOD: Between 2005 and 2014, we identified 276 patients with parapneumonic pleural effusion. Patients in the training set (n=201) were divided into two groups according to their treatment modality (non-surgery vs. surgery). Using multivariable logistic regression analysis, we devised a scoring system to guide surgical decision-making. The score was subsequently validated in an independent set of 75 patients. RESULTS: A white blood cell count >13,500/µL, pleuritic pain, loculations, and split pleura sign were identified as independent predictors of surgical treatment. A weighted score based on these factors was devised, as follows: white blood cell count >13,500/µL (one point), pleuritic pain (one point), loculations (two points), and split pleura sign (three points). A score >4 was associated with a surgical approach with a sensitivity of 93.4%, a specificity of 82.4%, and an area under curve (AUC) of 0.879 (95% confidence interval: 0.828-0.930). In the validation set, a sensitivity of 94.3% and a specificity of 79.6% were found (AUC=0.869). CONCLUSIONS: The proposed scoring system reliably identifies patients with parapneumonic pleural effusion who are candidates for surgery. Pending independent external validation, our score may inform the appropriate use of surgical interventions in this clinical setting.

Direct Revascularization With the Angiosome Concept for Lower Limb Ischemia: A Systematic Review and Meta-Analysis.

The angiosome concept provides practical information regarding the vascular anatomy of reconstructive and vascular surgery for the treatment of peripheral arterial occlusive disease and, particularly, critical lower limb ischemia.The aim of the study was to confirm the efficacy of direct revascularization with the angiosome concept (DR) for lower limb ischemia.Complementary manual searches were performed through the Pubmed, Cochrane Library, and EMBASE databases.We searched all randomized and nonrandomized studies (NRSs) comparing DR with indirect revascularization (IR) (without the angiosome concept) for lower limb ischemia. Only 9 nonrandomized controlled retrospective cohort studies were found and included. Trials published in any language were included.Primary endpoints were time to limb amputation and time to wound healing. Data extraction and trial quality assessment were performed by two authors independently. A third author was consulted for disagreements settlement and quality assurance.Five NRSs involving 779 lower limbs revealed that DR significantly improved the overall survival of limbs (hazard ratio [HR] 0.61; 95% confidence interval [CI] = 0.46-0.80; P < 0.001; I = 0%). In addition, DR significantly improved time to wound healing (HR 1.38; 95% CI = 1.13-1.69; P = 0.002; I = 0%, in 5 studies including 605 limbs).All included studies were retrospective comparative studies, and no consensus was obtained in describing wound conditions in the included studies.Our results suggested that treatment of lower limb ischemia using DR is more effective in salvaging limbs and healing wounds than IR is. Additional randomized controlled studies are necessary to confirm these results.

Carvedilol treatment after myocardial infarct decreases cardiomyocytic apoptosis in the peri-infarct zone during cardioplegia-induced cardiac arrest.

OBJECTIVE: In this study, experiments were designed to determine which parts and how carvedilol provided protection of the failed hearts under cardioplegia-induced hypoxia/reperfusion (H/R) insult. BACKGROUND: Carvedilol could improve the perioperative and postoperative prognosis of the heart failure patients. The mechanism of carvedilol in prevention of the occurrence of cardiomyocytic apoptosis and preservation of cardiac function had been rarely studied. METHODS: Fifty Sprague-Dawley rats treated with placebo or daily carvedilol after coronary artery ligation were divided into five groups (ligation only-group 2; ligation followed with cardioplegia-induced cardiac arrest-group 3; daily oral carvedilol treatment at 0.1, 1.0, or 10.0 mg/kg after ligation followed with cardioplegia-induced cardiac arrest-groups 4, 5, and 6), whereas another 10 animals received sham operation only (group 1), 30 days before ex vivo H/R injury. Failed hearts were harvested and received 1-h cardiac hypoxia with intermittent cold cardioplegia infusion and followed by 2-h reperfusion with warm oxygenated phosphate-buffered saline solution using a Langendorff apparatus. Perfusate was sampled at various time points. After H/R injury, the myocardium was carefully dissected into infarct, peri-infarct, and remote zones, which were used for further studies. In vitro H/R studies were carried on HL-1 cardiomyocytes to further explore the possible downstream pathways. RESULTS: Carvedilol could reduce the H/R-induced cardiomyocytic apoptosis and related proteins expression, especially in the peri-infarct zone, in a dose-dependent pattern. Carvedilol could also preserve cardiac contractility via modulation of the tumor necrosis factor α and interleukin 8 mRNA expression and reduction of Bcl-2 and cytochrome c protein production and decrease the occurrence of apoptosis ex vivo. In vitro experiments revealed that carvedilol exerted its antiapoptotic effect by way of phosphatidylinositol 3-kinase and MEK (mitogen-activated protein-kinase kinase), instead of protein kinase A, pathways. CONCLUSIONS: In the failed heart, pretreatment with carvedilol could preserve cardiac contractility during cardioplegia-induced myocardial H/R injury by lessening inflammation-related genes and expression of cytokines, decreasing apoptosis-related proteins production and diminishing the occurrence of cardiomyocytic apoptosis in the peri-infarct zone. The cardinal pathways of the antiapoptotic mechanism of carvedilol were PI3K- and MEK-related pathways.

MicroRNA-27a regulates cardiomyocytic apoptosis during cardioplegia-induced cardiac arrest by targeting interleukin 10-related pathways.

In this study, experiments were designed to determine whether microRNAs (miRNAs) play a role in the regulation or modulation of cardiomyocytic reactions under cardioplegia-induced cardiac arrest during cardiopulmonary bypass. MicroRNAs play powerful and unexpected roles in numerous cardiovascular diseases. MicroRNA-based therapeutics may provide a unique opportunity to translate this knowledge into the clinical setting. Sprague-Dawley rats (10 per group) were randomly divided into three groups: control, perfusion, and arrest groups. In the perfusion group, isolated hearts were perfused with oxygenated physiologic buffered solution for 3 h using a Langendorff apparatus. In the arrest group, cold crystalloid cardioplegia solution was used to induce and maintain cardiac arrest for 1 h; hearts were reperfused for 2 h with warm oxygenated phosphate-buffered saline solution. Cardiac miRNAs and protein expression patterns were detected using miRNA arrays and two-dimensional fluorescence difference gel electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Of 103 different miRNAs and 222 different proteins expressed in the three groups, miRNA-27a was the one considered to be related to the regulation of cardiomyocyte apoptosis by targeting the interleukin 10 pathway. Transfection of H9c2 cardiomyocytes with pre-miRNA-27a, which significantly decreased the mRNA and protein levels of interleukin 10 and increased expression of nuclear factor κB and its downstream cytokines during hypoxia/reperfusion injury, could activate caspase 3 and apoptosis. Our study demonstrated the altered expression of miRNAs in cardiomyocytes during cardioplegia-induced cardiac arrest. The involvement of miRNAs in cardiomyocytic apoptosis adds another level of complexity to gene regulation, which could open up novel avenues for cardiac protection strategies during cardiac surgery.

Cardiomyocytic apoptosis limited by bradykinin via restoration of nitric oxide after cardioplegic arrest.

BACKGROUND: Our previous studies revealed that cardioplegia-induced cardiac arrest under cardiopulmonary bypass (CPB) decreased cardiomyocytic nitric oxide and increased apoptosis. We hypothesized that pretreatment with bradykinin (BK) would improve the profile of anti-apoptotic proteins and inhibit cardiomyocytic apoptosis. MATERIALS AND METHODS: New Zealand white rabbits received total CPB. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points. Bradykinin and/or nitric oxide synthase (NOS) inhibitors or BK-receptor antagonists were infused systemically 30 min before beginning of CPB, and continued throughout the procedure. The ascending aorta was cross-clamped for 60 min while cold crystalloid cardioplegic solution was intermittently infused into the aortic root. The hearts were harvested and studied for evidence of apoptosis and ischemia/reperfusion induced inflammation-related cytokine production by cardiomyocytes. RESULTS: Our results revealed that bradykinin supplementation during cardioplegia could prevent I/R-induced inflammatory and apoptotic effects, which could be reversed with a NOS inhibitor. BK antagonists and NOS inhibitors worsened the inflammatory and apoptotic responses of cardiomyocytes, which could be reversed with an exogenous NO donor. CONCLUSIONS: Restoring the NO concentration after cardioplegia-induced cardiac arrest (CCA) under CPB with bradykinin could modulate (1) the nuclear translocation of NF-kappaB, (2) the plasma levels of inflammation-related cytokines, (3) the Bcl-2/Bax ratio, and (4) the occurrence of apoptosis. Exogenous bradykinin administration was associated with the myocardial apoptotic response by inhibition of NF-kappaB translocation, inflammatory cytokine production, Akt activation, and elevation of the Bcl-2/Bax ratio via a NO-mediated pathway.