Impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease patients complicated with end-stage renal disease.

It is controversial whether hemodialysis affects the efficacy of the antiplatelet agents. We aimed to investigate the impact of hemodialysis on efficacies of the antiplatelet agents in coronary artery disease (CAD) patients complicated with end-stage renal disease (ESRD). 86 CAD patients complicated with ESRD requiring hemodialysis were consecutively enrolled. After 5-day treatment with aspirin and clopidogrel or ticagrelor, the platelet aggregations induced by arachidonic acid (PLAA) or adenosine diphosphate (PLADP), and the P2Y12 reaction unit (PRU) were measured before and after hemodialysis. The propensity matching score method was adopted to generate a control group with normal renal function from 2439 CAD patients. In patients taking aspirin, the PLAA remained unchanged after hemodialysis. In patients taking clopidogrel, the PLADP (37.26 ± 17.04 vs. 31.77 ± 16.09, p = 0.029) and corresponding clopidogrel resistance (CR) rate (23 [48.9%] vs. 14 [29.8%], p = 0.022) significantly decreased after hemodialysis, though PRU remained unchanged. Subgroup analysis indicated that PLADP significantly decreased while using polysulfone membrane (36.8 ± 17.9 vs. 31.1 ± 14.5, p = 0.024). In patients taking ticagrelor, PLADP, and PRU remained unchanged after hemodialysis. ESRD patients had higher incidences of aspirin resistance (AR) and CR compared to those with normal renal function (AR: 16.1% vs. 0%, p = 0.001; CR: 48.4% vs. 24.8%, p = 0.024). Hemodialysis does not have negative effect on the efficacies of aspirin, clopidogrel and ticagrelor in ESRD patients with CAD. ESRD patients have higher incidences of AR and CR compared with those with normal renal function.Trial registration ClinicalTrials.gov Identifier: NCT03330223, first registered January 4, 2018.

An alternative to opioid-based intravenous patient controlled analgesia in severe burn patients undergoing full thickness split graft in upper limbs.

BACKGROUND: Opioids provide good analgesic effect in burn patients during acute phase, but these patients may develop tolerance after prolonged exposure. Alternative analgesic strategies such as peripheral nerve blocks appear to provide adequate pain control while sparing opioid-related side effects. The purpose of this study was to evaluate intravenous patient-controlled analgesia (IV-PCA) and continuous peripheral nerve block (CPNB-PCA) in severe burn patients with relatively young age undergoing repeated debridement and large-area full thickness skin graft (FTSG). METHODS: The records of victims in dust explosion in Taiwan in 2016 from Chang Gung Memorial Hospital Pain Service Database between 2016 June and 2017 December were evaluated. The patients' demographic data including age, gender, weight, burn area, degree of burn, type of PCA regimen (IV-PCA versus CPNB-PCA), size of FTSG, and adverse effects were collected. RESULTS: The total in-hospital morphine consumption was significantly lower in CPNB-PCA than IV-PCA group. A trend of decrease in numerical rating scores (NRS) was observed for both groups and CPNB group had comparable NRS than IV-PCA group at rest. On movement, CPNB grouped had significantly lower NRS than IV-PCA on post-operative day 3. CONCLUSION: Our study demonstrated that in patients requiring high dosage of opioid, CPNB may be a suitable alternative for pain control.

Update on MRI in pediatric intracranial germ cell tumors-The clinical and radiological features.

Intracranial germ cell tumors (iGCTs) are uncommon brain tumors that mainly occur in children. Differing in histology, location, and gender of the patients, iGCTs are often divided into germinomas and non-germinomatous germ cell tumors (NGGCTs). Early diagnosis and timely treatment are crucial to iGCTs, the subtypes of which have substantial variations. This review summarized the clinical and radiological features of iGCTs at different sites, and reviewed the recent advances in neuroimaging of iGCTs, which can help predict tumor subtypes early and guide clinical decision-making.

Altered brain structure in preschool-aged children with tetralogy of Fallot.

BACKGROUND: Neurodevelopmental abnormalities are prevalent in children with tetralogy of Fallot. Our aim was to investigate the structural brain alterations of preschool-aged children with tetralogy of Fallot and its correlation with neurodevelopmental outcome. METHODS: T1-weighted structural images were obtained from 25 children with tetralogy of Fallot who had undergone cardiopulmonary bypass surgery and from 24 normal controls. Cortical morphological indices including gray matter volume, cortical thickness, sulcal depth, gyrification, and cortical surface complexity were compared between the two groups. Neurodevelopmental assessments of the children with tetralogy of Fallot were performed with the Wechsler Preschool and Primary Scale of Intelligence. RESULTS: Cortical morphological differences between groups were distributed throughout the right caudal middle frontal gyrus, right fusiform gyrus, right lateral occipital gyrus, right precuneus, and left inferior parietal lobule. Among children with tetralogy of Fallot, altered cortical structures were correlated with the visual spatial index, working memory index, and perioperative variables. CONCLUSION: Our results suggested that abnormal cortical structure in preschool-aged children with tetralogy of Fallot may be the persistent consequence of delayed cortical development in fetuses and cortical morphology can be used as an early potential biomarker to capture regional brain abnormalities that are relevant to neurodevelopmental outcomes. IMPACT: Altered cortical structures in preschool-aged children with ToF were correlated with both neurodevelopmental outcomes and clinical risk factors. Cortical morphology can be used as an effective tool to evaluate neuroanatomical changes and detect underlying neural mechanisms in ToF patients. Abnormal cortical structure may be the continuous consequence of delayed fetal brain development in children with ToF.

Aberrant White Matter Organization Correlated With Neurodevelopment Outcomes in Tetralogy of Fallot: An Atlas-Based Diffusion Tensor Imaging Study.

BACKGROUND: White matter injury (WMI) and impaired neurodevelopment are common in children with congenital heart disease. However, the effect of WMI on neurodevelopmental outcomes is still rarely reported. In this study, we aimed to investigate microstructural changes in white matter (WM) and its relationship with neurodevelopmental outcomes and further explore the underlying neurophysiological mechanisms of neurocognitive impairments in the tetralogy of Fallot (ToF). METHOD: Diffusion tensor imaging (DTI) data were acquired in preschool-aged children with ToF (n = 29) and normal controls (NC, n = 19), and neurodevelopmental assessments were performed with the Wechsler Preschool and Primary Scale of Intelligence in ToF. The differences in DTI metrics including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were evaluated between ToF and NC. Correlations between WM microstructural changes and neurodevelopmental outcomes were further analyzed. RESULTS: Significant WM differences were found in the uncinate fasciculus, cingulum hippocampus, superior longitudinal fasciculus, and corticospinal tract between children with ToF and NC. Impaired WM integrity was correlated with the verbal comprehension index and working memory index in ToF. CONCLUSIONS: This study demonstrated WM microstructure injury, and this injury is related to worse language and working memory performance in preschool-aged children with ToF. These findings suggested that DTI metrics may be a potential biomarker of neurocognitive impairments in ToF and can be used to predict future neurodevelopmental outcomes, which also provide new insights into the underlying neurophysiological mechanisms of neurocognitive impairments in ToF.

Pharmacodynamic effects of indobufen compared with aspirin in patients with coronary atherosclerosis.

PURPOSE: This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis. METHODS: In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PLAA), and the secondary outcomes included plasma thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 (11-dh-TXB2) levels at the end of each treatment.  RESULTS: In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PLAA whereas indobufen group had significantly less suppressed PLAA. Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB2. All treatment regimens produced similar inhibition of 11-dh-TXB2. In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB2 at 8 h and 12 h after the last dose. CONCLUSIONS: Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily.

Serum uric acid level negatively correlated with the prevalence of clopidogrel low response in patients undergoing antiplatelet treatment with aspirin and clopidogrel.

BACKGROUND AND AIMS: It has been reported that elevated serum uric acid (SUA) is related to inflammation and potentially to platelet hyper-reactivity. However, the relationship between elevated SUA and residual platelet reactivity is uncertain in patients on dual antiplatelet treatment (DAPT) with aspirin and clopidogrel. METHODS AND RESULTS: A cross-sectional cohort study was conducted on 2569 patients undergoing DAPT with aspirin and clopidogrel. Patients' SUA levels, residual platelet aggregation, routine blood tests and clinical characteristics were recorded. The relationship between SUA level and residual platelet aggregation was assessed by correlation analysis, and the relationship between SUA level and the prevalence of clopidogrel low response (CLR) was assessed by multivariate logistic regression analysis. Adenosine diphosphate (ADP) induced platelet aggregation (PLADP) was higher in normal-SUA group than that in hyperuricemia group [30(21, 40) % vs. 27(19, 39) %, p = 0.032]. No significant difference was found for arachidonic acid (AA) induced platelet aggregation (PLAA) between the two groups [4(2, 5) % vs. 3(2, 5) %, p = 0.557]. The correlation between SUA and PLADP was statistically significant(r = -0.115, p < 0.001), while that between SUA and PLAA was non-significant (r = -0.012, p = 0.643). Using the multivariate logistic regression analysis, higher SUA concentration was associated with a decreased risk of clopidogrel low response (CLR) (OR [95%CI] = 0.997 [0.995-0.999], p = 0.001). CONCLUSION: This is the largest study to date showing that in patients receiving DAPT with aspirin and clopidogrel, SUA is independently and negatively associated with the prevalence of clopidogrel low response. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov Unique Identifier: NCT01955200.

Cyclic RGD functionalized liposomes targeted to activated platelets for thrombosis dual-mode magnetic resonance imaging.

Thrombotic disease is a serious threat to human health. The rapid and accurate detection of thrombosis is still a clinical challenge. To achieve the accurate diagnosis of thrombosis with magnetic resonance imaging (MRI), nanomaterials-based contrast agents have been developed in recent years. In this study, cyclic RGD functionalized liposomes targeted to the activated platelets are developed for thrombosis dual-mode MRI. The cyclic RGD functionalized liposomes (cRGD@MLP-Gd) encapsulated with gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and superparamagnetic iron oxide (SPIO) are prepared, and their thrombus-targeted T1 and T2 MRI potential is evaluated in vitro and in vivo. Results show that cRGD@MLP-Gd could actively bind to the activated platelets and gradually accumulate at the thrombus site with a T1 - T2 contrast enhancement imaging effect in vitro. In in vivo MRI experiments, cRGD@MLP-Gd exhibits a T2 contrast enhancement at 1 h after intravenous administration, followed by a visibly larger T1 contrast enhancement at the thrombus site. This dynamic property showed that cRGD@MLP-Gd could actively bind to thrombus and possessed an enhanced T1 and T2 dual-mode MRI effect in vivo. Our results establish the characterization, feasibility and superiority of cRGD@MLP-Gd for the rapid identification of thrombosis, showing great potential to improve diagnostic accuracy and sensitivity to thrombosis of the MRI technique.

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Platelet Reactivity and Early Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention and Treated With Aspirin and Clopidogrel.

BACKGROUND: The genetic determinants of response to clopidogrel and aspirin are incompletely characterized. Recently, PEAR1 (platelet endothelial aggregation receptor-1) rs12041331 polymorphism has been shown to influence the platelet reactivity, but its impact on cardiovascular outcomes remains unclear in patients treated with antiplatelet agents. METHODS AND RESULTS: In this prospective cohort study, 2439 Chinese patients with acute coronary syndrome or stable coronary artery disease undergoing coronary stent implantation and receiving clopidogrel and aspirin were consecutively recruited. Their platelet reactivity was determined by light transmission aggregometry at 5 and 30 days after coronary intervention. Genotyping was performed using an improved multiplex ligation detection reaction technique. All patients completed a 30-day follow-up for clinical outcomes. Genotyping for PEAR1 showed 768 (38.3%) GG homozygotes, 941 (46.9%) GA heterozygotes, and 298 (14.8%) AA homozygotes. The 30-day incidence of major adverse cardiovascular events, the composite of cardiovascular death, nonfatal myocardial infarction, and ischemic stroke were significantly higher in AA homozygotes than in non-AA homozygotes (adjusted hazard ratio, 2.78; 95% CI, 1.13-6.82; P=0.026), irrespective of CYP2C19*2 loss-of-function polymorphism and known outcome predictors including age, sex, smoking, and diabetes mellitus. The ADP-induced platelet aggregation was significantly lower in AA homozygotes than that in GG homozygotes at both time points, although no significant difference was found for the arachidonic acid-induced platelet aggregation among the 3 groups. CONCLUSIONS: About 15% of Chinese patients undergoing coronary stent implantation were AA homozygotes for PEAR1 rs12041331. These patients had ≈3-fold increase in short-term major adverse cardiovascular events risk compared with non-AA homozygotes, and the adverse clinical outcome is unlikely to be mediated by suboptimal pharmacological response to aspirin or clopidogrel. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01968499.

Perioperative transfusion-related acute lung injury: a retrospective analysis.

OBJECTIVE: Transfusion-related acute lung injury (TRALI) is the leading morbidity and mortality in hemotherapy in the United States. Although it is a serious complication of blood transfusion, it is still underestimated and under-reported because of under-recognition and misdiagnosis. In this report, we present 15 surgical patients who developed pulmonary complications secondary to blood transfusion during the perioperative period. METHODS: A 3-year retrospective analysis of 14,441 patients who received blood transfusion intraoperatively in our Taoyuan center was carried out. 15 patients suspected to be subject to TRALI perioperatively were sorted out for analysis of their clinical characteristics. RESULTS: All of the 15 patients received inhalational general anesthesia, of whom 10 were anesthetized with sevoflurane, four with desflurane, and one with isoflurane. One patient died on the first postoperative day due to multiorgan failure whereas 14 others who were managed with oxygen therapy or mechanical ventilation recovered uneventfully within 72 hours. CONCLUSIONS: TRALI must be recognized as one of the leading causes of mortality related to blood transfusion. Oxygen support is often sufficient in mild TRALI while ventilatory support is required in severe TRALI. The strategy to minimize such a risk using blood products from male donors or from female donors without history of pregnancy or having a negative leukocyte antibody screening can help reduce severe immune mediated TRALI.

Spontaneous remission of left bundle branch block immediately after denitrogenation with inhalation of 100% oxygen prior to anesthetic induction.

Complete left bundle branch blocks have focused our attention, primarily because they are a sign predictive of mortality and a predictor of coexisting cardiovascular disease. Left bundle branch block (LBBB) is usually permanent but may occur transiently or intermittently. Spontaneous remission of LBBB rarely occurs during anesthesia. We present two patients in whom chronic LBBB reverted to normal sinus rhythm shortly following denitrogenation with inhalation of 100% oxygen during induction of anesthesia.

Ultrasonic cardiac output monitor provides accurate measurement of cardiac output in recipients after liver transplantation.

BACKGROUND: The ultrasonic cardiac output monitor (USCOM; USCOM Pty. Ltd., Sydney, NSW, Australia) has been accepted as a noninvasive device for measuring cardiac function in various clinical conditions. The present study aimed at comparing the accuracy of this device with that of the thermodilution technique in recipients in the early postoperative period after liver transplantation. METHODS: Fifteen mechanically ventilated patients were studied on the first postoperative day after liver transplantation. We compared the left-sided and right-sided cardiac output (CO) determined by USCOM with that obtained from the thermodilution technique with a pulmonary artery catheter every 8 hours in the intensive care unit. Each patient received a total of four paired measurements. Bland-Altman analysis was used for bias and precision testing. The CO measured by USCOM and the thermodilution method were considered interchangeable if the limits of agreement lay within +/- 1 L per minute or 20% of the mean CO. RESULTS: Forty-eight paired left-sided CO measurements were obtained from 12 patients. Three patients were excluded due to unacceptable signals. Comparison of these two techniques revealed a bias of 0.13 L per minute and limits of agreement at -0.65 L and 0.92 L per minute. Fifty-six paired right-sided CO measurements were obtained from 14 patients with one patient excluded due to an unobtainable optimal signal. A bias of 0.11 L per minute with limits of agreement at -0.51 L and 0.72 L per minute were found for these two techniques. CONCLUSION: This is the first study to evaluate the accuracy of USCOM in the post-liver transplant setting. This device is accurate in measuring CO in liver transplant recipients postoperatively. Possible risks of arrhythmia, infection and pulmonary artery rupture can be avoided because of its noninvasive nature. USCOM should be considered as an alternative in hemodynamic monitoring after liver transplantation.

Reliability of a new ultrasonic cardiac output monitor in recipients of living donor liver transplantation.

The ultrasonic cardiac output monitor (USCOM) is a new Doppler device for noninvasive hemodynamic monitoring. The aim of this prospective nonrandomized study was to test the feasibility, perioperative reliability, and clinical applicability of using USCOM as an alternative to pulmonary artery catheterization in recipients of living donor liver transplantation. Thirteen patients scheduled to receive living donor liver transplants were initially recruited. Three were subsequently excluded prior to the commencement of surgery because of technical difficulties in obtaining diagnostic-quality images with USCOM. Ten patients proceeded to be studied. Cardiac output measurements by thermodilution and USCOM were compared at 30-minute intervals throughout the procedure and at 10 specific procedural reference points during the surgery when hemodynamic changes were most likely to be observed. The data were analyzed with Lin's concordance coefficient and Bland-Altman analysis. Two hundred ninety paired cardiac output values were obtained from the 10 patients. The concordance between both methods was excellent in 8 patients and satisfactory in 2. Bland-Altman analysis of all data produced a mean bias of - 0.02 L/minute for USCOM, and the 95% limits of agreement were -1.06 to +1.10 L/minute. Further analysis of the 10 reference time points showed minimal bias and high levels of agreement between the methods. We conclude that USCOM provides an accurate and noninvasive method for cardiac output measurement during liver transplantation. It may therefore represent an alternative to pulmonary artery catheter placement with consequent reduction in patient's risk and morbidity associated with catheterization. Liver Transpl 14:1029-1037, 2008. (c) 2008 AASLD.

Protection against large-volume regurgitated fluid aspiration by the ProSeal laryngeal mask airway.

The ProSeal laryngeal mask airway (PLMA) is designed to protect the airway from regurgitated fluid. However, successful channeling of large volumes of regurgitated fluid by PLMA is rarely reported. This case report states that a large volume of regurgitated fluid was successfully channeled by a PLMA. The patient was a healthy 43-year-old male, properly fasted, undergoing transurethral cystolithotomy under general anesthesia with a correctly-placed PLMA. Unexpectedly, a large volume of regurgitated fluid (> 500 mL) spurted out from the PLMA esophageal drainage tube 2 hours after surgery. Careful gastric decompression was performed and airway toilet showed no evidence of aspiration of gastric contents. An endotracheal tube was then placed in lieu of the PLMA for airway maintenance. By the end of surgery, 1300 mL of fluid was drained through the gastric tube. Extubation was smooth and the patient had an uneventful recovery. Further radiological examination revealed the existence of an unrecognized vesicorectal fistula, which allowed the cystoscopic irrigation fluid to escape to the GI tract, resulting in massive gastric regurgitation. The patient underwent fistula repair a week later and was discharged without further difficulty. This is a unique clinical case report to show PLMA can be effective in preventing aspiration when massive passive regurgitation occurs. Strategies in the management of massive regurgitation during PLMA use are discussed.

Application of wire-guided endobronchial blocker for one-lung ventilation in patient with tracheostomy--a case report.

One-lung ventilation (OLV) with a double-lumen endotracheal tube or Univent may be achieved difficulty in morbidly obese, mouth opening-limited or critically ill patients. Now, a new fiberoptically directed wire-guided endobronchial blocker (WEB) can be applied for these conditions. We report the use of a new endobronchial blocker in a pharyngeal cancer patient after pharyngectomy. The original 10# Shiley endotracheal tube was exchanged with reinforced cuffed tracheal tube. Then we use the WEB to achieve OLV. The WEB was guided by a loop, and through the appropriate position of left main bronchus by pediatric fiberoptic bronchoscope. Finally, OLV was accomplished smoothly with combination of a non-kinking endotracheal tube and a WEB.