The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis.

BACKGROUND: Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies. MATERIALS AND METHODS: A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022. RESULTS: Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18). CONCLUSION: BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.

Imaging in the COVID-19 era: Lessons learned during a pandemic.

The first year of the coronavirus disease 2019 (COVID-19) pandemic has been a year of unprecedented changes, scientific breakthroughs, and controversies. The radiology community has not been spared from the challenges imposed on global healthcare systems. Radiology has played a crucial part in tackling this pandemic, either by demonstrating the manifestations of the virus and guiding patient management, or by safely handling the patients and mitigating transmission within the hospital. Major modifications involving all aspects of daily radiology practice have occurred as a result of the pandemic, including workflow alterations, volume reductions, and strict infection control strategies. Despite the ongoing challenges, considerable knowledge has been gained that will guide future innovations. The aim of this review is to provide the latest evidence on the role of imaging in the diagnosis of the multifaceted manifestations of COVID-19, and to discuss the implications of the pandemic on radiology departments globally, including infection control strategies and delays in cancer screening. Lastly, the promising contribution of artificial intelligence in the COVID-19 pandemic is explored.

The Value of Web-Based Patient Education Materials on Transarterial Chemoembolization: Systematic Review.

BACKGROUND: Thousands of web searches are performed related to transarterial chemoembolization (TACE), given its palliative role in the treatment of liver cancer. OBJECTIVE: This study aims to assess the reliability, quality, completeness, readability, understandability, and actionability of websites that provide information on TACE for patients. METHODS: The five most popular keywords pertaining to TACE were searched on Google, Yahoo, and Bing. General website characteristics and the presence of Health On the Net Foundation code certification were documented. Website assessment was performed using the following scores: DISCERN, Journal of the American Medical Association, Flesch-Kincaid Grade Level, Flesch Reading Ease Score, and the Patient Education Materials Assessment Tool. A novel TACE content score was generated to evaluate website completeness. RESULTS: The search yielded 3750 websites. In total, 81 website entities belonging to 78 website domains met the inclusion criteria. A medical disclaimer was not provided on 28% (22/78) of website domains. Health On the Net code certification was present on 12% (9/78) of website domains. Authorship was absent on 88% (71/81) of websites, and sources were absent on 83% (67/81) of websites. The date of publication or of the last update was not listed on 58% (47/81) of websites. The median DISCERN score was 47.0 (IQR 40.5-54.0). The median TACE content score was 35 (IQR 27-43). The median readability grade level was in the 11th grade. Overall, 61% (49/81) and 16% (13/81) of websites were deemed understandable and actionable, respectively. Not-for-profit websites fared significantly better on the Journal of the American Medical Association, DISCERN, and TACE content scores. CONCLUSIONS: The content referring to TACE that is currently available on the web is unreliable, incomplete, difficult to read, understandable but not actionable, and characterized by low overall quality. Websites need to revise their content to optimally educate consumers and support shared decision-making. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020202747; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020202747.

Surgical versus percutaneous catheter placement for peritoneal dialysis: an updated systematic review and meta-analysis.

BACKGROUND: No consensus currently exists regarding the optimal approach for peritoneal dialysis catheter placement. We aimed to compare the outcomes of percutaneous and surgical peritoneal dialysis catheter placement. METHODS: A systematic review of the literature was performed using the MEDLINE, Cochrane Library, and Scopus databases (end-of-search date: August 29th, 2020). We included studies comparing percutaneous (blind, under fluoroscopic/ultrasound guidance, and "half-perc") and surgical peritoneal dialysis catheter placement (open and laparoscopic) in terms of their infectious complications (peritonitis, tunnel/exit-site infections), mechanical complications (leakage, inflow/outflow obstruction, migration, hemorrhage, hernia, bowel perforation) and long-term outcomes (malfunction, removal, replacement, surgery required, and mortality). RESULTS: Thirty-four studies were identified, including thirty-two observational studies (twenty-six retrospective and six prospective) and two randomized controlled trials. Percutaneous placement was associated with significantly lower rates of tunnel/exit-site infection [relative risk (RR) 0.72, 95% confidence interval (CI) 0.56-0.91], catheter migration (RR 0.68, 95% CI 0.49, 0.95), and catheter removal (RR 0.73, 95% CI 0.60-0.88). The 2-week and 4-week rates of early tunnel/exit-site infection were also lower in the percutaneous group (RR 0.45, 95% CI 0.22-0.93 and RR 0.41, 95% CI 0.27-0.63, respectively). No statistically significant difference was observed regarding other outcomes, including catheter survival and mechanical complications. CONCLUSION: Overall, the quality of published literature on the field of peritoneal dialysis catheter placement is poor, with a small percentage of studies being randomized clinical trials. Percutaneous peritoneal dialysis catheter placement is a safe procedure and may result in fewer complications, such as tunnel/exit-site infections, and catheter migration, compared to surgical placement. PROTOCOL REGISTRATION: PROSPERO CRD42020154951.

The role of liver transplantation for colorectal liver metastases: A systematic review and pooled analysis.

BACKGROUND: Liver transplantation (LT) has gained interest in the treatment of unresectable colorectal liver metastases (CRLM) over the last two decades. Despite the initial poor outcomes, recent reports from countries with graft abundance have provided further insights in the potential of LT as a treatment for unresectable CRLM. METHODS: A systematic literature search was conducted in the MEDLINE (PubMed), Embase, Scopus, Cochrane Library, Google Scholar, Virtual Health Library, Clinicaltrials.gov, and Web of Science databases (end-of-search date: January 27th, 2020) to identify relevant studies. Pooled overall and recurrence-free survival analysis at 6 months, 1, 2, 3, and 5 years was conducted with the Kaplan-Meier (Product Limit) method. RESULTS: Eighteen studies comprising 110 patients were included. The population consisted of 59.8% males with a mean age of 52.3 ± 9.3 years. CRLM diagnosis was synchronous in 83%, while 99% received chemotherapy, and 39% received liver resection prior to LT. The mean time from primary tumor resection to LT was 39.5 ± 32.5 months, the mean post-LT follow-up was 32.1 ± 22.2 months, and the mean time to recurrence was 15.0 ± 11.3 months. The pooled 6-month, 1-, 2-, 3-, and 5-year overall survival rates were 95.7% (95%CI: 89.1%-98.4%), 88.1% (95%CI: 79.6%-93.2%), 74.6% (95%CI: 64.2%-82.3%), 58.4% (95%CI: 47.2%-62.0%), and 50.5% (95%CI: 39.0%-61.0%), respectively. The pooled 6-months, 1-, 2-, 3-, and 5-year recurrence-free survival rates were 77.2% (95%CI: 67.2%-84.5%), 59.9% (95%CI: 49.0%-69.2%), 42.4% (95%CI: 31.8%-52.6%), 30.7% (95%CI: 20.9%-41.1%), and 25.6% (95%CI: 16.2%-36.0%), respectively. CONCLUSION: LT should be considered in patients with unresectable liver-only CRLM under strict selection criteria and only under well-designed research protocols. Ongoing studies are expected to further elucidate the indications and prognosis of patients undergoing LT for unresectable CRLM.

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

Microcatheter-Facilitated Primary Angioplasty in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Direct stenting is the best method for achieving reperfusion in primary percutaneous coronary intervention (PPCI). We hypothesized that the use of a microcatheter (MC) during PPCI when Thrombolysis in Myocardial Infarction (TIMI) flow ≤ 1 after wire crossing would allow visualization of the downstream artery with an optimal TIMI 3 flow at the end of the procedure. METHODS: In this pilot study, PPCI patients with TIMI flow ≤ 1 after wire crossing formed the MC group (n = 60); the MC was positioned in the distal part of the culprit artery and a small amount of contrast was injected through it to determine stent size and length to treat the culprit lesion. The MC group was compared with previous consecutive patients treated using standard PPCI (n = 94; similar characteristics except for the rate of previous percutaneous coronary intervention). RESULTS: In the MC group, downstream arteries were visualized in 98% of cases and direct stenting was achieved in 72% vs 31% (P < 0.0001). Final TIMI 3 flow was similar in both groups (97%). There was less manual thrombectomy (20% vs 63%; P < 0.001) and bailout glycoprotein IIb/IIIa inhibitor use (6.7% vs 29.8%; P < 0.002). The incidence of major adverse events (death, shock, severe arrhythmia) and left ventricular ejection fraction were similar. The peak cardiac enzymes level was significantly lower in the MC group. CONCLUSIONS: The MC strategy appears feasible and safe. It could allow exploring new strategies on the basis of more systematic direct stenting and prepared reperfusion by injecting drugs through the MC before reperfusion.

Improving cannulation time for extracorporeal life support in refractory cardiac arrest of presumed cardiac cause - Comparison of two percutaneous cannulation techniques in the catheterization laboratory in a center without on-site cardiovascular surgery.

BACKGROUND: Cardiac arrest (CA) without return of spontaneous circulation can be treated with veno-arterial extracorporeal membrane oxygenation (vaECMO) implemented surgically or percutaneously. We performed a study assessing time for vaECMO percutaneous cannulation in the catheterization laboratory. METHODS: Single-centre retrospective study in a University hospital without on-site cardiovascular surgery, including patients aged >18 receiving vaECMO for out- or in-hospital refractory CA of presumed cardiac cause between 2010 and 2016, cannulated by interventional cardiologists. Cannulation time using anatomic landmarks vessel puncture and conventional wires (first period) was compared with ultrasound guidance puncture and stiff wires (second period). Data are expressed as medians (interquartile range) and percentages. RESULTS: Forty-six patients were included, age 56 (49-62), 34 in the first period. Shockable initial rhythm occurred in 29 (63%), 36 (78%) had ischemic heart disease and 26 (57%) acute myocardial infarction (AMI). Out-of-hospital refractory CA occurred in 27 (59%) patients. Time from out-of-hospital refractory CA to admission was 100 (80-118) min. Cannulation was successful in 42 (91%) patients. Cannulation time was 14 (10-21) min, 17 (12-26) (first) and 8 (6-12) min (second period), p<0.001. Survival to discharge was 9%. In out-of-hospital versus in-hospital, time from CA to vaECMO was 120 (115-140) versus 82 (58-102) min, p=0.011, survival was 7% (two patients) versus 11% (two patients), p=0.35 respectively. All survivors had shockable initial rhythm. CONCLUSION: In these refractory CA patients with high prevalence of AMI and good feasibility of percutaneous vaECMO in the catheterization laboratory, cannulation time was shorter using ultrasound guidance and stiff wires.

Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial.

BACKGROUND: Elderly patients regularly receive bare-metal stents (BMS) instead of drug-eluting stents (DES) to shorten the duration of double antiplatelet therapy (DAPT). The aim of this study was to compare outcomes between these two types of stents with a short duration of DAPT in such patients. METHODS: In this randomised single-blind trial, we recruited patients from 44 centres in nine countries. Patients were eligible if they were aged 75 years or older; had stable angina, silent ischaemia, or an acute coronary syndrome; and had at least one coronary artery with a stenosis of at least 70% (≥50% for the left main stem) deemed eligible for percutaneous coronary intervention (PCI). Exclusion criteria were indication for myocardial revascularisation by coronary artery bypass grafting; inability to tolerate, obtain, or comply with DAPT; requirement for additional surgery; non-cardiac comorbidities with a life expectancy of less than 1 year; previous haemorrhagic stroke; allergy to aspirin or P2Y12 inhibitors; contraindication to P2Y12 inhibitors; and silent ischaemia of less than 10% of the left myocardium with a fractional flow reserve of 0·80 or higher. After the intended duration of DAPT was recorded (1 month for patients with stable presentation and 6 months for those with unstable presentation), patients were randomly allocated (1:1) by a central computer system (blocking used with randomly selected block sizes [two, four, eight, or 16]; stratified by site and antiplatelet agent) to either a DES or similar BMS in a single-blind fashion (ie, patients were masked), but those assessing outcomes were masked. The primary outcome was to compare major adverse cardiac and cerebrovascular events (ie, a composite of all-cause mortality, myocardial infarction, stroke, or ischaemia-driven target lesion revascularisation) between groups at 1 year in the intention-to-treat population, assessed at 30 days, 180 days, and 1 year. This trial is registered with ClinicalTrials.gov, number NCT02099617. FINDINGS: Between May 21, 2014, and April 16, 2016, we randomly assigned 1200 patients (596 [50%] to the DES group and 604 [50%] to the BMS group). The primary endpoint occurred in 68 (12%) patients in the DES group and 98 (16%) in the BMS group (relative risk [RR] 0·71 [95% CI 0·52-0·94]; p=0·02). Bleeding complications (26 [5%] in the DES group vs 29 [5%] in the BMS group; RR 0·90 [0·51-1·54]; p=0·68) and stent thrombosis (three [1%] vs eight [1%]; RR 0·38 [0·00-1·48]; p=0·13) at 1 year were infrequent in both groups. INTERPRETATION: Among elderly patients who have PCI, a DES and a short duration of DAPT are better than BMS and a similar duration of DAPT with respect to the occurrence of all-cause mortality, myocardial infarction, stroke, and ischaemia-driven target lesion revascularisation. A strategy of combination of a DES to reduce the risk of subsequent repeat revascularisations with a short BMS-like DAPT regimen to reduce the risk of bleeding event is an attractive option for elderly patients who have PCI. FUNDING: Boston Scientific.

Pulmonary alveolar proteinosis and Niemann Pick disease type B: An unexpected combination.

BACKGROUND: Pulmonary involvement in Niemann-Pick disease (NPD) is a common finding, especially in type B. It usually manifests with symptoms of restrictive lung disease appearing in adulthood but showing gradual deterioration over time. Treatment options have been dramatically limited, with whole lung lavage offering only temporary improvement. Pulmonary alveolar proteinosis (PAP) has been previously mentioned as part of lung disease in NPD, but only in rare cases of type C2. This is the first study that reports the coexistence of autoimmune PAP with NPD type B. CASE PRESENTATION: An 8 year old female patient with the diagnosis of NPD type B and a 2-year history of respiratory symptoms, presented with another episode of severe respiratory distress. Chest imaging revealed a "crazy paving pattern", raising concern for PAP. After admission to the intensive care unit and application of non-invasive positive pressure ventilation, a whole lung lavage was performed with return of a milky-appearing proteinaceous fluid. Her status post-lavage was markedly improved, while genetic testing placed the diagnosis of autoimmune PAP. The patient was initiated on inhaled GM-CSF treatment and shows a beneficial outcome to date. CONCLUSIONS: In spite of the patient's symptoms being consistent with NPD type of lung involvement, clinical findings raised the suspicion of an underlying disorder, which surprisingly proved to be PAP. The detection of anti-GM-CSF autoantibodies in our patient allowed the initiation of inhaled GM-CSF treatment, which is likely to prove more beneficial in her prognosis than repeated lung lavages.

High platelet reactivity on aspirin in patients with acute ST elevation myocardial infarction.

BACKGROUND: Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI. METHODS: We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year. RESULTS: We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE. CONCLUSION: HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i.

Sporadic versus inflammatory bowel disease-related colorectal adenocarcinoma: lessons learned from a single institution experience.

PURPOSE: Inflammatory bowel disease (IBD) - related colorectal adenocarcinoma (CAC) is known to impose a less favorable prognosis than its sporadic counterpart. The determining factor in the prognosis of IBD patients is the early endoscopic detection of commonly occult pre-cancerous lesions. This retrospective study attempted to highlight the distinctive features of IBD-related CAC, as well as the importance of implementing an acceptable surveillance protocol in IBD patients. METHODS: The medical records and biopsies of all IBD patients undergoing surgery and of surgical patients with sporadic CAC, admitted in the 5-year period 2010-2014, were examined. Overall, 26 clinicopathological parameters were collected and compared between the two groups. RESULTS: A total of 370 patients with sporadic CAC and 103 patients with IBD were included in the study, of which 8.7% (9/103) proved to have CAC. Cancer in IBD patients appeared at a younger age, had a larger maximum diameter and was more likely to have multiple synchronous locations and a signet-ring cell differentiation (p<0.05). Only 25% of IBD patients with CAC had previously followed correct surveillance. CONCLUSIONS: The aggressive features of IBD-related CAC, as well as the rising incidence of poorly-surveilled IBD patients that eventually progress to cancer, reflect the necessity of establishing dedicated IBD centers for their optimal follow-up.

Predictors of high on-aspirin platelet reactivity in high-risk vascular patients treated with single or dual antiplatelet therapy.

Aspirin is the key treatment in the secondary prevention of atherothrombosis. Interindividual variability of response has been linked to a higher risk for ischemic events. The aim of this study was to identify clinical and biologic factors predicting high on-aspirin platelet reactivity (HPR) in a high-risk, "real-world" population of vascular patients. All platelet testing performed from 2011 to 2013 in consecutive patients receiving long-term treatment with aspirin for coronary or cerebrovascular disease was retrospectively analyzed. Indications for platelet testing were recurrent ischemic events or high-risk angioplasty. HPR was defined as aggregation intensity≥20% using light-transmission aggregometry with arachidonic acid 0.5 mg/ml. Collagen-epinephrine platelet function analysis was also performed (threshold<165 seconds). Cardiovascular risk factors, usual biologic parameters, and antiplatelet treatment were recorded. A total of 1,508 patients were included (mean age 63 years, 71% men, 23% with diabetes). Antiplatelet treatment was aspirin alone in 333 patients and dual-antiplatelet therapy in 1,175 patients. HPR was found in 11.1% of patients. In multivariate analysis, independent predictive factors of HPR on light-transmission aggregometry with arachidonic acid were diabetes mellitus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.39 to 3.16), age (OR 1.25, 95% CI 1.06 to 1.47), fibrinogen level (OR 1.20, 95% CI 1.02 to 1.42), and von Willebrand factor level (OR 1.06, 95% CI 1.03 to 1.09). On light-transmission aggregometry with arachidonic acid and collagen-epinephrine platelet function analysis, fibrinogen remained the main factor associated with HPR (OR 1.33, 95% CI 1.19 to 1.61). Similar results were found in patients treated with aspirin alone or dual-antiplatelet therapy. A fibrinogen level>4.0 g/L was associated with a 3.9-fold increased risk for HPR in patients aged <75 years. In conclusion, fibrinogen level was the major predictor of HPR on aspirin in this large population of high-risk vascular patients.

Influence of α-stat and pH-stat blood gas management strategies on cerebral blood flow and oxygenation in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest: a crossover study.

OBJECTIVES: In patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest, two blood gas management strategies are used regarding the PaCO2 target: α-stat or pH-stat. We aimed to compare the effects of these strategies on cerebral blood flow and oxygenation. DESIGN: Prospective observational single-center crossover study. SETTING: ICU of University hospital. PATIENTS: Twenty-one therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest more than 18 years old without history of cerebrovascular disease were included. INTERVENTIONS: Cerebral perfusion and oxygenation variables were compared in α-stat (PaCO2 measured at 37 °C) versus pH-stat (PaCO2 measured at 32-34 °C), both strategies maintaining physiological PaCO2 values: 4.8-5.6 kPa (36-42 torr). MEASUREMENTS AND MAIN RESULTS: Bilateral transcranial middle cerebral artery flow velocities using Doppler and jugular vein oxygen saturation were measured in both strategies 18 hours (14-23 hr) after the return of spontaneous circulation. Pulsatility and resistance indexes and cerebral oxygen extraction were calculated. Data are expressed as median (interquartile range 25-75) in α-stat versus pH-stat. No differences were found in temperature, arterial blood pressure, and oxygenation between α-stat and pH-stat. Significant differences were found in minute ventilation (p = 0.006), temperature-corrected PaCO2 (4.4 kPa [4.1-4.6 kPa] vs. 5.1 kPa [5.0-5.3 kPa], p = 0.0001), and temperature-uncorrected PaCO2 (p = 0.0001). No differences were found in cerebral blood velocities and pulsatility and resistance indexes in the overall population. Significant differences were found in jugular vein oxygen saturation (83.2% [79.2-87.6%] vs. 86.7% [83.2-88.2%], p = 0.009) and cerebral oxygen extraction (15% [11-20%] vs. 12% [10-16%], p = 0.01), respectively. In survivors, diastolic blood velocities were 25 cm/s (19-30 cm/s) versus 29 cm/s (23-35 cm/s) (p = 0.004), pulsatility index was 1.10 (0.97-1.18) versus 0.94 (0.89-1.05) (p = 0.027), jugular vein oxygen saturation was 79.2 (71.1-81.8) versus 83.3% (76.6-87.8) (p = 0.033), respectively. However, similar results were not found in nonsurvivors. CONCLUSIONS: In therapeutic hypothermia-treated patients after out-of-hospital cardiac arrest at physiological PaCO2, α-stat strategy increases jugular vein blood desaturation and cerebral oxygen extraction compared with pH-stat strategy and decreases cerebral blood flow velocities in survivors.

Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry.

BACKGROUND: There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. METHODS AND RESULTS: The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. CONCLUSION: This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Biological efficacy of twice daily aspirin in type 2 diabetic patients with coronary artery disease.

BACKGROUND: Diabetes is associated with a high rate of events after acute coronary syndrome and percutaneous coronary intervention despite aspirin treatment. Once daily aspirin might not provide 24-hour stable biological efficacy in patients with diabetes. We compared the biological efficacy of the same daily dose of aspirin given either once (OPD) or divided twice per day in a population of diabetic patients with previous coronary artery disease. METHODS: Ninety-two consecutive diabetic patients with at least 1 criteria of time-dependent aspirin efficacy, elevated high-sensibility C-reactive protein (hs-CRP), fibrinogen, platelet count, or active smoking were prospectively included. Consecutive patients were randomly treated with 150-mg aspirin daily given either OPD (150 mg in the morning) or twice per day (75 mg in the morning and 75 mg in the evening) in a crossover study. The main outcome was platelet reactivity to arachidonic acid (0.5 mg/mL) measured by light transmission aggregometry at trough level before morning aspirin intake. RESULTS: Mean maximum aggregation intensity triggered by arachidonic acid was 19.7% ± 15.4% on OPD and 11.9% ± 10.4% on twice per day (P < .0001). Biological resistance (maximum aggregation intensity ≥20%) was observed in 42% of patients on OPD and 17% on twice per day (P < .001). Of the 39 patients with biological resistance on OPD, 24 (62%) overcame resistance on twice per day. Of the 16 resistant on twice per day, only 1 patient (6%) overcame resistance on OPD. Results were concordant with global evaluation of platelet reactivity by Platelet Function Analyzer-100. A better twice per day efficacy was independent of clopidogrel cotreatment. CONCLUSION: In a population of diabetic patients with coronary artery disease and a high risk of time-dependent aspirin resistance, aspirin divided twice per day can significantly decrease the rate of biological loss of efficacy at trough level.

24-hour time-dependent aspirin efficacy in patients with stable coronary artery disease.

Aspirin-induced cyclooxygenase (COX)-1 acetylation is irreversible and it is assumed that the platelet thromboxane-A2 aggregation pathway is inhibited for at least 24 hours (h) after aspirin ingestion. However, time course of biological efficacy of daily low-dose aspirin has rarely been assessed in patients with coronary artery disease (CAD). We aimed to assess the 24-h biological efficacy of daily low-dose aspirin in CAD patients. The peak and trough (2 h-24 h) effect of a chronic treatment with once daily dose aspirin were studied in 150 consecutive stable CAD patients. The main outcome measure was light transmission aggregometry (LTA) triggered with 0.5 mg/ml arachidonic acid (AA). In the last 47 consecutive patients, additional tests were conducted at 6, 12, 16, 20 h after last aspirin administration. 4.7% of the patients had significant aggregation (>20% maximal intensity LTA-AA) 2 h after aspirin ingestion and 24.7% at 24 h (p<0.0001). The more precise assessments in the last 47 patients showed that significant platelet aggregation progressively reappeared with time after aspirin intake (2 h--4% of patients, 6 h-- 4%, 12 h--11%, 16 h--16%, 20 h--19% and 24 h--28%). Concordant results were observed using production of thromboxane-B2 and other techniques evaluating AA-induced platelet aggregation/activation. No significant differences were found between lower (75-100 mg/day) and higher (>100 mg/day) dose aspirin. Such aspirin «resistance¼ at 24 h after ingestion was related to biological inflammatory markers, current smoking and diabetes. In conclusion, once daily aspirin does not provide stable 24-h antiplatelet protection in a significant proportion of CAD patients. Any biological assessment of aspirin efficacy should take time since last aspirin intake into consideration.