Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.

Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs. PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion. Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial. Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted. Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation. By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia. ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The \u201cPAC-MAN\u201d sign: an insidious complication after transcatheter aortic valve deployment

Transcatheter aortic valve implantation (TAVI) is now a viable and effective alternative to conventional surgical aortic valve replacement for high-risk patients with severe aortic stenosis. Despite its percutaneous and less invasive nature, TAVI is associated with the potential for several intraprocedural complications, which have been recently updated and standardized. Some of them, such as those relating to valve deployment and/or positioning, occur less frequently but they could however represent very serious and life-threatening complications. We report the case of an insidious TAVI complication that required a combined fluoroscopic/echocardiographic approach in order to allow a correct deployment of the transcatheter prosthesis. Our case report highlights this potentially specific under-deployment of large CoreValve prosthesis. Medico-surgical community involved in TAVI must be nowaware of this newtype of complication allowing its successful management

Total percutaneous femoral vessels cannulation for minimally invasive mitral valve surgery

BACKGROUND: Minimally invasive mitral valve surgery (MIMVS) has experienced several technological changes in the last two decades. Our aim was to describe one of the most recent improvements, the utilization of a total percutaneous femoral vessels cannulation technique during MIMVS. METHODS: We performed a retrospective observational analysis of this technique among 300 consecutive MIMVS patients, with particular focus on cannulation aspects of MIMVS, its success rate and potential complications. RESULTS: From October 2008 to December 2012, 300 patients (60% males) were operated on. Mean age was 62.9\ub116.4 years. Indications for operation included mitral valve repair (93%) and mitral valve replacement (7%). Two femoral arterial catheterizations failed and required conversion to sternotomy. The complications on the arterial side were: 5 (1.6%) cases of bleeding during the introduction of Prostar leading to a preoperative surgical hemostasis; 2 (0.6%) retroperitoneal bleeds during cardiopulmonary bypass requiring difficult surgical control but with an uneventful follow-up; 6 (2%) bleeding episodes after removal of the arterial cannula easily controlled by direct surgical revision; 1 (0.3%) arterio-venous fistula requiring a surgical correction on postoperative day 32; 1 (0.3%) patient had a transitory claudication due to a superficial femoral artery thrombosis progressively compensated by the collateral circulation. There were no postoperative bleeding complications. There were no other complications linked to the femoral cannulations or to the groin occurred during the follow-up. The percentage of uneventful arterial cannulations was 80% among the first 50 patients (N=10 out of 50) and 98.8% thereafter (N=3 out of 250). CONCLUSIONS: Total percutaneous femoral vessels cannulation technique is particularly suitable for MIMVS with a high success rate and few complications after a short learning curve. With the advent of the percutaneous approach, the traditional complications of the groin incision have completely disappeared in modern operations with no groin infection, hematoma or lymphocele

Identification and characterization of two genes (MIP-1 beta, VE-CADHERIN) implicated in acute rejection in human heart transplantation : Use of murine models in tandem with cDNA arrays

International audienceBackground - Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. Methods and Results - Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n = 3), allografts (n = 4), and not transplanted hearts (n = 4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1 beta (MIP-1 beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n = 10) or grade IB (n = 10) or IIIA (n = 10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. Conclusions - We have demonstrated that the upregulation of MIP-1 beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection

Infective endocarditis and neurologic events:indications and timing for surgical interventions

A therapeutic dilemma arises when infective endocarditis (IE) is complicated by a neurologic event. Postponement of surgery up to 4 weeks is recommended by the guidelines, however, this negatively impacts outcomes in many patients with an urgent indication for surgery due to uncontrolled infection, disease progression, or haemodynamic deterioration. The current literature is ambiguous regarding the safety of cardiopulmonary bypass in patients with recent neurologic injury. Nevertheless, most publications demonstrate a lower risk for secondary haemorrhagic conversion of uncomplicated ischaemic lesions than the risk for recurrent embolism under antibiotic treatment. Here, we discuss the current literature regarding neurologic stroke complicating IE with an indication for surgery

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion.

The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the hypoperfusion intensity ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities. Retrospective multicenter international study including patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24 hours from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of 4 comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients and (2) 1 prospective thrombectomy study where perfusion imaging was acquired per protocol, but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time and fast progressors as EIGR ≥10 mL/h. The HIR, defined as the proportion of time-to-maximum (Tmax) &gt;6 second with Tmax &gt;10 second volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients. Overall, 1,127 patients were included (CT, n = 471; MRI, n = 656). Median age was 74 years (interquartile range [IQR] 62-83), 52% were male, median NIH Stroke Scale was 16 (IQR 9-21), median HIR was 0.42 (IQR 0.26-0.58), and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: The proportion of fast progressors was 4% in the first HIR quartile (i.e., excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (p &lt; 0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (p &lt; 0.001 and p = 0.030, respectively). The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers