Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

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Background: Selective deep biliary cannulation is the first and the most important step before further biliary therapy. Transpancreatic sphincterotomy (TPS), and needle knife fistulotomy (NKF) were commonly used in patients with difficult cannulation, but few studies compare the outcome between TPS and NKF. Methods: A total of 78 patients who met the criteria of difficult cannulation in the National Taiwan University hospital from October 2015 to October 2017 were retrospectively reviewed. Their baseline demographics, success rate of biliary cannulation, and the rate of adverse events were assessed. Results: 31 patients and 47 patients underwent TPS and NKF for difficult biliary access, respectively. The characteristics of the 2 groups were similar, but patients in TPS group had more frequent pancreatic duct cannulation. Bile duct cannulation was successful in 23 patients (74.2%) in the TPS group and 39 (83.0%) in the NKF group (P = 0.34). There was no difference between the TPS and NKF in the rate of adverse events, including post-ERCP pancreatitis (PEP) (16.1% vs. 6.4%, p = 0.17), and hemorrhage (3.2% vs. 8.5%, p = 0.35). No perforation occurred. Conclusions: Both TPS and NKF have good biliary access rate in patient with difficult cannulation. TPS has acceptable successful rate and similar complication rate, compared with NKF.

: Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.