Qualitative versus automatic evaluation of CT perfusion parameters in acute posterior circulation ischaemic stroke

Purpose To compare the diagnostic accuracy (ACC) in the detection of acute posterior circulation strokes between qualitative evaluation of software-generated colour maps and automatic assessment of CT perfusion (CTP) parameters. Methods Were retrospectively collected 50 patients suspected of acute posterior circulation stroke who underwent to CTP (GE “Lightspeed”, 64 slices) within 24 h after symptom onset between January 2016 and December 2018. The Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was used for quantifying the extent of ischaemic areas on non-contrast (NC)CT and colour-coded maps generated by CTP4 (GE) and RAPID (iSchemia View) software. Final pc-ASPECTS was calculated on follow-up NCCT and/or MRI (Philips Intera 3.0 T or Philips Achieva Ingenia 1.5 T). RAPID software also elaborated automatic quantitative mismatch maps. Results By qualitative evaluation of colour-coded maps, MTT-CTP4D and Tmax-RAPID showed the highest sensitivity (SE) (88.6% and 90.9%, respectively) and ACC (84% and 88%, respectively) compared with the other perfusion parameters (CBV, CBF). Baseline NCCT and CBF provided by RAPID quantitative perfusion mismatchmaps had the lowest SE (29.6%and 6.8%, respectively) and ACC (38% and 18%, respectively). CBF and Tmax assessment provided by quantitative RAPID perfusion mismatch maps showed significant lower SE and ACC than qualitative evaluation. No significant differences were found between the pc-ASPECTSs assessed on colour-coded MTT and Tmax maps neither between the scores assessed on colourcoded CBV-CTP4D and CBF-RAPID maps. Conclusion Qualitative analysis of colour-codedmaps resultedmore sensitive and accurate in the detection of ischaemic changes than automatic quantitative analysis

Morbidity and Mortality in Patients with Idiopathic Pulmonary Fibrosis Undergoing Diagnostic Surgical Lung Biopsy

Morbidity and Mortality In Patients With Idiopathic Pulmonary Fibrosis Undergoing Diagnostic Surgical Lung Biopsy.Previous studies have shown conflicting results about safety of surgical lung biopsy (SLB) in usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) patients. Study design: we performed a retrospective analysis of all patients who underwent SLB between 2003 and 2013 at the University Hospital of Modena (Italy), to assess morbidity and mortality among patients with UIP/IPF , as compared to patients with other diffuse parenchymal lung diseases (non UIP/IPF). Results: we analyzed 73 patients with (n=29) and without (n=44) UIP/IPF, in which medical history, histology, and survival status were collected. UIP/IPF was diagnosed according to international guidelines. In 59 patients lung biopsy was performed via video-assisted thoracoscopy; in 14 patients thoracotomy was conducted. No intraoperative complications were observed. Postoperative complications were not significantly different between groups and consisted of fever (n=1 in UIP/IPF group; n=4 in non-UIP/IPF group), pneumothorax (n=1 in non-UIP/IPF), pleural effusion (n=1 in non-UIP/IPF), and acute exacerbation (n=1 in both groups, who died). There was no 30-day, 60-day and 90-day mortality. Conclusions: we conclude that surgical lung biopsy can be safely performed in patients with suspected UIP/IPF

Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction of histone H3K27 trimethylation as a novel pathway of acquired resistance to tyrosine kinase inhibitors (TKIs) and cytotoxic drugs in AML. Low EZH2 protein levels correlated with poor prognosis in AML patients. Suppression of EZH2 protein expression induced chemoresistance of AML cell lines and primary cells in vitro and in vivo. Low EZH2 levels resulted in derepression of HOX genes, and knockdown of HOXB7 and HOXA9 in the resistant cells was sufficient to improve sensitivity to TKIs and cytotoxic drugs. The endogenous loss of EZH2 expression in resistant cells and primary blasts from a subset of relapsed AML patients resulted from enhanced CDK1-dependent phosphorylation of EZH2 at Thr487. This interaction was stabilized by heat shock protein 90 (HSP9O) and followed by proteasomal degradation of EZH2 in drug-resistant cells. Accordingly, inhibitors of HSP9O, CDK1 and the proteasome prevented EZH2 degradation, decreased HOX gene expression and restored drug sensitivity. Finally, patients with reduced EZH2 levels at progression to standard therapy responded to the combination of bortezomib and cytarabine, concomitant with the re-establishment of EZH2 expression and blast clearance. These data suggest restoration of EZH2 protein as a viable approach to overcome treatment resistance in this AML patient population

IER-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Thrombectomy for Stroke

Background and Purpose - As a reliable scoring system to detect the risk of symptomatic intracerebral hemorrhage after thrombectomy for ischemic stroke is not yet available, we developed a nomogram for predicting symptomatic intracerebral hemorrhage in patients with large vessel occlusion in the anterior circulation who received bridging of thrombectomy with intravenous thrombolysis (training set), and to validate the model by using a cohort of patients treated with direct thrombectomy (test set). Methods - We conducted a cohort study on prospectively collected data from 3714 patients enrolled in the IER (Italian Registry of Endovascular Stroke Treatment in Acute Stroke). Symptomatic intracerebral hemorrhage was defined as any type of intracerebral hemorrhage with increase of 654 National Institutes of Health Stroke Scale score points from baseline 6424 hours or death. Based on multivariate logistic models, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve. Results - National Institutes of Health Stroke Scale score, onset-to-end procedure time, age, unsuccessful recanalization, and Careggi collateral score composed the IER-SICH nomogram. After removing Careggi collateral score from the first model, a second model including Alberta Stroke Program Early CT Score was developed. The area under the receiver operating characteristic curve of the IER-SICH nomogram was 0.778 in the training set (n=492) and 0.709 in the test set (n=399). The area under the receiver operating characteristic curve of the second model was 0.733 in the training set (n=988) and 0.685 in the test set (n=779). Conclusions - The IER-SICH nomogram is the first model developed and validated for predicting symptomatic intracerebral hemorrhage after thrombectomy. It may provide indications on early identification of patients for more or less postprocedural intensive management