Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.     

Clot Burden Score and Collateral Status and Their Impact on Functional Outcome in Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Collateral status and thrombus length have been independently associated with functional outcome in patients with acute ischemic stroke. It has been suggested that thrombus length would influence functional outcome via interaction with the collateral circulation. We investigated the individual and combined effects of thrombus length assessed by the clot burden score and collateral status assessed by a FLAIR vascular hyperintensity–ASPECTS rating system on functional outcome (mRS).MATERIALS AND METHODS:Patients with anterior circulation acute ischemic stroke due to large-vessel occlusion from the ASTER and THRACE trials treated with endovascular thrombectomy were pooled. The clot burden score and FLAIR vascular hyperintensity score were determined on MR imaging obtained before endovascular thrombectomy. Favorable outcome was defined as an mRS score of 0–2 at 90 days. Association of the clot burden score and the FLAIR vascular hyperintensity score with favorable outcome (individual effect and interaction) was examined using logistic regression models.RESULTS:Of the 326 patients treated by endovascular thrombectomy with both the clot burden score and FLAIR vascular hyperintensity assessment, favorable outcome was observed in 165 (51%). The rate of favorable outcome increased with clot burden score (smaller clots) and FLAIR vascular hyperintensity (better collaterals) values. The association between clot burden score and functional outcome was significantly modified by the FLAIR vascular hyperintensity score, and this association was stronger in patients with good collaterals, with an adjusted OR = 6.15 (95% CI, 1.03–36.81).CONCLUSIONS:The association between the clot burden score and functional outcome varied for different collateral scores. The FLAIR vascular hyperintensity score might be a valuable prognostic factor, especially when contrast-based vascular imaging is not available.

Therapeutic reperfusion with endovascular thrombectomy (EVT) is consistently associated with a better long-term functional outcome in anterior circulation acute ischemic stroke (AIS).¹ Early reperfusion is the mainstay of therapy because it strongly predicts functional outcome.² Many factors impact clinical outcomes, including the extent of clot and collateral supply.^3–7The clot burden score (CBS) assessed by the T2* MR imaging sequence (T2*-CBS), which was adapted from the CTA-CBS,⁸ has been used to assess the extent of the clot⁹ and has been independently associated with functional outcome in patients undergoing EVT.¹⁰Good collaterals have been related to better clinical outcome through 2 distinct mechanisms. First, collaterals are thought to contribute to prolonged penumbra sustenance.^11,12 Second, good retrograde collateral filling beyond the occlusion could promote successful reperfusion by providing more access to thrombolytics at the distal end of the clot and robust collaterals dissolving clot fragments in the distal vasculature.^13,14 The Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration analysis suggested a benefit with EVT across all strata of collateral circulation status;¹⁵ however, patients with poor collaterals are less likely to benefit from EVT than those with better collaterals.Most interesting, FLAIR vascular hyperintensity (FVH) on baseline MR imaging could indicate the formation of a leptomeningeal collateral circulation and serve as a prognostic marker for patients with AIS.^16-18 Both collaterals and the CBS were separately associated with functional outcome in patients undergoing EVT,^10,16 but their combined effect regarding clinical outcome is still poorly understood and has been assessed and quantified only with CTA or contrast-enhanced MRA in patients with AIS.^14,15 Furthermore, the lack of adjustment for possible confounders because of the small number of patients with very low collateral scores might also have influenced results in these studies.The purpose of this study was to determine whether there is an association between the CBS and FVH score and whether the association between the CBS and functional outcome is modified by the FVH score for patients who were treated by EVT for large-vessel occlusion within the framework of the Contact Aspiration versus Stent Retriever for Successful Revascularization (ASTER) and the THRombectomie des Artères CErebrales (THRACE) randomized trials.^19,20