The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of patients with intracranial atherosclerotic disease (ICAD). The guidelines were prepared following the Standard Operational Procedure of the European Stroke Organisation guidelines and according to GRADE methodology. ICAD represents a major cause of ischemic stroke worldwide, and patients affected by this condition are exposed to a high risk for future strokes and other major cardiovascular events, despite best medical therapy available. We identified 11 relevant clinical problems affecting ICAD patients and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions. The first two questions refer to the asymptomatic stage of the disease, which is being increasingly detected thanks to the routine use of noninvasive vascular imaging. We were not able to provide evidence-based recommendations regarding the optimal detection strategy and management of asymptomatic ICAD, and further research in the field is encouraged as subclinical ICAD may represent a big opportunity to improve primary stroke prevention. The second block of PICOs (3–5) is dedicated to the management of acute large vessel occlusion (LVO) ischemic stroke caused by ICAD, a clinical presentation of this disease that is becoming increasingly relevant and problematic, since it is associated with more refractory endovascular reperfusion procedures. An operational definition of probable ICAD-related LVO is proposed in the guideline. Despite the challenging context, no dedicated randomized clinical trials (RCTs) were identified, and therefore the guideline can only provide with suggestions derived from observational studies and our expert consensus, such as the escalated use of glycoprotein IIb-IIIa inhibitors and angioplasty/stenting in cases of refractory thrombectomies due to underlying ICAD. The last block of PICOs is devoted to the secondary prevention of patients with symptomatic ICAD. Moderate-level evidence was found to recommend against the use of oral anticoagulation as preferred antithrombotic drug, in favor of antiplatelets. Low-level evidence based our recommendation in favor of double antiplatelet as the antithrombotic treatment of choice in symptomatic ICAD patients, which we suggest to maintain during 90 days as per our expert consensus. Endovascular therapy with intracranial angioplasty and or stenting is not recommended as a treatment of first choice in high-grade symptomatic ICAD (moderate-level evidence). Regarding neurosurgical interventions, the available evidence does not support their use as front line therapies in patients with high-grade ICAD. There is not enough evidence as to provide any specific recommendation regarding the use of remote ischemic conditioning in ICAD patients, and further RCTs are needed to shed light on the utility of this promising therapy. Finally, we dedicate the last PICO to the importance of aggressive vascular risk factor management in ICAD, although the evidence derived from RCTs specifically addressing this question is still scarce.

/pdf/european-stroke-organisation-guidelines-on-treatment-of-160nf0cg.pdf

European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease

Preclinical studies in cell culture systems as well as in whole animal chronic kidney disease (CKD) models showed that parathyroid hormone (PTH), oxidized at the 2 methionine residues (positions 8 and 18), caused a loss of function. This was so far not considered in the development of PTH assays used in current clinical practice. Patients with advanced CKD are subject to oxidative stress, and plasma proteins (including PTH) are targets for oxidants. In patients with CKD, a considerable but variable fraction (about 70 to 90%) of measured PTH appears to be oxidized. Oxidized PTH (oxPTH) does not interact with the PTH receptor resulting in loss of biological activity. Currently used intact PTH (iPTH) assays detect both oxidized and non-oxPTH (n-oxPTH). Clinical studies demonstrated that bioactive, n-oxPTH, but not iPTH nor oxPTH, is associated with mortality in CKD patients.

/pdf/why-current-pth-assays-mislead-clinical-decision-making-in-1c7qeitghc.pdf

Why Current PTH Assays Mislead Clinical Decision Making in Patients with Secondary Hyperparathyroidism.

Chronic kidney disease mineral and bone disorder may persist after successful kidney transplantation. Persistent hyperparathyroidism has been identified in up to 80% of patients throughout the first year after kidney transplantation. International guidelines lack strict recommendations about the management of persistent hyperparathyroidism. However, it is associated with adverse graft and patient outcomes, including higher fracture risk and an increased risk of all-cause mortality and allograft loss. Secondary hyperparathyroidism may be treated medically (vitamin D, phosphate binders and calcimimetics) or surgically (parathyroidectomy). Guideline recommendations suggest medical therapy first but do not clarify optimal parathyroid hormone targets or indications and timing of parathyroidectomy. There are no clear guidelines or long-term studies about the impact of hyperparathyroidism therapy. Parathyroidectomy is more effective than medical treatment, although it is associated with increased short-term risks. Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes. We now propose a roadmap for the management of secondary hyperparathyroidism in patients eligible for kidney transplantation that includes the indications and timing (pre- or post-kidney transplantation) of parathyroidectomy, the evaluation of parathyroid gland size and the integration of parathyroid gland size in the decision-making process by a multidisciplinary team of nephrologists, radiologists and surgeons. 

/pdf/oup-accepted-manuscript-n0uyxuqv.pdf

OUP accepted manuscript

Background Rescue intracranial stenting (RIS) can be used in refractory large vessel occlusion (LVO) after mechanical thrombectomy (MT). We aimed to assess the safety and efficacy of RIS versus a propensity matched sample of patients with persistent LVO. Methods We retrospectively analysed a multicenter retrospective pooled cohort of patients with anterior LVO (2015−2021) treated with MT, and identified patients with at least three passes and a modified Thrombolysis In Cerebral Infarction (mTICI) score of 0 to 2a. Propensity score matching was used to account for determinants of outcome in patients with or without RIS. The study outcomes included 3 months modified Rankin Scale (mRS) and symptomatic hemorrhagic transformation (HT). Results 420 patients with a refractory anterior occlusion were included, of which 101 were treated with RIS (mean age 69 years). Favorable outcome (mRS 0–2) was more frequent in patients with a patent stent at day 1 (53% vs 6%, P<0.001), which was independently associated with an early dual antiplatelet regimen (P<0.05). In the propensity matched sample, patients treated with RIS versus without RIS had similar rates of favorable outcomes (36.8% vs 30.3%, P=0.606). Patients with RIS showed a favorable shift in the overall mRS distributions (common adjusted OR 0.74, 95% CI 0.60 to 0.91, P=0.006). Symptomatic HT was marginally more frequent in the RIS group (9% vs 3%, P=0.07), and there was no difference in 3-month mortality. Conclusion In selected patients with a refractory intracranial occlusion despite at least three thrombectomy passes, RIS may be associated with an overall shift towards more favorable clinical outcome, and no significant increase in the odds of symptomatic HT or death.

Rescue intracranial permanent stenting for refractory occlusion following thrombectomy: a propensity matched analysis

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of acute ischemic stroke worldwide. Patients with acute large vessel occlusion due to underlying ICAD (ICAD-LVO) often do not achieve successful recanalization when undergoing mechanical thrombectomy (MT) alone, requiring rescue treatment, including intra-arterial thrombolysis, balloon angioplasty, and stenting. Therefore, early detection of ICAD-LVO before the procedure is important to enable physicians to select the optimal treatment strategy for ICAD-LVO to improve clinical outcomes. Early diagnosis of ICAD-LVO is challenging in the absence of consensus diagnostic criteria on noninvasive imaging and early digital subtraction angiography. In this review, we summarize the clinical and diagnostic criteria, prediction of ICAD-LVO prior to the procedure, and EVT strategy of ICAD-LVO and provide recommendations according to the current literature. 

Endovascular Treatment for Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Disease

Background/Aims: Cinacalcet is one of the important treatments of secondary hyperparathyroidism (SHPT). We evaluated the role of computed tomography (CT) for parathyroid glands (PTGs) to determine the response to cinacalcet therapy in dialysis patients. Methods: In study 1, we compared the predictive cutoff values of the largest volume or diameter of PTGs on ultrasonography or CT for achievement of target intact parathyroid hormone (iPTH) level according to K/DOQI guideline after cinacalcet treatment in a single dialysis center. In study 2, the role of the cutoff diameter of PTGs on CT in predicting responsive to cinacalcet therapy was reevaluated in dialysis patients with SHPT in multiple centers. Results: In study 1, among the total population of 26 patients, the number of patients with baseline iPTH over 600 pg/mL was 16 (61%). In study 2, it was 45 (54%), among 82 patients. In study 1, the number of PTGs equal to or larger than the cutoff value (≥ 11.2 mm) on CT, not ultrasonography, was significantly higher in non-responders than in responders (p=0.038). In study 2, the proportion of patients with PTGs ≥ 11.2 mm on CT was significantly higher in non-responders than responders (p=0.003). Multivariate analysis showed that pretreatment iPTH (odds ratio [OR] 1.498, p=0.003) and the existence of enlarged PTGs on CT (OR 8.940, p=0.015) were significant clinical factors affecting the response to cinacalcet. Conclusions: The diameter of PTGs on CT could predict the response to cinacalcet in dialysis patients with SHPT.

/pdf/diameter-of-parathyroid-glands-measured-by-computed-31t511as0p.pdf

Diameter of Parathyroid Glands Measured by Computed Tomography as a Predictive Indicator for Response to Cinacalcet in Dialysis Patients with Secondary Hyperparathyroidism

PURPOSE
The assessment of metastatic cervical lymph nodes in head and neck squamous cell carcinoma patients is crucial; as such, many studies focusing on non-invasive imaging techniques to evaluate metastatic cervical lymph nodes have been performed. The aim of our study was to assess the usefulness of elasticity values on diffusion weighted imaging (DWI)-based virtual MR elastography in the evaluation of metastatic cervical lymph nodes from head and neck squamous cell carcinoma.


METHODS
Two head and neck radiologists measured the elasticity values of 16 metastatic cervical lymph nodes from head and neck squamous cell carcinoma and 13 benign cervical lymph nodes on DWI-based virtual MR elastography maps. Mean, minimum, maximum, and median elasticity values were evaluated for lymph nodes between the two groups and interobserver agreement in measuring the elasticity was also evaluated.


RESULTS
The mean, maximum, and median elasticity values of metastatic cervical lymph nodes were significantly higher than those of benign cervical lymph nodes (P = 0.001, 0.01, and 0.002, respectively). Diagnostic accuracy, sensitivity, and specificity of the mean elasticity were 82.8%, 93.8%, and 69.2%, respectively. Interobserver agreement was excellent for the mean and median elasticity (intraclass correlation coefficients were 0.98 for both).


CONCLUSION
Estimated elasticity values based on DWI-based virtual MR elastography show significant difference between benign and metastatic cervical lymph nodes from head and neck squamous cell carcinoma. While precise modulation of MR sequences and calibration parameters still needs to be established, elasticity values can be useful in differentiating between these lymph nodes.

Evaluating the Elasticity of Metastatic Cervical Lymph Nodes in Head and Neck Squamous Cell Carcinoma Patients Using DWI-based Virtual MR Elastography.


 Tetraspanin 12 (TSPAN12), a member of the tetraspanin family that are increasingly known to be involved in various mechanisms of tumor progression, mediates various cellular signaling processes in cancer cells. With respect to the brain, previous studies have shown that TSPAN12 is related with the maturation of a membrane-associated metalloproteinase 10 and the production of amyloid β plaque, but there are no studies related to brain tumors to date. Therefore, we designed this study to investigate the role of TSPAN 12 on malignant glioma (MG) cells and patients. TSPAN12 silencing in MG cells significantly progressed cell proliferation, migration and invasion capacities, and extracellular matrix adhesion ability as well as stem cell properties, in vitro. Mechanistically, we identified that FAK and ERK signaling were involved in MG cells with TSPAN12 expression. Moreover, clinical analysis of MG patient tissues microarray showed that the expression level of TSPAN12 was negatively correlated with the prognosis in MG patients. Collectively, more studies are needed, but we suggest that TSPAN12 can be used as an alternative biomarker to predict the prognosis of MG patient and help develop MG treatment strategies.

/pdf/biom-38-tetraspanin-12-as-a-tumor-suppressor-and-biomarker-2ud7yxva.pdf

Biom-38. tetraspanin 12 as a tumor suppressor and biomarker predicting good prognosis of malignant glioma

Imaging finding and analysis of brain lymphoma in contrast-enhanced fluid attenuated inversion recovery sequence.

Celebrating 30 Years of the Korean Society of Interventional Neuroradiology.

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