Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases.

Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs

Portal vein thrombosis and outcomes for pediatric liver transplant candidates and recipients in the United States

The effect of occlusive portal vein thrombosis (PVT) on the mortality of pediatric liver transplant candidates and recipients is poorly defined. Using standard multivariate techniques, we studied the relationship between PVT and waiting‐list and posttransplant survival rates with data from the Scientific Registry of Transplant Recipients (September 2001 to December 2007). In all, 5087 liver transplant candidates and 3630 liver transplant recipients were evaluated during the period. PVT was found in 1.4% of the liver transplant candidates (n = 70) and in 3.7% of the liver transplant recipients (n = 136). PVT was not associated with increased wait‐list mortality [hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.5‐2.4, P = 0.77]. Conversely, PVT patients had a significantly lower unadjusted survival rate in the posttransplant period ( P = 0.01). PVT was independently associated with increased posttransplant mortality in multivariate models (30‐day survival: HR = 2.9, 95% CI = 1.6‐5.3, P = 0.001; overall survival: HR = 1.7, 95% CI = 1.1‐2.4, P = 0.01). The presence of PVT in pediatric liver candidates was not associated with increased wait‐list mortality but was clearly associated with posttransplant mortality, especially in the immediate postoperative period. Liver Transpl 17:1066–1072, 2011. © 2011 AASLD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87010/1/22371_ftp.pd

A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram.

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adulthood. Despite multimodality treatments, including maximal safe resection followed by irradiation and chemotherapy, the median overall survival times range from 14 to 16 months. However, a small subset of GBM patients live beyond 5 years and are thus considered long-term survivors. Methods: A retrospective analysis of the clinical, radiographic, and molecular features of patients with newly diagnosed primary GBM who underwent treatment at The University of Texas MD Anderson Cancer Center was conducted. Eighty patients had sufficient quantity and quality of tissue available for next-generation sequencing and immunohistochemical analysis. Factors associated with survival time were identified using proportional odds ordinal regression. We constructed a survival-predictive nomogram using a forward stepwise model that we subsequently validated using The Cancer Genome Atlas. Results: Univariate analysis revealed 3 pivotal genetic alterations associated with GBM survival: both high tumor mutational burden ( Conclusions: Our newly devised long-term surviva

Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging

Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. However, timely molecular diagnostic testing for patients with brain tumors is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. In this study, we developed DeepGlioma, a rapid ($< 90$ seconds), artificial-intelligence-based diagnostic screening system to streamline the molecular diagnosis of diffuse gliomas. DeepGlioma is trained using a multimodal dataset that includes stimulated Raman histology (SRH); a rapid, label-free, non-consumptive, optical imaging method; and large-scale, public genomic data. In a prospective, multicenter, international testing cohort of patients with diffuse glioma ($n=153$) who underwent real-time SRH imaging, we demonstrate that DeepGlioma can predict the molecular alterations used by the World Health Organization to define the adult-type diffuse glioma taxonomy (IDH mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular classification accuracy of $93.3\pm 1.6\%$. Our results represent how artificial intelligence and optical histology can be used to provide a rapid and scalable adjunct to wet lab methods for the molecular screening of patients with diffuse glioma.Comment: Paper published in Nature Medicin

Single Center Review of Femoral Arteriovenous Grafts for Hemodialysis

It is unclear how to manage high risk hemodialysis patients who present with an indwelling catheter. The National Kidney Foundation Practice Guidelines urge prompt removal of the catheter, but the guidelines do not specifically address the problem of patients whose only option is a femoral arteriovenous (AV) graft.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41306/1/268_2005_Article_62.pd

Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel

BackgroundDespite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies.ObjectiveTo develop guidelines for CCM management.MethodsThe Angioma Alliance ( www.angioma.org ), the patient support group in the United States advocating on behalf of patients and research in CCM, convened a multidisciplinary writing group comprising expert CCM clinicians to help summarize the existing literature related to the clinical care of CCM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and radiology standards, (4) neurosurgical considerations, and (5) neurological considerations. The group reviewed literature, rated evidence, developed recommendations, and established consensus, controversies, and knowledge gaps according to a prespecified protocol.ResultsOf 1270 publications published between January 1, 1983 and September 31, 2014, we selected 98 based on methodological criteria, and identified 38 additional recent or relevant publications. Topic authors used these publications to summarize current knowledge and arrive at 23 consensus management recommendations, which we rated by class (size of effect) and level (estimate of certainty) according to the American Heart Association/American Stroke Association criteria. No recommendation was level&nbsp;A (because of the absence of randomized controlled trials), 11 (48%) were level&nbsp;B, and 12 (52%) were level&nbsp;C. Recommendations were class&nbsp;I in 8 (35%), class&nbsp;II in 10 (43%), and class&nbsp;III in 5 (22%).ConclusionCurrent evidence supports recommendations for the management of CCM, but their generally low levels and classes mandate further research to better inform clinical practice and update these recommendations. The complete recommendations document, including the criteria for selecting reference citations, a more detailed justification of the respective recommendations, and a summary of controversies and knowledge gaps, was similarly peer reviewed and is available on line www.angioma.org/CCMGuidelines