Curriculum Research: Disseminating Neuropalliative Care Education Through an Adaptable Curriculum: A Multisite Feasibility Trial.

Introduction And Problem Statement: Neurologic disease is a leading cause of disability and death worldwide. As the global population ages, the burden of these diseases is expected to increase. Despite this increased clinical need, neurology trainees are seldom taught skills and concepts in palliative care.

An Individualized Yoga Intervention for People with Functional Neurological Disorder: Case Series.

Functional neurological disorder (FND) is a heterogeneous condition of neurological symptoms that cannot be linked to a specific neurological cause. Yoga combines movement, breathing, and meditation and has established mind-body effects for people who are managing both psychological and neurological conditions. This case series describes key components of a yoga program for people with FND, evaluating feasibility, acceptability, and efficacy via self-report surveys, clinical assessments, and postintervention interview.

B-cell Receptor Pathway Mutations Are Infrequent in Patients with Chronic Lymphocytic Leukemia on Continuous Ibrutinib Therapy.

Purpose: Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited.

Experimental Design: We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients with previously untreated (n = 238) or relapsed/refractory (n = 150) CLL across five clinical trials.

First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial.

iLLUMINATE is a randomized, open-label phase III study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or <65 years with coexisting conditions. Patients received oral ibrutinib 420 mg once daily until disease progression or unacceptable toxicity or six cycles of oral chlorambucil, each in combination with six cycles of intravenous obinutuzumab.

Up to 6.5 years (median 4 years) of follow-up of first-line ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and high-risk genomic features: integrated analysis of two phase 3 studies.

Genomic abnormalities, including del(17p)/ mutation, del(11q), unmutated IGHV, and mutations in , , , and predict poor outcomes with chemoimmunotherapy in chronic lymphocytic leukemia. To better understand the impact of these high-risk genomic features on outcomes with first-line ibrutinib-based therapy, we performed pooled analysis of two phase 3 studies with 498 patients randomized to receive ibrutinib- or chlorambucil-based therapy with median follow-up of 49.1 months.

COVID-19 manifestations in people with Parkinson's disease: a USA cohort.

Background: With the explosion of COVID-19 globally, it was unclear if people with Parkinson's disease (PD) were at increased risk for severe manifestations or negative outcomes.

Objectives: To report on people with PD who had suspected or confirmed COVID-19 to understand how COVID-19 manifested in PD patients.

Methods: We surveyed PD patients who reported COVID-19 to their Movement Disorders specialists at Columbia University Irving Medical Center and respondents from an online survey administered by the Parkinson's Foundation that assessed COVID-19 symptoms, general clinical outcomes and changes in motor and non-motor PD symptoms.

Phase 1b/2 study of ibrutinib and lenalidomide with dose-adjusted EPOCH-R in patients with relapsed/refractory diffuse large B-cell lymphoma.

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is difficult to cure; non-germinal center B-cell-like (non-GCB) and activated B-cell-like (ABC) DLBCL have worse outcomes than GCB DLBCL. Ibrutinib and lenalidomide are synergistic in vitro in ABC DLBCL and may augment salvage chemotherapy. In part 1 of this phase 1b/2 study (NCT02142049), patients with relapsed/refractory DLBCL received ibrutinib 560 mg and escalating doses of lenalidomide on Days 1-7 with DA-EPOCH-R (Days 1-5) in 21-day cycles.

Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis.

Advanced marginal zone lymphoma (MZL) is an incurable B-cell malignancy dependent on B-cell receptor signaling. The phase 2 PCYC-1121 study demonstrated the safety and efficacy of single-agent ibrutinib 560 mg/d in 63 patients with relapsed/refractory MZL treated with prior rituximab (RTX) or rituximab-based chemoimmunotherapy (RTX-CIT). We report the final analysis of PCYC-1121 with median follow-up of 33.

An Overview of the Current State and the Future of Ataxia Treatments.

Cerebellar ataxia can be caused by a variety of disorders, including degenerative processes, autoimmune and paraneoplastic illness as well as by gene mutations inherited in autosomal dominant, autosomal recessive, or X-linked fashions. In this review, we highlight the treatments for cerebellar ataxia in a systematic way, to provide guidance for clinicians who treat patients with cerebellar ataxia. In addition, we review therapies currently under development for ataxia, which we feel is currently one of the most exciting fields in neurology.

Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma.

This phase 1b/2, multicenter, open-label study evaluated ibrutinib plus durvalumab in relapsed/refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). Patients were treated with once-daily ibrutinib 560 mg plus durvalumab 10 mg/kg every 2 weeks in 28-day cycles in phase 1b without dose-limiting toxicities, confirming the phase 2 dosing. Sixty-one patients with FL (n = 27), germinal center B-cell (GCB) DLBCL (n = 16), non-GCB DLBCL (n = 16), and unspecified DLBCL (n = 2) were treated.

Stroke Severity Affects Timing: Time From Stroke Code Activation to Initial Imaging is Longer in Patients With Milder Strokes.

Optimizing the time it takes to get a potential stroke patient to imaging is essential in a rapid stroke response. At our hospital, door-to-imaging time is comprised of 2 time periods: the time before a stroke is recognized, followed by the period after the stroke code is called during which the stroke team assesses and brings the patient to the computed tomography scanner. To control for delays due to triage, we isolated the time period after a potential stroke has been recognized, as few studies have examined the biases of stroke code responders.

Acute Presentation of Nonmotor Symptoms in Parkinson's Disease.

There are a few syndromes involving the nonmotor symptoms of Parkinson's disease and other movement disorders that can quickly lead to severe morbidity and mortality, and, as such, need rapid identification and management. Among these are neuroleptic malignant syndrome, serotonin syndrome, dopamine agonist withdrawal syndrome, and dystonic storm. It is important to maintain a high index of suspicion for these disorders as lack of identification can lead to death.

Recurrent rearrangements of the Myb/SANT-like DNA-binding domain containing 3 gene (MSANTD3) in salivary gland acinic cell carcinoma.

Pathogenic gene fusions have been identified in several histologic types of salivary gland neoplasia, but not previously in acinic cell carcinoma (AcCC). To discover novel gene fusions, we performed whole-transcriptome sequencing surveys of three AcCC archival cases. In one specimen we identified a novel HTN3-MSANTD3 gene fusion, and in another a novel PRB3-ZNF217 gene fusion.

Integrative Genomics Implicates EGFR as a Downstream Mediator in NKX2-1 Amplified Non-Small Cell Lung Cancer.

NKX2-1, encoding a homeobox transcription factor, is amplified in approximately 15% of non-small cell lung cancers (NSCLC), where it is thought to drive cancer cell proliferation and survival. However, its mechanism of action remains largely unknown. To identify relevant downstream transcriptional targets, here we carried out a combined NKX2-1 transcriptome (NKX2-1 knockdown followed by RNAseq) and cistrome (NKX2-1 binding sites by ChIPseq) analysis in four NKX2-1-amplified human NSCLC cell lines.

Identification of recurrent SMO and BRAF mutations in ameloblastomas.

Here we report the discovery of oncogenic mutations in the Hedgehog and mitogen-activated protein kinase (MAPK) pathways in over 80% of ameloblastomas, locally destructive odontogenic tumors of the jaw, by genomic analysis of archival material. Mutations in SMO (encoding Smoothened, SMO) are common in ameloblastomas of the maxilla, whereas BRAF mutations are predominant in tumors of the mandible. We show that a frequently occurring SMO alteration encoding p.

Impaired virion secretion by hepatitis B virus immune escape mutants and its rescue by wild-type envelope proteins or a second-site mutation.

Hepatitis B virus immune escape mutants have been associated with vaccine failure and reinfection of grafted liver despite immune prophylaxis, but their biological properties remain largely unknown. Transfection of 20 such mutants in a human hepatoma cell line identified many with severe impairment in virion secretion, which can be rescued to various extents by coexpression of wild-type envelope proteins or introduction of a novel glycosylation site. Consistent with their role in maintaining intra- or intermolecular disulfide bonds, cysteine residues within the "a" determinant are critical for virion secretion.

Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection.

The phosphoinositide 3-kinase (PI3K) signaling pathway is significantly altered in a wide variety of human cancers, driving cancer cell growth and survival. Consequently, a large number of PI3K inhibitors are now in clinical development. To begin to improve the selection of patients for treatment with PI3K inhibitors and to identify de novo determinants of patient response, we sought to identify and characterize candidate genomic and phosphoproteomic biomarkers predictive of response to the selective PI3K inhibitor, GDC-0941, using the NCI-60 human tumor cell line collection.

SMURF1 amplification promotes invasiveness in pancreatic cancer.

Pancreatic cancer is a deadly disease, and new therapeutic targets are urgently needed. We previously identified DNA amplification at 7q21-q22 in pancreatic cancer cell lines. Now, by high-resolution genomic profiling of human pancreatic cancer cell lines and human tumors (engrafted in immunodeficient mice to enrich the cancer epithelial fraction), we define a 325 Kb minimal amplicon spanning SMURF1, an E3 ubiquitin ligase and known negative regulator of transforming growth factor β (TGFβ) growth inhibitory signaling.

Impairment of hepatitis B virus virion secretion by single-amino-acid substitutions in the small envelope protein and rescue by a novel glycosylation site.

Mutations in the S region of the hepatitis B virus (HBV) envelope gene are associated with immune escape, occult infection, and resistance to therapy. We previously identified naturally occurring mutations in the S gene that alter HBV virion secretion. Here we used transcomplementation assay to confirm that the I110M, G119E, and R169P mutations in the S domain of viral envelope proteins impair virion secretion and that an M133T mutation rescues virion secretion of the I110M and G119E mutants.

Genomic instability in breast cancer: pathogenesis and clinical implications.

Breast cancer is a heterogeneous disease, appreciable by molecular markers, gene-expression profiles, and most recently, patterns of genomic alteration. In particular, genomic profiling has revealed three distinct patterns of DNA copy-number alteration: a "simple" type with few gains or losses of whole chromosome arms, an "amplifier" type with focal high-level DNA amplifications, and a "complex" type marked by numerous low-amplitude changes and copy-number transitions. The three patterns are associated with distinct gene-expression subtypes, and preferentially target different loci in the genome (implicating distinct cancer genes).

Genomic and functional analysis identifies CRKL as an oncogene amplified in lung cancer.

DNA amplifications, leading to the overexpression of oncogenes, are a cardinal feature of lung cancer and directly contribute to its pathogenesis. To uncover such novel alterations, we performed an array-based comparative genomic hybridization survey of 128 non-small-cell lung cancer cell lines and tumors. Prominent among our findings, we identified recurrent high-level amplification at cytoband 22q11.

Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery.

Background: Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes-luminal A, luminal B, ERBB2-associated, basal-like and normal-like-with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs).

CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer.

Breast cancer exhibits clinical and molecular heterogeneity, where expression profiling studies have identified five major molecular subtypes. The basal-like subtype, expressing basal epithelial markers and negative for estrogen receptor (ER), progesterone receptor (PR) and HER2, is associated with higher overall levels of DNA copy number alteration (CNA), specific CNAs (like gain on chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of tumor subtypes may provide new opportunities for therapy.