tbuckley/cabot-search huggingface dataset:
Compensation Strategies for Gait Impairments in Parkinson Disease
Authors: Jorik Nonnekes, Evžen Ružicka, Alice Nieuwboer, Mark Hallett, Alfonso Fasano, Bastiaan R. Bloem
Journal: JAMA Neurology (2019)

Patients with Parkinson disease can use a wide variety of strategies to compensate for their gait impairments. Examples include walking while rhythmically bouncing a ball, crossing the legs when walking, or stepping over an inverted cane. An overview and classification of the many available compensation strategies may contribute to understanding their underlying mechanisms and developing focused rehabilitation techniques. Moreover, a comprehensive summary of compensation strategies may help patients by allowing them to select a strategy that best matches their needs and preferences and health care professionals by permitting them to incorporate these into their therapeutic arsenal. To create this overview, this narrative review discusses collected video recordings of patients who spontaneously informed clinicians about the use of self-invented tricks and aids to improve their mobility.Fifty-nine unique compensation strategies were identified from approximately several hundred videos. Here, these observed strategies are classified into 7 main categories for elaboration on their possible underlying mechanisms. The overarching working mechanisms involve an allocation of attention to gait, the introduction of goal directedness, and the use of motor programs that are less automatized than those used for normal walking.Overall, these compensation strategies seem to appeal to processes that refer to earlier phases of the motor learning process rather than to a reliance on final consolidation. This review discusses the implications of the various compensation strategies for the management of gait impairment in Parkinson disease.
Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With <i>BRAF</i> V600E–Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study
Authors: Eric Van Cutsem, Sanne Huijberts, Axel Grothey, Rona Yaeger, Pieter-Jan Cuyle, Elena Elez, Marwan Fakih, Clara Montagut, Marc Peeters, Takayuki Yoshino, Harpreet Wasan, Jayesh Desai, Fortunato Ciardiello, Ashwin Gollerkeri, Janna Christy-Bittel, Kati Maharry, Victor Sandor, Jan H.M. Schellens, Scott Kopetz, Josep Tabernero
Journal: Journal of Clinical Oncology (2019)

PURPOSE To determine the safety and preliminary efficacy of selective combination targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (mCRC) in the safety lead-in phase of the open-label, randomized, three-arm, phase III BEACON Colorectal Cancer trial ( ClinicalTrials.gov identifier: NCT02928224; European Union Clinical Trials Register identifier: EudraCT2015-005805-35). PATIENTS AND METHODS Before initiation of the randomized portion of the BEACON Colorectal Cancer trial, 30 patients with BRAF V600E–mutant mCRC who had experienced treatment failure with one or two prior regimens were to be recruited to a safety lead-in of encorafenib 300 mg daily, binimetinib 45 mg twice daily, plus standard weekly cetuximab. The primary end point was safety, including the incidence of dose-limiting toxicities. Efficacy end points included overall response rate, progression-free survival, and overall survival. RESULTS Among the 30 treated patients, dose-limiting toxicities occurred in five patients and included serous retinopathy (n = 2), reversible decreased left ventricular ejection fraction (n = 1), and cetuximab-related infusion reactions (n = 2). The most common grade 3 or 4 adverse events were fatigue (13%), anemia (10%), increased creatine phosphokinase (10%), increased AST (10%), and urinary tract infections (10%). In 29 patients with BRAF V600E–mutant tumors (one patient had a non– BRAF V600E–mutant tumor and was not included in the efficacy analysis), the confirmed overall response rate was 48% (95% CI, 29.4% to 67.5%), median progression-free survival was 8.0 months (95% CI, 5.6 to 9.3 months), and median overall survival was 15.3 months (95% CI, 9.6 months to not reached), with median duration of follow-up of 18.2 months (range, 16.6 to 19.8 months). CONCLUSION In the safety lead-in, the safety and tolerability of the encorafenib, binimetinib, and cetuximab regimen is manageable and acceptable for initiation of the randomized portion of the study. The observed efficacy is promising compared with available therapies and, if confirmed in the randomized portion of the trial, could establish this regimen as a new standard of care for previously treated BRAF V600E–mutant mCRC.
Overlap of Bullous, Anti–Laminin-332, and Anti-p200 Pemphigoid With Concomitant Anti–Contactin-1–Positive Inflammatory Polyneuropathy Treated With Intravenous Immunoglobulins as a Manifestation of Epitope Spreading
Authors: Alexander Wald, Enno Schmidt, Ferdinand Toberer, Alexander Gutschalk, Kristin Rentzsch, Alexander H. Enk, Jochen H. O. Hoffmann
Journal: JAMA Dermatology (2019)

This case report describes a patient who experienced bullous, anti–laminin-332, and anti-p200 pemphigoid with concomitant anti–contactin-1–positive inflammatory polyneuropathy treated with intravenous immunoglobulins as a manifestation of epitope spreading.
Nasal High-Flow Therapy: Role of F<scp>i</scp><sub>O<sub>2</sub></sub> in the ROX Index
Authors: Stanislav Tatkov
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

other biomarker data) in chronic obstructive pulmonary disease (COPD).The main purpose behind our review of biomarkers in COPD (1) was to draw the reader's attention away from statistical differences and to the complexity of interpreting what appears to be straightforward data.This is central to the potential use of markers for understanding the pathophysiology of a disease, developing disease-specific treatments, and managing patients.As indicated in our review, sRAGE is a measurable serum factor that acts as a decoy for ligand binding, thereby reducing the inflammation pathway activated by cellular RAGE binding within the lung or peripherally.We noted the overall variability of this marker in COPD, as well as some factors that may influence its measurement in individuals.In our review, we cited the publication by Iwamoto and colleagues, who demonstrated that smoking alone decreased sRAGE in both control subjects and patients with COPD (2).Pouwels and colleagues discuss this important issue in more detail while highlighting the controversy in the literature regarding the effects of smoking (3), together with their own data using two validated assays to demonstrate an acute smoking effect in both healthy control subjects and patients with COPD (4).This effect is rapid after 2 days of abstention and is similar in control subjects and patients with COPD, suggesting that it is mainly a smoking effect (at least in the circulation).In addition, they remind us that exacerbations do not reduce sRAGE except in hospitalized patients with severe disease of both viral and bacterial causes, although with complete overlap of patient data points (except for two outliers in the stable state), indicating that individual patient values are not discriminatory.They also remind us of a further complicating issue of ligand binding (5), including the binding to integrins (6), that may also affect the measurement of circulating sRAGE.Importantly, the letter reminds readers that in COPD biomarker studies, just the smoking issue alone adds a major degree of complexity for interpretation.It is also worth noting that the sRAGE reduction seen in patients with COPD and smokers is also a feature of idiopathic pulmonary fibrosis (7), a condition with a totally different pathology, and therefore is likely to be a nonspecific feature of inflammation.Whether it can be used as a marker of different clinical types once COPD has been confirmed, or as a marker of effective treatment in some instances remains to be determined.
QIM19-135: The Quality Oncology Practice Initiative Program: Experience in Spain
Authors: Rafael López, Antonio Antón, Enrique Aranda, Alfredo Carrato, Manuel Constenla, Juan Jesús Cruz, Eduardo Díaz-Rubio, Margarita Feyjóo, Jesús García-Foncillas, Pere Gascón, Vicente Guillem, Ilse Lugo, Álvaro Rogado, Carlos Camps
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Patient quality care is a discipline that has acquired enormous relevance in today’s healthcare. The Quality Oncology Practice Initiative (QOPI) is a referral worldwide in terms of quality for oncology practices. The ECO Foundation is a foundation of experts representing the major Spanish hospitals involved in the treatment of cancer patients. ECO reached an agreement with ASCO to involve Spanish hospitals in the QOPI program. Methods: 6 rounds of data collection have taken place (Fall 2015 to Round 1 2018). Practices had to register online and submit data into the QOPI platform, and the ECO Foundation offered all centers the necessary support. 17 Spanish hospitals have participated in the 6 rounds, and 7 of them have repeated participation. Core and lung cancer modules were completed. Results: During the 6 rounds, 1,877 charts were submitted by the Spanish practices. In most of the rounds, the highest scores were: pathology report confirming malignancy; number of chemotherapy cycles documented; patient consent for chemotherapy; and 5 measures of the lung cancer module. The lowest scores were: chemotherapy treatment summary provided to patient within 3 months of chemotherapy end; chemotherapy treatment summary provided or communicated to practitioner(s) within 3 months of chemotherapy end; smoking/tobacco use cessation counselling recommended to smokers/tobacco users in past year; and tobacco cessation counselling administered or patient referred in past year. The percentage of participating practices that presented results higher than 70% was successively 64%, 50%, 75%, and 100% in the last 3 rounds. For the 7 hospitals that repeated participation, 3 reported an improvement of their global scores. Regarding QOPI Certification, 3 Spanish hospitals received this accreditation in September 2017 and one in June 2018. Conclusions: These preliminary results are a good starting point for the continued implementation of the QOPI program in Spain, thus providing a well-structured approach to analyze cancer care. The ECO Foundation will continue pursuing excellence and quality with further activities like the QOPI Certification program and Quality Training Program, these being performed for the first time in Spain in 2017 and 2018, respectively.
Violence and mortality in Rohingya migrants from the Northern Rakhine State, Myanmar
Authors: Delan Devakumar, Sylvia Garry, Marion Birch
Journal: The Lancet Planetary Health (2019)

The plight of the Rohingya people represents one of the key humanitarian issues of our time. This population, the largest stateless group in the world, has been persecuted within Myanmar, with many fleeing across the border to Bangladesh and to other countries.1 The study by Parveen Parmar and colleagues2 is particularly prescient given that Bangladesh has planned to stop accepting Rohingya migrants.3 Numerous eye-witness and case reports have emerged describing the degree of violence faced by the Rohingya, yet accurate estimates of overall mortality are largely missing.
Distinct mutation spectrum, clinical outcome and therapeutic responses of typical complex/monosomy karyotype acute myeloid leukemia carrying<i>TP53</i>mutations
Authors: Garret M. K. Leung, Chunxiao Zhang, Nelson K. L. Ng, Ning Yang, Stephen S. Y. Lam, Chun H. Au, Tsun L. Chan, Edmond S. K. Ma, Sze P. Tsui, Ho W. Ip, Jason C. C. So, Margaret H. L. Ng, Kelvin C. K. Cheng, Kit F. Wong, Lisa L. P. Siu, Sze F. Yip, Shek Y. Lin, June S. M. Lau, Tsan H. Luk, Harold K. K. Lee, Chi K. Lau, Bonnie Kho, Yok L. Kwong, Anskar Y. H. Leung
Journal: American Journal of Hematology (2019)

Abstract The present study aimed to define a subtype of complex/monosomal karyotype (CK/MK) acute myeloid leukemia (AML) by its distinct clinical features, p53 signaling and responses to p53 targeting agents. Ninety‐eight young adults (range: 21‐60 years; median: 49 years) with CK/MK AML were studied. They received standard induction, consolidation and allogeneic hematopoietic stem cell transplantation from siblings or matched unrelated donors if available. Chromosomal abnormalities most commonly affected chromosome 5 (30%), 7 (22%) and 17 (21%). Next generation sequencing of a 54‐myeloid gene panel were available in 76 patients. Tumor protein 53 ( TP53 ) mutations were most common (49%) and associated with the presence of −5/5q‐ ( P &lt; .001) and −17/17p‐ ( P &lt; .001), but not −7/7q‐ ( P = .370). This “typical” CK/MK AML subtype was associated with significantly lower presenting white cell counts, higher number of karyotypic abnormalities, and inferior leukemia‐free and overall survivals, compared with CK/MK AML without the typical features. Blood or bone marrow samples from typical CK/MK AML patients showed defective p53 signaling upon induction by etoposide. In vitro drug sensitivity analysis showed that they were sensitive to APR‐246 that targeted mutant p53, but resistant to MDM2 antagonist MI‐77301. Novel therapeutic strategies targeting TP53 mutations in CK/MK AML should be developed and tested in clinical trials.
C-Myc Driven Tolerogenic Tumor Microenvironment (TME) in Mantle Cell Lymphoma (MCL) Is Overcome By Bromodomain Inhibition
Authors: Fengdong Cheng, Yuan Ren, Jie Chen, Zi Wang, Tao Li, Kieron Dunleavy, Jianqing Lin, James Bradner, Mitchell R. Smith, Bijal D. Shah, Eduardo Sotomayor, Jianguo Tao
Journal: Blood (2018)
Malignant Perivascular Epithelioid Cell Tumor of Lung on FDG PET/CT
Authors: Jiyong Wu, Lei Jiang, Fengxian Zhang, Yan Huang, Huoqiang Wang
Journal: Clinical Nuclear Medicine (2019)

Chest CT images were acquired in a 67-year-old man to evaluate a left lung mass revealed by chest radiography. The image findings suggested possible pulmonary malignancy. FDG PET/CT was performed for staging, which showed the abnormally increased activity in the lung mass with hypermetabolic lymph node. Pathology from the biopsy confirmed malignant perivascular epithelioid cell tumor.
Abstract 17749: Rescue of Established Pulmonary Hypertension by a High Density Lipoprotein Mimetic Peptide
Authors: Soban Umar, Rangarajan D Nadadur, Kaveh Navab, Gabriel Wong, Greg Hough, David Ross, Alan M Fogelman, Mohamad Navab, Mansoureh Eghbali
Journal: Circulation (2012)

INTRODUCTION Vascular disorders involve complex interactions between oxidized lipids, macrophages, smooth muscle cells and endothelium. Pulmonary hypertension (PH) is characterized by pulmonary vas...
HSR19-110: Predicting Candidates for Cytoreductive Surgery and HIPEC: The Role of Computed Tomography and Diagnostic Laparoscopy
Authors: Leigh Selesner, Gabrielle Gauvin, Dorotea Mutabdzic, Eileen O’Halloran, Maxwell Kilcoyne, Kwan-Keat Ang, Jeffrey Farma, Elin Sigurdson, Sanjay Reddy
Journal: Journal of the National Comprehensive Cancer Network (2019)

Introduction: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) has led to improved survival in select patients with peritoneal surface malignancies. Predicting the volume of disease and any unresectable disease is important for determining CS candidacy. Computed tomography (CT) scan is the preoperative assessment of choice, and diagnostic laparoscopy (DL) is also supported in the literature but has not been widely adopted. In this study, we report our experience comparing and evaluating the role of imaging and DL in the preoperative assessment of patients being considered for CS/HIPEC. Methods: Patients considered for CS/HIPEC at our tertiary cancer center between January 2012 and December 2017 were included. Diagnostic modality sensitivity and specificity were calculated by comparing findings on CT scan and DL to findings at the time of laparotomy and on final pathology. Specificity and sensitivity of the 2 modalities were compared using the McNemar Chi-square test. Results: Our analysis included 71 patients (60.5% male, mean age of 54.9) seen in consultation for CS/HIPEC. Primary cancer diagnosis was 57.7% colorectal cancer, 25.4% pseudomyxoma peritonei, 8.5% mesothelioma, and 8.5% adenocarcinoma of unknown primary. DL was done in 42.3% of patients (median time of 30 days between CT and DL) and an open procedure was done directly after CT in 39.4% (median interval time of 39 days). Findings of DL identified 70% as being unresectable and hence ineligible for HIPEC. The median interval time between 2 operations was 29 days (range, 16–42). When comparing diagnostic modalities to open surgery and final pathology, CT had a sensitivity and specificity of 48.2% and 76.4% and DL, 68.2% and 88.9%, respectively. DL was significantly more sensitive and specific than CT (χ2=5.54; P &lt;.0186) at predicting ascites, small bowel, omental, liver, and lymph node involvement. Conclusion: Our results support the recommendation for performing DL prior to open exploration in patients considered for CS/HIPEC. In our cohort, DL was significantly more sensitive and specific than CT in predicting disease volume and distribution. While there is obviously greater risk to an invasive modality compared to non-invasive CT scan, routine performance of DL can potentially avoid laparotomy without CS/HIPEC in a large proportion of patients. These results will be used to inform the next phase of our study: a prospective clinical trial.
Breast Phyllodes Tumors Recruit and Repolarize Tumor-Associated Macrophages via Secreting CCL5 to Promote Malignant Progression, Which Can Be Inhibited by CCR5 Inhibition Therapy
Authors: Yan Nie, Hongyan Huang, Mingyan Guo, Jiewen Chen, Wei Wu, Wende Li, Xiaoding Xu, Xiaorong Lin, Wenkui Fu, Yandan Yao, Fang Zheng, Man-Li Luo, Phei Er Saw, Herui Yao, Erwei Song, Hai Hu
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Malignant phyllodes tumor (PT) is a fast-progression neoplasm derived from periductal stromal cells of the breast, which currently still lack effective treatment strategies. Our previous studies showed that the high density of tumor-associated macrophages (TAM) plays an important role in the malignant progression of PTs. TAMs secreted large amount of CCL18 to promote myofibroblast differentiation and invasion via binding to its receptor PIPTNM3 on myofibroblasts. Herein, we investigate the mechanism of how TAMs are recruited and repolarized by PTs to drive the malignant progression. Experimental Design: The cytokines secreted by PTs were identified by the cytokine array. The clinical and pathologic correlations of the cytokine with PTs were estimated with IHC. The mechanisms of the cytokine that recruited and polarized the macrophage were explored with a coculture model of primary PT cells and macrophages in vitro and in vivo. The patient-derived xenografts (PDX) of malignant PTs were used to evaluate the therapeutic effect of CCR5 inhibitor. Results: A high level of malignant PT-secreted CCL5 correlated with poor outcome of PTs and could be an independent prognostic factor of PTs. CCL5 bound to its receptor, CCR5, on macrophages thus activated AKT signaling to recruit and repolarize TAMs. Subsequently, the TAMs released CCL18 to further promote the aggressive phenotype of malignant PTs by enhancing and maintaining the myofibroblast differentiation and invasion in vitro and in vivo. In a murine PDX model of human malignant PTs, the CCL5–CCR5 axis blocked by maraviroc, an FDA-proved CCR5 inhibitor, prevented recruitment of monocytes to the tumor and dramatically suppressed tumor growth. Conclusions: Our findings indicate that malignant PTs recruit and repolarize TAMs through a CCL5-CCR5–driven signaling cascade. Thus, a positive feedback loop of CCL5-CCR5 and CCL18-PIPTNM3 between myofibroblast and TAMs is constituted to drive the malignant progression of PTs. Furthermore, targeting CCR5 with maraviroc represents a potential clinically available strategy to treat malignant PTs.
Delivery Room Resuscitation of Extremely Preterm Infants
Authors: Jeffrey Perlman
Journal: JAMA (2019)

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Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation
Authors: Nasser Alhajj, Zabliza Zakaria, Idanawati Naharudin, Fakhrul Ahsan, Wenji Li, Tin Wui Wong
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation. Blending nanoparticles with lactose microparticles (∼5 µm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000 (PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products (fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.
Health care and mental wellbeing in the transgender and gender-diverse Chinese population
Authors: Xuequan Zhu, Yue Gao, Amy Gillespie, Ying Xin, Ji Qi, Jianjun Ou, Shaoling Zhong, Ke Peng, Tingting Tan, Chaoyue Wang, Runsen Chen
Journal: The Lancet Diabetes & Endocrinology (2019)
18F-FDG PET/CT in Urachal Abscess
Authors: Anthime Flaus, Maria-Giulia Longo, Marine Dematons, Denise Granjon, Nathalie Prevot
Journal: Clinical Nuclear Medicine (2019)

We report interesting images of a pelvic mass in an 11-year-old girl. She presented with fever, chronic fatigue, and weight loss without abdominal pain. Abdominal ultrasound, contrast-enhanced CT, and F-FDG PET/CT were equivocal. F-FDG PET/CT revealed an irregular, intense FDG-avid pelvic mass in close contact with the bladder. Both infectious and malignancy complications were suspected, but pathological examination confirmed a urachal abscess. As most of the urachal carcinomas are mucinous adenocarcinomas with low or non-FDG uptake, intense uptake might indicate an abscess rather than a carcinoma.