tbuckley/cabot-search huggingface dataset:
A Strawberry Milkshake
Authors: Jenny C. Dohlman
Journal: Annals of Internal Medicine (2018)

On Being a Doctor2 October 2018A Strawberry MilkshakeJenny C. Dohlman, MDJenny C. Dohlman, MDCambridge Health Alliance/Harvard Medical School, Boston, Massachusetts (J.C.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-1730 Audio Reading - “A Strawberry Milkshake” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Strawberry Milkshake," by J.C. Dohlman. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail When you are an intern, the hours between 6:00 and 8:00 a.m. are a busy time. Learn about overnight events on the patients you are caring for. Hear the stories of new patients who came to the floor overnight. Check on labs, vitals, new imaging studies. Meet new patients. Say hello to old ones. Perhaps meet family members who come with their own set of worries and questions. Listen to hearts, palpate ankles. Beckon foreign-language interpreters. Hear new symptoms as well as old ones. “Are you feeling better, worse, or the same?” “Yes, I can get you some ginger ale.” ... Author, Article, and Disclosure InformationAffiliations: Cambridge Health Alliance/Harvard Medical School, Boston, Massachusetts (J.C.D.)Corresponding Author: Jenny C. Dohlman, MD, 1493 Cambridge Street, Cambridge, MA 02139. PreviousarticleNextarticle Advertisement Audio Reading - “A Strawberry Milkshake” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Strawberry Milkshake," by J.C. Dohlman. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 2 October 2018Volume 169, Issue 7Page: 504-505KeywordsEmotionsFearFoodNursesPneumoniaSaltsSleepTeaVital signsWalking ePublished: 2 October 2018 Issue Published: 2 October 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Precise Spatiotemporal Interruption of Regulatory T-cell–Mediated CD8+ T-cell Suppression Leads to Tumor Immunity
Authors: Xiaoyu Zhou, Shushu Zhao, Yue He, Shuang Geng, Yan Shi, Bin Wang
Journal: Cancer Research (2018)

Abstract Tumors can develop despite the presence of competent host immunity via a complex system of immune evasion. One of the most studied factors originating from the host is immune suppression by regulatory T cells (Treg). Ample laboratory and clinical evidence suggests that Treg ablation leads to robust antitumor immune activation. However, how Tregs specifically achieve their suppression in the context of tumor progression is not entirely clear, particularly with regard to the timing and location where Treg inhibition takes place. In this work, we report that Tregs migrate to tumor-draining lymph nodes (TDLN) and block expression of sphingosine-1-phosphate receptor 1 (S1P1) on CD8+ T cells. This event trapped the CD8+ T cells in the TDLN and served as a facilitating factor for tumor growth. Intriguingly, minimalistic depletion of Tregs in TDLN in a short window following tumor inoculation was sufficient to restore CD8+ T-cell activities, which resulted in significant tumor reduction. Similar treatments outside this time frame had no such effect. Our work therefore reveals a subtle feature in tumor biology whereby Tregs appear to be driven by newly established tumors for a programmed encounter with newly activated CD8+ T cells in TDLN. Our results suggest the possibility that clinical interception of this step can be tested as a new strategy of cancer therapy, with expected high efficacy and low systemic side effects. Significance: These findings reveal a strong tumor suppressive effect invoked by minimal blockade of tumor draining lymph node regulatory T cells during early versus late tumorigenesis.
An interprofessional pathway for patients initiating treatment with palbociclib: Optimization of toxicity monitoring.
Authors: Alia Thawer, Susan Singh, Angela Boudreau, Lori Mackinnon, Lisa Ng, Shikha Lawrence, Flay Charbonneau, Jordan Stinson, Deana Slater, Maureen E. Trudeau, Sonal Gandhi
Journal: Journal of Clinical Oncology (2018)

268 Background: CDK 4/6 Inhibitors such as palbociclib in combination with hormonal therapy are considered the new standard of care for eligible advanced breast cancer patients with ER positive, HER2 negative disease. These agents have toxicities warranting standardized monitoring algorithms. Methods: An interprofessional pathway was created for palbociclib that identified key patient milestones and responsibilities of different care providers. Blood work (BW) parameters for dose interruption/reduction were specified, with a minimum absolute neutrophil count (ANC) of 1 as the threshold for continuing therapy. A retrospective chart audit was conducted to assess adherence to the biweekly BW and toxicity assessment pathway. Toxicity results were compared to the PALOMA-2 trial. Results: Consecutive patients were assessed between June 2016 and August 2017. Median follow up was 193 days. Twenty five patients before and 24 patients post algorithm implementation were included. Median age was 59, and 80% had &gt;2 lines of prior systemic treatment. Dose reductions were observed in 57% of patients, 84% for neutropenia (Table 1). This is higher than documented in PALOMA-2. Instances where BW and clinic assessment were indicated and completed went from 43% to 69% and 32% to 67% respectively. Conclusions: Our study included heavily pre-treated patients and used an ANC treatment continuation threshold of 1 as opposed to 0.5; this might explain the increased incidence of neutropenia and dose modifications. This algorithm, with defined provider roles and patient milestones, appears feasible and effective in standardizing follow up and optimizing patient care.[Table: see text]
Molecular mechanism of ion-pair releasing from acrylic pressure sensitive adhesive containing carboxyl group: Roles of doubly ionic hydrogen bond in the controlled release process of bisoprolol ion-pair
Authors: Hanqing Zhao, Chao Liu, Degong Yang, Xiaocao Wan, Rui Shang, Peng Quan, Liang Fang
Journal: Journal of Controlled Release (2018)
Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid
Authors: Lingfei Han, Lejian Hu, Fulei Liu, Xin Wang, Xiaoxian Huang, Bowen Liu, Feng Feng, Wenyuan Liu, Wei Qu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The application of paclitaxel (PTX) in clinic has been restricted due to its poor solubility. Several traditional nano-medicines have been developed to improve this defect, while they are still lack of tumor targeting ability and rapid drug release. In this work, an amphiphilic polymeric micelle of hyaluronic acid (HA) - all-trans-retinoid acid (ATRA) with a disulfide bond, was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with self-assembling to micelles in water, the delivery system displayed satisfying drug loading capacities for both PTX (32.62% ± 1.39%) and ATRA, due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles (HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides, HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16F10 cells. Due to these properties, cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly, HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore, redox-sensitive HA-SS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.
Airway fractal dimension predicts respiratory morbidity and mortality in COPD
Authors: Sandeep Bodduluri, Abhilash S. Kizhakke Puliyakote, Sarah E. Gerard, Joseph M. Reinhardt, Eric A. Hoffman, John D. Newell, Hrudaya P. Nath, MeiLan K. Han, George R. Washko, Raúl San José Estépar, Mark T. Dransfield, Surya P. Bhatt, COPDGene Investigators
Journal: Journal of Clinical Investigation (2018)

Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling. Characterization of airway changes on computed tomography has been challenging due to the complexity of the recurring branching patterns, and this can be better measured using fractal dimensions.We analyzed segmented airway trees of 8,135 participants enrolled in the COPDGene cohort. The fractal complexity of the segmented airway tree was measured by the Airway Fractal Dimension (AFD) using the Minkowski-Bougliand box-counting dimension. We examined associations between AFD and lung function and respiratory morbidity using multivariable regression analyses. We further estimated the extent of peribronchial emphysema (%) within 5 mm of the airway tree, as this is likely to affect AFD. We classified participants into 4 groups based on median AFD, percentage of peribronchial emphysema, and estimated survival.AFD was significantly associated with forced expiratory volume in one second (FEV1; P < 0.001) and FEV1/forced vital capacity (FEV1/FVC; P < 0.001) after adjusting for age, race, sex, smoking status, pack-years of smoking, BMI, CT emphysema, air trapping, airway thickness, and CT scanner type. On multivariable analysis, AFD was also associated with respiratory quality of life and 6-minute walk distance, as well as exacerbations, lung function decline, and mortality on longitudinal follow-up. We identified a subset of participants with AFD below the median and peribronchial emphysema above the median who had worse survival compared with participants with high AFD and low peribronchial emphysema (adjusted hazards ratio [HR]: 2.72; 95% CI: 2.20-3.35; P < 0.001), a substantial number of whom were not identified by traditional spirometry severity grades.Airway fractal dimension as a measure of airway branching complexity and remodeling in smokers is associated with respiratory morbidity and lung function change, offers prognostic information additional to traditional CT measures of airway wall thickness, and can be used to estimate mortality risk.ClinicalTrials.gov identifier: NCT00608764.This study was supported by NIH K23 HL133438 (SPB) and the COPDGene study (NIH Grant Numbers R01 HL089897 and R01 HL089856). The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, Sunovion and GlaxoSmithKline.
Abstract 19517: Circulating Factors Contribute to PDE5-Mediated Pathological Myocardial Remodeling in Single Ventricle Congenital Heart Disease
Authors: Anastacia M Garcia, Stephanie J Nakano, Brian L Stauffer, Carmen C Sucharov, Shelley D Miyamoto
Journal: Circulation (2016)

Introduction: Single ventricle congenital heart disease (SV) is fatal without intervention, and maladaptive myocardial remodeling and eventual heart failure (HF) is a major cause of morbidity and m...
Incidence of diabetes and hyperglycemia among patients receiving glucocorticoids with chemotherapy.
Authors: Dylan M. Zylla, Grant Steele, Grace Gilmore, Janet Davidson, Anders Carlson
Journal: Journal of Clinical Oncology (2018)

286 Background: Over 30 million adults in the U.S. have diabetes (DM), 7 million of which are undiagnosed. Patients with DM undergoing cancer treatment have been shown to have increased rates of complications and shorter survival. Patients commonly receive glucocorticoids (GC) with chemotherapy (CT), which may lead to hyperglycemia. Data regarding the optimal approach to screening and outpatient management of patients receiving CT with GC is lacking. We sought to describe the incidence of diabetes, hyperglycemia, and implemented a quality improvement project to refer eligible patients for DM education and management. Methods: We identified 100 patients with cancer starting a new CT regimen including GC. We obtained screening labs, baseline random glucose, HbA1c, and body-mass index (BMI) for each patient prior to starting CT. Follow-up glucose values were obtained with each cycle; patients were followed for a maximum of 3 cycles of CT. Patients with a baseline HbA1c ≥6.5%, a baseline random glucose ≥200mg/dL, follow up glucose ≥200mg/dL, and/or a prior DM diagnosis were referred to the Park Nicollet International Diabetes Center (IDC) to receive DM education and management. Results: 23% of patients had known DM and 17% had known prediabetes prior to their first CT cycle. Baseline HbA1c values were ≥6.5% in 18% of patients, 5.7-6.4% in 39% of patients, and ≤5.6% in 43% of patients. Among the 18 patients with baseline HbA1c ≥6.5%, 13 had known DM, 1 had known prediabetes, and 4 were undiagnosed. 67% of our study population had a baseline BMI ≥25. 12 patients had at least one follow up glucose ≥200mg/dL. Of those 12, 92% had known DM, 67% had a baseline HbA1c ≥6.5%, and 75% had a baseline BMI ≥25. 29 patients met IDC referral criteria, however, only 14 were ultimately seen in consultation. Conclusions: Adding HbA1c to baseline laboratory evaluations identified individuals with undiagnosed DM. DM history, baseline HbA1c, and BMI were associated with hyperglycemic events among patients receiving CT with GC. Future studies are needed to evaluate the impact of DM education and management on both glycemic control and clinical outcomes.
Quality improvement and safety curriculum for hematology/oncology fellows at Columbia University.
Authors: Melissa Kate Accordino, Mark L. Heaney
Journal: Journal of Clinical Oncology (2018)

247 Background: It is imperative to provide Hem/Onc fellows with experiential training in quality improvement (QI) and patient safety methodology. Our objective was to design a curriculum that would provide experience in designing, implementing, and analyzing a QI/safety project with the ultimate aim of engagement in QI/safety efforts throughout their careers. Methods: The curriculum focused on experiential learning and was led by a faculty member with QI/safety methodology training who provided didactics and supervisory support of the projects. Fellows worked in groups (3-5 fellows) to implement a project. Plan-Do-Study-Act (PDSA) methodology was introduced early in the academic year and workshops continued over a one-year time period. At the year end, projects were presented at an institution-wide symposium. Two cohorts (2015-2016, 2017-2018) have completed the curriculum. Results: Program efficacy was measured in several ways. The QIKAT-R tool was administered prior to the curriculum in August 2015 (n = 12) and at completion June 2016 (n = 14). At baseline, the mean score was 3.97 (out of 9) which improved to 7.57 at completion. Comfort level with QI also increased by 42.9%. Annual ACGME survey questions pertaining to an institutional culture of patient safety increased from 88% (2015) to 100% (2016 and 2018) and participation in QI increased from 53% (2015) to 95% (2106) to 100% (2018). Further, fellows (n = 33) successfully completed nine projects which included: improvement of fertility preservation, improvement in the adequacy of bone marrow aspirates performed by fellows, increasing genetic counseling referrals in select patients with colorectal cancer, improvement in smoking cessation counseling, increasing timely chemotherapy order entry, and reduction of unnecessary heparin induced thrombocytopenia antibody testing. The curriculum is currently being adapted to other fellowship programs at Columbia. Conclusions: Our curriculum is an effective method to teach fellows at Columbia University Medical Center a skill set necessary to conduct successful QI/safety projects. PDSA methodology of small cycles of change can be used life-long to continuously assess and improve care quality and safety.
Fatigue in systemic lupus erythematosus and other autoimmune skin diseases
Authors: M. Tarazi, R.G. Gaffney, D. Pearson, C.J. Kushner, V.P. Werth
Journal: British Journal of Dermatology (2018)

Fatigue is a well‐established symptom in systemic lupus erythematosus (SLE), but has not been well characterized in other skin‐limited autoimmune diseases such as cutaneous lupus erythematosus (CLE), amyopathic dermatomyositis (ADM) or autoimmune blistering diseases (AIBD). In this retrospective study, we compared fatigue in controls (n = 84) with that in patients enrolled in prospective longitudinal databases with SLE (n = 165), CLE (n = 226), ADM (n = 136) and AIBD (n = 79). We used the 36‐Item Short Form Survey (SF‐36) vitality scale to analyse median scores and the percentages of patients with clinically significant fatigue (defined as a score ≤ 35) between experimental groups and controls. Median and interquartile range (IQR) vitality scores demonstrated greater fatigue in the experimental groups (SLE 35, IQR 20–55; CLE 50, IQR 30–70; ADM 50, IQR 30–65; AIBD 55, IQR 35–70) than in controls (73, IQR 65–85) (P < 0·05 for each experimental group vs. control). The SLE group had worse fatigue than all of the other groups (P < 0·05 SLE vs. each group), but there was no difference between the CLE, ADM or AIBD groups (all P > 0·05). In addition, the experimental groups had more clinically significant fatigue (score ≤ 35) (SLE 44·2%, CLE 25·2%, ADM 31·6%, AIBD 24·1%) than controls (2%) (P < 0·01 for each experimental group vs. control). The SLE group had more clinically significant fatigue than the CLE group (P < 0·01); however, there was no difference in clinically significant fatigue between SLE and either ADM (P = 0·17) or AIBD (P = 0·055). These findings demonstrate that patients with skin‐limited autoimmune disease experience more fatigue than controls. Fatigue is an important symptom that negatively affects quality of life for patients. It should be addressed by clinicians and measured in future clinical trials.
The effects of pH, surfactant, ion concentration, coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals
Authors: Shuzhen Ren, Mingyu Liu, Chao Hong, Guowen Li, Jiabin Sun, Jianying Wang, Lei Zhang, Yan Xie
Journal: Acta Pharmaceutica Sinica B (2018)

Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin (MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate (IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin–isonicotinamide (MYR–INM) and myricetin–caffeine (MYR–CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure. The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer (CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR–INM (1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.
Communication among oncology teams at an academic center.
Authors: Christopher Edward Jensen, Amy Iarrobino Laughlin, Daniel Jeffrey Landsburg
Journal: Journal of Clinical Oncology (2018)

166 Background: Effective communication is essential to ensure optimal care for oncology patients admitted to the hospital and safe transitions between care settings. Methods: A questionnaire adapted from the Collaboration and Satisfaction about Care Decisions survey instrument addressing inpatient/outpatient communication was sent to nurses and physicians who cared for patients admitted to the housestaff oncology services at the University of Pennsylvania from 10/2016-2/2017. Questions addressed care plan formulation, communication, and satisfaction with medical decision making on a seven-point Likert scale. Contextual interviews with stakeholders were also conducted. Iterative adjusted rounding pilots were implemented in PDSA cycles including rounding checklist, multi-disciplinary rounds and a two-step paging process to inform nurses of teams’ rounding times. Results: For 66 respondents, the ranges of mean score for each question by provider type were: oncology nurses (4.07-4.29, n = 28), medicine interns (4.33-5.11, n = 9) and residents (4.00-4.83, n = 12), oncology fellows (5.00-7.00, n = 1), and oncology attendings inpatient (5.56-5.89, n = 9) and outpatient (4.71-5.57, n = 7). Given the lowest scores among nurses, rounding interventions targeting nursing attendance on rounds were trialed. Baseline data demonstrated nursing presence on rounds for 47.0% (95% CI: 37.2-56.8%) of patients. During a pilot of the two-step paging process, the rate increased to 63.1% (55.6-70.6%; p = 0.01 for two-sided Z test). A balancing metric of time per patient did not vary significantly before and during the pilot process. Contextual interviews surrounding interventions suggested several barriers to systematically restructuring provider rounds: time limitations for team rounds, frequent rotation of providers and variations in rounding styles as dictated by attending physicians. Conclusions: Satisfaction regarding the care of acutely ill oncology patients appears to negatively correlate with face-to-face time spent with patients in the inpatient setting. These findings provided the basis for a series of pilots of modified rounding models with a focus on integrating nursing staff into provider rounds, which have been difficult to sustain