tbuckley/cabot-search huggingface dataset:
A Burnout's Rehab
Authors: Diana Pi
Journal: Annals of Internal Medicine (2019)

On Being a Doctor20 August 2019A Burnout's RehabDiana Pi, MDDiana Pi, MDWestlake, Ohio (D.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-2911 Audio Reading - “A Burnout's Rehab” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “A Burnout's Rehab” by Diana Pi, MD 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 For 20 years, I was a generalist at a hospital-based outpatient practice. After following us for weeks, a team of consultants sat us down and unloaded ways to improve our efficiency. My hardest change: 20-minute appointments for new patients. Months later, I hung up my white coat and walked out hugging a plastic crate containing everything I cared to keep from my professional life—two diplomas, a board certificate, two flash drives, a stethoscope, a backup stethoscope, an otoscope, and a no-name vine that had survived on indirect sunlight in my office for decades.I was 49. And burned out.My ... Author, Article, and Disclosure InformationAffiliations: Westlake, Ohio (D.P.)Corresponding Author: Diana Pi, MD, 25739 Briarwood Court, Westlake, OH 44145; e-mail, diana.pi.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “A Burnout's Rehab” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “A Burnout's Rehab” by Diana Pi, MD 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 20 August 2019Volume 171, Issue 4Page: 295-296KeywordsBlindnessChartsNursesRabbitsReasoningSmellStomachSweatThoraxTraumatic brain injury ePublished: 20 August 2019 Issue Published: 20 August 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prognosis of colorectal cancer varies in different high-risk conditions.
Authors: Markku Aarnio, Harri K Mustonen, Jukka-Pekka Mecklin, Heikki Järvinen
Journal: Annals of Internal Medicine (1998)

Variation in prognosis between different colorectal cancer (CRC) patient groups was studied by comparing the survival rates of patients belonging to three cancer predisposition groups with those with sporadic CRC. The high-risk groups included 43 members of hereditary nonpolyposis colorectal cancer (HNPCC) families, 25 patients with familial adenomatous polyposis (FAP) and 33 patients with underlying ulcerative colitis (UC). The control group included 122 consecutive sporadic CRC patients. Cumulative 5-year survival was highest in HNPCC (86%), which is significantly better than in sporadic colorectal cancer (59%, hazard ratio 0.41, P = 0.02). Cancer associated with UC had a 5-year survival rate of 39%, which is significantly less than in sporadic cancer (hazard ratio 1.83, P = 0.03). There was no significant difference in the survival between patients with FAP and patients with sporadic CRC (hazard ratio 1.27, P = 0.5). Exclusion of cases detected by screening examinations slightly reduced the survival ra...
Histologic and clinical cross-sectional study of chronic hair loss in patients with cutaneous chronic graft-versus-host disease
Authors: Dustin H. Marks, Jason S. Naftulin, Lauren R. Penzi, Athena Manatis-Lornell, Mariko R. Yasuda, Clifford M. Chapman, Sowmya R. Rao, Arturo Saavedra, Maryanne M. Senna
Journal: Journal of the American Academy of Dermatology (2019)
Clinical behavior and prognosis of lymph-nodal Merkel cell carcinoma (MCC) in the absence of a primary tumor.
Authors: Manuela Albertelli, Antongiulio Faggiano, Franco Grimaldi, Pietro Ameri, Giovannella Palmieri, Giovanni Scarpelli, Piera Federico, Claudio Bellevicine, Giancarlo Troncone, Federica Grillo, Francesco Minuto, Lucio Crino, Annamaria Colao, Diego Ferone, Piero Ferolla
Journal: Journal of Clinical Oncology (2012)

e19038 Background: MCC is a rare cutaneous neuroendocrine neoplasm characterized by an aggressive behavior and a high recurrence rate, generally associated with poor prognosis. Nodal and distant metastases are frequent. Aim of this study was to report histological, clinical and prognostic features of a series of 12 patients with nodal MCC in the lack of evidence of a primary. Methods: The cases were collected from a multicentric database: mean age at diagnosis was 67 years; F:M ratio was 1:1.4; mean follow up was 54 months (8-108). Involved nodal sites were: inguinal (9) and axillar (3). All cases had typical MCC immunoprofile: neuroendocrine (CgA, NSE, Syn) and epithelial (CK 20 dot-like) marker positivity. Complete and extensive clinical, dermatologic, radiologic and endoscopic work-up was performed. All patients underwent surgical excision; in one case chemotherapy, in another case biotherapy and in one further case radiotherapy was administered. Results: All cases were in stage III of disease, according to AJCC. All patients were alive without recurrence at the time of the study. The overall mean survival was 52 months. The 4-yr survival was 100%. Conclusions: In patients with nodal metastases of MCC in the absence of a primary lesion, survival seems to be more similar to stage I rather than stage III, since 4-yr survival is reported about 60% for stage III disease in MCC. This finding must still be completely explained. Regression of a small skin primary with nodal metastases or alternatively a primary nodal MCC might be hypothesized. In conclusion, the unknown primary nodal metastatic skin MCC seems to be associated with a more favorable prognosis.
Phase II study of aflibercept (VEGF trap) in recurrent inoperable stage III or stage IV melanoma of cutaneous or ocular origin
Authors: A. A. Tarhini, S. Christensen, P. Frankel, K. Margolin, C. Ruel, J. Shipe-Spotloe, M. DeMark, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2009)

9028 Background: Aflibercept is a fusion protein combining the Fc portion of human IgG 1 with the extracellular ligand-binding domains of human VEGFR1 and VEGFR2, acting as a high-affinity soluble VEGF receptor and potent angiogenesis inhibitor. Methods: Phase II study of aflibercept in patients with inoperable stage III or IV melanoma who had received no prior chemotherapy or hormonal therapy. A 2-stage design was adopted focusing upon response rate (RECIST) and 4-month PFS rate. First stage accrual of 21 patients was specified, while final accrual of 41 is planned, with adequate response/4 month PFSR. Aflibercept was given at 4 mg/kg IV every 2 weeks. Response was assessed every 8 weeks. Results: Twenty seven patients (16 male, 11 female), age 23–83 (median 58) have been enrolled to date. All had AJCC stage IV melanoma (3M1a, 3M1b, 21M1c). Karnofsky PS: 100 (13), 90 (11) or 80 (3). Nine patients had primary ocular melanoma, 16 cutaneous and 2 unknown primary site. A total of 160 cycles have been administered (median 4; range 1–18). Grade 3/4 toxicities included cerebral ischemia (1 patient; 4%), confusion (1; 4%), thrombocytopenia (1; 4%), hypertension (7; 26%), hypotension (1; 4%), left ventricular diastolic dysfunction (1; 4%), fatigue (1; 4%), proteinuria (4; 15%), extraocular muscle paresis (1; 4%), renal failure (1; 4%), back pain (1; 4%), headache (1; 4%). Interim analysis was conducted after the first 21 patients (stage 1). Eight (1 M1a, 1M1b, 6M1c; 4 ocular, 3 cutaneous, 1 unknown primary) of the first 21 patients had at least 4 months of PFS (10 out of 27; 2 additional patients with cutaneous melanoma had SD: 1M1a and 1M1c). One patient (23 rd ; cutaneous, M1c) had a confirmed complete remission. Four patients were taken off study prior to response evaluation for toxicity (3) or treatment refusal (1). One patient is currently disease free who was not evaluable for response (previous surgery and radiofrequency ablation of measurable disease site). Eleven patients had progression. Conclusions: Aflibercept can be administered with acceptable toxicity, and exhibits promising antitumor efficacy against advanced melanoma. This study continues second stage accrual with anticipated closure before June 2009. [Table: see text]
PARP Inhibition Suppresses GR–MYCN–CDK5–RB1–E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer
Authors: Bo Liu, Likun Li, Guang Yang, Chuandong Geng, Yong Luo, Wenhui Wu, Ganiraju C. Manyam, Dimitrios Korentzelos, Sanghee Park, Zhe Tang, Cheng Wu, Zhenyang Dong, Michael Sigouros, Andrea Sboner, Himisha Beltran, Yu Chen, Paul G. Corn, Michael T. Tetzlaff, Patricia Troncoso, Bradley Broom, Timothy C. Thompson
Journal: Clinical Cancer Research (2019)

In this study, we addressed the underlying mechanisms for the association between enzalutamide (ENZ) treatment and neuroendocrine prostate cancer (NEPC), and the critical involvement of MYCN, and loss of RB1 function in neuroendocrine differentiation (NED) of prostatic epithelial cells, and the development of NEPC. We further sought to determine whether PARP inhibition could suppress NEPC, and to identify molecular determinants of this therapeutic activity.We used a novel prostate cancer patient-derived xenograft (PDX) treatment model, prostatic adenocarcinoma and NEPC cell lines, an NEPC organoid line, and NEPC xenograft models to address the mechanistic basis of ENZ-induced NED, and to analyze suppression of NED and NEPC growth by PARP inhibition.We identified an ENZ treatment-associated glucocorticoid receptor (GR)-MYCN-CDK5-RB1-E2F1 signaling pathway that drives NED in prostatic adenocarcinoma PDX and cell line models. Mechanistically, long-term ENZ treatment transcriptionally upregulates signaling of the GR-MYCN axis, leading to CDK5R1 and CDK5R2 upregulation, Rb1 phosphorylation, and N-Myc-mediated and E2F1-mediated NED gene expression. Importantly, olaparib (OLA) or talazoparib (TALA) suppressed these activities, and the combination of OLA and dinaciclib (DINA), an inhibitor of CDK2 and CDK5, which also inhibits Rb1 phosphorylation, suppressed NED and significantly improved therapeutic efficiency in NEPC cells in vitro and in NEPC tumors in vivo.The results of our study indicate an important role of GR-MYCN-CDK5R1/2-RB1-NED signaling in ENZ-induced and PARP inhibitor-suppressed NEPC. We also demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models.
The Safety and Efficacy of Tranexamic Acid in Adult Spinal Deformity Surgery: A Systematic Review and Meta-Analysis
Authors: Dhwani Hariharan, Marco Mammi, Kelicia Daniels, Nayan Lamba, Kerilyn Petrucci, Christian D. Cerecedo-Lopez, Joanne Doucette, Alexander F. C. Hulsbergen, Stefania Papatheodorou, Linda S. Aglio, Timothy R. Smith, Rania A. Mekary, Hasan Zaidi
Journal: Drugs (2019)
Outcomes of Childhood Acute Lymphoblastic Leukemia with CNS-2, CNS-3 and Traumatic Lumbar Puncture with Blasts in Two Eras of Taiwan Pediatric Oncology Group (TPOG)-ALL-2002 Study with or without Cranial Radiation
Authors: Hsi-Che Liu, Meng-Ju Li, Hsiu-Ju Yen, Dong-Tsamn Lin, Tang-Her Jaing, Ting-Chi Yeh, Jen-Yin Hou, Der-Cherng Liang
Journal: Blood (2016)
Spatially selective activation of the visual cortex via intraneural stimulation of the optic nerve
Authors: Vivien Gaillet, Annarita Cutrone, Fiorenzo Artoni, Paola Vagni, Ariastity Mega Pratiwi, Sandra Alejandra Romero, Dario Lipucci Di Paola, Silvestro Micera, Diego Ghezzi
Journal: Nature Biomedical Engineering (2019)
Do no harm: a roadmap for responsible machine learning for health care
Authors: Jenna Wiens, Suchi Saria, Mark Sendak, Marzyeh Ghassemi, Vincent X. Liu, Finale Doshi-Velez, Kenneth Jung, Katherine Heller, David Kale, Mohammed Saeed, Pilar N. Ossorio, Sonoo Thadaney-Israni, Anna Goldenberg
Journal: Nature Medicine (2019)
Exploring tumor clonal evolution in bone marrow of patients with diffuse large B-cell lymphoma by deep IGH sequencing and its potential relevance in relapse
Authors: Jiao Ma, David Redmond, Ayako Miyaguchi, Anna S. Nam, Kui Nie, Susan Mathew, Olivier Elemento, Wayne Tam
Journal: Blood Cancer Journal (2019)

Dear Editor,Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and accounts for 30-40% of all B-cell non-Hodgkin lymphoma (NHLs) 1,2 .Many patients respond to the first-line regimens such as R-CHOP 3 .However, up to one-third of patients have refractory and relapse disease associated with poor outcome.DLBCL is heterogeneous with respect to morphologic, immunophenotypic, and molecular features 4 , and encompasses numerous variants, subgroups, and subtypes.Approximately 10-15% of DLBCL patients have bone marrow (BM) involvement [5][6][7] .Morphologically, lymphoma involvement in the BM of DLBCL patients can either be classified as large B-cell lymphoma (histologically concordant) or indolent, low-grade B-cell lymphoma (histologically discordant).Tumor clonal dynamics and evolution in the BM of patients with DLBCL have not yet been studied in detail.Questions remain whether the lymphomatous involvement in BM in DLBCL patients represents a direct dissemination of tumor cells from the dominant tumor clones in the nodal or extranodal location to the BM.It is also unknown whether tumor-related cells can be detected in the BM when there is no morphologic evidence of lymphoma, and whether detection of these cells can have
Abstract 15065: Early and Mid-Term Outcomes in High-Risk Single Ventricle Patients Undergoing Hybrid versus Norwood Palliation
Authors: Christopher T Sower, Jennifer C Romano, Sunkyung Yu, Ray Lowery, Veronica Zitterman, Sara K Pasquali, Jeffrey D Zampi
Journal: Circulation (2018)

Introduction: While overall outcomes have improved for single ventricle (SV) patients undergoing stage 1 palliation, substantial morbidity and mortality remain for those with high-risk characterist...
Red Cell Alloimmunisation Is Associated with Development of Autoantibodies and Increased Red Cell Transfusion Requirements in Myelodysplastic Syndromes (MDS)
Authors: Deepak Singhal, Monika M Kutyna, Rakchha Chhetri, Amilia Wee, Sophia Hague, Lakshmi Nath, Shriram V Nath, Romi Sinha, Nicholas Wickham, Ian D Lewis, David M Ross, Peter G Bardy, Luen Bik To, John Reynolds, Erica Wood, David John Roxby, Devendra K Hiwase
Journal: Blood (2017)
Efficacy and Safety of Subcutaneous or Intravenous Administration of Rituximab in Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Final Results of the Randomized, Open-Label, Crossover, PrefMab Study
Authors: Mathias J Rummel, Tae Min Kim, Franco Aversa, Wolfram Brugger, Enrico Capochiani, Caterina Plenteda, Francesca Re, Peter Task, Christine McIntyre, Oliver Meier, Stuart Osborne, Rodney Smith, Andrew Grigg
Journal: Blood (2017)
Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer
Authors: Paweł Bieniasz-Krzywiec, Rosa Martín-Pérez, Manuel Ehling, Melissa García-Caballero, Sotiria Pinioti, Samantha Pretto, Roel Kroes, Chiara Aldeni, Mario Di Matteo, Hans Prenen, María Virginia Tribulatti, Oscar Campetella, Ann Smeets, Agnes Noel, Giuseppe Floris, Jo A. Van Ginderachter, Massimiliano Mazzone
Journal: Cell Metabolism (2019)
The role of HER3 on HER2-driven gallbladder carcinogenesis and possible HER2/HER3 targeting therapy by pertuzumab for gallbladder canrcinoma
Authors: T. Kawamoto, K. Ishige, H. Sugiyama, K. Onuki, S. Krishnamurthy, M. Thomas, M. Yamamoto, J. Shoda
Journal: Journal of Clinical Oncology (2009)

e22083 Background: ErbB2 has been known to be important for gallbladder carcinogenesis. Supporting this, the gene amplification of HER2 was found in ca. 20% of human gallbladder carcinoma (GBC) (Kawamoto, et al. Gastrointest Cancer Res 2007). Following these results, a Phase II study of trastuzumab for treatment of GBC (NSC 688097) is being conducted. Although the mechanism of HER2 activation is not well understood, the role of HER3 in HER2-driven tumorigenesis has been discussed and we have concluded that HER2/HER3 heterodimerization might be important for GBC cell proliferation (ASCOGI 2009, ab#155). In this study, we determined HER family expressions in human GBC and examined the effect of pertuzumab against human GBC cell lines. Methods: Tissues from 47 GBCs and 6 non-cancerous gallbladders were examined. All cases were screened for HER1, HER2, HER3 expressions by immunohistochemistry (IHC) and those HER family gene amplification by fluorescence in situ hybridization (FISH) were performed. 6 human GBC cell lines were also analyzed by Western blotting and FISH as well and their growth assays were investigated with heregulin stimulation to confirm the existence of HER2/HER3 heterodimerization. Then, GBC cells were cultured with heregulin and various doses of pertuzumab for 72 hours and CCK-8 assay was performed. Results: HER3, HER2 and HER1 overexpression by IHC was found in 34%, 32% and 19% of GBCs, respectively. Phosphorylated (p-) HER2 and p-HER1 were found in 23% and 11% of GBCs, respectively. FISH analysis was considered successful in the same serial sections. HER3, HER2 and HER1 FISH (+) was found in 26%, 19% and 4% of GBCs, respectively. Three of 6 GBC cell lines were recognized their growth curves with heregulin were increasing. These 3 cell lines showed good responses to the treatment with pertuzumab. Conclusions: More than 20% of GBC over-expressed either HER2 or HER3. These HER2 and HER3 may form heterodimer, which in turn results in the activation of HER2. The cell lines proliferating with the administration of heregulin showed good responses to the pertuzumab treatment. Therefore, HER2/HER3 heterodimerization may be an ideal biomarker for the treatment by pertuzumab and this agent may be a new therapeutic regimen for GBC. No significant financial relationships to disclose.
Baseline albumin (b-alb) as a potential predictive biomarker for the efficacy of bevacizumab (B) therapy (tx) in patients (pts) with advanced pancreas cancer (APCA): A comparative analysis.
Authors: Ludmila Katherine Martin, Susan Michelle Geyer, Anissa Bingman, Mark M. Zalupski, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2012)

4039 Background: Phase III studies of B in unselected pts with APCA have demonstrated no improvement in outcome. Recent data suggest certain subsets of APCA patients may benefit from B. Lower b- alb results in a 15-20% increased rate of B clearance that may decrease exposure to B. The resulting clinical implications are not well understood. We evaluated the potential predictive and prognostic role of b-alb in pts with APCA receiving gemcitabine (G)-based tx with or without B. Methods: Relevant data were collected from 3 prospective phase II studies of G-based tx. Pts were grouped according to exposure to B (Gr 1) or no B (Gr 2) and by b-alb &lt; 3.4 g/dL (&lt; LLN) or &gt; 3.4 g/dL (&gt;LLN). Univariate and multivariate analyses of clinical outcome (OS, TTP) were conducted for each group and all pts. Results: 100 pts (46M, 54F) with median age 63 (range 28-82) were included. 94% had stage IV. Median b-alb was similar in both groups. Clinical outcomes by alb are outlined in the table. In Gr 1 but not Gr 2, b-alb &gt; 3.4 g/dL was significantly associated with improved OS and TTP. For pts with b-alb &gt;3.4 g/dL, maintenance of alb &gt;3.4 g/dL throughout tx was significantly associated with improved survival in Gr 1 but not Gr 2. Multivariate analysis revealed significant association between alb &gt; 3.4 and OS regardless of B status (p=0.004) although this was strongly influenced by the survival differential in Gr 1. Conclusions: APCA pts with b-alb &gt; 3.4 g/dL appear to derive significant benefit from B and this benefit is most pronounced in pts who maintain alb &gt; 3.4 g/dL throughout B tx. This finding was not observed in pts treated without B. b-alb &gt; 3.4 g/dL including maintenance of alb &gt; 3.4 g/dL during B tx may predict for improved efficacy of B in APCA. These findings require further investigation in larger prospective trials. [Table: see text]
CD33 splice site genotype was not associated with outcomes of patients receiving the anti-CD33 drug conjugate SGN-CD33A
Authors: Michele Stanchina, Alessandro Pastore, Sean Devlin, Christopher Famulare, Eytan Stein, Justin Taylor
Journal: Journal of Hematology & Oncology (2019)

We tested whether a single nucleotide polymorphism (SNP) that affects splicing of CD33 predicted response to treatment in adults with acute myeloid leukemia (AML) who received the novel CD33 antibody-drug conjugate SGN-CD33A. This genotype, for the CD33 splice site SNP rs12459419, was not associated with clinical response (30% CR/CRi in both groups), event-free survival, or overall survival.
Radiographic lung volumes predict progression to COPD in smokers with preserved spirometry in SPIROMICS
Authors: Mehrdad Arjomandi, Siyang Zeng, Igor Barjaktarevic, R. Graham Barr, Eugene R. Bleecker, Russell P. Bowler, Russell G. Buhr, Gerard J. Criner, Alejandro P. Comellas, Christopher B. Cooper, David J. Couper, Jeffrey L. Curtis, Mark T. Dransfield, MeiLan K. Han, Nadia N. Hansel, Eric A. Hoffman, Robert J. Kaner, Richard E. Kanner, Jerry A. Krishnan, Robert Paine, Stephen P. Peters, Stephen I. Rennard, Prescott G. Woodruff
Journal: European Respiratory Journal (2019)

The characteristics that predict progression to overt chronic obstructive pulmonary disease (COPD) in smokers without spirometric airflow obstruction are not clearly defined. We conducted a post hoc analysis of 849 current and former smokers (≥20 pack–years) with preserved spirometry from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort who had baseline computed tomography (CT) scans of lungs and serial spirometry. We examined whether CT-derived lung volumes representing air trapping could predict adverse respiratory outcomes and more rapid decline in spirometry to overt COPD using mixed-effect linear modelling. Among these subjects with normal forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) ratio, CT-measured residual volume (RV CT ) to total lung capacity (TLC CT ) ratio varied widely, from 21% to 59%. Over 2.5±0.7 years of follow-up, subjects with higher RV CT /TLC CT had a greater differential rate of decline in FEV 1 /FVC; those in the upper RV CT /TLC CT tertile had a 0.66% (95% CI 0.06%–1.27%) faster rate of decline per year compared with those in the lower tertile (p=0.015) regardless of demographics, baseline spirometry, respiratory symptoms score, smoking status (former versus current) or smoking burden (pack–years). Accordingly, subjects with higher RV CT /TLC CT were more likely to develop spirometric COPD (OR 5.7 (95% CI 2.4–13.2) in upper versus lower RV CT /TLC CT tertile; p&lt;0.001). Other CT indices of air trapping showed similar patterns of association with lung function decline; however, when all CT indices of air trapping, emphysema, and airway disease were included in the same model, only RV CT /TLC CT retained its significance. Increased air trapping based on radiographic lung volumes predicts accelerated spirometry decline and progression to COPD in smokers without obstruction.