tbuckley/cabot-search huggingface dataset:
Impact of direct-acting antivirals and 12-week sustained viral response on clinical outcomes in patients with hepatitis C and hepatocellular carcinoma.
Authors: William M Kamp, Cortlandt Sellers, Stacey Stein, Joseph K Lim, Hyun S. Kevin Kim
Journal: Journal of Clinical Oncology (2019)

397 Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and hepatitis C viral infections (HCV). Methods: Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Results: Nine hundred ninety-six patients met inclusion criteria (mean age 62.8±10.2 yrs, 79% male). Four hundred seventy-eight (50%) patients received interventional oncology (catheter-based therapies, ablation and combination locoregional therapies), 141 (15%) received supportive care (palliative or no treatment), 125 (13%) received a transplant, 112 (14%) had tumor resection and 94 (12%) received chemotherapy or radiation as their primary treatment. Median overall survival (OS) of the entire cohort was 24.2 months (95% CI: 20.9-27.9). Transplant patients were excluded from further analysis. Four hundred seventy patients had HCV (56%). One hundred twenty-three patients received one or more DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCC occurrence and recurrence were reported in 29 (26%) and 38 (45%) patients, respectively, after DAA therapy. HCV-positive and HCV-negative patients had similar survival (OS 20.7 mo vs 17.4 mo, p=0.22). Patients receiving DAA therapy had a higher OS of 71.8 mo (CI: 39.5-not reached) vs 11.6 mo (CI: 9.8-14.5) for patients without DAA therapy (p&lt;0.0001). DAA patients who achieved SVR12 had a higher OS of 75.6 mo (CI: 49.2-not reached) vs the non-SVR12 group (26.7 mo, CI: 13.7-31.1, p&lt;0.0001). Multivariable analysis (MVA) showed that AJCC, Child-Pugh Score, MELD, tumor size, tumor location and treatment allocation had independent influence on survival for the cohort (p&lt;0.05). In HCV patients, AJCC, MELD, tumor location, treatment allocation and DAA were significant (p&lt;0.05). In patients receiving DAA, only MELD score and SVR12 remained significant factors (p&lt;0.05). Conclusions: DAA therapy and achieving SVR12 is associated with increased overall survival in HCC patients with HCV. This analysis supports the importance of treating HCV to SVR12 as part of HCC management.
Digital-Droplet PCR, an Accurate Method for IG/TR PCR-MRD Stratification in Childhood Acute Lymphoblastic Leukemia
Authors: Irene Della Starza, Vittorio Nunes, Federica Lovisa, Daniela Silvestri, Marzia Cavalli, Andrea Garofalo, Mimma Campeggio, Lucia Anna De Novi, Carlotta Oggioni, Andrea Biondi, Anna Guarini, Maria Grazia Valsecchi, Valentino Conter, Giuseppe Basso, Robin Foà, Giovanni Cazzaniga
Journal: Blood (2018)
Case 4-2019: An 18-Year-Old Man with Abdominal Pain and Hematochezia
Authors: Helen M. Shields, Fabian J. Scheid, Theodore T. Pierce, Karin L. Andersson, Mark F. Conrad, Martin G. Rosenthal, Scott D. Martin
Journal: New England Journal of Medicine (2019)

An 18-year-old man was admitted to the hospital because of fevers, abdominal pain, and hematochezia. After admission, temperatures as high as 40.2°C occurred. Cultures of blood that had been drawn 11 hours before admission revealed Klebsiella pneumoniae and gram-positive cocci. A diagnostic test was performed.
Outcomes for Hemodialysis Patients Given Cardiopulmonary Resuscitation for Cardiac Arrest at Outpatient Dialysis Clinics
Authors: Patrick H. Pun, Matthew E. Dupre, Monique A. Starks, Clark Tyson, Kimberly Vellano, Laura P. Svetkey, Steen Hansen, Brian G. Frizzelle, Bryan McNally, James G. Jollis, Sana M. Al-Khatib, Christopher B. Granger
Journal: Journal of the American Society of Nephrology (2019)

Out-of-hospital cardiac arrest, the leading cause of death among patients on hemodialysis, occurs frequently within outpatient dialysis centers. Practice guidelines recommend resuscitation training for all dialysis clinic staff and on-site defibrillator availability, but the extent of staff involvement in cardiopulmonary resuscitation (CPR) efforts and its association with outcomes is unknown.We used data from the Cardiac Arrest Registry to Enhance Survival and the Centers for Medicare & Medicaid Services dialysis facility database to identify patients who had cardiac arrest within outpatient dialysis clinics between 2010 and 2016 in the southeastern United States. We compared outcomes of patients who received dialysis staff-initiated CPR with those who did not until the arrival of emergency medical services (EMS).Among 398 OHCA events in dialysis clinics, 66% of all patients presented with a nonshockable initial rhythm. Dialysis staff initiated CPR in 81.4% of events and applied defibrillators before EMS arrival in 52.3%. Staff were more likely to initiate CPR among men and witness cardiac arrests, and were more likely to provide CPR within larger dialysis clinics. Staff-initiated CPR was associated with a three-fold increase in the odds of hospital discharge and favorable neurologic status on discharge. There was no overall association between staff-initiated defibrillator use and outcomes, but there was a nonsignificant trend toward improved survival to hospital discharge in the subgroup with shockable initial cardiac arrest rhythms.Dialysis staff-initiated CPR was associated with a large increase in survival but was only performed in 81% of cardiac arrest events. Further investigations should focus on understanding the potential facilitators and barriers to CPR in the dialysis setting.
Physicians’ Perspectives on FDA Approval Standards and Off-label Drug Marketing
Authors: Aaron S. Kesselheim, Steven Woloshin, Zhigang Lu, Frazer A. Tessema, Kathryn M. Ross, Lisa M. Schwartz
Journal: JAMA Internal Medicine (2019)

This nationwide survey of US primary care internists and medical specialists evaluates physicians' attitudes about the US Food and Drug Administration's drug approval standards and off-label drug marketing.
Abstract 17501: Coronary Artery Disease in Women is Predicted by a Combined Assessment of Carotid and Femoral Plaque Burden
Authors: Kayla Colledanchise, Laura-Eve Mantella, Marie-France Hétu, Milena Bullen, Joseph Abunassar, Amer M Johri
Journal: Circulation (2017)

Introduction: Cardiovascular risk remains difficult to assess in women. It is known that femoral plaque development precedes adverse cardiovascular events, such as myocardial infarction. The purpose of this study was to determine the value of a femoral plaque burden assessment, alone or combined with carotid plaque, for identifying significant angiographic coronary artery disease (CAD) in men and women. Methods: Patients referred for coronary angiography underwent same-day carotid and femoral ultrasound. The extent of coronary artery luminal narrowing was established by a 4-segment model to produce an overall angiographic score. Logistic regression models were used to determine the association of carotid and femoral total plaque area (TPA) with significant CAD (≥50% stenosis) when adjusted for age, sex, and risk factors. Optimal cut-off values of plaque burden were determined using areas under receiver operating characteristic curves (AUC). Results: After adjustment, increased femoral, carotid, and combin...
Spontaneous Transdifferentiation from Small Cell Lung Carcinoma to Squamous Cell Carcinoma
Authors: Kousuke Watanabe, Hidenori Kage, Aya Shinozaki-Ushiku, Shinji Kohsaka, Daiya Takai, Jun Nakajima, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Takahide Nagase
Journal: Journal of Thoracic Oncology (2019)
NRASG12V-Mediated Self-Renewal Signaling in Self-Renewing AML Stem Cells.
Authors: Marie Lue Antony, Klara Noble-Orcutt, Karen Sachs, Anna Khoroshilov, Daniel Chang, Alexandria Hillesheim, Hesham Mohei, Merve Pamukcuoglu, Christine Bergene, David A. Largaespada, Zohar Sachs
Journal: Blood (2018)
Safety and Efficacy of Acalabrutinib Plus Bendamustine and Rituximab (BR) in Patients with Treatment-Naive (TN) or Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL)
Authors: Tycel J. Phillips, Stephen D. Smith, Wojciech Jurczak, Tadeusz Robak, Don Stevens, Charles M. Farber, John M. Pagel, Kami J. Maddocks, Ian W. Flinn, Wieslaw W. Jedrzejczak, Andre Goy, Pier Luigi Zinzani, Jan Zaucha, Morton Coleman, Tianling Chen, Sun Ku Lee, Wei Liang, Anna Seto, Michael Wang
Journal: Blood (2018)
Primary Pulmonary Paraganglioma Revealed by FDG PET/CT
Authors: Guohua Shen, Minggang Su, Anren Kuang
Journal: Clinical Nuclear Medicine (2019)

Primary pulmonary paraganglioma is a rare type of extra-adrenal paragangliomas arising from neuroectodermal-derived paraganglionic tissue. We report herein the case of a 49-year-old woman with a round-like well-defined nodule in the right middle lobe detected by chest CT. FDG PET/CT also revealed this homogeneous nodule with increased FDG accumulation. Finally, the patient underwent right middle lobe resection, and the pathological findings demonstrated the diagnosis of pulmonary paraganglioma.
QoL from TASCO1: Health-related quality of life of trifluridine/tipiracil-bevacizumab and capecitabine-bevacizumab as first-line treatments in metastatic colorectal cancer patients not eligible for intensive chemotherapy—Results from the TASCO1 phase II study.
Authors: Vladimir Moiseyenko, Mark P. Saunders, Harpreet Singh Wasan, Guillem Argiles, Christophe Borg, Geert-Jan Creemers, Mikhail Fedyanin, Robert Glynne-Jones, Per Pfeiffer, Cornelis J. A. Punt, Daniil Stroyakovskiy, Albert J. Ten Tije, Agnes W Van de Wouw, Akira Kanehisa, Ronan Fougeray, Javier Sabater, Nadia Amellal, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2019)

676 Background: TASCO1 is a phase II study which evaluated the safety and efficacy of trifluridine/tipiracil + bevacizumab (TT-B) and capecitabine + bevacizumab (C-B) in first-line unresectable mCRC patients non-eligible for intensive therapy. Promising activity was shown on progression-free survival with TT-B (9.2 months) and C-B (7.8 months). Here we present the Quality of Life (QoL) analysis of the two treatment arms. Methods: In TASCO1, patients were randomized 1:1 to receive TT-B (n = 76) on a four-week cycle or C-B (n = 77) on a three-week cycle. QoL was assessed in TASCO1 at baseline and at each 12 weeks thereafter, until discontinuation of study treatment, using the QLQ-C30 and QLQ-CR29 questionnaires. Responses were described separately in each arm using descriptive statistics. Results: For QLQ-C30, 121 patients completed baseline questionnaire. No clinically relevant difference was observed on treatment in mean change of score from baseline for the global health status, functioning scales, and for most of the symptom scales, except for nausea/vomiting and diarrhoea (worsening in the TT-B group and stable in the C-B group for both symptoms), fatigue (stable in the TT-B group and worsening in the C-B), loss appetite (worsening in the two groups) and insomnia (improvement in the two groups). For QLQ-CR29, 117 patients completed baseline questionnaire. No clinically relevant difference on treatment was observed in mean change of score from baseline for most of items except for the following: hair loss, trouble with taste (worsening for both symptoms in the TT-B group while stable for hair loss and improvement for trouble with taste in the C-B group), sore skin, dry mouth (stable in the TT-B group and worsening in the C-B group for both symptoms), and anxiety (stable in the TT-B group and improvement in the C-B group). Conclusions: The Global Health Scale was maintained in Trifluridine/tipiracil+bevacizumab arm as well as in the capecitabine+bevacizumab arm. No clinically relevant difference from baseline was observed over time in both groups except for few sub-scales. Clinical trial information: NCT02743221.
Image Analysis of Esophageal Biopsies and Cytosponge Specimens Stained for Eosinophil Peroxidase Identifies Subjects with Eosinophilic Esophagitis
Authors: Suzanne M. Barshow, Kelly P. Shim, Thomas S. Smyrk, Debra M. Geno, Alfred D. Doyle, Elizabeth A. Jacobsen, Jeffrey A. Alexander, Jennifer L. Horsley-Silva, Rebecca C. Fitzgerald, James J. Lee, Evan S. Dellon, Matthew A. Rank, Hirohito Kita, David A. Katzka, Benjamin L. Wright
Journal: Journal of Allergy and Clinical Immunology (2019)
Evaluation of the re-introducing FOLFOX or XELOX ± bevacizumab in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy (REACT study).
Authors: Shigeyoshi Iwamoto, Masahito Kotaka, Taro Ikumoto, Daisuke Sakai, Toshihiro Kudo, Akihito Tsuji, Yoshihito Ide, Mutsumi Fukunaga, Ken Konishi, Naotoshi Sugimoto, Takayasu Kurata, Akiyoshi Kanazawa, Taroh Satoh, Takeharu Yamanaka, Naohiro Tomita
Journal: Journal of Clinical Oncology (2019)

634 Background: Chemotherapy in relapsed colon cancer patients (pts) treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of re-introducing FOLFOX or XELOX ± bevacizumab therapy for recurrent colorectal cancer pts after adjuvant chemotherapy including oxaliplatin. Methods: Pts with past history of adjuvant chemotherapy including oxaliplatin (FOLFOX, XELOX or SOX) with a cumulative dose of more than 400 mg/m 2 , and recurrence observed by imaging after more than 6 months post adjuvant chemotherapy participated in this trial. Primary endpoints were response rate (RR) and disease control rate (DCR). Key secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS) and safety. Results: A total of 31 pts were enrolled between Oct 2012 and Oct 2016. Of 29 eligible pts, 7 received FOLFOX ± bevacizumab, and 22 received XELOX ± bevacizumab. 28 of the pts received bevacizumab. The RR was 66.7% (95% CI, 46.0-83.5) and the DCR was 88.9% (95% CI, 70.8-97.6). The RR for oxaliplatin free-interval was 100.0% (n = 4, 95% CI, 39.8-100.0) in 6 to 12 months, 60.9% (n = 25, 95% CI, 38.5-80.3%) over 12 month, respectively. Median PFS, TTF and OS were 10.9 months (95% CI, 7.0-19.0), 6.3 months (95% CI, 2.8-8.0) and 29.1 months (95% CI, 20.3-53.3). The most common grade 3 or 4 adverse event was hypertension (19.4%). Grade 3 or worse peripheral sensory neuropathy developed only two pts (6.5%). Allergic reactions occurred in 12.9% of the pts, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Conclusions: Re-introduction of oxaliplatin was feasible and achieved high RR or DCR in after more than 6 months post adjuvant chemotherapy including oxaliplatin. Clinical trial information: UMIN000006523.
Allogeneic Hematopoietic Cell Transplantation for Severe Idiopathic Aplastic Anemia Older Than 40y
Authors: Hawk Kim, Yunsuk Choi, Sung-Soo Yoon, Soo-Mee Bang, Hyeoung-Joon Kim, Sang Kyun Sohn, Yeung-Chul Mun, Young Rok Do, Yong Park, Ji Hyun Lee, Sung Hwa Bae, Ho Sup Lee, Min Kyoung Kim, Won-Sik Lee, Jeong-Yeal Ahn, Kyoo-Hyung Lee
Journal: Blood (2018)
Clinical impact of newly developed sarcopenia after surgical resection for gastric cancer.
Authors: Beom Jin Kim, Eun Sun Lee, Jae Yong Park, Jae Gyu Kim
Journal: Journal of Clinical Oncology (2019)

145 Background: The purpose of this study was to investigate the risk factors and the clinical impact of of newly developed sarcopenia after surgical resection on the prognosis in patients undergoing radical gastrectomy for gastric cancer. Methods: We retrospectively reviewed clinicopathological data from 430 consecutive GC patients who underwent surgical resection at Chung-Ang University Hospital between January 2011 and December 2015. Their skeletal muscle mass and abdominal fat volume were measured by abdominal CT imaging. Results: A total of 425 patients were analyzed in the study. The mean age was 62 years old and male were 301 (70.8%). Of these, 42 patients (9.9%) were diagnosed as pre-operative sarcopenia. Compared with non-sarcopenic group, pre-operative sarcopenia groups showed more female, higher BMI, less alcoholic, and less smoking. However, there was no significant difference in 5-year overall survival and disease free survival between the groups (p=0.836 and p=0.638, respectively). Among 381 non-sarcopenic patients, 48 patients (12.6%) were diagnosed as newly developed sarcopenia in one year after gastric resection. Compared with non-sarcopenic group, the newly developed sarcopenic group showed more male, more undifferentiated tumor, lower hemoglobin level, less alcoholic, less smoking, and presence of diabetes mellitus. Furthermore, newly developed sarcopenic group showed more total fat area, especially more subcutaneous fat area and lower VFA / SFA ratio in the abdominal CT imaging. However, there was no significant difference in the 5-year overall survival and disease free survival among non-sarcopenic, sarcopenic, and newly developed sarcopenic groups (p=0.521 and p=0.534, respectively). The relationship between preoperative body fat volume and postoperative muscle mass showed a significant correlation (rho = 0.296, p &lt;0.001), but only BMI was significantly associated with long term survival. Conclusions: Although newly developed sarcopenia after surgery did not affect the survival rate, patients with nutritional risk of sarcopenia after surgical resection may require early evaluation of nutritional status and nutritional support.
Abstract 12871: Maternal Obesity is Sufficient to Induce Transgenerational Cardiac Mitochondrial Dysfunction in Mice
Authors: Jeremie L Ferey, Attila Kovacs, Abhinav Diwan, Kelle H Moley
Journal: Circulation (2018)

Introduction: Maternal obesity is correlated with increased risk of cardiovascular disease in the offspring in humans. We have observed impaired mitophagy in oocytes of obese mouse dams. Whether th...
Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons
Authors: Chiharu Kawakami, Seiya Yamayoshi, Miki Akimoto, Kazuya Nakamura, Hideka Miura, Seiichiro Fujisaki, David J. Pattinson, Kohei Shimizu, Hiroki Ozawa, Tomoko Momoki, Miwako Saikusa, Atsuhiro Yasuhara, Shuzo Usuku, Ichiro Okubo, Takahiro Toyozawa, Shigeo Sugita, Derek J. Smith, Shinji Watanabe, Yoshihiro Kawaoka
Journal: Eurosurveillance (2019)

Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA). Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA. We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets.Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season. The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades. Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.Multiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
RCP threatened with judicial review over assisted dying poll
Authors: Richard Hurley
Journal: BMJ (2019)

The Royal College of Physicians has been threatened with legal action by the former chair of its ethics committee over a poll it is conducting to gauge the views of members and fellows on assisted dying.1

The college currently opposes assisted dying (that is, doctors being allowed to prescribe lethal drugs for terminally ill people to hasten their own death in specific situations). It has said that it will move to a neutral position unless at least 60% of votes in a poll being sent out in the first week of February are either in favour of or opposed to a change in the law.2 It intends to announce the results in March.

But John Saunders, an RCP fellow …
Immune Progression Within the Memory CD4+ T Cell Compartment is a Marker of Heightened Clinical Sensitivity for Patients with Peanut Allergy
Authors: Bert Ruiter, Neal P. Smith, Brinda Monian, Andy Tu, Elizabeth Fleming, Yamini V. Virkud, Sarita U. Patil, Todd M. Gierahn, Charles A. Whittaker, J. Christopher Love, Wayne G. Shreffler
Journal: Journal of Allergy and Clinical Immunology (2019)
Association of Statin Adherence With Mortality in Patients With Atherosclerotic Cardiovascular Disease
Authors: Fatima Rodriguez, David J. Maron, Joshua W. Knowles, Salim S. Virani, Shoutzu Lin, Paul A. Heidenreich
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Statins decrease mortality in those with atherosclerotic cardiovascular disease (ASCVD), but statin adherence remains suboptimal. <h3>Objective</h3> To determine the association between statin adherence and mortality in patients with ASCVD who have stable statin prescriptions. <h3>Design, Setting, and Participants</h3> This retrospective cohort analysis included patients who were between ages 21 and 85 years and had 1 or more<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>codes for ASCVD on 2 or more dates in the previous 2 years without intensity changes to their statin prescription who were treated within the Veterans Affairs Health System between January 1, 2013, and April 2014. <h3>Exposures</h3> Statin adherence was defined by the medication possession ratio (MPR). Adherence levels were categorized as an MPR of less than 50%, 50% to 69%, 70% to 89%, and 90% or greater. For dichotomous analyses, adherence was defined as an MPR of 80% or greater. <h3>Main Outcomes and Measures</h3> The primary outcome was death of all causes adjusted for demographic and clinical characteristics, as well as adherence to other cardiac medications. <h3>Results</h3> Of 347 104 eligible adults with ASCVD who had stable statin prescriptions, 5472 (1.6%) were women, 284 150 (81.9%) were white, 36 208 (10.4%) were African American, 16 323 (4.7%) were Hispanic, 4093 (1.2%) were Pacific Islander, 1293 (0.4%) were Native American, 1145 (0.3%) were Asian, and 1794 (0.5%) were other races. Patients taking moderate-intensity statin therapy were more adherent than patients taking high-intensity statin therapy (odds ratio [OR], 1.18; 95% CI, 1.16-1.20). Women were less adherent (OR, 0.89; 95% CI, 0.84-0.94), as were minority groups. Younger and older patients were less likely to be adherent compared with adults aged 65 to 74 years. During a mean (SD) of 2.9 (0.8) years of follow-up, there were 85 930 deaths (24.8%). Compared with the most adherent patients (MPR ≥ 90%), patients with an MPR of less than 50% had a hazard ratio (HR; adjusted for clinical characteristics and adherence to other cardiac medications) of 1.30 (95% CI, 1.27-1.34), those with an MPR of 50% to 69% had an HR of 1.21 (95% CI, 1.18-1.24), and those with an MPR of 70% to 89% had an HR of 1.08 (95% CI, 1.06-1.09). <h3>Conclusions and Relevance</h3> Using a national sample of Veterans Affairs patients with ASCVD, we found that a low adherence to statin therapy was associated with a greater risk of dying. Women, minorities, younger adults, and older adults were less likely to adhere to statins. Our findings underscore the importance of finding methods to improve adherence.