tbuckley/cabot-search huggingface dataset:
The Coronary Arteriogram
Authors: Herbert L. Abrams, Douglass F. Adams
Journal: New England Journal of Medicine (1969)

IndicationsAngina Pectoris in Young AdultsIn this group of patients it is essential to know the degree of coronary-artery involvement from the points of view of both prognosis and potential therapeutic intervention. Proudfit75 failed to find a correlation between coronary arteriography and the duration, distribution or factors precipitating chest pain. Baltaxe et al.76 were unable to document the expected correlation between the levels of hypercholesterolemia and the severity of coronary disease defined by the coronary arteriogram. Precise anatomic and hemodynamic evaluation in these patients is thus of great importance.Angina Pectoris in the Presence of Normal Resting and Exercise . . .
Letter to the Editor: Noninvasive Markers of Advanced Liver Fibrosis in HBV/HIV Coinfected Patients
Authors: Rui Huang, Jian Wang, Xiaomin Yan, Zhaoping Zhang, Chao Wu
Journal: Hepatology (2019)

Supported by the National Science and Technology Major Project of China (2018ZX10302205), National Natural Science Foundation of China (81672025 and 81702011), Natural Science Foundation of Jiangsu Province for Young Scholar (BK20160121), Jiangsu Science and Technology Development Plan (BE2017605), Jiangsu Provincial Medical Innovation Team (CXTDA2017005), and Nanjing Medical Science and Technique Development Foundation (QRX17121). Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest the article by Sterling et al.1 They concluded that vibration‐controlled transient elastography (VCTE) would be a better biomarker of advanced fibrosis than aspartate aminotransferase‐to‐platelet ratio index (APRI) or Fibrosis‐4 index (FIB‐4) in hepatitis B virus/human immunodeficiency virus coinfected patients.1 We thought that several points require clarification. First, the median length of biopsy liver samples was 17 mm (interquartile range [IQR]: 14‐23.5 mm), indicating that most sample lengths were less than 20 mm in this study.1 Additionally, the portal tracts of biopsy samples were not provided.1 According to the consensus guidelines, biopsy liver samples of at least 20 mm or at least 11 portal tracts should be considered ideal to stage fibrosis accurately with a semiquantitative score.2 Thus, the risk for false evaluation of fibrosis stages might exist due to the insufficient sample length. The performance of noninvasive markers would also be questioned, because the diagnostic value is compared with fibrosis staging, the performance of which is limited by sampling variability.2 Furthermore, liver stiffness was used to predict advanced fibrosis by Sterling et al.1 We noted that the median body mass index (BMI) of patients was 26.3 kg/m2 (IQR: 22.4, 30.6 kg/m2), indicating that most patients were overweight or even obese.1 However, liver stiffness by VCTE is not as reliable in patients with high BMI.2 Both overweight and obesity may significantly affect the accuracy of VCTE, because adipose tissue may attenuate the elastic wave.2 Thus, it would be more convincing if the whole distribution of BMI had been provided. In addition, extrahepatic cholestasis and congestive heart failure may also lead to overestimation of liver stiffness.2 However, these comorbidities were not evaluated, which might have affected the results. Moreover, when evaluating the noninvasive biomarkers, factors that may affect the components of noninvasive biomarkers should be taken into consideration. Platelet as an important component of FIB‐4 and APRI is subject to many factors including infections, chronic inflammatory diseases, hematological disorders, and drug use.2 The existence of these comorbidities, which was not assessed, might have also affected the diagnostic accuracy of FIB‐4 and APRI. Finally, only a small number (n = 61) of patients had all three noninvasive makers, which emphasizes the need for further validation in larger cohorts.
Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer—Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial
Authors: Pirkko-Liisa Kellokumpu-Lehtinen, Marie Hjälm-Eriksson, Camilla Thellenberg-Karlsson, Lennart Åström, Lars Franzen, Ann-Sofie Fransson, Markku J. Leskinen, Mihalj Zeke, Teppo Huttunen, Claes Ginman
Journal: European Urology (2019)
Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer
Authors: Leora Horn, Jennifer G. Whisenant, Heather Wakelee, Karen L. Reckamp, Huan Qiao, Ticiana A. Leal, Liping Du, Jennifer Hernandez, Vincent Huang, George R. Blumenschein, Saiama N. Waqar, Sandip P. Patel, Jorge Nieva, Geoffrey R. Oxnard, Rachel E. Sanborn, Tristan Shaffer, Kavita Garg, Allison Holzhausen, Kimberly Harrow, Chris Liang, Lee P. Lim, Mark Li, Christine M. Lovly
Journal: Journal of Thoracic Oncology (2019)

Despite initial effectiveness of ALK receptor tyrosine kinase inhibitors (TKIs) in patients with ALK+ NSCLC, therapeutic resistance will ultimately develop. Serial tracking of genetic alterations detected in circulating tumor DNA (ctDNA) can be an informative strategy to identify response and resistance. This study evaluated the utility of analyzing ctDNA as a function of response to ensartinib, a potent second-generation ALK TKI.Pre-treatment plasma was collected from 76 patients with ALK+ NSCLC who were ALK TKI-naive or had received prior ALK TKI, and analyzed for specific genetic alterations. Longitudinal plasma samples were analyzed from a subset (n = 11) of patients. Analysis of pre-treatment tumor biopsy specimens from 22 patients was compared with plasma.Disease-associated genetic alterations were detected in 74% (56 of 76) of patients, the most common being EML4-ALK. Concordance of ALK fusion between plasma and tissue was 91% (20 of 22 blood and tissue samples). Twenty-four ALK kinase domain mutations were detected in 15 patients, all had previously received an ALK TKI; G1269A was the most prevalent (4 of 24). Patients with a detectable EML4-ALK variant 1 (V1) fusion had improved response (9 of 17 patients; 53%) to ensartinib compared to patients with EML4-ALK V3 fusion (one of seven patients; 14%). Serial changes in ALK alterations were observed during therapy.Clinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs.
Prognostic value of post-induction PET/CT in untreated multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT).
Authors: Lale Kostakoglu, David Dingli, Meral Beksac, Elena Zamagni, Tomer Martin Mark, Ajai Chari, Brian M Elliott, Val J. Lowe, Elgin Ozkan, Cristina Nanni, Ozlem Kucuk, Stefano Fanti, Morton Coleman, Sundar Jagannath
Journal: Journal of Clinical Oncology (2012)

e21006 Background: Induction with novel biological agents has significantly improved progression free survival (PFS) of MM pts. However, role and timing of ASCT is unclear and there remains a need for a practical means to predict post-ASCT outcome. Our goal was to determine the prognostic value of FDG PET/CT (PET) after induction therapy (IT) in comparison with other prognostic factors and International Myeloma Working Group (IMWG) response criteria. Methods: Prospective, multicenter study of 113 newly diagnosed MM pts undergoing IT+ASCT. IT was not controlled and consisted of 2 or 3 novel agent combinations. The tested variables to predict PFS are shown in table. Two PET scoring systems were used: Score1, positive&gt;marrow uptake; Score2, positive&gt;liver uptake. ROC analysis determined the SUV cut-off. Results: With a median follow-up of 29.5 mo 56 (49.6%) pts relapsed (median PFS: 24.3 mo). Results are displayed in table. Post-IT, when a "+" PET (Score2) was associated with less than a VGPR response, relapses occurred in 83% of pts vs. in only 30% when PET was "-" and pts were in CR or VGPR. Multivariate analysis revealed only ISS to be an independent predictor of PFS (p=0.014). Conclusions: Post-IT a "-" PET associated with CR+VGPR suggests a durable response. Qualitative PET evaluation using a more liberal threshold (liver) to define positivity can be used to accurately assess response in MM. These data failed to prove the post-IT IMWG and PET response to be independent prognosticators while ISS was a superior predictor. This may be attributed to inadequate sample size, nonuniform pre- and post-ASCT treatments, varying follow-up times. Further analyses with stratifying various prognostic indicators and therapy schemes in a larger population are underway to determine a definitive role for PET as a predictor of post-ASCT outcome. [Table: see text]
The effect of gastrectomy in regorafenib treated GIST patients on outcome and drug exposure.
Authors: Nielka P. Van Erp, Floor Lubberman, Winette T.A. Van Der Graaf, Lei Xu, Adriaan Cleton, Hans Gelderblom
Journal: Journal of Clinical Oncology (2019)

e22511 Background: Gastrointestinal stromal tumour (GIST) is one of the most common soft tissue sarcoma subtypes. Regorafenib is the approved third line treatment after imatinib and sunitinib. Often GIST patients have an altered gastro-intestinal tract due to resection of the primary tumour. Gastric surgery may influence the exposure of orally administered TKIs. We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome. Methods: Efficacy and pharmacokinetic data from 133 GIST patients included in a phase III trial were analysed. Patients were subdivided into two groups according to the extent of the gastrectomy (no/non-significant gastrectomy and major gastrectomy). Progression free survival (PFS) on regorafenib was measured and regorafenib and its pharmacological active metabolites plasma exposure (C av ) were measured. Results: A total of 133 patient were included of which 27 underwent major gastrectomy. In patients with no/non significant gastrectomy the median PFS was 145 (IQR 43-281) days. The PFS in patients with a major gastrectomy was 172 (IQR 57-280) days. Regorafenib pharmacokinetic samples were collected in 80 patients of which 19 patients with a major gastrectomy and 61 patients with no/ non-significant gastric surgery. The average free aggregate concentration of regorafenib including the metabolites M-2 and M-5 was 6.9 µmol/L (CV% 44.5) and 6.7 µmol/L (CV% 46.5) in patient with major gastrectomy and no or non significant gastrectomy respectively. Conclusions: Our study shows that major gastrectomy did not influence plasma exposure of regorafenib and metabolites. In addition, no difference in progression free survival between the subgroups was seen.
Salt-inducible kinases dictate parathyroid hormone 1 receptor action in bone development and remodeling
Authors: Shigeki Nishimori, Maureen J. O’Meara, Christian D. Castro, Hiroshi Noda, Murat Cetinbas, Janaina da Silva Martins, Ugur Ayturk, Daniel J. Brooks, Michael Bruce, Mizuki Nagata, Wanida Ono, Christopher J. Janton, Mary L. Bouxsein, Marc Foretz, Rebecca Berdeaux, Ruslan I. Sadreyev, Thomas J. Gardella, Harald Jüppner, Henry M. Kronenberg, Marc N. Wein
Journal: Journal of Clinical Investigation (2019)

The parathyroid hormone 1 receptor (PTH1R) mediates the biologic actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP). Here, we showed that salt-inducible kinases (SIKs) are key kinases that control the skeletal actions downstream of PTH1R and that this GPCR, when activated, inhibited cellular SIK activity. Sik gene deletion led to phenotypic changes that were remarkably similar to models of increased PTH1R signaling. In growth plate chondrocytes, PTHrP inhibited SIK3, and ablation of this kinase in proliferating chondrocytes rescued perinatal lethality of PTHrP-null mice. Combined deletion of Sik2 and Sik3 in osteoblasts and osteocytes led to a dramatic increase in bone mass that closely resembled the skeletal and molecular phenotypes observed when these bone cells express a constitutively active PTH1R that causes Jansen's metaphyseal chondrodysplasia. Finally, genetic evidence demonstrated that class IIa histone deacetylases were key PTH1R-regulated SIK substrates in both chondrocytes and osteocytes. Taken together, our findings establish that SIK inhibition is central to PTH1R action in bone development and remodeling. Furthermore, this work highlights the key role of cAMP-regulated SIKs downstream of GPCR action.
Leukemia evolving from paroxysmal nocturnal hemoglobinuria
Authors: Hassan Awada, Shafia Rahman, Jibran Durrani, Mohammad F. Asad, Cassandra M. Kerr, Vera Adema, Ashwin Kishtagari, Amy Graham, Christina A. Snider, Sunisa Kongkiatkamon, Yasunobu Nagata, Bhumika J. Patel, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Valeria Visconte
Journal: Leukemia (2019)
A simple modification in technique preserves oblique muscle fibers during peroral endoscopic myotomy
Authors: Zaheer Nabi, Mohan Ramchandani, Rama Kotla, Radhika Chavan, Santosh Darisetty, D. Nageshwar Reddy
Journal: Endoscopy (2019)

A 15-year old boy was diagnosed with type II achalasia cardia at our hospital and peroral endoscopic myotomy (POEM) was performed by the posterior route (5 o'clock). The standard steps of the POEM procedure included: mucosal incision, submucosal tunneling, myotomy, and closure of the incision with endoclips [1]. We incorporated an important modification in our myotomy technique in order to preserve the oblique muscle fibers close to the gastroesophageal junction.
Extreme Risk Protection Orders Intended to Prevent Mass Shootings
Authors: Garen J. Wintemute, Veronica A. Pear, Julia P. Schleimer, Rocco Pallin, Sydney Sohl, Nicole Kravitz-Wirtz, Elizabeth A. Tomsich
Journal: Annals of Internal Medicine (2019)

Urgent, individualized interventions to reduce firearm access, such as extreme risk protection orders (ERPOs, colloquially known as "red flag" orders), provide a rapid, focused response when risk for imminent firearm violence is high. Studies to date suggest such interventions are most commonly used to prevent suicide and are effective. Authorizing legislation has often been enacted after public mass shootings but, to our knowledge, there have been only 2 reported cases of ERPO use in efforts to prevent mass shootings. California enacted the nation's first ERPO statute, which took effect in January 2016. The authors are evaluating that statute's implementation and effectiveness and are seeking to obtain court records for all 414 cases occurring in 2016 to 2018. Based on 159 records received thus far, this article presents an aggregate summary and individual histories for a preliminary series of 21 cases in which ERPOs were used in efforts to prevent mass shootings. Most subjects were male and non-Hispanic white; the mean age was 35 years. Most subjects made explicit threats and owned firearms. Four cases arose primarily in relation to medical or mental health conditions, and such conditions were noted in 4 others. Fifty-two firearms were recovered. As of early August 2019, none of the threatened shootings had occurred, and no other homicides or suicides by persons subject to the orders were identified. It is impossible to know whether violence would have occurred had ERPOs not been issued, and the authors make no claim of a causal relationship. Nonetheless, the cases suggest that this urgent, individualized intervention can play a role in efforts to prevent mass shootings, in health care settings and elsewhere. Further evaluation would be helpful.
Association of Smoking Cessation With Subsequent Risk of Cardiovascular Disease
Authors: Meredith S. Duncan, Matthew S. Freiberg, Robert A. Greevy, Suman Kundu, Ramachandran S. Vasan, Hilary A. Tindle
Journal: JAMA (2019)

<h3>Importance</h3> The time course of cardiovascular disease (CVD) risk after smoking cessation is unclear. Risk calculators consider former smokers to be at risk for only 5 years. <h3>Objective</h3> To evaluate the association between years since quitting smoking and incident CVD. <h3>Design, Setting, and Participants</h3> Retrospective analysis of prospectively collected data from Framingham Heart Study participants without baseline CVD (original cohort: attending their fourth examination in 1954-1958; offspring cohort: attending their first examination in 1971-1975) who were followed up through December 2015. <h3>Exposures</h3> Time-updated self-reported smoking status, years since quitting, and cumulative pack-years. <h3>Main Outcomes and Measures</h3> Incident CVD (myocardial infarction, stroke, heart failure, or cardiovascular death). Primary analyses included both cohorts (pooled) and were restricted to heavy ever smokers (≥20 pack-years). <h3>Results</h3> The study population included 8770 individuals (original cohort: n = 3805; offspring cohort: n = 4965) with a mean age of 42.2 (SD, 11.8) years and 45% male. There were 5308 ever smokers with a median 17.2 (interquartile range, 7-30) baseline pack-years, including 2371 heavy ever smokers (406 [17%] former and 1965 [83%] current). Over 26.4 median follow-up years, 2435 first CVD events occurred (original cohort: n = 1612 [n = 665 among heavy smokers]; offspring cohort: n = 823 [n = 430 among heavy smokers]). In the pooled cohort, compared with current smoking, quitting within 5 years was associated with significantly lower rates of incident CVD (incidence rates per 1000 person-years: current smoking, 11.56 [95% CI, 10.30-12.98]; quitting within 5 years, 6.94 [95% CI, 5.61-8.59]; difference, −4.51 [95% CI, −5.90 to −2.77]) and lower risk of incident CVD (hazard ratio, 0.61; 95% CI, 0.49-0.76). Compared with never smoking, quitting smoking ceased to be significantly associated with greater CVD risk between 10 and 15 years after cessation in the pooled cohort (incidence rates per 1000 person-years: never smoking, 5.09 [95% CI, 4.52-5.74]; quitting within 10 to &lt;15 years, 6.31 [95% CI, 4.93-8.09]; difference, 1.27 [95% CI, −0.10 to 3.05]; hazard ratio, 1.25 [95% CI, 0.98-1.60]). <h3>Conclusions and Relevance</h3> Among heavy smokers, smoking cessation was associated with significantly lower risk of CVD within 5 years relative to current smokers. However, relative to never smokers, former smokers' CVD risk remained significantly elevated beyond 5 years after smoking cessation.
LMO2 Confers Synthetic Lethality to PARP Inhibition in DLBCL
Authors: Salma Parvin, Ariel Ramirez-Labrada, Shlomzion Aumann, XiaoQing Lu, Natalia Weich, Gabriel Santiago, Elena M. Cortizas, Eden Sharabi, Yu Zhang, Isidro Sanchez-Garcia, Andrew J. Gentles, Evan Roberts, Daniel Bilbao-Cortes, Francisco Vega, Jennifer R. Chapman, Ramiro E. Verdun, Izidore S. Lossos
Journal: Cancer Cell (2019)
Infections Are Associated with Higher Risk of Venous Thromboembolism in Hospitalized Children with Nephrotic Syndrome
Authors: Jennifer Goldman, Shannon L Carpenter, Ashley K Sherman, David Selewski, Mahmoud Kallash, Cheryl Tran, Meredith Seamon, Chryso Katsoufis, Isa Ashoor, Katarina Supe-Markovina, Joel D Hernandez, Cynthia Silva, Nilka De Jesus Gonzalez, Tetyana Vasylyeva, Cassandra Formeck, Christopher Woll, Rasheed Gbadegesin, Pavel Geier, Prasad Devarajan, William E Smoyer, Bryce A. Kerlin, Michelle Rheault
Journal: Blood (2016)
ZBTB7A Mediates the Transcriptional Repression Activity of the Androgen Receptor in Prostate Cancer
Authors: Dong Han, Sujun Chen, Wanting Han, Shuai Gao, Jude N. Owiredu, Muqing Li, Steven P. Balk, Housheng Hansen He, Changmeng Cai
Journal: Cancer Research (2019)

Abstract Loss of expression of context-specific tumor suppressors is a critical event that facilitates the development of prostate cancer. Zinc finger and BTB domain containing transcriptional repressors, such as ZBTB7A and ZBTB16, have been recently identified as tumor suppressors that play important roles in preventing prostate cancer progression. In this study, we used combined ChIP-seq and RNA-seq analyses of prostate cancer cells to identify direct ZBTB7A-repressed genes, which are enriched for transcriptional targets of E2F, and identified that the androgen receptor (AR) played a critical role in the transcriptional suppression of these E2F targets. AR recruitment of the retinoblastoma protein (Rb) was required to strengthen the E2F–Rb transcriptional repression complex. In addition, ZBTB7A was rapidly recruited to the E2F–Rb binding sites by AR and negatively regulated the transcriptional activity of E2F1 on DNA replication genes. Finally, ZBTB7A suppressed the growth of castration-resistant prostate cancer (CRPC) in vitro and in vivo, and overexpression of ZBTB7A acted in synergy with high-dose testosterone treatment to effectively prevent the recurrence of CRPC. Overall, this study provides novel molecular insights of the role of ZBTB7A in CRPC cells and demonstrates globally its critical role in mediating the transcriptional repression activity of AR. Significance: ZBTB7A is recruited to the E2F–Rb binding sites by AR and negatively regulates the transcriptional activity of E2F1 on DNA replication genes.
Case 26-2019: A 27-Year-Old Woman with Opioid Use Disorder and Suicidal Ideation
Authors: Mladen Nisavic, Efren J. Flores, Marilyn Heng, Nicholas J. Kontos, Nadia Quijije
Journal: New England Journal of Medicine (2019)

A 27-year-old homeless woman was evaluated at this hospital because of a suicide attempt. Three weeks before admission, she began to use intranasal heroin daily. While she was in the hospital, pain developed after dislocation of both the right and left elbows. Management decisions were made.
Nitrated food proteins induce a regulatory immune response associated with allergy prevention after oral exposure in a Balb/c mouse food allergy model
Authors: Nazanin Samadi, Martina Klems, Denise Heiden, Renate Bauer, Claudia Kitzmüller, Eleonore Weidmann, Davide Ret, Anna S. Ondracek, Albert Duschl, Jutta Horejs‐Hoeck, Eva Untersmayr
Journal: Allergy (2019)

Food allergy is associated with a high personal health and economic burden. For immunomodulation toward tolerance, food compounds could be chemically modified, for example, by posttranslational protein nitration, which also occurs via diet-derived nitrating agents in the gastrointestinal tract.We sought to analyze the effect of pretreatment with nitrated food proteins on the immune response in a mouse food allergy model and on human monocyte-derived dendritic cells (moDCs) and PBMCs.The model allergen ovalbumin (OVA) was nitrated in different nitration degrees, and the secondary structures of proteins were determined by circular dichroism (CD). Allergy-preventive treatment with OVA, nitrated OVA (nOVA), and maximally nitrated OVA (nOVAmax) were performed before mice were immunized with or without gastric acid-suppression medication. Antibody levels, regulatory T-cell (Treg) numbers, and cytokine levels were evaluated. Human moDCs or PBMCs were incubated with proteins and evaluated for expression of surface markers, cytokine production, and proliferation of Th2 as well as Tregs.In contrast to OVA and nOVA, the conformation of nOVAmax was substantially changed. nOVAmax pretreated mice had decreased IgE as well as IgG1 and IgG2a levels and Treg numbers were significantly elevated, while cytokine levels remained at baseline level. nOVAmax induced a regulatory DC phenotype evidenced by a decrease of the activation marker CD86 and an increase in IL-10 production and was associated with a higher proliferation of memory Tregs.Oral pretreatment with highly nitrated proteins induces a tolerogenic immune response in the food allergy model and in human immune cells.