tbuckley/cabot-search huggingface dataset:
Characterization of the tumor mutation burden in hepatobiliary tumors.
Authors: Ramya Thota, Bryce Christensen, Gail Fulde, Mark Andrew Lewis, Derrick S. Haslem, Terence Duane Rhodes, Lincoln Nadauld, Tyler Barker
Journal: Journal of Clinical Oncology (2019)

295 Background: Hepatobiliary tumors are aggressive tumors with emerging evidence for increasing sensitivity to immune checkpoint inhibitors (ICI). Tumor mutation burden (TMB) was found to be a quantitative biomarker associated with production of neoantigens within the tumor and predict the sensitivity to immune therapy. Herein, we explore the TMB as a potential biomarker of response to immune therapy in hepatobiliary tumors. Methods: We retrospectively assessed all patients with hepatobiliary malignancies who have undergone next generation sequencing (NGS) between January 2013 and September 2018. We then analyzed the tumor mutation burden of these tumors and also identified frequency of patients with no clinically actionable mutations. Results: Of the 65 total patients with hepatobiliary tumors, 49 patients (75%) had at least one clinically actionable mutation while 16 patients (25%) had no clinically actionable mutations. Among 65 patients, 44 patients had hepatocellular carcinoma, 15 patients had cholangiocarcinoma and 6 patients had gallbladder carcinoma. The TMB data is available for 15 patients. The mean TMB reported was 2.7 (1.16 – 4.25), which suggests low mutation burden in general in all our HB tumors. Among the patients with available TMB, the underlying risk factor was noted as hepatitis C in 3, NASH in 1, others in 6, unknown in 5 patients. Conclusions: Our data suggests the TMB in hepatobiliary tumors is low in general irrespective of their underlying risk factors. Future larger studies are needed to evaluate TMB as a potential biomarker in hepatobiliary tumors to help select patients that will benefit from immune therapy.
GADD45b Plays an Essential Role in the G-CSF Triggered Granulocytic Differentiation of Human Hematopoietic Cells
Authors: Perihan Mir, Masoud Nasri, Benjamin Dannenmann, Maksim Klimiankou, Betuel Findik, Regine Bernhard, Michael A. Rieger, Cornelia Zeidler, Lothar Kanz, Karl Welte, Julia Skokowa
Journal: Blood (2018)
Nivolumab for Squamous-Cell Cancer of Head and Neck
Authors: Sander Bins, Esther van Meerten, Ron H J Mathijssen
Journal: New England Journal of Medicine (2017)

Nivolumab for Squamous-Cell Cancer of Head and NeckTo the Editor: A new class of toxic effects has emerged with cancer immunotherapy.Endocrine immune-related adverse events are especially interesting because they are frequent but rarely require the discontinuation of treatment.Moreover, immunotherapy offers a promising model for the study of some autoimmune endocrinopathies that are rare in the general population and whose pathophysiological mechanisms are not fully known.In this regard, precise definitions of endocrine immune-related adverse events in immunotherapy trials are a pending issue in this field.Ferris et al. (Nov.10 issue) 1 report the results of nivolumab treatment in patients with squamous-cell carcinoma of the head and neck.They report three possible cases of autoimmune hypophysitis as three separate endocrine immunerelated adverse events (hypophysitis, hypopituitarism, and secondary adrenocortical insufficiency).Regarding thyroid-related adverse events, events of "blood TSH [thyrotropin] increased" and hypothyroidism were reported independently.Furthermore, "abnormal thyroid-function test" was considered to be a separate endocrine immune-related adverse event; this ambiguous term could include patients with the sick euthyroid syndrome, which is considered to be a physiological response to illness. 2 These imprecise terms, which have been used recurrently in various studies, 3,4 contribute to the underdiagnosis or overdiagnosis of endocrine immune-related adverse events.These terms hinder the appropriate investigation of endocrine immune-related adverse events, so it would be prudent to avoid them in future trials of cancer immunotherapy.
Pharmacological Treatments for Neonatal Abstinence Syndrome
Authors: Timothy Disher, Courtney Gullickson, Balpreet Singh, Chris Cameron, Leah Boulos, Louis Beaubien, Marsha Campbell-Yeo
Journal: JAMA Pediatrics (2019)

<h3>Importance</h3> Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment. <h3>Objective</h3> To compare pharmacological therapies for neonatal abstinence syndrome. <h3>Data Sources</h3> Systematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018). <h3>Study Selection</h3> Randomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.). <h3>Data Extraction and Synthesis</h3> Data extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)–Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis. <h3>Main Outcomes and Measures</h3> The primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes. <h3>Results</h3> Eighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, −12.75 [95% CI, −17.97 to −7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, −11.43 [95% CI, −16.95 to −5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision. <h3>Conclusions and Relevance</h3> The current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.
Monoclonal Antibody against CXCL1 (HL2401) as a Novel Agent in Suppressing IL6 Expression and Tumoral Growth
Authors: Makito Miyake, Hideki Furuya, Sayuri Onishi, Kanani Hokutan, Satoshi Anai, Owen Chan, Sixiang Shi, Kiyohide Fujimoto, Steve Goodison, Weibo Cai, Charles J. Rosser
Journal: Theranostics (2019)

Rationale:The expression of the chemokine (C-X-C motif) ligand 1 (CXCL1), an inflammatory protein, has been reported to be up-regulated in many human cancers.The mechanisms through which aberrant cellular CXCL1 levels promote specific steps in tumor growth and progression are unknown.Methods: We described the anticancer effects and mechanism of action of HL2401, a monoclonal antibody directed at CXCL1 with in vitro and in vivo data on bladder and prostate cancers.Results: HL2401 inhibited proliferation and invasion of bladder and prostate cells along with disrupting endothelial sprouting in vitro.Furthermore, novel mechanistic investigations revealed that CXCL1 expression stimulated interleukin 6 (IL6) expression and repressed tissue inhibitor of metalloproteinase 4 (TIMP4).Systemic administration of HL2401 in mice bearing bladder and prostate xenograft tumors retarded tumor growth through the inhibition of cellular proliferation and angiogenesis along with an induction of apoptosis.Our findings reveal a previously undocumented relationship between CXCL1, IL6 and TIMP4 in solid tumor biology.Principal conclusions: Taken together, our results argue that CXCL1 plays an important role in sustaining the growth of bladder and prostate tumors via up-regulation of IL6 and down-regulation of TIMP4.Targeting these critical interactions with a CXCL1 monoclonal antibody offers a novel strategy to therapeutically manage bladder and prostate cancers.
Gender Equity in Clinical Dermatology—Reason for Optimism
Authors: Mackenzie R. Wehner, Haley B. Naik, Eleni Linos
Journal: JAMA Dermatology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Predictors of survival in rectal squamous cell carcinoma: An analysis from the National Cancer Database (NCDB).
Authors: Sri Harsha Tella, Anuhya Kommalapati, Gaurav Goyal, Amit Mahipal
Journal: Journal of Clinical Oncology (2019)

672 Background: Rectal squamous cell carcinoma (RSCC) is a rare form of gastrointestinal malignancy. Using the NCDB, we determined the prognostic factors and survival outcomes of RSCC in the United States. Methods: We identified histologically confirmed cases of RSCC from the National Cancer Data Base (2004-2015). Univariate and multivariable methods were used to assess factors associated with survival. Kaplan-Meier method and log-rank test were used to perform overall survival (OS) analysis. Results: Of the 5,527 cases included in our analysis, 67% were female. Median age at diagnosis was 61 years and did not differ by sex. The proportion of patients with stage 1, 2, 3 and 4 diseases were 22%, 16%, 20%, and 11%, respectively (30% unknown stage). Among the ones who received surgical resection of primary tumor, 41%, 30%, 20% and 8% are of stages 1, 2, 3 and 4 respectively. The rate of R0 resection was 54%, 63%, 55% and 38% in stage 1, 2, 3 and 4, respectively. The R0 resection rate was much higher in patients who received neoadjuvant chemo or radiation therapy or both (87%, 78%, 74%, and 57% in stages I, 2, 3 and 4, respectively) as compared to that of their counterparts. On stage wise sub-group OS analysis, stage 1-3 patients had OS benefit from surgery (as compared to no-surgery) (145 vs 90 months, p&lt;0.001) as opposed to 4 disease (16 vs 11 months, p=0.06). Adjuvant radiation therapy improved the median OS in stage 1-3 patients (as compared to no-adjuvant radiation) in patients with positive surgical margins (not reached vs 40 months, p&lt;0.0001). Patients with stage 4 disease treated with radiation therapy had a better median OS than those without (16 vs 6 months, p&lt;0.0001). On therapy wise sub-group analysis, the patients who received surgery only had a median OS of 145 months; surgery + chemoradiation (adjuvant and neoadjuvant) = not reached; whereas patients with chemoradiation only had median OS of 80 months. Conclusions: This is the largest registry-based study on RSCC to date. RSCC had a diverse OS varied significantly according to stage of the disease at presentation and therapy received. Surgical resection of primary tumor was associated with improved OS as compared to that of patients who received chemoradiation.
Abstract 17514: The North American Atrial Septal Defect Pulmonary Hypertension (NAAPH) Study: Efficacy of PAH Therapy in ASD Closure
Authors: Elisa A Bradley, Naser Ammash, Sara C Martinez, Camden Hebson, Kelly Chin, Jasmine Grewal, Jamil Abdoulhosn, Harsimran S Singh, Joseph Billadello, Murali Chakinala, Curt Daniels, Ali N Zaidi
Journal: Circulation (2017)

Introduction: Congenital heart disease patients with systemic-to-pulmonary shunts, such as an atrial septal defect (ASD) associated with pulmonary arterial hypertension (ASD-PAH) are classified as ...
GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute leukaemia in remission: final results of quality of life and long-term outcome analysis of a phase 3 randomised study
Authors: Francesca Bonifazi, Carlos Solano, Christine Wolschke, Mariarosaria Sessa, Francesca Patriarca, Francesco Zallio, Arnon Nagler, Carmine Selleri, Antonio Maria Risitano, Giuseppe Messina, Wolfgang Bethge, Pilar Herrera, Anna Sureda, Angelo Michele Carella, Michele Cimminiello, Stefano Guidi, Jürgen Finke, Roberto Sorasio, Christelle Ferra, Jorge Sierra, Domenico Russo, Edoardo Benedetti, Giuseppe Milone, Fabio Benedetti, Marion Heinzelmann, Domenico Pastore, Manuel Jurado, Elisabetta Terruzzi, Franco Narni, Andreas Völp, Francis Ayuk, Tapani Ruutu, Nicolaus Kröger
Journal: The Lancet Haematology (2019)
Busulfan, Cyclophosphamide and Melphalan As Conditioning Regimen for Pediatric Patients with AML in 1st or 2nd CR: A Retrospective Analysis from the AIEOP HSCT Registry
Authors: Annalisa Ruggeri, Marco Zecca, Franca Fagioli, Adriana Balduzzi, Mattia Algeri, Manuela Tumino, Mimmo Ripaldi, Riccardo Masetti, Francesco Saglio, Attilio Rovelli, Franco Locatelli
Journal: Blood (2018)
Education from other journals #12
Authors: Darren Patrick Moloney, Ronan Kearney, Matthew Cosgrave, Christina Le
Journal: British Journal of Sports Medicine (2019)

### Orthop J Sports Med 2018 ;6:2325967118784897

Rotator cuff disorders are the most common cause of shoulder pain in the general population. Unfortunately, the diagnosis of a rotator cuff tear is not always obvious and can present a diagnostic dilemma, especially in the older patients. When uncertainty exists, expensive imaging such as MRI may be required to aid diagnosis.

When it comes to the clinical examination of a shoulder, there are an abundance of ‘special tests’, although individually these tests are limited in diagnostic accuracy for rotator cuff tears. Would not it be great if a battery of clinical tests could predict the likelihood of a tear? Such a tool would be convenient for the primary care physician whose access to ultrasound or MRI is often limited and costly.

In this analysis of 301 patients, four diagnostic variables: male sex, Jobe’s test (empty can test), lift-off test and external rotation strength ratio were highly predictive of a rotator cuff tear in patients ≥45 years of age with >4 weeks of shoulder pain.

Take home message: This diagnostic aid has the potential to improve clinical identification of rotator …
Abstract 16862: The Relationship Between Left Ventricular Ejection Fraction and Survival From 146,706 Patients in a Large Regional Health System
Authors: Gregory J Wehner, Christopher M Haggerty, Jonathan D Suever, Linyuan Jing, Joseph B Leader, H L Kirchner, Joseph N Manus, Christopher W Good, Brandon K Fornwalt
Journal: Circulation (2017)

Introduction: The assessment of cardiac function is critical for treating patients across many medical specialties, and left ventricular ejection fraction (LVEF) is the most widely used measure of ...
Potency and Selectivity of BTK Inhibitors in Clinical Development for B-Cell Malignancies
Authors: Allard Kaptein, Gerjan de Bruin, Maaike Emmelot-van Hoek, Bas van de Kar, Anouk de Jong, Michael Gulrajani, Dennis Demont, Todd Covey, Diana Mittag, Tjeerd Barf
Journal: Blood (2018)
Re: Timu J. Murtola, Hemo Syvälä, Teemu Tolonen, et al. Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy—A Randomized, Double-blind, Placebo-controlled Clinical Trial. Eur Urol 2018;74:697–701
Authors: Jae Heon Kim, Benjamin I. Chung
Journal: European Urology (2019)
PD-1 antibody combined with COX inhibitor in MSI-h/dMMR or high TMB colorectal cancer: A single arm phase II study.
Authors: Zehua Wu, Yanhong Deng, Jianwei Zhang, Huabin Hu, Yue Cai, Jiayu Ling, Ru Deng
Journal: Journal of Clinical Oncology (2019)

TPS729 Background: Programmed death protein 1 (PD-1) antibody has been to approved in patients with MSI-H/dMMR colorectal cancer and has achieved significant efficacy. It's also reported that tumor mutation burden (TMB) may be another biomarker of response to PD-1 therapy. But there were about 50-60% of patients with MSI-H/dMMR were insensitive to PD-1 antibody. Cyclooxygenase (COX) inhibitor has been proved to prevent adenomas in colorectal and it is safe for most of the patients. Preclinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors. Methods: This single arm, phase II trial will assess the efficacy and safety of combination of PD-1 antibody and COX inhibitor in patients with MSI-H/dMMR or high tumor mutation burden colorectal cancer. Patients diagnosed with MSI-H/dMMR or high tumor mutation burden colorectal cancer which was unresectable and had at least one lines of chemotherapy fail or refuse to receive chemotherapy were eligible. Eligible patients were assigned to receive BAT1306 (100 mg once every three weeks) plus COX inhibitor (aspirin 200 mg every day or Celebrex 400 mg every day). Chest/abdomen/pelvic CT with IV contrast will be performed to assess clinical response. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety and duration of response. Adverse events are graded per NCI CTCAE v4.03 and will be monitored for 30 days after treatment. Patients will be followed for survival. Planned enrollment is 54 patients. Clinical trial information: NCT03638297.
A Dynamic <i>Cis</i>-Regulation Pattern Underlying Epithelial Ovarian Cancer Susceptibility
Authors: Jiyeon Choi, Kevin M. Brown
Journal: Cancer Research (2019)

Abstract Efforts from the past decade in genomic analyses improved our understanding of genetic susceptibility to epithelial ovarian cancer (EOC). While genome-wide association studies (GWAS) have successfully identified approximately 40 genomic loci contributing to risk, a functional understanding of the molecular mechanisms underlying all but a few of these loci is lacking. The work by Buckley and colleagues has comprehensively characterized an EOC locus on chromosome band 9p22.2, identifying cis-regulatory functional sequence variants underlying multiple independent GWAS signals at 9p22.2 both within enhancer elements, as well as within a nuclear scaffold/matrix attachment region. Their findings further provide evidence implicating the basonuclin 2 (BNC2) gene in EOC risk and broaden the understanding of ovarian cancer biology. See related article by Buckley et al., p. 467
The Impact of Front-Line Ibrutinib Dose Reduction and Interruption on Outcomes in Chronic Lymphocytic Leukemia (CLL) Patients
Authors: Joanna Rhodes, Paul M. Barr, Chaitra S. Ujjani, Chadi Nabhan, Constantine S. Tam, Ryan Jacobs, Frederick Lansigan, Brian T. Hill, Danielle M. Brander, Mazyar Shadman, Alan P Skarbnik, Jeffrey J. Pu, Alison R. Sehgal, John M. Pagel, John N. Allan, Kaitlin Kennard, Bruce D. Cheson, Douglas F. Beach, Bhavisha Patel, Krista Isaac, Hande H. Tuncer, Richard R. Furman, Anthony R. Mato
Journal: Blood (2017)
Abstract 122: Sivelestat Sodium Hydrate Treatment for Patients with Kawasaki Disease refractory to initial intravenous immunoglobulin therapy
Authors: Ryota Ebata, Kumi Yasukawa, Yuko Saito, Kouji Higashi, Nobuyuki Takada, Fumie Takechi, Naoki Saito, Hironobu Kobayashi, Naoki Shimojo
Journal: Circulation (2015)

Background: There are still no definite treatments for refractory Kawasaki disease (KD). In this pilot study, we evaluated the safety and efficacy of a new protocol consisting of sivelestat sodium hydrate (SSH) combined with additional intravenous immune globulin (IVIG) for KD patients who were resistant to initial IVIG therapy. Methods: We prospectively collected clinical data of KD patients who were resistant to initial IVIG (2g/kg for one day) and received SSH (0.2mg/kg/hour for consecutive 5 days) combined with additional IVIG (2g/kg for one day) as a second-line therapy at Chiba University hospital between December 2006 and March 2014. We defined patients who remained febrile (37.5°C or more of an axillary temperature) after 36 to 48 hours after start of initial IVIG therapy or who had recrudescent fever associated with other symptoms of Kawasaki disease as being resistant to initial IVIG. Results: Thirty five KD patients were enrolled in this study. No serious adverse effect was noted. The median total duration of fever was 8 days (range 6 to 17 days) and the incidence of coronary artery lesion (CAL) was 5.7% (2 of 35 patients). Among a total of 35 patients, 24 (69%) of them responded promptly to be afebrile 36 to 48 hours after the start of the additional IVIG with SSH. One of these 24 patients developed CAL. The other 11 (31%) failed to become afebrile 36 to 48 hours after the start of the additional IVIG with SSH therapy. Of these 11 patients, one developed CAL. Before initial IVIG, there was no difference in demographic and laboratory data except the age, body weight and % Neutrophils. However, after initial IVIG therapy, there appeared significant difference in % Neutrophils and C-reactive protein levels and both of which were higher in additional IVIG with SSH therapy non-responders than in responders. Conclusions: Additional IVIG combined with SSH for the additional treatment of KD patients who were refractory to initial IVIG therapy was safe and the incidence of CAL is acceptable considering the severity of patients in this study.
Association of asthma with osteopenia, osteoporosis, osteomalacia and pathological fractures United States adults
Authors: Mohammed Shaheen, Jonathan I. Silverberg
Journal: Journal of Allergy and Clinical Immunology (2019)

Previous studies examining the relationship between asthma, osteoporosis, and pathological fractures found conflicting results. We sought to determine whether asthma is associated with osteoporosis and fractures in US adults. We analyzed data for 198,102,435 children and adults, including 10,127,807 with asthma from the 2006–2012 National Emergency Department Sample, including a 20% cross-sectional sample of emergency care visits throughout the US. In pooled analysis across all 7 years, patients with asthma had significantly higher odds of osteopenia (multivariable logistic regression; adjusted odds ratio [95% confidence intervals]: 1.454 [1.406-1.504]), osteoporosis (1.849 [1.817-1.881]), osteomalacia (1.997 [1.605-2.485]), ankylosing spondylitis (1.487 [1.377-1.606]), and pathological fractures (1.238 [1.204-1.273]). Similarly, asthma was associated with higher odds of osteoporosis (P<0.0001 for all), osteopenia (P<0.0001 for all) and ankylosing spondylitis (P≤0.02 for all) in all 7 years, and osteomalacia in 6 of 7 years (P<0.02 for 2007-2012). There was significant sex- and age-related differences of the associations of asthma with these comorbidities. Asthma was associated with osteopenia, osteoporosis, osteomalacia, ankylosing spondylitis and pathologic fractures.