tbuckley/cabot-search huggingface dataset:
Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial
Authors: Julio Rosenstock, Ronnie Aronson, George Grunberger, Markolf Hanefeld, PierMarco Piatti, Pierre Serusclat, Xi Cheng, Tianyue Zhou, Elisabeth Niemoeller, Elisabeth Souhami, Melanie Davies
Journal: Diabetes Care (2016)

To evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug.After a 4-week run-in to optimize metformin and stop other oral antidiabetic drugs, participants (N = 1,170, mean diabetes duration ∼8.8 years, BMI ∼31.7 kg/m2) were randomly assigned to open-label once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum insulin dose of 60 units/day, or to once-daily Lixi (20 μg/day) while continuing with metformin. The primary outcome was HbA1c change at 30 weeks.Greater reductions in HbA1c from baseline (8.1% [65 mmol/mol]) were achieved with iGlarLixi compared with iGlar and Lixi (-1.6%, -1.3%, -0.9%, respectively), reaching mean final HbA1c levels of 6.5% (48 mmol/mol) for iGlarLixi versus 6.8% (51 mmol/mol) and 7.3% (56 mmol/mol) for iGlar and Lixi, respectively (both P < 0.0001). More subjects reached target HbA1c <7% with iGlarLixi (74%) versus iGlar (59%) or Lixi (33%) (P < 0.0001 for all). Mean body weight decreased with iGlarLixi (-0.3 kg) and Lixi (-2.3 kg) and increased with iGlar (+1.1 kg, difference 1.4 kg, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was similar with iGlarLixi and iGlar (1.4 and 1.2 events/patient-year) and lower with Lixi (0.3 events/patient-year). iGlarLixi improved postprandial glycemic control versus iGlar and demonstrated considerably fewer nausea (9.6%) and vomiting (3.2%) events than Lixi (24% and 6.4%, respectively).iGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA1c reductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi.
Bagpipe lung; a new type of interstitial lung disease?
Authors: Jenny King, Malcolm Richardson, Anne-Marie Quinn, Jayne Holme, Nazia Chaudhuri
Journal: Thorax (2016)

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease mediated by an immunological response to an inhaled antigen and can progress to disabling or fatal lung disease. It is related to occupational or other environmental exposures. In a significant proportion of patients, the antigen is often difficult to identify from the clinical history.1 This case highlights the importance of a careful clinical history including hobbies, because in this case, playing the bagpipes, we feel, was very relevant to the development of HP. We were able to isolate various fungal species from the bagpipes. There have been isolated case reports of musicians developing HP.2 ,3 Clinicians need to be aware of this potential trigger for developing HP, and wind instrument players need to be aware of the importance of regularly cleaning their instruments to minimise this risk.

A 61-year-old man was referred to the interstitial lung disease (ILD) clinic in April 2014 with a 7-year history of dry cough and progressive breathlessness despite immunosuppressive therapy, leading to a reduction in exercise tolerance from over 10 kilometres to 20 metres. He had a prior diagnosis since 2009 of HP based on high-resolution CT (HRCT) and biopsy findings from his referring hospital. He did not have any exposure to birds or pigeons. His house showed no evidence of mould or water damage, and he had no symptoms of connective tissue disease. The precipitating trigger for his HP was unknown. His symptoms were insidious and progressive, with the exception of a 3-month period in 2011 when he went to live in Australia. He reported that during this time his symptoms rapidly improved and that he was able to walk 10 kilometres on the beach without stopping. On returning to the UK, his breathing deteriorated rapidly. There was no significant medical history. He …
Discovery and Characterization of Chemical Inhibitors of UBC13.
Authors: Charitha Madiraju, Shu-ichi Matsuzawa, Robert Ardecky, Ian Pass, Tram Ngo, Yasuko Matsuzawa, Carina Wimer, Michael Cuddy, Paul Diaz, Correa Ricardo, Craig Tamble, Chih-Wen Shu, Anthony Pinkerton, Eduard Sergienko, Chris Hassig, Thomas Chung, John C. Reed
Journal: Blood (2012)
Brain Metastases Mimicking Hyperostosis Frontalis Interna on 99mTc HDP Bone Scintigraphy
Authors: Sae-Ryung Kang, Jahae Kim, Seong Young Kwon, Jung-Joon Min, Hee-Seung Bom, Myung-Hee Sohn, Ho-Chun Song
Journal: Clinical Nuclear Medicine (2016)

Symmetric bifrontal uptake of bone-seeking agents is usually considered as the main feature of hyperostosis frontalis interna in postmenopausal elderly women. This finding is not uncommon in elderly women because of the change in their hormonal level. However, in the present case, a 66-year-old woman with intra-axial brain metastases of breast cancer showed symmetric bifrontal uptake on bone scintigraphy. Therefore, symmetric bifrontal uptake should not always be considered as a definite indicator of hyperostosis frontalis interna. Further evaluation such as SPECT/CT is needed for evaluation of brain metastases especially in cancer patients.
Preventing Prescription Opioid Abuse
Authors: Daniel A. Busch
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phase I dose escalation study of pan-histone deacetylase (HDAC) inhibitor abexinostat in combination with cisplatin in patients with advanced non-keratinizing nasopharyngeal carcinoma.
Authors: Boon C. Goh, Ruey-Long Hong, Wan-Teck Lim, Frédérique Cantero, Chee-Seng Tan, Renata Robert
Journal: Journal of Clinical Oncology (2014)

e17059 Background: Non-keratinizing nasopharyngeal carcinoma (NPC) is associated with the Epstein-Barr Virus (EBV), and sensitive to chemotherapy and radiotherapy. Cisplatin-based combination therapy is the most effective treatment for metastatic NPC. Abexinostat, a pan-HDAC inhibitor, exhibited synergistic effects in combination with cisplatin in NPC tumor cell lines, either EBV-positive or negative. A phase I dose-escalation study was performed to determine the maximal tolerated dose, dose-limiting toxicities (DLTs) of abexinostat with a fixed dose of cisplatin in patients with relapsed or refractory advanced NPC. Methods: Abexinostat was administered BID on days 1-4 and 8-11 of a 21-day cycles. Cisplatin dose (75mg/m2) was given on day 3. Abexinostat treatment started 2 days before to induce biological modifications in tumor cells prior to chemotherapy to maximize the synergistic effect. Since toxicities related to cisplatin are cumulative, dose-dependent and may be irreversible, the combination was limited to 6 cycles. The starting dose of abexinostat was 80mg BID. Results: 8 heavily pretreated patients were included and treated, 6 were evaluated for DLT. Two DLTs (fatigue grade 3) were observed at 80mg BID. Thus, abexinostat was de-escalated to 40mg BID while keeping the same cisplatin dose. One DLT was observed (acute renal impairment grade 3) at this dose. However, due to lower recruitment rate than expected, the study was closed without reaching the primary objective.Four out of these 6 patients received the combination treatment for at least 2 cycles. Two patients achieved Partial Response with a decrease of 30% and 50%, and 2 had Stable Disease after 2 cycles. For 2 patients, quantifiable EBV copy numbers were correlated with the tumor response. However, 2 patients withdrew due to fatigue and anemia after 3 cycles, and one patient could not restart the treatment due to delayed recovery. Conclusions: Abexinostat 80mg BID and 40mg BID appears active in combination with cisplatin 75mg/m2 in patients with advanced NPC. However, there are tolerability issues with this combination that need to be considered and overcome. Clinical trial information: ISRCTN96922360.
Reply to Fabio Zattoni, Filiberto Zattoni, and Laura Evangelista's Letter to the Editor re: Marlon Perera, Nathan Papa, Daniel Christidis, et al. Sensitivity, Specificity, and Predictors of Positive 68 Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2016;70:926–37
Authors: Nathan Papa, Marlon Perera, Michael S Hofman, Damien Bolton, Nathan Lawrentschuk
Journal: European Urology (2016)
Impact of KRAS,BRAF,PI3K,NRAS gene mutation in stage II-III colon cancer.
Authors: Lin Gui, Jianfei Wang, Yinchen Shen, Xiaoyan Qian, Shuai Wang, Xiaohong Han, Yuankai Shi
Journal: Journal of Clinical Oncology (2015)

e14638 Background: The epidermal growth factor receptor (EGFR) signaling pathway act as a pivot role in carcinogenesis and progression of colorectal cancer (CRC). However, whether mutations in KRAS together with downstream factors BRAF, PI3K and NRAS influence tumor behavior is still unclear for stage II-III colon cancer. Methods: Sanger sequencing was performed in 137 stage II-IIIcolon cancer samples, KRAS (codons 12, 13 and 61), BRAF (exon 11 and exon 15),PI3K(exon 9 and exon 20) and NRAS(codons12,13 and 61) status was analyzed with patients clinicopathological characteristics. Disease- free survival (DFS) and overall survival (OS) were together investigated. Results: One hundred and four stage III and 33 stage II colon cancer were involved in analysis. All patients received only chemotherapy (FOLFOX or XELOX) after resection. 38.97% (53/136) tumors harbored a KRAS mutation, 8.02% (11/137) harbored a BRAF mutation, 16.03% (21/131) harbored a PI3K mutation and 1.51% (2/132) harbored a NRAS mutation.NRAS mutation(codon 12 and 61)existed only in stage II colon cancer.Female patients shared a higher BRAF (V600E) mutation (12.1% vs 2.53%), PI3K exon 20 mutations appeared more frequently in patients younger than 60 years (P < 0.05). Moreover, KRAS codon 13 mutation was higher in smokers (13.6% vs 1.9%) and tumors with better differentiation showed a higher KRAS codon 12 mutation (P = 0.044). No significant association was found between tumor location, relapse, T or N stage,DFS,OS (tumor stage subgroup involved) and gene mutation(mutant subtype involved). Conclusions: NRAS mutation was rare in stage II-III colon cancer, which only appeared in stage II tumors. Gene mutation varied in patients with different clinicopathological characteristics. KRAS, BRAF, PI3K and NRAS mutation might not act as biomarkers for tumor relapse and survival of stage II-IIIpatients.
Impact Of Response Duration and Maintenance Therapy After Autologous Stem Cell Transplantation On Long-Term Survival In Multiple Myeloma Patients
Authors: Nicola Lehners, Christiane Heiss, Soh-Yun Kim, Thomas Hielscher, Jens Hillengass, Gerlinde Egerer, Anthony D. Ho, Kai Neben, Hartmut Goldschmidt, Marc S. Raab
Journal: Blood (2013)
Comparison of molecular alteration in glioblastoma tumors from old and young patients.
Authors: Joanne Xiu, Sandeep K. Reddy, Santosh Kesari, Stephanie Elizabeth McLaughlin, Raymond J. Hohl, Geoffrey Barger, Amy B. Heimberger
Journal: Journal of Clinical Oncology (2016)

2056 Background: GBM patients (pts.) aged 70 yrs or older have a poorer prognosis than younger pts. IDH1/2 mutations are more prevalent in younger GBM pts. and confer a more favorable prognosis. We compared molecular alterations between younger pts. (YP; 18 < age < 45), and older pts. (OP; age > = 70), with additional stratification for wild type IDH1/2 status. Methods: GBM tumors submitted for tumor profiling between 2009 and Jan 2016 were tested with NextGen sequencing (SEQ), immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH), fragment analysis (FA) and promoter methylation (Me). Retrospective analysis was performed on 375 GBM’s (YP = 197, OP = 178). Pediatric tumors were excluded. Chi-square was used for exploratory analyses and significance was defined as p < 0.05. Results: Alterations including overexpression of ALK (29% vs. 4.2%), RRM1 (47% vs. 32%) and mutations of ATRX (73% vs. 11%), BRAF (9.3% vs. 1.7%), IDH1 (24% vs. 3%), PDGFRA (7% vs. 0), PTPN11 (6.6% vs. 1%) and TP53 (58% vs. 26%) were significantly more prevalent in YP (N = 197). In contrast, PTEN mutation was significantly more frequent in OP (N = 178; 26% vs. 13%). PTEN loss by IHC was equal between YP and OP (22% vs. 21%). Pts. with known wild type IDH1/2 status were compared between YP and OP (N = 72 and 95). Significantly higher expression of TOPO1 was seen in YP (63% vs. 45%) while MGMT-Me was less common in YP (29% vs. 48%). The differences in ALK IHC (27% vs. 4.5%), mutations of BRAF (12% vs. 1%), PDGFRA (4%, vs. 0), PTPN11 (7% vs. 1%) and TP53% (42% vs. 25%) were significant. cKIT and PDGFRA co-amplifications were seen in 2 out of 3 tumors from OP with wild type IDH1/2 while no cKIT or PDGFRA amplification was seen in YP (0/6). No significant differences were seen in YP vs. OP for EGFRvIII (12% vs. 14%), PD-L1 expression on tumor cells (19% vs. 8.3%) or PD-1 expression on TIL (42% vs. 54%). Conclusions: Significant molecular differences were seen between older and younger GBM pts. Alterations seen in OP, including PTEN mutation and cKIT/PDGFRA coamplification were previously associated with recurrent tumors and poor survival, and may underlie the poor prognosis observed in OP. These results suggest and may guide which pts. will benefit from targeted therapies in future studies.
Novel baseline predictors of adverse events during oral immunotherapy in children with peanut allergy
Authors: Yamini V. Virkud, A. Wesley Burks, Pamela H. Steele, Lloyd J. Edwards, Jelena P. Berglund, Stacie M. Jones, Amy M. Scurlock, Tamara T. Perry, Robert D. Pesek, Brian P. Vickery
Journal: Journal of Allergy and Clinical Immunology (2016)
The Spectrum Of Cold Agglutinin Disease At The Era Of Rituximab: A Retrospective Study On 48 Patients
Authors: Mathilde Lamarque, Véronique Leblond, Bruno R. Varet, Sylvain Choquet, Jean Paul Vernant, Richard Delarue, Bertrand Godeau, Olivier Hermine, Marc Michel
Journal: Blood (2013)
A clinical variable-based predictive model of delayed clearance of high dose methotrexate (HDMTX) in patients (pts) with primary CNS lymphoma (PCNSL).
Authors: Yu Yuan, Brandy Strickland Snyder, Greg B. Russell, Glenn Jay Lesser
Journal: Journal of Clinical Oncology (2016)

2040 Background: HDMTX remains the backbone of therapy for pts with PCNSL and delayed clearance may lead to higher rates of treatment-induced toxicities. It is unknown whether readily available pre-treatment clinical variables other than creatinine clearance (CrCl) are predictive of delayed clearance. Methods: A retrospective single-center study of pts (Age ≥ 18 years) receiving HDMTX (≥ 1 g/m2, range 1-8g/m2) with biopsy confirmed PCNSL was performed. Variables studied included patient demographics (age, gender, ECOG); past medical history (DM, HTN, CHF, liver disease, MRI with contrast within 48 hours); MTX history (MTX dose [mg/m2], cycle number, number of prior HDMTX cycles, days between HDMTX cycles, history of prior delayed clearance [MTX level of ≥ 0.30 micromol/L at 48 hours]); lab abnormalities (CrCl, elevated liver enzymes, hypoalbuminemia [< 3.5g/dL], low total protein [ < 6 g/dL]); and medication use (steroid, rituximab, and concurrent use of renal tubular competitors). Results: We identified 34 pts with PCNSL who received 191 cycles of HDMTX from 2003-2014. 75/191 cycles had delayed clearance at 48 hours. Significant variables identified in univariate analysis (age, pretreatment creatinine, DM, HTN, hypoalbuminemia) were used to construct a multivariate model which demonstrated that delayed MTX clearance was significantly more common in pts with a history of DM (p = 0.0002, OR 1.32, 95% CI [1.14, 1.54]), HTN (p = 0.0013, OR 1.25, [1.09, 1.43]), and hypoalbuminemia (p = 0.025, OR 1.18, [1.02, 1.36]). Conclusions: Higher rates of delayed clearance following HDMTX administration were seen in pts with a history of DM, HTN, and hypoalbuminemia. A larger sample size is needed to generate a quantitative model from these preliminary observations that would allow individualized dosing modifications to avoid delayed MTX clearance.
High hospital research participation and improved colorectal cancer survival outcomes: a population-based study
Authors: Amy Downing, Eva JA Morris, Neil Corrigan, David Sebag-Montefiore, Paul J Finan, James D Thomas, Michael Chapman, Russell Hamilton, Helen Campbell, David Cameron, Richard Kaplan, Mahesh Parmar, Richard Stephens, Matt Seymour, Walter Gregory, Peter Selby
Journal: Gut (2016)

<h3>Objective</h3> In 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals. <h3>Design</h3> Data for patients diagnosed with CRC in England in 2001–2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation. <h3>Results</h3> Most of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer ‘centres of excellence’, although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (p&lt;0.001) and improved survival (p&lt;0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in postoperative mortality of 1.5% (6.5%–5%, p&lt;2.2×10<sup>−6</sup>) and an improvement in survival (p&lt;10<sup>−19</sup>; 5-year difference: 3.8% (41.0%–44.8%)) comparing high participation for ≥4 years with 0 years. <h3>Conclusions</h3> There is a strong independent association between survival and participation in interventional clinical studies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation.
Mismatched Family Member Donor Transplantation for Patients with Refractory Hematologic Malignancies: Long-Term Followup of a Prospective Clinical Trial.
Authors: Gregory A. Hale, Kimberly A. Kasow, Renee Madden, Usman Yusuf, Edwin Horwitz, Raymond Barfield, Joseph Woodard, Wing H. Leung, Kumar Srivastava, Rupert Handgretinger
Journal: Blood (2006)
Pim2 is important for regulating DNA damage response in multiple myeloma cells
Authors: J Ramachandran, L Santo, K T Siu, C Panaroni, N Raje
Journal: Blood Cancer Journal (2016)

Pan proviral integrations of Moloney virus (PIM) inhibition in multiple myeloma (MM) results in reduced cell viability in tested human-derived MM cell lines and reduces tumor burden in xenograft mouse models, making PIMs important therapeutic targets for the disease. PIM kinase inhibitors are currently being tested clinically in MM. We sought to elucidate the role of the various PIMs in MM. Our data demonstrate that Pim2 has a significant role in MM cell cytotoxicity. Our data provide evidence for a novel role for Pim2 in the regulation of the DNA damage response (DDR). Knockdown of Pim2 upregulates several downstream DDR markers, mimicking the effects of doxorubicin (Dox) treatment of MM cells, and suggesting a role for the kinase as a negative regulator of this pathway. Dox-induced DNA damage results in a decrease in Pim2 levels, placing the kinase directly downstream of the site of Dox-DNA binding. Overexpression of Pim2 confers a slight survival advantage against Dox through antiapoptotic activity, further underscoring its relevance in the DDR pathway. These data provide insights into a novel mechanism of PIM kinase activity and provide the framework for designing therapeutic approaches in MM.
A Probable Case of Central Centrifugal Cicatricial Alopecia Encountered in Mark Twain’s Autobiography
Authors: Alexandra C. Villasante Fricke, Mariya Miteva
Journal: JAMA Dermatology (2016)

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