tbuckley/cabot-search huggingface dataset:
Safety and efficacy of CPX-351 in younger patients &lt; 60 years old with secondary acute myeloid leukemia: An updated analysis.
Authors: Amanda Cecile Przespolewski, Chetasi Talati, Salman Fazal, Pankit Vachhani, Srinivasa Sanikommu, Swapna Thota, Jeffrey Baron, Elizabeth A. Griffiths, James E. Thompson, Kendra Lynn Sweet, Eunice S. Wang
Journal: Journal of Clinical Oncology (2019)

e18530 Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) have poor long-term outcomes following standard induction chemotherapy with 7+3. In 2017 CPX-351 was FDA approved for upfront treatment of s-AML. The phase 3 trial demonstrated improved overall survival in pts aged 60-75 years old. Although CPX-351 treatment is indicated in all adults with s-AML, it is unclear whether CPX-351 is safe and effective in younger pts &lt; 60 years. We sought to address this unanswered question by retrospective review of clinical experience since FDA approval. Methods: Medical records were retrospectively reviewed at five large academic centers to identify pts aged 18-59 years old with untreated s-AML, prior cytotoxic therapy, or AML-MRC treated with CPX-351 as induction therapy. Results: 30 pts with confirmed s-AML received CPX-351 therapy. Mean age was 53 years (range 23 – 59), 18 were male (60%). The majority (60%, N = 18) had AML-MRC, 7 (23%) had treatment-related AML (t-AML) and 6 (20%) had antecedent MDS. 6 pts had received prior HMA therapy. 19 pts had a complex karyotype (70%), and 4 patients were found to have a normal karyotype (15%). The most common molecular event was TP53 mutation observed in 10 pts (36%), followed by FLT3-ITD identified in 4 pts (14%). Overall response rate (CR/CRi/PR) was 46.7% with 5 CR (17.2%), 3 CRi (10.3%), and 6 PR (20.7%). The remaining pts (15/29, 51.7%) were non-responders. 8 pts have received an allogenic stem cell transplant. The most common AE was infection (80%, 24/30) with 4 clinically significant bleeding events. Thirty-day mortality was 13.3%, with 60-day mortality of 16.7%. Overall survival was 7 months (range 0.5 – 12.4 months), with mean follow up of 4.4 months. Conclusions: This multi-institutional retrospective analysis suggests that CPX-351 results in lower response rates (CR/CRi 27.6%) and shorter overall survival (7 mos) than reported in the recently published phase 3 trial in pts aged 60-75 years old. Potential explanations for this discrepancy include short follow up, small sample size, retrospective design, and the significant proportions of pts with complex karyotype and TP53 mutations. Historically, patients &lt; 65 years old with s-AML have had a reported overall survival of approximately 7 months. Further investigation of this regimen in younger pts with s-AML as compared with 7+3 and other approaches is warranted.
The Bionic Radiologist: avoiding blurry pictures and providing greater insights
Authors: Marc Dewey, Uta Wilkens
Journal: npj Digital Medicine (2019)

Radiology images and reports have long been digitalized. However, the potential of the more than 3.6 billion radiology examinations performed annually worldwide has largely gone unused in the effort to digitally transform health care. The Bionic Radiologist is a concept that combines humanity and digitalization for better health care integration of radiology. At a practical level, this concept will achieve critical goals: (1) testing decisions being made scientifically on the basis of disease probabilities and patient preferences; (2) image analysis done consistently at any time and at any site; and (3) treatment suggestions that are closely linked to imaging results and are seamlessly integrated with other information. The Bionic Radiologist will thus help avoiding missed care opportunities, will provide continuous learning in the work process, and will also allow more time for radiologists' primary roles: interacting with patients and referring physicians. To achieve that potential, one has to cope with many implementation barriers at both the individual and institutional levels. These include: reluctance to delegate decision making, a possible decrease in image interpretation knowledge and the perception that patient safety and trust are at stake. To facilitate implementation of the Bionic Radiologist the following will be helpful: uncertainty quantifications for suggestions, shared decision making, changes in organizational culture and leadership style, maintained expertise through continuous learning systems for training, and role development of the involved experts. With the support of the Bionic Radiologist, disparities are reduced and the delivery of care is provided in a humane and personalized fashion.
Prediagnosis cardiovascular risk and subsequent myocardial infarction (MI) among lymphoma survivors.
Authors: Talya Salz, Emily Craig Zabor, Peter de Nully Brown, Susanne Oksbjerg Dalton, Nirupa Jaya Raghunathan, Matthew J. Matasar, Richard Steingart, Henrik Hjalgrim, Lena Specht, Kevin C. Oeffinger, Christoffer Johansen
Journal: Journal of Clinical Oncology (2019)

7564 Background: Chest radiation is associated with increased risk of MI among lymphoma survivors. The extent to which pre-existing cardiovascular risk factors also contribute to risk is understudied. We investigated this association among a national population of lymphoma survivors with a full range of cardiovascular risk factors. Methods: Using Danish population-based registries, we identified all adults diagnosed with aggressive non-Hodgkin lymphoma or Hodgkin lymphoma from 2000-2010 and followed them from 1 year after diagnosis through 2016. MI was ascertained from the nationwide Hospital Discharge Register and Cause of Death Register. Cardiovascular risk factors (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at lymphoma diagnosis were ascertained algorithmically using the National Prescription Register and the Hospital Discharge Register. Controlling for age, sex, histology, receipt of chest radiation, and prevalent cardiovascular diseases, we used multivariable Cox regression to test the association between pre-existing cardiovascular risk factors and subsequent MI. Results: Among 4246 survivors of lymphoma, median age at diagnosis was 60 (interquartile range 45-70 years); median follow-up was 6.9 years (range 0-16 years). 115 survivors were diagnosed with MI. Before lymphoma diagnosis, 28% of survivors had ≥1 cardiovascular risk factor, and 16% of survivors received chest radiation. In multivariable analysis, survivors who received chest radiation had an increased risk of MI compared to survivors who did not (HR=1.92 [95% CI=1.16-3.17]). Survivors with ≥1 cardiovascular risk factor had an increased risk of MI compared to survivors with none (HR = 2.44 [95% CI=1.65-3.62]). Conclusions: In a large, well-characterized, nationally representative study of contemporarily treated lymphoma survivors, prevalent hypertension, dyslipidemia, and diabetes were associated with later MI. Findings suggest that pre-existing cardiovascular risk factors confer the same amount of MI risk as does chest radiation. To prevent MI among survivors, decisions about post-treatment monitoring should address prevalent cardiovascular risk.
Interim results from a phase Ib/II clinical study of the glutaminase inhibitor telaglenastat (CB-839) in combination with azacitidine in patients with advanced myelodysplastic syndrome (MDS).
Authors: Veronica Guerra, Courtney Denton Dinardo, Marina Konopleva, Jan Andreas Burger, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Kimberley Sheppard, Guillermo Garcia-Manero, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2019)

7037 Background: Glutaminase (GLS) is an enzyme that catalyzes conversion of glutamine to glutamate, providing key metabolic fuel for tumor cells. GLS is highly expressed in AML and high-risk MDS, particularly in the setting of complex cytogenetics. Preclinical studies of primary AML cells demonstrate dependence on glutamine; glutaminase inhibition led to reduced cell growth and induced apoptosis. This study was designed to evaluate the safety and efficacy of the oral glutaminase inhibitor CB-839 in combination with azacitidine for MDS. Methods: This is a single arm Phase Ib/II trial of CB-839, evaluating the dose of 600 mg BID orally daily in combination with azacitidine (AZA) for intermediate and high-risk MDS in 28-day cycles. The primary outcome for the Phase 1 portion was to confirm the safety and recommended Phase 2 dose of CB-839 in combination with AZA. Secondary endpoints evaluate efficacy and clinical activity using IWG response criteria for MDS including hematological improvement (HI), complete response (CR), marrow CR (mCR), stable disease (SD) and no response (NR). Results: A total of 10 pts with MDS were enrolled; the Phase I portion is now complete, confirming CB-839 600 mg BID with standard AZA. Median age was 71 [47-76], 90% were men. 7 pts were treatment naïve, 3 pts had prior HMA exposure. 6 pts were intermediate-2, and 4 pts intermediate-1 by IPSS with high-risk mutations. 3 pts had complex cytogenetics. The most frequent mutations were ASXL1 (n = 5), TET2 (n = 4) and TP53 (n = 4). Median number of cycles was 3 [1-9]. The most common non-hematological AEs were grade 1-3 nausea (60%) and constipation (50%). No DLTs were identified; one pt experienced grade 3 transaminitis requiring dose reduction of CB-839 (to 400 mg BID) with resolution. Seven pts (70%) achieved mCR/CR with HI, 2 pts had SD, and 1 pt had NR. The median time to mCR was 3 months [1-3]. 4 pts proceed to hematologic stem cell transplant (HSCT) after 2-4 cycles. 1 pt progressed to AML after 3 cycles of therapy, and 3 pts remain on study. Conclusions: 600 mg BID CB-839 is safe and well tolerated in combination with azacitidine in pts with MDS. The Phase II portion is ongoing. Clinical trial information: NCT03047993.
The Challenge of Defining Alzheimer Disease Based on Biomarkers in the Absence of Symptoms
Authors: Teresa Gomez-Isla, Matthew P. Frosch
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Randomized controlled trial (RCT) of a patient navigation (PN) intervention to increase early access to supportive care (SC) for patients with metastatic cancer in a resource-limited setting.
Authors: Enrique Soto Perez De Celis, Yanin Chavarri Guerra, Wendy Alicia Ramos-Lopez, Alfredo Covarrubias-Gómez, Africa Navarro-Lara, Paulina Quiroz, Sofia Sanchez, Natasha Alcocer, Mirza Alcalde Castro, Jose Carlos Aguilar Velazco, Alexandra Bukowski, Juan Alberto Chavarri Maldonado, Sergio Contreras-Garduño, Lindsay Krush, Itoro E. Inoyo, Andrea Medina-Campos, María Luisa Moreno-García, Viridiana Pérez-Montessoro, Paul E. Goss
Journal: Journal of Clinical Oncology (2019)

11505 Background: Early integration of SC to the treatment of advanced cancer can improve outcomes, but this may be challenging in developing countries due to a lack of resources and knowledge. In this RCT, we examined whether PN could improve early access to SC among Mexican patients with metastatic solid tumors as recommended by ASCO guidelines. Methods: Adult patients with newly-diagnosed metastatic cancer were randomly assigned to PN or standard oncologic care. At baseline, a navigator assessed the patients’ SC needs (depression, anxiety, fatigue, pain, caregiver burden) using validated questionnaires administered with an electronic tablet. For those in the PN arm, a personalized SC plan was created and implemented by a multidisciplinary team (palliative care, physical therapy, geriatrics, psychology, psychiatry). The primary outcome was access to SC, defined as receipt of SC interventions in the first 3 months (mo) after diagnosis. Secondary outcomes included advanced directive (AD) completion (for patients with expected survival ≤6 mo in accordance to Mexican law), changes in SC needs, and changes in quality of life (assessed using FACT-G). Results: 133 patients (median age 60, range 23-93; 52% male) were randomized (66 PN, 67 control). 61% of patients had gastrointestinal tumors. 94% of patients in the PN arm completed baseline assessments and received recommendations from the navigator. At 3 mo, 37 patients died or were lost to follow-up (16 PN, 21 control; p = 0.45), and 96 completed assessments. SC interventions were provided to 73% of patients in the PN arm and 24% of controls (p &lt; 0.01). In the PN arm, 48% of 29 eligible patients completed AD, compared to 0% of eligible controls (p &lt; 0.01). At 3 mo, patients in the PN arm were significantly less likely to report moderate/severe pain than controls (10 vs 33%, p = 0.006). There were no significant differences in other symptoms or in FACT-G scores (76 vs 76.3, p = 0.46) between PN and control arms at 3 mo. Conclusions: PN can lead to significant improvements in early access to SC, AD completion, and pain control among patients with metastatic cancer treated in a resource-limited setting. Clinical trial information: NCT03293849.
HER2 assessment and Ki-67 labeling index in a cohort of male breast cases: The Ich Network on Cancer Research (INCaRe) experience.
Authors: Giovanna Masci, Michele Caruso, Agnese Losurdo, Piermario Salvini, Carlo Carnaghi, Luca Di Tommaso, Monica Zuradelli, Giovanna Manuguerra, Selene Rota, Rosa Anna Aiello, Giuseppe Gullo, Rosalba Torrisi, Giordano D. Beretta, Armando Santoro
Journal: Journal of Clinical Oncology (2012)

623 Background: The overall incidence of male breast cancers (MBC) is around 1% of all breast cancers and is on the rise.Most of our current knowledge regarding its biology and treatment strategies has been extrapolated from its female counterpart. However, from literature data, it is more and more evident that MBC has biological differences compared with female breast cancer (FBC). While hormone receptors are more frequently positive in MBC than in FBC, HER-2 seems to be less expressed in MBC than in FBC, with data ranging from 0 to 18%; no data on Ki-67 have been so far reported. Methods: We retrospectively analyzed the immunohistochemical expression of hormone receptors status, HER-2 protein expression, and Ki-67 in 76 consecutive MBCs, treated within the Humanitas Institutes Network on Cancer Research (INCaRe). HER-2 determinations were carried out according to ASCO/ACP and NEQAS guidelines: cases with score 2+ at IHC were further examined by fluorescent in situ hybridation (FISH). Results: From 2000 to 2011, we treated 76 male breast cases (age 25-87, median 64): 72 patients (94%) had ductal carcinoma and 4 had rare histotypes (2 papillary, 1 mucinous and 1 cribryform). Thirthy-two of 76 patients (42%) had positive axillary lymph-nodes, while 6 (8%) were metastatic at diagnosis. Of these, estrogen receptor and progesterone receptor were positive in 96% and 93% patients respectively; HER-2, evaluable in 67 patients, was positive in 11 (16%). Ki-67 was evaluable in 75 patients and was &gt; 20% in 24 cases (32%), with 20/24 (26%) with Ki-67 &gt; 30%. Grading was evaluable in 65 patients: G1 in 2 (3%), G2 in 41(63%) and G3 in 22 (34%), respectively. Conclusions: In these series, MBC show different patterns from FBC, with some favorable aspects such as higher hormone receptor status and much lower HER-2 expression and some unfavorable features, such as higher Ki-67 values. Although further studies are needed to confirm these data, different treatment strategies would be suggested in MBC than its female counterpart.
Integrative Genomic Characterization Identifies Molecular Subtypes of Lung Carcinoids
Authors: Saurabh V. Laddha, Edaise M. da Silva, Kenneth Robzyk, Brian R. Untch, Hua Ke, Natasha Rekhtman, John T. Poirier, William D. Travis, Laura H. Tang, Chang S. Chan
Journal: Cancer Research (2019)

Lung carcinoids (LC) are rare and slow growing primary lung neuroendocrine tumors. We performed targeted exome sequencing, mRNA sequencing, and DNA methylation array analysis on macro-dissected LCs. Recurrent mutations were enriched for genes involved in covalent histone modification/chromatin remodeling (34.5%; MEN1, ARID1A, KMT2C, and KMT2A) as well as DNA repair (17.2%) pathways. Unsupervised clustering and principle component analysis on gene expression and DNA methylation profiles showed three robust molecular subtypes (LC1, LC2, LC3) with distinct clinical features. MEN1 gene mutations were found to be exclusively enriched in the LC2 subtype. LC1 and LC3 subtypes were predominately found at peripheral and endobronchial lung, respectively. The LC3 subtype was diagnosed at a younger age than LC1 and LC2 subtypes. IHC staining of two biomarkers, ASCL1 and S100, sufficiently stratified the three subtypes. This molecular classification of LCs into three subtypes may facilitate understanding of their molecular mechanisms and improve diagnosis and clinical management. SIGNIFICANCE: Integrative genomic analysis of lung carcinoids identifies three novel molecular subtypes with distinct clinical features and provides insight into their distinctive molecular signatures of tumorigenesis, diagnosis, and prognosis.
Abstract 155: ATF6 is a Mediator of Cardiac Hypertrophy During Pressure Overload in the Mouse Heart
Authors: Robert N Correll, Jeffrey M Lynch, Michelle A Sargent, Allen J York, Jeffery D Molkentin
Journal: Circulation Research (2017)

The endoplasmic reticulum (ER) stress response is one of many signaling events activated in the heart in response to injury and/or cardiac hypertrophy, although the role that this response pathway plays in such events remains under investigation. Recently, our laboratory demonstrated that overexpression of thrombospondin-4 (Thbs4) resulted in a protective ER stress response via activation of activating transcription factor 6 (ATF6), and that mice gene-deleted for Thbs4 demonstrated compromised ER stress signaling and decreased survival after transverse aortic constriction (TAC) or myocardial infarction (MI) surgery. Here we confirm that Thbs4-mediated expansion of the ER compartment requires ATF6 and examine whether the protective ER stress response mediated by transgenic overexpression of Thbs4 is eliminated when crossed with gene-deleted mice lacking ATF6. We also examined cardiac-specific transgenic mice overexpressing the transcriptionally-active ATF6 N-terminus, as well as mice gene-deleted for ATF6, in combination with disease stimuli including TAC and MI surgery. We find that ATF6 proteins are required for compensatory hypertrophy in the mouse heart and that loss of these proteins results in accelerated decompensation and failure, likely due to reductions in ER folding capacity that is required for the increased protein production necessary for cardiac hypertrophy. These results firmly position ATF6 as an essential regulator of compensatory cardiac hypertrophy during disease.
Хронический гепатит С и синдром перегрузки железом
Authors: E.Z. Burnevich, M.V. Severov, M.M Severova
Journal: GASTROENTEROLOGY (2014)

В статье рассматриваются вопросы патогенеза и коррекции синдрома перегрузки железом у пациентов с хроническим вирусным гепатитом С. Уделено внимание применению комбинации пегилированного ИФН-α и рибавирина, а также кровопусканиям как адъювантному компоненту противовирусной терапии.
Incidence and outcomes of cutaneous angiosarcoma: A SEER population-based study
Authors: Rosalynn R.Z. Conic, Giovanni Damiani, Alice Frigerio, Sheena Tsai, Nicola L. Bragazzi, Thomas W. Chu, Natasha A. Mesinkovska, Shlomo A. Koyfman, Nikhil P. Joshi, G. Thomas Budd, Allison Vidimos, Brian R. Gastman
Journal: Journal of the American Academy of Dermatology (2019)
Editor's Note: A Novel Peptide Specifically Binding to Interleukin-6 Receptor (gp80) Inhibits Angiogenesis and Tumor Growth
Authors: Jen-Liang Su, Kuo-Pao Lai, Chi-An Chen, Ching-Yao Yang, Pei-Sheng Chen, Chiao-Chia Chang, Chia-Hung Chou, Chi-Lun Hu, Min-Liang Kuo, Chang-Yao Hsieh, Lin-Hung Wei
Journal: Cancer Research (2019)

The editors were made aware of concerns regarding potential manipulation of data in this article (1). An internal review by the editors determined that in Fig. 3A, the P-ERK Western blot bands in lanes 3 and 4 appear to be spliced together. In addition, the same Western blot image appears to have been used in Fig. 3C (STAT3) and Fig. 6B (β-actin). Because satisfactorily corrected figures could not be provided, the editors are publishing this note to alert readers to these concerns.
Not on My Watch
Authors: Arjun Gupta
Journal: JAMA Oncology (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 Oncology 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 Oncology journal