tbuckley/cabot-search huggingface dataset:
Although Cardiac Rehab Saves Lives, Few Eligible Patients Take Part
Authors: Rita Rubin
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 9478: Malignant Early Repolarisation is Relatively Frequent in Young Athletes
Authors: Marcello Di Valentino, Patrick Siragusa, Giorgio Moschovitis, Augusto Gallino, Andrea Menafoglio
Journal: Circulation (2012)

Background: early repolarisation in infero-lateral leads (ER), a common ECG pattern in athletes, has been recently linked with an increased risk of cardiac death. Some phenotypes of ER seems to be more “malignant”: J waves in inferior leads with horizontal/descending ST pattern particularly with J wave amplitude &gt; 2 mm. The aim of this study was to assess the proportion of “malignant” ER in a cohort of young athletes. Methods: ECG was analysed as part of a prospective study about the impact of cardiovascular screening with ECG in young (14-35 years) athletes. ER was defined as J point elevation ≥ 1 mm in 2 or more contiguous leads (except V1-V3). Following features were noted: localisation of ER (inferior, lateral or infero-lateral), amplitude of J point, morphology of J wave (notch, slurred or indeterminate), ST segment pattern (ascending, horizontal/descending). Results: ECG of 1070 athletes (75 % males, age 19.7 ± 6.3 years) was analysed. An ER pattern was present in 383 athletes (36 %). Localisation of ER was infero-lateral in 40%, lateral in 32 % and inferior in 28%. Maximal amplitude of J point was ≥ 2 mm in 25 % of ER pattern. The morphology of J wave was notch in 55 %, slurred in 26 % and indeterminate in 19 %. The ST segment was ascending in 77 % and horizontal/descending in 23 %. ER with a horizontal/descending ST pattern in inferior leads (“malignant” ER) represented 23 % of total ER and was present in 8 % of athletes, with J wave amplitude &gt; 2 mm in 2 % of athletes (5% of total ER). No athlete with ER suffered from syncope of undetermined origin or had family history of premature sudden death. Conclusions: ER in young athletes is generally characterised by a notch J wave in lateral leads with ascending ST pattern. The “malignant” phenotype is however relatively frequent. This should be take into account before drawing premature conclusion about risk stratification in this young healthy population.
Cancer and the Circadian Clock
Authors: Ayesha A. Shafi, Karen E. Knudsen
Journal: Cancer Research (2019)

The circadian clock is a master regulator of mammalian physiology, regulating daily oscillations of crucial biological processes and behaviors. Notably, circadian disruption has recently been identified as an independent risk factor for cancer and classified as a carcinogen. As such, it is imperative to discern the underpinning mechanisms by which circadian disruption alters cancer risk. Emergent data, reviewed herein, demonstrate that circadian regulatory functions play critical roles in several hallmarks of cancer, including control of cell proliferation, cell death, DNA repair, and metabolic alteration. Developing a deeper understanding of circadian-cancer regulation cross-talk holds promise for developing new strategies for cancer interception, prevention, and management.
K+-Cl− cotransporter 1 (KCC1): a housekeeping membrane protein that plays key supplemental roles in hematopoietic and cancer cells
Authors: A. P. Garneau, S. Slimani, L. E. Tremblay, M. J. Fiola, A. A. Marcoux, P. Isenring
Journal: Journal of Hematology & Oncology (2019)

During the 1970s, a Na+-independent, ouabain-insensitive, N-ethylmaleimide-stimulated K+-Cl− cotransport mechanism was identified in red blood cells for the first time and in a variety of cell types afterward. During and just after the mid-1990s, three closely related isoforms were shown to account for this mechanism. They were termed K+-Cl− cotransporter 1 (KCC1), KCC3, and KCC4 according to the nomenclature of Gillen et al. (1996) who had been the first research group to uncover the molecular identity of a KCC, that is, of KCC1 in rabbit kidney. Since then, KCC1 has been found to be the most widely distributed KCC isoform and considered to act as a housekeeping membrane protein. It has perhaps received less attention than the other isoforms for this reason, but as will be discussed in the following review, there is probably more to KCC1 than meets the eye. In particular, the so-called housekeeping gene also appears to play crucial and specific roles in normal as well as pathological hematopoietic and in cancer cells.
The number of metastatic lymph node in N3M0 breast cancer and influence on survival.
Authors: Mustafa Solak, Fatma P. Turkoz, Özge Keskin, Hilbrahim Petekkaya, Saim Furkan Sarici, Taner Babacan, ECE Esin, Sercan Aksoy, Kadri Altundag
Journal: Journal of Clinical Oncology (2013)

e12563 Background: To evaluate the impact of the number of metastatic lymph node (MLN) in N3M0 breast cancer patients with a sufficient lymph node sampling. Methods: 200 patients with histopathologically confirmed N3M0 breast cancer were analyzed. Patients were divided into three groups according to the MLN; i) MLN:10-15, ii) MLN:16-20, iii) MLN:&gt;20. Pearson Chi-square test and Kaplan-Meier test were used. Results: 25 patients had T1, 91 had T2, 69 had T3 and 15 had T4 tumor. The number of median MLN was 15 (10-48). HER-2, ER and PR status were similar. There were no significant differences in age at diagnosis, menopausal status, stage, grade and treatment among groups (p&gt;0,05). The median follow-up period was 41.5 months. The median OS was 100, 98 and 58 months in group I, II and III, respectively (p=0.06). When we analyzed for two groups; the median OS was significantly shorter in patients with &gt;20 MLN than patients with 10-15 MLN (98 vs. 58 months; p=0.04). We found no significant difference in DFS (p=0.52). The patients with &gt;20 MLN had increased risk of mortality compared to patients with 10-15 MLN (adjusted-HR 1.96 (95%CI 1.1-3.5); p=0.025). Conclusions: To define the subgroups according to MLN in N3 disease may help determining the high-risk patients and making decision in clinical practice. However this finding should be supported by larger studies.
Factors Predicting Early Mortality in Newly Diagnosed Myelodysplastic Syndrome (MDS): A Population Based Study
Authors: Annie M. Jacobsen, Jenny Poynter, Michaela Richardson, Phuong L. Nguyen, Betsy A Hirsch, Adina Cioc, Michelle A. Roesler, Erica D. Warlick
Journal: Blood (2018)
Phase Ib/II trial of lenvatinib plus pembrolizumab in urothelial cancer.
Authors: Nicholas J. Vogelzang, Carlos A. Encarnacion, Allen Lee Cohn, Christopher DiSimone, Drew W. Rasco, Donald A. Richards, Matthew H. Taylor, Corina E. Dutcus, Daniel E. Stepan, Robert Charles Shumaker, Matthew Guo, Emmett V. Schmidt, James Walter Mier
Journal: Journal of Clinical Oncology (2019)

11 Background: Pembrolizumab (PEM), an anti-PD-1 antibody, is approved for advanced urothelial cancer in the second-line setting (objective response rate [ORR] 21%) and in the first-line setting for patients (pts) ineligible for cisplatin with combined positive score ≥10 or ineligible for platinum-based chemotherapy (ORR 29%). Tyrosine kinase inhibitors such as lenvatinib (LEN; a multikinase inhibitor of VEGFR 1-3, FGFR 1-3, PDGFRα, RET and KIT) have demonstrated activity in urothelial cancer and may reverse the immunosuppressive environment that leads to immuno-oncology (IO) failure. We present a phase 1b/2 trial of LEN + PEM in advanced urothelial cancer. Methods: In this multicenter, open-label study, pts with confirmed metastatic urothelial cancer and ECOG PS of 0 or 1 received oral LEN 20 mg/day + PEM (200 mg Q3W, IV). Pts were not preselected for PD-L1 status. The phase 2 primary end point was investigator-assessed ORR at week 24 (ORR wk24 ) per immune-related RECIST (irRECIST). Secondary end points included ORR, duration of response (DOR), and progression-free survival (PFS). Results: At data cutoff (March 1, 2018), 20 pts were enrolled: 9 (45%) PD-L1(+), 5 (25%) PD-L1(-); 6 (30%) not tested. 4 Pts (20%) were treatment-naïve; 11 (55%) and 5 (25%) pts had had 1 and 2 lines of prior anticancer therapies, respectively. No pt had received prior IO. ORR wk24 was 25% (95% CI: 8.7–49.1). 18 (90%) pts had ≥1 treatment-related adverse event (TRAE). Grade 3 and 4 TRAEs occurred in 5 (25%) and 5 (25%) pts, respectively. There was 1 fatal TRAE (gastrointestinal hemorrhage). The most common any-grade TRAEs were proteinuria (45%), diarrhea (40%), fatigue (30%), hypertension (30%), and hypothyroidism (30%). Conclusions: LEN + PEM demonstrated activity in this study of pts with advanced urothelial cancer, which included pts receiving later-line treatment, and deserves further investigation. Clinical trial information: NCT02501096. [Table: see text]
Safety and efficacy of four drug regimens in newly diagnosed multiple myeloma: Systematic review.
Authors: Udhayvir Singh Grewal, Rajshekhar Chakraborty, Fazal I Raziq, Afia Ashraf, Ammara Majeed, Vikas Kapoor, Anne Hubben, Rujul Parikh, Midhat Lakhani, Azka Latif, Atlantis Dawn Russ, Faiz Anwer
Journal: Journal of Clinical Oncology (2019)

e19537 Background: To improve outcomes, multiple agents with varied mechanisms of action targeting different multiple myeloma (MM) clones are needed. Methods: Systematic review of ongoing phase I-III clinical trials in newly diagnosed multiple myeloma (NDMM) was performed, (PRISMA guidelines) using 5 databases. Results: 8 trials n = 1,990 patients included (Table 1). We evaluated the efficacy of following four drug combinations Isatuximab (Isa), bortezomib (V), lenalidomide (R)dexamethasone (d) (Isa-VRd) Daratumumab (Dara) plus V, Melphalan (M) and Prednisone (P) (Dara-VMP) vs VMP Dara-VRd vs VRd Carfilzomib (K), Cyclophosphamide (C), R, Dexamethasone (KCRD) vs an immunomodulatory agent containing triplet (CTD/CRD) Dara with Ixazomib (I), R,d (Dara- IRd) Dara, Cyclophosphamide (Cy), V,d (Dara-CyBord) Elotuzumab (Elo) VRd Dara with K,R,d (Dara- KRd) For transplant-eligible patients, Dara-VRd demonstrated the best treatment response (VGPR = 100%, CR rate = 63% and 15 months PFS = 94%). Dara-VMP (ORR = 90.9%,VGPR+ = 72.9%, mPFS at 27. 8 m = NR) and Isa+VRd (ORR = 93%, VGPR = 71.43%, 7.5 m PFS = 100%) were associated with improvement in OR in transplant ineligible patients. Dara-KRd showed excellent efficacy (ORR = 100%, ≥VGPR = 86%) with 100% 6 m PFS. Conclusions: Four-drug regimens have improved efficacy (higher ORR, deeper response, higher proportion of MRD negativity and higher ≥VGPR responses) compared to three-drug regimens in NDMM, with a comparable incidence of toxicities. Longer follow-up is needed. [Table: see text]
Steroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism
Authors: Karl-Heinz Storbeck, Lina Schiffer, Elizabeth S Baranowski, Vasileios Chortis, Alessandro Prete, Lise Barnard, Lorna C Gilligan, Angela E Taylor, Jan Idkowiak, Wiebke Arlt, Cedric H L Shackleton
Journal: Endocrine Reviews (2019)

Abstract Steroid biosynthesis and metabolism are reflected by the serum steroid metabolome and, in even more detail, by the 24-hour urine steroid metabolome, which can provide unique insights into alterations of steroid flow and output indicative of underlying conditions. Mass spectrometry–based steroid metabolome profiling has allowed for the identification of unique multisteroid signatures associated with disorders of steroid biosynthesis and metabolism that can be used for personalized approaches to diagnosis, differential diagnosis, and prognostic prediction. Additionally, steroid metabolome analysis has been used successfully as a discovery tool, for the identification of novel steroidogenic disorders and pathways as well as revealing insights into the pathophysiology of adrenal disease. Increased availability and technological advances in mass spectrometry–based methodologies have refocused attention on steroid metabolome profiling and facilitated the development of high-throughput steroid profiling methods soon to reach clinical practice. Furthermore, steroid metabolomics, the combination of mass spectrometry–based steroid analysis with machine learning–based approaches, has facilitated the development of powerful customized diagnostic approaches. In this review, we provide a comprehensive up-to-date overview of the utility of steroid metabolome analysis for the diagnosis and management of inborn disorders of steroidogenesis and autonomous adrenal steroid excess in the context of adrenal tumors.
Cutaneous Scapular Lesion in an Elderly Woman
Authors: Nicole Brighi, Giuseppe Lamberti, Davide Campana
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
Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry
Authors: Sandra J. Guzmán-Castañeda, Esteban L. Ortega-Vega, Jacobo de la Cuesta-Zuluaga, Eliana P. Velásquez-Mejía, Winston Rojas, Gabriel Bedoya, Juan S. Escobar
Journal: Gut Microbes (2019)

Cardiometabolic affections greatly contribute to the global burden of disease. The susceptibility to obesity, cardiovascular disease, and type-2 diabetes, conditions that add to the cardiometabolic syndrome (CMS), was associated with the ancestral genetic composition and gut microbiota. Studies explicitly testing associations between genetic ancestry and gut microbes are growing. We here examined whether the host genetic ancestry was associated with gut microbiota composition, and distinguished the effects of genetic ancestry and non-genetic factors on human cardiometabolic health. We performed a cross-sectional study with 441 community-dwelling Colombian mestizos from five cities spanning the Andes, Pacific, and Caribbean coasts. We characterized the host genetic ancestry by genotyping 40 ancestry informative markers; characterized gut microbiota through 16S rRNA gene sequencing; assessed diet intake, physical activity, cigarette, and medicament consumption; and measured cardiometabolic outcomes that allowed calculating a CMS risk scale. On average, each individual of our cohort was 67 ± 6% European, 21 ± 5% Native American and 12 ± 5% African. Multivariable-adjusted generalized linear models showed that individuals with higher Native American and African ancestries had increased fasting insulin, body mass index and CMS risk, as assessed by the CMS risk scale. Furthermore, we identified 21 OTUs associated to the host genetic ancestry and 20 to cardiometabolic health. While we highlight novel associations between genetic ancestry and gut microbiota, we found that the effect of intestinal microbes was more likely to explain the variance in CMS risk scale than the contributions of European, Native American and African genetic backgrounds.
Trastuzumab-containing therapies: Activity beyond disease progression in M.B.C.—A pivotal experience
Authors: S. Del Bianco, R. Rondinelli
Journal: Journal of Clinical Oncology (2006)

10788 Background: To evaluate Trastuzumab containing successive therapies activity in patients with overexpressing metastatic breast cancer (MBC). To determine the response rate (RR), time to progression (TTP) and overall survival (OS). Methods: Pivotal study of Trastuzumab (TZB) activity in HER-2 overexpressing MBC patients enrolled in our institution from 2000 to 2005. Results: 12 pts have been evaluated. Median age: 56; 8/12 postmenopausal,. 10/12 received adjuvant chemotherapy. Hormonal receptors: 8/12 positive, 4/12 negative. 8/12 pts had visceral disease. 11/12 had metastases in ≥ 2 locations. 5/12 pts received TZB as front line for MBC. Median previous lines: 2 (0–5). TZB was first time combined as follows: paclitaxel 7/12, docetaxel 4/12, (1/12 TZB alone). Asintomatic cardiac disfunction (LVEF reduction &gt;10%) or CHF occurred in 1/12 pts (=CHF) after 46 months of TZB-treatment, with cardiac function progressively improving after standard medical care. RR for the 1 st line (TZB containing): 11/12 (CR 3/12, PR 8/12), stable disease (S): 1/12, Clinical benefit (CB) 12/12, Median TTP 9.5 m (3–61+). 9/12 pts received a 2 nd TZB containing therapy. RR for 2 nd TZB-containing line: 4/8 (CR 0/8), SD 4/8, CB: 8/8; Median TTP: 8 months (3–14). All the 8/8 pts received a 3 rd TZB- containing therapy. RR for 3 rd TZB-containing line: 5/8 (CR 1/8), SD: 3/8, CB:8/8; Median TTP: 9 months (1–11). 4/8 pts have received a 4 th or more TZB containing therapy with some long-lasting RR still presents at this time. Median overall survival is 33.5 months (9–61+). Conclusions: TZB-containing therapies beyond disease progression in MBC shows an interesting activity even in heavily pre-treated women. Small number of patients perhaps, do not allow to draw any final conclusion. No significant financial relationships to disclose.
Targeting MYC activity in double-hit lymphoma with MYC and BCL2 and/or BCL6 rearrangements with epigenetic bromodomain inhibitors
Authors: Weiping Li, Shiv K. Gupta, Weiguo Han, Ryan A. Kundson, Sara Nelson, Darlene Knutson, Patricia T. Greipp, Sherine F. Elsawa, Eduardo M. Sotomayor, Mamta Gupta
Journal: Journal of Hematology & Oncology (2019)

Double/triple-hit lymphomas (DHL/THL) account for 5–10% of diffuse large B cell lymphoma (DLBCL) with rearrangement of MYC and BCL2 and/or BCL6 resulting in MYC overexpression. Despite the poor prognosis of DHL, R-CHOP chemotherapy remains the treatment backbone and new targeted therapy is needed. We performed comprehensive cytogenetic studies/fluorescence in situ hybridization on DLBCL and Burkitt lymphoma cell lines (n = 11) to identify the DHL/THL DLBCL in vitro model. We identified MYC/IG in Raji and Ramos (single hit); MYC/IG-BCL2 (DHL) in DOHH2, OCI-LY1, SUDHL2, and OCI-LY10; MYC/IG-BCL2/BCL6 (THL) in VAL; and no MYC rearrangement in U2932 and HBL1 (WT-MYC). Targeting MYC in the DHL/THL DLBCLs through bromodomain extra-terminal inhibitors (BETi) (JQ1, I-BET, and OTX015) significantly (p < 0.05) reduced proliferation, similar to WT-MYC cells, accompanied by decreased MYC but not BCL2 protein. Moreover, BETi suppressed MYC transcription and decreased BRD4 binding to MYC promoter in DHL cells. CD47 and PD-L1 are immunoregulatory molecules often expressed on tumors and regulated by MYC. High levels of surface CD47 but not surface PD-L1 was observed in DHL/THL, which was reduced by JQ1 treatment. BETi in combination with Pan-HDAC inhibitor had a limited effect on survival of DHL/THL, while combination of BETi and BCL2 inhibitor (ABT-199) had a significant (p < 0.005) inhibitory effect on survival followed by BCL-XL inhibition. Overall, the data suggests that MYC-expressing DLBCLs are probably addicted to the MYC-oncogenic effect regardless of MYC rearrangements. In summary, we identified an in vitro model for DHL/THL DLBCLs and provide evidence for the therapeutic potential of BET inhibitor alone or in combination with BCL2 inhibitor.
Induction chemotherapy for organ preservation versus surgery for advanced oral cavity squamous cell carcinoma (OCSCC).
Authors: Steven Bennett Chinn, Mathew E Spector, Emily Light, Tasha Lotus Lin, Theodoros Nicholas Teknos, Mark E Prince, Carol Rossier Bradford, Susan Urba, Thomas E Carey, Gregory T. Wolf, Avraham Eisbruch, Francis P. Worden, Douglas Brian Chepeha
Journal: Journal of Clinical Oncology (2012)

e16014 Background: The objective of the study is to evaluate the outcomes of an induction selection (IS) concurrent chemotherapy protocol versus primary surgical extirpation in advanced OCSCC. Methods: Retrospective quasi-experimental comparison of patients treated by IS versus surgery. The cohorts were matched based on pretreatment characteristics and compared in an intent-to-treat model.19 patients were accrued with resectable stage III/IV OCSCC without bone involvement between 2000-2002 into a phase II IS trial using 1 cycle of IS to select patients for definitive chemoradiation (CRT). Tumor response was evaluated 3-weeks post-infusion. Patients with &gt;50% response underwent concurrent CRT (70Gy; 35 fractions with concurrent cisplatin 100mg/m2 or carboplatin (AUC 6) every 3-weeks for 3 cycles). Those with &lt;50% underwent surgical treatment and radiation therapy. A comparison cohort of patients with primary surgical extirpation was selected from an OCSCC database from 1998-2009. The surgical cohort of 53 patients was identified based on comparable pretreatment variables to the IS cohort. There was no difference in age, gender, pre-treatment AJCC stage, T-class, N-class, smoking status, alcohol status, or subsite between the two cohorts. Results: Kaplan-Meier estimates demonstrated overall survival (OS) at 5-years was 32% in the IS group and 64% in the surgical cohort. Disease-specific survival (DSS) at 5-years was 46% in the IS group and 76% in the surgical cohort. Local-regional control (LRC) at 5-years was 26% in the IS cohort and 72% in the surgical cohort. Multivariable analysis demonstrated significantly better OS, DSS and LRC (p=0.03, p=0.001 and p=0.0002 respectively) in the surgical cohort compared to the IS cohort. Conclusions: Primary surgical treatment showed significantly better OS, DSS and LRC compared to IS in this quasi-experimental designed comparison. These findings support surgery as the principal treatment for OCSCC.