tbuckley/cabot-search huggingface dataset:
IgM myeloma: A multicenter retrospective study of 134 patients
Authors: Jorge J. Castillo, Artur Jurczyszyn, Lucie Brozova, Edvan Crusoe, Jacek Czepiel, Julio Davila, Angela Dispenzieri, Marion Eveillard, Mark A. Fiala, Irene M. Ghobrial, Alessandro Gozzetti, Joshua N. Gustine, Roman Hajek, Vania Hungria, Jiri Jarkovsky, David Jayabalan, Jacob P. Laubach, Barbara Lewicka, Vladimir Maisnar, Elisabet E. Manasanch, Philippe Moreau, Elizabeth A. Morgan, Hareth Nahi, Ruben Niesvizky, Claudia Paba‐Prada, Tomas Pika, Ludek Pour, John L. Reagan, Paul G. Richardson, Jatin Shah, Ivan Spicka, Ravi Vij, Anna Waszczuk‐Gajda, Morie A. Gertz
Journal: American Journal of Hematology (2017)

Abstract IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by &gt;10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL −1 with 19% of patients presenting with levels &gt;6,000 mg dL −1 . International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t (11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival ( P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.
Abstract 15589: Relationship Between Left Atrial Volume Index and Left Atrial Appendage Function in Patients With Non-Valvular Atrial Fibrillation and a Cha2ds2-vasc Score of 0-1
Authors: Keisuke Minami, Masaki Izumo, Kihei Yoneyama, Yoshihiro J Akashi
Journal: Circulation (2015)

Introduction: The management of patients with non-valvular atrial fibrillation (NVAF) and low CHA2DS2-VASc scores remains controversial. Left atrial appendage (LAA) function is a known risk factor for embolisms. Hypothesis: In this study, we aimed to investigate the value of the relationship between transthoracic echocardiography (TTE) parameters and LAA function in low-risk (CHA2DS2-VASc score, 0-1) patients with NVAF. Methods: This retrospective study included 370 consecutive patients with NVAF who underwent both TTE and transesophageal echocardiography (TEE). The LAA emptying flow velocity was assessed using TEE. We established that an LAA emptying flow velocity of &lt;25 cm/s was associated with a high risk of thrombus formation. Results: Of the 370 patients, 146 (40%) had a CHA2DS2-VASc score of 0-1. These patients with low-risk NVAF were further stratified into the low-flow (LAA emptying flow velocity &lt; 25 cm/s, n = 19) and normal-flow (LAA emptying flow velocity ≥ 25 cm/s, n = 127) groups according to LAA function (atrial fibrillation during TEE: n = 63). The age, gender, CHA2DS2-VASc score, and left ventricular ejection fraction did not differ between the two groups. The low-flow group had a significantly greater left atrial volume index (LAVI) than the normal-flow group (51.6 ± 19.8 vs. 32.3 ± 12.1 ml/m2, p &lt; 0.01). A LAVI of 37.8 ml/m2 predicted a LAA emptying flow velocity of &lt;25 cm/s with a sensitivity of 73% and specificity of 83% among patients with low-risk atrial fibrillation (area under the curve, 0.818, p &lt; 0.001, Figure). Conclusions: Approximately 13% of patients with NVAF and CHA2DS2-VASc score of 0-1 had reduced LAA emptying flow velocity as well as left atrial enlargement. The use of LAVI may improve the current embolism risk stratification system among these patients.
Abstract 264: Out-of-Hospital Cardiac Arrest: The Cumulative Effect of Bystander Cardiopulmonary Resuscitation, Automated External Defibrillator and Automated Load Distributing Band Device Use on Return of Spontaneous Circulation
Authors: Nabil El Sanadi, Todd Leduc, Gabriel Thornton, David Erdman, Jason Mansour, Trine Engebretsen Labbe
Journal: Circulation Research (2012)

Introduction : Early bystander C.P.R., A.E.D. use and continuous chest compressions are essential elements of the a.h.a. “chain of survival”. Bystander C.P.R. and A.E.D. use in urban settings are becoming more prevalent. The use of an automated load distributing band (l.d.b.) device for O.H.C.A. management in a large metropolitan area by paramedics was implemented in the winter of 2007; in 9 municipalities, 582 paramedics were trained to use the l.d.b. device as part of a.l.s. measures. A retrospective paramedic “run-sheet” review was performed from 4/2008 - 8/2009 for all nontraumatic adult cardiac arrests. R.O.S.C. on arrival to the emergency departments (e.d.) was the endpoint. Methods: 86 adult nontraumatic O.H.C.A. rehorts were found. each of the prehospital reports were reviewed. Utstein data elements were collected. bystander C.P.R. with “caller-aided” dispatch, A.E.D. use, paramedic use of standard a.h.a. resuscitation alogarthythms in addition to use of an automated l.d.b. device use (auto pulse® zoll) was recorded. Minitab 15 statistical software was used to evaluate the data. The cumulative effect of sequential “chain-of-survival” components was calculated. Results: the mean age was 63 Y.O.; there were 58 males and 28 females. The initial rhythm was: v.fib, pulseless v.tach, P.E.A., or asystole. Chain of survival cumulative synergistic effect on R.O.S.C. Conclusion: When bystander C.P.R., in addition to A.E.D. and autopulse were utilized synegistically, R.O.S.C. on e.d. arrival was 71%. When bystander C.P.R. and autopulse were used (without A.E.D. use) only 49% of patients had R.O.S.C. on e.d. arrival. Which is higher than previously reported: Hallstrom et al. (2006): 26% and Ong et al. (2006): 35%. When the l.d.b. device was used with a.l.s., R.O.S.C. was only 20%; which may be due to delayed care; since no efforts were made to resuscitate patients until the paramedics arrived. Our data reaffirms that early bystander C.P.R. and A.E.D. use are essential for achieving a high rate of R.O.S.C.
Irinotecan (CPT-11) in combination with raltitrexed (TX) in patients with previously untreated, advanced colorectal cancer (ACC) patients. Preliminary results of a phase I/II trial
Authors: F. Losa, H. Manzano, P. Vicente, J. Rifa, J. Ocaña, M. Balcells, D. Mediavilla, L. Heras
Journal: Journal of Clinical Oncology (2004)

3675 Background: CPT-11 and TX are active agents in ACC. We present the preliminary results of a phase I/II study of CPT-11 and TX, administered biweekly in previously untreated ACC patients. The main study objective was to determine the optimal dose for this combination, and to evaluate efficacy and safety profiles. Methods: Patients with previously untreated, histologically confirmed, unresectable ACC were included if they had measurable disease; adequate bone marrow, liver and renal functions; life expectancy > 3 months; Karnofsky Index ≥ 60%, and written informed consent. Patients received CPT-11 at different dose levels (level I: 180 mg/m2; level II: 200 mg/m2; level III: 250 mg/m2) administered as a 30 minute IV infusion, combined with TX at a fixed dose of 2 mg/m2 administered as a 15 minute IV infusion. The combination is given on day 1 every 14 days. Response is evaluated every 5 infusions (1 cycle). A maximum of 2 cycles are planned. Results: 11 patients have been included to date, 9 in level I and 2 in level II. Median age is 64.57 years (σ 8.10). PS 0 /1:33,3% /66 .7%. Metastases were present in 1 site in 22% of patients and at >1 site in 77.8% of patients. 68 infusions have been administered. 8 patients have completed the first cycle (5 infusions) and 3 patients have completed the second cycle (10 infusions). The preliminary results of phase I have not established the maximim-tolerated dose (MTD) because only 1 patient has presented an episode of dose-limiting toxicity (DLT), in this case level 1 liver toxicity (transaminase). 6 patients have been assessed for response: 1 achieved complete response, 2 partial response, disease stabilized in 1 patient and the disease progressed in 1 patient during treatment. Conclusions: The MTD has not yet been established, but the study is on-going. Preliminary results suggest that this regimen is active and has a good safety profile. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Prasfarma/Almirall
Cannabis Use and Risk for Substance Use Disorders and Mood or Anxiety Disorders
Authors: Kevin P. Hill
Journal: JAMA (2017)

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
Gemcitabine (GEM) as salvage therapy in patients (pts) with advanced colorectal cancer (CRC) refractory to 5-fluorouracil (FU), irinotecan (IRI) and oxaliplatin (OXA)
Authors: S. Lonardi, M. K. Paris, M. Stefani, C. Caroti, M. D'Amico, A. Jirillo, P. Pronzato, L. Gallo, S. Monfardini, C. Aschele
Journal: Journal of Clinical Oncology (2004)

3577 Background: Sequential combinations of FU and IRI or OXA are currently used as 1st and 2nd line therapy for advanced CRC. Multiple trials are also investigating the concomitant use of the three drugs up-front. Progressing pts with an acceptable PS often continue to require treatment. GEM has shown clinical activity in adenocarcinomas of multiple sites and has a favorable toxicity profile. Methods: Since September 2000, 41 pts with progressive advanced CRC (males/females: 27/14; median age 66; ECOG PS 0/1/2: 10/25/6) previously treated with FU, IRI and OXA were accrued in a phase II study of GEM (1000 mg/m2 weekly x 7, then weekly x 3 q 4 weeks) with abrogation of progression as the main end-point. 22 pts had been treated with a triple combination including FU, IRI and OXA as 1st line therapy receiving GEM as 2nd line treatment, while for 19 pts GEM was given as salvage treatment after a median of 2 previous CT lines (range 2–4). Results: Overall, 71 cycles (1 cycle=8 weeks) were delivered (92.6% of the planned weekly administrations). The median number of cycles administered to each patient was 2 (range 1–4) and the median number of weeks of CT was 7 (range 6–22). Only 29/425 (6.8%) weeks of GEM were delayed while 39/425 (9.2%) were delivered at a reduced dose. Toxicity was mild with only 1 and 7 of the pts experiencing grade IV (neutropenia) and grade III (1 vomiting, 1 asthenia, 3 thrombocytopenia and 1 neutropenia) events, respectively. Flu-like syndrome was observed in 16 pts, of which only 3 complained of grade II. 3 pts are still completing the first cycle. Response was analysed on all the other pts according to the intention-to-treat principle (n=38) and 1 PR, 2 MR, 17 SD and 18 PD were observed. Overall, disease control was obtained in 20 of 37 cases, equally distributed in the two subgroups (54.5% in the cohort receiving GEM as 2nd line treatment and 50.0% in the group receiving GEM as salvage therapy; p=0.78, chi-square test). Conclusions: These data suggest that GEM is well tolerated and may abrogate disease-progression in approximately half of the pts refractory to FU, IRI and OXA. A larger confirmatory trial is planned. No significant financial relationships to disclose.
Development of renal cell carcinoma in patients with primary uveal melanoma.
Authors: Matias Emanuel Valsecchi, Aakanksha Asija, Takami Sato, Carol L Shields, Jerry A Shields, Jennifer Richards-Yutz, Arupa Ganguly, Michael J. Mastrangelo, Jianqing Lin
Journal: Journal of Clinical Oncology (2013)

e15563 Background: Somatic mutations of BRCA1 associated protein1 (BAP1), a tumor suppressor gene, located on chromosome 3p21.1 is found in 50% of primary uveal melanoma (UM) and has been linked to an aggressive phenotype. It is recently reported that somatic BAP1 mutation is also found in 15% of renal cell carcinomas (RCC). We hypothesize that germ line or somatic mutation of BAP1 may contribute the carcinogenesis of patients (pts) who have both UM and RCC. Methods: Retrospective chart review on patients with primary UM treated at Wills Eye Institute and Thomas Jefferson University between 1997 and 2012 revealed 15 patients with both UM and histologically proven RCC. Clinical information on these patients was analyzed. Tumor tissue and blood specimens were also collected for BAP1 gene mutation analysis. Results: Of the 15 patients, 12 (80%) were males. Median age at diagnosis of UM was 57 years old. Six of these patients developed liver metastasis on follow-up (40%). From 8 patients whose pathology data on RCC were available, 6 of them were clear cell type (75%), one was papillary type-1 and one was multilocular cystic subtype. The diagnosis of RCC proceeded the UM diagnosis in 5 of 15 patients, while the diagnoses were made concurrently in 4 patients. Six patients were diagnosed with UM first. For pts who had genetic testing on UM, chromosome 3 abnormalities are the most common abnormalities found. Peripheral blood specimens were tested for 2 patients and germ-line BAP1 mutation was not discovered. Detailed tumor tissue BAP1 mutation analysis is ongoing. Conclusions: The development of RCC is relative common for UM and the molecular mechanism is being determined. It is male dominant in sex and mostly clear cell type in histology of RCC. Further gene mutation analysis and its association with clinical data will be reported.
Reevaluating Postnatal Steroids for Extremely Preterm Infants to Prevent Lung Disease
Authors: Neil Marlow
Journal: JAMA (2017)

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
New graded prognostic index (GPI) for melanoma patients with brain metastasis (MBM).
Authors: Vyshak Alva Venur, Susmita Sakruti, Lingling Du, Jaskirat Singh Randhawa, Eberechi Sandra Agwa, Erin Sennett Murphy, Jennifer Yu, Samuel T. Chao, John H. Suh, Paul Elson, Lilyana Angelov, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2014)

9089 Background: Melanoma is the third most common cause of brain metastasis (BM) and graded prognostic assessment (GPA) is used as a prognostic index for MBM. We evaluated prognostic factors that predict overall survival (OS) in MBM treated at a single tertiary care institution. A preliminary data was presented at ASCO 2013. Methods: With IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify MBM treated between 1999 and 2011. OS from the diagnosis of MBM was the primary end point.Cox proportional hazard models were used for data analysis. Stepwise variable selection was used to identify independent prognostic factors. Results: 176 MBM charts were reviewed and 159 were included for analysis. Primary site of melanoma was head and neck in 27 (22%), trunk and abdomen in 48 (39%), limbs in 46 (37%) and uvea in 2 (2%) patients. Karnofsky performance scale (KPS) was 90-100 in 67 patients (44%), 70-80 in 70 (46%) and <70 in 15 (10%) patients. Single BM was noted in 48 (31%), 2-3 BM in 52 (34%) and more than 3 was seen in 55 (35%) patients. One hundred, twenty two patients (76%) were symptomatic at diagnosis. One hundred, eight (68%) patients had supratentorial BM, 45 (28%) had both supra-and infratentorial and 6 (4%) had only infratentorial BM. Initial therapy included stereotactic radiosurgery (SRS) in 50 (31%) patients, whole brain radiation (WBRT) in 36 (23%), surgery (S) + WBRT in 30 (19%), WBRT + SRS in 24 (15%) and S + SRS in 9 (6%) patients, while 3 patients underwent only S, 6 patients were observed. Median OS from diagnosis of BM was 5.7 months (95% C.I. 4.4-6.8). The conventional disease specific GPA for MBM that includes KPS and number of brain metastasis was prognostic for survival (p<.0001). On multivariate analysis, the number of extracranial metastasis (ECM) at diagnosis of BM was prognostic for OS. Conclusions: A new GPI for MBM with KPS, number of BM and number of ECM is proposed. Factor Median Survival (months) p value KPS 90-100 7.2 0.001 70-80 5.3 <70 2.1 Number of BM 1 7.4 0.002 2-3 6.7 >3 4.4 Number of ECM 0 8.9 <0.001 1-2 6.7 3 4.4 >4 2.6
A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid Signaling
Authors: Asaf Vivante, Nina Mann, Hagith Yonath, Anna-Carina Weiss, Maike Getwan, Michael M. Kaminski, Tobias Bohnenpoll, Catherine Teyssier, Jing Chen, Shirlee Shril, Amelie T. van der Ven, Hadas Ityel, Johanna Magdalena Schmidt, Eugen Widmeier, Stuart B. Bauer, Simone Sanna-Cherchi, Ali G. Gharavi, Weining Lu, Daniella Magen, Rachel Shukrun, Richard P. Lifton, Velibor Tasic, Horia C. Stanescu, Vincent Cavaillès, Robert Kleta, Yair Anikster, Benjamin Dekel, Andreas Kispert, Soeren S. Lienkamp, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2017)

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene ( NRIP1 ) in all seven affected members. NRIP1 encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity. Unlike wild-type NRIP1, the altered NRIP1 protein did not translocate to the nucleus, did not interact with RAR α , and failed to inhibit retinoic acid–dependent transcriptional activity upon expression in HEK293 cells. Notably, we also showed that treatment with retinoic acid enhanced NRIP1 binding to RAR α . RNA in situ hybridization confirmed Nrip1 expression in the developing urogenital system of the mouse. In explant cultures of embryonic kidney rudiments, retinoic acid stimulated Nrip1 expression, whereas a pan-RAR antagonist strongly reduced it. Furthermore, mice heterozygous for a null allele of Nrip1 showed a CAKUT-spectrum phenotype. Finally, expression and knockdown experiments in Xenopus laevis confirmed an evolutionarily conserved role for NRIP1 in renal development. These data indicate that dominant NRIP1 mutations can cause CAKUT by interference with retinoic acid transcriptional signaling, shedding light on the well documented association between abnormal vitamin A levels and renal malformations in humans, and suggest a possible gene-environment pathomechanism in this disease.
Comparing two methods of meta-analysis in clinical research - individual patient data-based (IPD) and literature-based abstracted data (AD) methods: Analyzing five oncology issues involving more than 10,000 patients in randomized clinical trials (RCTs)
Authors: E. Bria, R. J. Gralla, H. Raftopoulos, D. Giannarelli
Journal: Journal of Clinical Oncology (2007)

6512 Background: Meta-analyses are one of the highest recommendations levels in Evidence-Based Medicine (EBM). Recently, meta-analyses have increased using either IPD or AD methods. Controversy exists regarding reliability, applicability and feasibility of the different methods to draw conclusions from conflicting RCTs and to estimate magnitude of benefit of different treatments. Methods: As seen in the table , we selected 5 major issues in 3 malignancies subjected to IPD meta-analysis, and then conducted AD meta-analyses from publications of the individual studies, using published methods (Bria, Cancer Treat Rev 2006). We required that &gt;90% of patient numbers for both IPD and AD analyses be available. Event-based relative risk ratios (RRs) with 95% confidence intervals (CI) were derived. Fixed- and random-effect models, and absolute benefits (AB) were calculated. Correlations between IPD Hazard Ratios (HRs) and AD-RRs were estimated using a linear regression model according to Pearson (r) and R 2 coefficients (parametric) and Spearman (Rho) coefficient (non- parametric). Results: Results are below. A strong linear correlation exists between IPD-HRs and AD-RRs (r=0.994, R 2 =0.989; p&lt;0.001; Rho=1.00). Conclusions: The strong correlation supports using high quality meta-analyses with either method to resolve major issues. Differences exist between the methods: IDP is well-suited for sensitivity analyses and for hypothesis generation involving issues not originally anticipated; AD is a practical method allowing EBM to be applied rapidly to major issues in oncology in a timely fashion. No significant financial relationships to disclose. [Table: see text]