tbuckley/cabot-search huggingface dataset:
Small cell carcinoma of the cervix.
Authors: D. M. Graham, K. A. Cadoo, J. McCaffrey, D. N. Carney
Journal: Journal of Clinical Oncology (2010)

e15560 Background: Extrapulmonary small cell carcinoma (EPSCC) is rare, comprising < 5% of small cell carcinomas (SmCC). EPSCC of the cervix, which accounts for 5% of invasive cervical carcinomas, is often diagnosed at an early stage and may have a better prognosis than EPSCC affecting other sites. Cervical EPSCC has distinctive clinical and pathologic features, resembling SmCC of the lung. The rarity of the condition hampers the performance of large, controlled studies, such that treatment recommendations are based primarily on retrospective case series. Methods: We report 5 cases of primary cervical EPSCC, diagnosed between January 2008 and December 2009. In each case, diagnosis was confirmed by cervical biopsy, with whole body CT and bone scan or PET/CT performed for staging. Limited disease was defined as EPSCC confined to the cervix and adjacent lymph nodes, with disease beyond those parameters classified as extensive stage. Results: At diagnosis, 2 patients (40%) had extensive disease (age 42, 45). These patients were treated with 6 cycles of carboplatin and etoposide. Both had a partial response, but progressed within 4 months of treatment completion and underwent further chemotherapy. One patient died 16 months from diagnosis, while the second patient has stable disease 22 months following diagnosis.Three patients (60%) had limited disease at diagnosis (age range 26-32). Treatment comprised systemic chemotherapy followed by radiation therapy. Two patients (66%) had a complete response (CR) following platinum and etoposide. A third patient, who was 23 weeks pregnant at diagnosis, received cyclophosphamide and doxorubicin prior to delivery at 35 weeks gestation. As she had only partially responded, carboplatin and etoposide were administered post-partum resulting in a CR. All 3 patients are currently receiving radiation treatment and are disease free, a median of 9 months following diagnosis. Conclusions: Management of cervical EPSCC is based on the principles of treatment for pulmonary SmCC. Reported median survival is 2-3 years with improved outcomes reported in young patients who present with limited disease, and receive multimodality therapy, in keeping with our results. No significant financial relationships to disclose.
Case 23-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Stuart E. Lind, Debra A. Bell
Journal: New England Journal of Medicine (1986)

Presentation of CaseAn 80-year-old woman was admitted to the hospital because of anemia.She was in good health until four months earlier, when she consulted a physician because of increasing fatigue and exertional dyspnea. The hematocrit was 22 percent, although it had ranged between 40 and 42 percent in the past. She was admitted to another hospital, where a barium-enema examination was reported to show retained stool and a redundant colon. An air-contrast upper gastrointestinal study was reported to be negative except for an irregular esophageal mucosa. Colonoscopic examination was attempted, but the examiner was unable to enter the . . .
Life-Threatening Childhood Obesity and Legal Intervention
Authors: Carol Erskine
Journal: JAMA (2011)

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
Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications
Authors: Brigitte Ranque, Aymeric Menet, Pierre Boutouyrie, Ibrahima Bara Diop, Samuel Kingue, Mamadou Diarra, Roland N’Guetta, Dapa Diallo, Saliou Diop, Ibrahima Diagne, Ibrahima Sanogo, Aissata Tolo, David Chelo, Guillaume Wamba, Jean Paul Gonzalez, Cochise Abough’elie, Cheick Oumar Diakite, Youssouf Traore, Gaëlle Legueun, Indou Deme-Ly, Blaise Felix Faye, Moussa Seck, Boidy Kouakou, Ismael Kamara, Sylvain Le Jeune, Xavier Jouven
Journal: Circulation (2016)

Background: Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications. Methods: The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries. Results: Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s, P &lt;0.0001), and lower in SS-Sβ 0 than in SC-Sβ + phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria. Conclusions: PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.
Social and Economic Factors in Patients With Coronary Disease
Authors: Mohammadreza Hojat
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The study reported by Dr Case and colleagues<sup>1</sup>that living alone is an independent risk factor in a recurrent major cardiac event is interesting. The significance of loneliness as a risk factor could have been even greater had information concerning the individual's perception of the extent of experiencing loneliness been taken into consideration. According to the cognitive-attributional model of loneliness,<sup>2</sup>the negative consequences of loneliness are related to the perception of attributes such as causality, stability, and controllability rather than physical isolation. Furthermore, it has been shown that a person's dissatisfaction with, rather than the size of, his or her social network contributes to loneliness.<sup>3</sup> The empirical data reported by Case and colleagues support the proposition made by Lynch<sup>4</sup>that loneliness "can break the human heart." In his book,<i>The Broken Heart: The Medical Consequences of Loneliness</i>, Lynch proposed that loneliness contributed significantly
Case 56-1964
Authors: Alexander Leaf, Benjamin Castleman
Journal: New England Journal of Medicine (1964)

Presentation of CaseA seventy-seven-year-old man entered the hospital because of weakness.He had been well until the onset of fatigue four months previously. During the three months before admission he was anorectic and lost 37 pounds in weight. A barium-enema examination and a gastrointestinal study performed at another hospital were interpreted as negative. He became progressively confused and was intermittently incontinent of urine and feces. Nocturia developed two months before admission, and he experienced lumbar pain during the month before entry.There was no history of dysuria, hematuria, pyuria, urinary retention, edema, orthopnea, paroxysmal nocturnal dyspnea, constipation, food intolerance, . . .
Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma
Authors: Linlin Xu, Khalid S. Mohammad, Hao Wu, Colin Crean, Bradley Poteat, Yinghua Cheng, Angelo A. Cardoso, Christophe Machal, Helmut Hanenberg, Rafat Abonour, Melissa A. Kacena, John Chirgwin, Attaya Suvannasankha, Edward F. Srour
Journal: Cancer Research (2016)

Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166+ multiple myeloma cells homed more efficiently than CD166- cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells. CD166 deficiency in multiple myeloma cell lines or CD138+ bone marrow cells from multiple myeloma patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Furthermore, CD166 deficiency in multiple myeloma cells also reduced the formation of osteolytic disease in vivo after intratibial engraftment. Mechanistic investigation revealed that CD166 expression in multiple myeloma cells inhibited osteoblastogenesis of bone marrow-derived osteoblast progenitors by suppressing Runx2 gene expression. Conversely, CD166 expression in multiple myeloma cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in multiple myeloma cell homing to the bone marrow and multiple myeloma progression, rationalizing its further study as a candidate therapeutic target for multiple myeloma treatment. Cancer Res; 76(23); 6901-10. ©2016 AACR.
The p62-ZZ Domain Inhibitor XRK3F2 Alters Myeloma-Induced Suppression of Osteoblast Differentiation and Is Highly Cytotoxic to Myeloma Cells in Combination with Bortezomib
Authors: Rebecca Silbermann, Dan Zhou, Jumpei Teramachi, Xiang-Qun Xie, G. David Roodman, Noriyoshi Kurihara
Journal: Blood (2014)
Effect of nivolumab (NIVO) in combination with ipilimumab (IPI) versus IPI alone on quality of life (QoL) in patients (pts) with treatment-naïve advanced melanoma (MEL): Results of a phase II study (CheckMate 069).
Authors: Amy Pickar Abernethy, Michael Andrew Postow, Jason Alan Chesney, Kenneth F. Grossmann, Fiona Taylor, Cheryl Coon, Isabelle Gilloteau, Homa Dastani, Paul Gagnier, Caroline Robert
Journal: Journal of Clinical Oncology (2015)

9029 Background: New therapies in advanced MEL improve survival, but QoL preservation is uncertain. NIVO (a PD-1 immune checkpoint inhibitor) and IPI are each approved as monotherapy for advanced MEL. In a phase II, randomized, double-blind study, NIVO (1 mg/kg every 3 weeks [wks; Q3W]; 4 doses) combined with IPI (3 mg/kg Q3W; 4 doses) followed by NIVO (3 mg/kg Q2W) significantly improved response rate and progression-free survival (PFS) versus IPI (3 mg/kg Q3W; 4 doses), with a manageable safety profile, in treatment-naïve pts with advanced MEL. Methods: In this study, QoL measured by EORTC QLQ-C30 and EQ-5D was evaluated at baseline (BL) and Q6W treatment cycles for the first 6 months. Mean changes and non-parametric comparisons are reported. Further analyses are planned to examine longitudinal QoL and the relationship between clinical and pt outcomes. Results: Pts received NIVO + IPI (n = 95) or IPI (n = 47). Adjusted completion rates at BL for EQ-5D utilities and EORTC QLQ-C30, respectively, were 64% and 65% with NIVO + IPI and 77% and 79% with IPI; rates remained stable throughout the study except a notable reduction at wk 13 in NIVO + IPI (48%). While completion rates remained similar to BL in the 2 arms after wk 13, pt numbers for IPI were substantially reduced after wk 13 (n ≤ 14) due to disease progression (median PFS: 3.7 months) or toxicity. NIVO + IPI and IPI had similar mean EORTC QLQ-C30 global health scores at BL (76.9 vs 80.9), wk 7 (69.2 vs 74.5) and wk 13 (78.5 vs 72.2), and similar mean EQ-5D utility index scores at BL (0.861 vs 0.847), wk 7 (0.788 vs 0.789) and wk 13 (0.894 vs 0.834). A transient deterioration in EQ-5D utilities was noted at wk 7 for NIVO + IPI (−0.071; n = 53; P= 0.023) and IPI (−0.055; n = 35; P= 0.140), but scores returned to BL levels at wk 13 and were maintained with NIVO + IPI beyond wk 13 after the switch to NIVO alone. Similar results were noted with EORTC QLQ-C30 scales. Conclusions: NIVO + IPI and IPI alone maintained QoL to a similar level in treatment-naïve pts with advanced MEL, with NIVO + IPI providing superior tumor response and PFS. Studies with increased follow up and pt numbers are needed to confirm these results. Clinical trial information: NCT01927419.
Activation Status of Residual Host Dendritic Cells (DCs) but Not Their Number Governs Donor Lymphocyte Infusion (DLI)-Mediated Responses after Major Histocompatibility Complex (MHC)-Matched AlloBMT.
Authors: Nadira Durakovic, Karl B. Bezak, Ephraim J. Fuchs, Luznik Leo
Journal: Blood (2004)
Risks Associated With Opioid Use
Authors: Russell K. Portenoy
Journal: JAMA (2013)

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
Co-treatment of statins and erlotinib to induce growth arrest and apoptosis in primary TKI-resistant non-small cell lung cancer (NSCLC)-cell lines.
Authors: Christoph Minichsdorfer, Duygu Aydemir
Journal: Journal of Clinical Oncology (2015)

e22181 Background: K-Ras mutations and amplification of MET lead to resistance to tyrosine kinase-inhibitor (TKI) treatment in NSCLC cell lines. HMG-CoA reductase inhibitors are widely prescribed and well tolerated drugs. However, the majority of statins are metabolized in the liver by Cyp3A4, which may lead to interactions with Erlotinib. Therefore we tested the efficacy of Erlotinib with either Fluvastatin or Pitavastatin (Statins), which are both not metabolized by Cyp3A4, for the treatment of primary TKI-resistant NSCLC celllines. Methods: Experiments were carried out with human NSCLC celllines A549 (K-RAS mutation), Calu-6 (K-RAS mutation, P53 mutation), HCC 827 (EGFR mutation, Erlotinib sensitive) and H1993 (MET amplification). Apoptosis was measured by the activity of caspase 3 by cleavage of specific fluorescent caspase substrates, by binding of AnnexinV by FACS analysis or by the cleavage of PARP by Western blot. Inhibition of growth was assessed by MTS assays. The effect of either drug alone or in combination on phosphorylation of AKT and ERK1/2 was evaluated by Western blot. Results: Erlotinib inhibited the growth of HCC 827 cells but had no effect on A549, Calu6 and H1993. Statins led to growth inhibition in all 4 cell lines investigated in a dose dependant manner. However, the combination of statins and Erlotinib was significantly more effective than either drug alone. Erlotinib and Statins failed to induce apoptosis when used as single drugs in A549, Calu6 or H1993. However when a combination of TKI and Statin was used, a significant increase in caspase 3 activity and in the ratio of annexin V positive cells was seen. Moreover an increased cleavage of PARP was shown in the combination treatment. Importantly the activation of survival pathways mediated by phosphorylation of AKT was markedly decreased, by the combined treatment of Erlotinib with either Statin in A549, Calu6 and H1993 cells. ERK 1/2 phosphorylation was reduced in H1993 and Calu6 cells upon combined treatment. Conclusions: Our data indicate, that the treatment of primary EGFR-TKI resistant cells (A549, Calu6 and H1993) with Erlotinib in combination with each Statin leads to growth arrest and apoptosis.
Response to taxane chemotherapy as first subsequent therapy after abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post-hoc analysis of COU-AA-302.
Authors: Johann Sebastian De Bono, Matthew Raymond Smith, Fred Saad, Dana E. Rathkopf, Peter F.A. Mulders, Eric Jay Small, Neal D. Shore, Karim Fizazi, Peter De Porre, Thian San Kheoh, Jinhui Li, Mary Beth Todd, Thomas W. Griffin, Charles J. Ryan
Journal: Journal of Clinical Oncology (2015)

184 Background: In study COU-AA-302 of chemotherapy-naïve men with mCRPC, AA plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival vs placebo plus prednisone (P). There is limited information about response to subsequent therapy after AA. In this post hoc analysis of pts in the AA treatment arm who progressed, we evaluated the clinical outcome to chemotherapy as first subsequent therapy. Methods: In COU-AA-302, 546 pts were randomized and received AA. Clinical outcome and discontinuation data from pts receiving chemotherapy as first subsequent therapy after progressing on AA were collected retrospectively and source verified. Median time to prostate-specific antigen (PSA) progression was estimated using the Kaplan-Meier method. Results: 73% (365/502; 44 still continuing on AA) of pts in the AA treatment arm received ≥ 1 subsequent therapy. Chemotherapy, docetaxel (DOC) or cabazitaxel (CBZ), was the most common first subsequent therapy. As of March 2014, following AA on study 53% (265/502) of pts received taxane chemotherapy (261 DOC, 4 CBZ) as first subsequent therapy. Median duration of first subsequent chemotherapy, mainly DOC, was 3 months (IQR, 1.0-5.0). Results are summarized (Table). Conclusions: This post hoc analysis describes antitumor activity in pts who progressed with AA and received taxane chemotherapy as first subsequent therapy. Despite the limitations of a retrospective analysis, these data support further assessment of subsequent therapies following AA treatment for mCRPC. Clinical trial information: NCT00887198. [Table: see text]
Women with Moderate and Severe Von Willebrand Disease Have a High Morbidity of Gynecological and Obstetric Bleeding
Authors: Eva de Wee, Marieke Knol, Eveline Mauser-Bunschoten, Anske van der Bom, Manon Degenaar-Dujardin, Jeroen C.J. Eikenboom, Karin Fijnvandraat, Arja de Goede-Bolder, Britta Laros-van Gorkom, Paula Ypma, Sonja Zweegman, Karina Meijer, Frank W.G. Leebeek
Journal: Blood (2010)
Familial chilblain lupus due to a gain-of-function mutation in STING
Authors: Nadja König, Christoph Fiehn, Christine Wolf, Max Schuster, Emanuel Cura Costa, Victoria Tüngler, Hugo Ariel Alvarez, Osvaldo Chara, Kerstin Engel, Raphaela Goldbach-Mansky, Claudia Günther, Min Ae Lee-Kirsch
Journal: Annals of the Rheumatic Diseases (2016)

Familial chilblain lupus is a monogenic form of cutaneous lupus erythematosus caused by loss-of-function mutations in the nucleases TREX1 or SAMHD1. In a family without TREX1 or SAMHD1 mutation, we sought to determine the causative gene and the underlying disease pathology. Exome sequencing was used for disease gene identification. Structural analysis was performed by homology modelling and docking simulations. Type I interferon (IFN) activation was assessed in cells transfected with STING cDNA using an IFN-β reporter and Western blotting. IFN signatures in patient blood in response to tofacitinib treatment were measured by RT-PCR of IFN-stimulated genes. In a multigenerational family with five members affected with chilblain lupus, we identified a heterozygous mutation of STING, a signalling molecule in the cytosolic DNA sensing pathway. Structural and functional analyses indicate that mutant STING enhances homodimerisation in the absence of its ligand cGAMP resulting in constitutive type I IFN activation. Treatment of two affected family members with the Janus kinase (JAK) inhibitor tofacitinib led to a marked suppression of the IFN signature. A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus. These findings expand the genetic spectrum of type I IFN-dependent disorders and suggest that JAK inhibition may be of therapeutic value.
Time to Give Up on Cardioprotection?
Authors: Gerd Heusch, Tienush Rassaf
Journal: Circulation Research (2016)

The mortality from acute myocardial infarction (AMI) remains significant, and the prevalence of post-myocardial infarction heart failure is increasing. Therefore, cardioprotection beyond timely reperfusion is needed. Conditioning procedures are the most powerful cardioprotective interventions in animal experiments. However, ischemic preconditioning cannot be used to reduce infarct size in patients with AMI because its occurrence is not predictable; several studies in patients undergoing surgical coronary revascularization report reduced release of creatine kinase and troponin. Ischemic postconditioning reduces infarct size in most, but not all, studies in patients undergoing interventional reperfusion of AMI, but may require direct stenting and exclusion of patients with &gt;6 hours of symptom onset to protect. Remote ischemic conditioning reduces infarct size in patients undergoing interventional reperfusion of AMI, elective percutaneous or surgical coronary revascularization, and other cardiovascular surgery in many, but not in all, studies. Adequate dose-finding phase II studies do not exist. There are only 2 phase III trials, both on remote ischemic conditioning in patients undergoing cardiovascular surgery, both with neutral results in terms of infarct size and clinical outcome, but also both with major problems in trial design. We discuss the difficulties in translation of cardioprotection from animal experiments and proof-of-concept trials to clinical practice. Given that most studies on ischemic postconditioning and all studies on remote ischemic preconditioning in patients with AMI reported reduced infarct size, it would be premature to give up on cardioprotection.