tbuckley/cabot-search huggingface dataset:
Randomized phase II study of panitumumab (Pmab) plus irinotecan (CPT-11) versus cetuximab (Cmab) plus CPT-11 in patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) following treatment with fluoropyrimidine, CPT-11, and oxaliplatin (L-OHP) chemotherapy: WJOG6510G.
Authors: Daisuke Sakai, Hiroya Taniguchi, Takao Tamura, Naotoshi Sugimoto, Taito Esaki, Hiroyuki Okuda, Toshihiko Matsumoto, Kentaro Yamazaki, Tadamichi Denda, Kensei Yamaguchi, Takashi Tsuda, Ayumu Hosokawa, Akitaka Makiyama, Kazutoshi Tobimatsu, Fuminori Goda, Satoshi Otsu, Junji Kishimoto, Narikazu Boku, Shinichiro Nakamura, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2014)

TPS3654 Background: Pmab and Cmab are known to be effective in KRAS WT mCRC. Recent study showed that Pmab and Cmab monotherapy were comparable in patients with KRAS WT mCRC previously treated with fluoropyrimidine-, L-OHP-, and CPT-11- based regimens. However, it is not clear whether their combination therapy with CPT-11 confers similar benefit. Methods: This randomized phase II study of Pmab + CPT-11 or Cmab + CPT-11 recruits patients with mCRC with KRAS WT from 45 sites in Japan. Primary objective is progression free survival (PFS), with a non-inferiority margin of 1.3 (80% CI). Median PFS with both arms is assumed to be 6.0 months. Secondary objectives are overall survival, response rate, disease control rate, and safety. Eligibility: Patients with proven colorectal adenocarcinoma with KRAS (exon 2) WT; unresectable metastatic disease; failed prior regimens containing CPT-11 and L-OHP and fluoropyrimidine; age>=20years; ECOG performance status 0-2; evaluable disease, as defined by the RECIST criteria v1.1; adequate hematologic, renal, hepatic and metabolic function; expected survival>=90 days; written informed consent obtained from the patient. Patients are randomized after stratification by site; PS; refractory or intolerance for L-OHP; previous use of bevacizumab to receive either arm A) Cmab (400 mg/m2 followed by 250 mg/m2 weekly) + CPT-11 (150mg/m2 every 2 weeks) or arm B) Pmab (6 mg/kg every 2 weeks) + CPT-11 (same dose as arm A). Status: Opened to accrual December 2011, at 31 Jan 2014 93/120 patients have been enrolled. Clinical trial information: UMIN000006643.
Older people with anaemia have higher mortality after stroke, finds study
Authors: Susan Mayor
Journal: BMJ (2016)

Risk for older anaemics after stroke

Older people with anaemia have higher mortality for up to one year after having a stroke, an analysis of stroke registry data and a systematic review have shown.1

Anaemia is common in patients with acute stroke, with hospital studies reporting a prevalence of around 30%. It is associated with increased mortality in a range of conditions—including chronic kidney disease, heart failure, and acute coronary syndromes—but observational studies of the impact of anaemia on stroke have shown conflicting results so guidelines have been unable to define optimal treatment for patients …
Lung macrophages: old hands required rather than new blood?
Authors: Karl J Staples
Journal: Thorax (2016)

Macrophages are key sentinel cells of the lung, clearing inhaled particulates and micro-organisms from the airway. These cells perform this function without provoking inflammatory responses that could lead to pneumonias. Previous work suggested that the lung macrophage population was maintained by the recruitment of blood monocytes.1 However, this observation was made in transplanted lungs where macrophages had been depleted, either by hypoxia or chemotherapy. More recent work in murine models using cell fate mapping demonstrated that lung macrophages are generated early in embryonic development initially in the foetal yolk sac and slightly later in the foetal liver.2 Macrophages that arise from these sources then seed the lung, where they reside as a self-renewing population with little further recruitment from blood monocytes.

The relevance and translation of these murine findings to the ontogeny of human lung macrophages has remained unclear. The study by Eguiluz-Gracia et al 3 has provided some intriguing evidence regarding the stability and longevity of the lung macrophage population. This study prospectively followed 10 gender mismatched lung transplant patients for 2 years. Transbronchial biopsies were collected at regular intervals throughout the follow-up period. The macrophage populations in these biopsies were analysed for known macrophage markers, indicators of proliferation and, importantly, in situ hybridisation for the X and Y chromosomes to differentiate between recipient and donor cells. Comparisons to normal lung tissue obtained from cancer resections, suggest that there is no significant difference in the total number of macrophages in transplanted lung tissue across the 2 years. Moreover, while there was a large amount of inter-individual variation the abundance of donor-derived macrophages was largely unchanged …
A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees.
Journal: Circulation (1994)

BACKGROUND Functional benefit in heart failure due to idiopathic dilated cardiomyopathy has been observed after beta-blockade, but improvement in survival has not been established in a large-scale randomized trial. This was the main objective of the Cardiac Insufficiency Bisoprolol Study (CIBIS). METHODS AND RESULTS Six hundred forty-one patients with chronic heart failure of various etiologies and a left ventricular ejection fraction of &lt; 40% entered this placebo-controlled, randomized, double-blind study. Patients were in New York Heart Association functional class III (95%) or IV (5%) at inclusion. All received background diuretic and vasodilator therapy (an angiotensin-converting enzyme inhibitor in 90% of cases). A total of 320 patients was randomized to bisoprolol and 321 to placebo. Mean follow-up was 1.9 years. Bisoprolol was well tolerated without between group difference in premature treatment withdrawals (82 on placebo, 75 on bisoprolol; NS). The observed difference in mortality between groups did not reach statistical significance: 67 patients died on placebo, 53 on bisoprolol (P = .22; relative risk, 0.80; 95% confidence interval, 0.56 to 1.15). No significant difference was observed in sudden death rate (17 on placebo, 15 on bisoprolol) or death related to documented ventricular tachycardia or fibrillation (7 on placebo, 4 on bisoprolol). Bisoprolol significantly improved the functional status of the patients; fewer patients in the bisoprolol group required hospitalization for cardiac decompensation (90 on placebo versus 61 on bisoprolol, P &lt; .01), and more patients improved by at least one New York Heart Association functional class (48 on placebo versus 68 on bisoprolol, P = .04) by the end of follow-up period. CONCLUSIONS These results confirm previous trials evidence that a progressively increasing dose of beta-blocker in severe heart failure confers functional benefit. Subgroup analysis suggested that benefit from beta-blockade therapy was greater for those with nonischemic cardiomyopathy. However, improvement in survival while on beta-blockade remains to be demonstrated.
Opiate Use in London
Authors: A. F. TEGGIN
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Blumberg et al in their article "Opiate Use in London" (232:1131, 1975) describe two groups of patients seen at drug dependency clinics. The group that was not treated with maintenance opiates ("no-script group") tended to use barbiturates more than the "scriptgroup"; also, they tended to have more physical complications, more overdoses, more illegal activities, and more unemployment than the treated group. The implication in the article is that if this group of patients were prescribed opiates, these complications would be avoided; this I dispute. Many patients who present themselves at drug dependency clinics are individuals with personality disorders of the sociopathic type; they are unemployed, have long criminal records, and tend to abuse alcohol and barbiturates. They may have experimented with opiates on odd occasions, but are usually not opiate-dependent and often have no opiates in their urine—as Blumberg et al found. Their motives for attending a
Extracellular matrix protein Matrilin-4 regulates stress-induced HSC proliferation via CXCR4
Authors: Hannah Uckelmann, Sandra Blaszkiewicz, Claudia Nicolae, Simon Haas, Alexandra Schnell, Stephan Wurzer, Raimund Wagener, Attila Aszodi, Marieke Alida Gertruda Essers
Journal: The Journal of Experimental Medicine (2016)

During homeostasis, hematopoietic stem cells (HSCs) are mostly kept in quiescence with only minor contribution to steady-state hematopoiesis. However, in stress situations such as infection, chemotherapy, or transplantation, HSCs are forced to proliferate and rapidly regenerate compromised hematopoietic cells. Little is known about the processes regulating this stress-induced proliferation and expansion of HSCs and progenitors. In this study, we identified the extracellular matrix (ECM) adaptor protein Matrilin-4 (Matn4) as an important negative regulator of the HSC stress response. Matn4 is highly expressed in long-term HSCs; however, it is not required for HSC maintenance under homeostasis. In contrast, Matn4 is strongly down-regulated in HSCs in response to proliferative stress, and Matn4 deficiency results in increased proliferation and expansion of HSCs and progenitors after myelosuppressive chemotherapy, inflammatory stress, and transplantation. This enhanced proliferation is mediated by a transient down-regulation of CXCR4 in Matn4−/− HSCs upon stress, allowing for a more efficient expansion of HSCs. Thus, we have uncovered a novel link between the ECM protein Matn4 and cytokine receptor CXCR4 involved in the regulation of HSC proliferation and expansion under acute stress.
Massive Parallel Sequencing of Full-Length B-Cell Receptor Sequences Reveals HLA-Dependent Shaping of the B-Cell Immune Repertoire
Authors: Marvyn T. Koning, Sander A.J. van der Zeeuw, Marcelo Navarrete, Cornelis A.M. van Bergen, Valeri Nteleah, Marieke Griffioen, Szymon M. Kiełbasa, Hendrik Veelken
Journal: Blood (2014)
Barriers to colorectal cancer screening among African American population.
Authors: Z. M. Bo, V. Ghevariya, M. Ahluwalia, K. Veerabhadrappa, G. M. Villani, S. Anand
Journal: Journal of Clinical Oncology (2010)

1568 Background: African-Americans have the highest incidence and mortality rates of colorectal cancer (CRC) among all races in the United States. Colonoscopy as a screening modality is underutilized, particularly among African Americans. The objective of this study was to explore CRC screening knowledge, attitudes, barriers, and preferences among urban African Americans as a prelude to the development of appropriate interventions to improve CRC screening rates within the community. Methods: We administered a questionnaire to 2000 respondents living in urban downtown Brooklyn and were eligible for CRC screening. The entire questionnaire was designed to explore CRC screening knowledge, attitudes, barriers and preferences. Results: Data from 1,510 African Americans were analyzed. Most participants (87%) were educated and 97% were earning incomes above poverty level. Seven hundred and fourteen participants (47%) receive routine medical care and 640 subjects (42%) had heard about colon cancer from their physician. Advice from a physician was the most common reason for having screening colonoscopy (37%), while concern for the colon cancer prompted 31% to undergo colonoscopy. The majority (75%) of participants did not know that colon cancer runs in families and only 26% were aware that a major goal of colonoscopy was the detection and removal of the precancerous polyps. The screening colonoscopy rate among our study group was only 31%. Pain/discomfort (49%) and fear of complication (24%) were major reasons for not having a colonoscopy. Insurance issues were a deterrent for only 4 responders. Conclusions: Colonoscopy rates are disturbingly low in urban African American population, a phenomenon not explained by income or educational status. Our data suggests that limited utilization of health care resources, lack of knowledge about CRC, lack of consistent physician referral and lack of effective CRC screening educational programs play a larger role in low CRC screening rates among our study participants. These findings highlight the importance of consistent, quality access to the health care system, physician counseling and aggressive health educational campaigns with regular reinforcement in order to increase screening rates. No significant financial relationships to disclose.
Nifedipine for Hypertensive Emergencies
Authors: Andrea Semplicini
Journal: JAMA (1997)

<h3>To the Editor.</h3> —We read with interest the report of Dr Grossman and colleagues<sup>1</sup>and the accompanying Editorial by Dr Winker<sup>2</sup>on sublingual nifedipine capsules. We recently performed a systematic search of the available literature on the use of short-acting nifedipine preparations in hypertensive emergencies and reached different conclusions. We retrieved 76 uncontrolled and 45 comparison studies from the EM Base and the Derwent Drug File databases between January 1977 and March 1996. The search included published articles and abstracts, but duplicate publications were excluded. The results are summarized in Table 1. The number of effectively treated cases is underestimated owing to publication bias. Therefore, the risk of serious adverse effects per treated patient should even be lower. Moreover, based on our findings as well as those of Grossman et al, adverse effects are more likely to occur in older patients, who are at higher risk of developing hypoperfusion of the
Ultrasociality and the sexual divisions of labor
Authors: Pamela Lyon, Linnda R Caporael
Journal: Behavioral and Brain Sciences (2016)

The ultrasociality thesis proposes that the same "mechanistic evolutionary forces" may be at work in the evolution of insect eusociality and human ultrasociality in relation to agriculture. Wide variation in the reproductive division of labor among differing highly social phyla points to a resemblance of outcomes arising from very different selective environments and possibly different forces.
IgH Gene Rearrangements Are Strongly Associated with Hyperdiploidy Variant Multiple Myeloma in Korea: A Contradiction to the Pathogenetic Pathway of IgH Tranlocations in Non Hyperdiploidy Variant.
Authors: Hee Won Moon, Tae Young Kim, Seong- Ho Kang, Hyun-Sook Chi, Eul Zu Seo, Chan Jeoung Park, Honggu Chun, Hee Chan Kim, Sung-Soo Yoon, Seonyang Park, Byoung Kook Kim, Han Ik Cho, Dong Soon Lee
Journal: Blood (2005)
Radiation Oncologist Concerns About Increased Electronic Brachytherapy Use for Skin Cancer—Reply
Authors: Eleni Linos, Marta VanBeek, Jack S. Resneck
Journal: JAMA Dermatology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Red Blood Cell Transfusion Strategies and Health Care–Associated Infection
Authors: Tetsuji Fujita
Journal: JAMA (2014)

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
Antitumor Properties of an IgG2-Enhanced Next-Generation MET Monoclonal Antibody That Degrades Wild-Type and Mutant MET Receptors
Authors: Yan Yang, Sreekala Mandiyan, Brett S. Robinson, Gerald McMahon
Journal: Cancer Research (2016)

A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14-mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb) that block MET-dependent signaling and tumor growth. In particular, the MET mAb KTN0073 and KTN0074 bind the Sema/PSI domain, at overlapping but distinct epitopes, preventing HGF interaction with MET and triggering receptor ubiquitination and degradation. Notably, both mAbs also triggered degradation of oncogenic MET exon 14 mutants, which propagate more durable MET signals due to a defect in receptor degradation. Mechanistic investigations showed that both mAbs engaged a pathway distinct from HGF-induced receptor degradation and protease-mediated shedding, independently of signaling driven by the exon 14-encoded sequences in the intracellular juxtamembrane region of the MET receptor. Grafting the mAb variable regions onto the IgG2 constant region dramatically enhanced the tumor inhibitory activities of KTN0073 but not KTN0074, suggesting a specific influence of antibody isotype of the epitopes for these two MET mAbs. Overall, our results highlight KTN0073 as a novel IgG2-based MET mAb that acts through exon 14-independent mechanisms to degrade the MET receptor, potentially offering a therapeutic tool to treat a broader range of human tumors where MET is exon 14 mutated or amplified. Cancer Res; 76(19); 5788-97. ©2016 AACR.
Margaret McCartney: Staff hold the answer to our failing NHS
Authors: Margaret McCartney
Journal: BMJ (2016)

The NHS will not suddenly fail. Instead, it’s being made to fail in degrees.

The workplace will become unbearably stressful. Staff will leave or work fewer hours. Patients will be less well cared for as gaps on rotas widen. General practices will go bust. Schoolchildren will read the headlines, see the hours doctors work, and think: maybe medicine’s not for me.

The small cracks in the NHS that have been papered over with goodwill and vocation are gaping now, for the stock ingredients are running out. Staff are exhausted and distressed, practising in …
Specific MLL Fusion Partners Affect the Sensitivity of Human and Murine Leukemic Cell Lines to Demethylating Agents
Authors: Atsushi Fujiki, Toshihiko Imamura, Hideki Yoshida, Yoshifumi Hirashima, Mitsuru Miyachi, Shigeki Yagyu, Kanji Sugita, Hajime Hosoi
Journal: Blood (2010)
Admission for infection is linked to increased suicide risk
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Patients admitted to hospital because of infections have a 42% increased risk of death by suicide, a study published in JAMA Psychiatry has found.1

Infection and inflammation have increasingly been linked with a potential critical role in psychiatric disorders and suicidal behaviour, so the researchers attempted to estimate the association between admission for infection and the risk of death by suicide. They used data from Danish longitudinal registers on 7.22 million people aged over 15 living in Denmark …
Les premières 48 heures de l’investigation d’une épidémie de légionellose aux Pays-Bas
Authors: J. E. van Steenbergen, F. A.N. Slijkerman, P Speelman
Journal: Eurosurveillance (1999)

La Westfriese Flora est une exposition florale qui a lieu chaque annee durant une semaine a Bovenkarspel, au nord ouest des Pays-Bas, parallelement a des manifestations organisees par les agriculteurs et les consommateurs dans les memes locaux. Cette annee, l’exposition s’est tenue du 19 au 28 fevrier et a attire 80 000 visiteurs de tout le pays. A l’issue de cette exposition, 181 personnes qui l’avaient visitee durant la seconde moitie de la semaine ont declare une pneumonie a Legionella et 21 en sont decedees (1,2). Cet article decrit les enquetes et les actions menees au cours des deux premiers jours, ayant conduit a une alerte nationale et a la formulation d’hypotheses de travail pour la suite de l’enquete.