tbuckley/cabot-search huggingface dataset:
First in Human Study with GSK2857916, an Antibody Drug Conjugated to Microtubule-Disrupting Agent Directed Against B-Cell Maturation Antigen (BCMA) in Patients with Relapsed/Refractory Multiple Myeloma (MM): Results from Study BMA117159 Part 1 Dose Escalation
Authors: Adam D. Cohen, Rakesh Popat, Suzanne Trudel, Paul G Richardson, Ed N. Libby, Nikoletta Lendvai, Larry D. Anderson, Heather J. Sutherland, Stephen DeWall, Catherine E Ellis, Zangdong He, Jolly Mazumdar, Catherine Wang, Joanna B. Opalinska, Peter M. Voorhees
Journal: Blood (2016)
Tetracycline Toxicity in A Nonpregnant Woman
Authors: Ivan Damjanov
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Fatal complications of tetracycline intravenously administered have been reported several times in pregnant women,<sup>1-3</sup>but it is less generally appreciated that the same effects may be induced in the absence of pregnancy. Peters et al<sup>4</sup>have recently presented six well-documented cases in nonpregnant women who had clinical and autopsy findings entirely comparable to those previously described in pregnant patients. It is probable that considerably more cases are unrecognized. The present communication deals with a young woman in whom the fatal postoperative course was attributed to tetracycline toxicity. <h3>Report of a Case:—</h3> A 20-year-old nulligravida white female was admitted with pain in the right upper quadrant of the abdomen, nausea, and vomiting of three months' duration. Her health previously had been excellent. Two days prior to admission she had become slightly jaundiced. A clinical diagnosis of cholecystitis was made, and four days after admission, cholesystectomy and
Associations Between Hospital Characteristics, Measure Reporting, and the Centers for Medicare &amp; Medicaid Services Overall Hospital Quality Star Ratings
Authors: John O. DeLancey, Jeffrey Softcheck, Jeanette W. Chung, Cynthia Barnard, Allison R. Dahlke, Karl Y. Bilimoria
Journal: JAMA (2017)

This study uses CMS Overall Hospital Quality Star Rating data to estimate associations between hospital characteristics, number and types of measures reported, and the CMS Hospital Quality Star Ratings.
Effect of MDV3100, an androgen receptor signaling inhibitor, on tumor growth of estrogen and androgen receptor-positive (ER+/AR+) breast cancer xenografts.
Authors: Anthony D. Elias, Dawn R. Cochrane, Britta M. Jacobsen, Diana M. Cittelly, Erin N. Howe, Annie Jean, Nicole S. Spoelstra, Andrew A Protter, Jennifer K. Richer
Journal: Journal of Clinical Oncology (2012)

564 Background: The androgen receptor (AR) is detected by immunohistochemistry in approximately 75% of all invasive breast cancer; with ~88% of ER+ tumors expressing AR. Potent inhibition of AR activity could be a therapeutic strategy in ER+/AR+ breast cancer. MDV3100 is an androgen receptor signaling inhibitor (ARSI), which inhibits AR activity via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation, and inhibition of nuclear AR-DNA binding. MDV3100 has demonstrated an overall survival benefit in men with post-docetaxel prostate cancer. Methods: Two ER+/AR+ breast cancer cell lines, MCF7 and BCK4 (recently derived from a pleurocentesis), were used to assess the proliferative effect of dihydrotestosterone (DHT) and estradiol (E2). The efficacy of MDV3100 at blocking DHT-mediated proliferation was compared to bicalutamide in ER+/AR+ breast cancer cells. MCF7 xenograft studies were performed to determine if MDV3100 can affect DHT or E2 mediated proliferation in vivo. Results: Both bicalutamide and MDV3100 inhibited DHT-mediated proliferation of ER+/AR+ cell lines. Although MDV3100 binds AR very effectively and does not bind ER, it also uniquely inhibited E2-mediated proliferation, while bicalutamide slightly enhanced E2 mediated proliferation. Results presented here demonstrate that MDV3100 inhibited E2-stimulated tumor growth of MCF7 mammary xenografts as effectively as tamoxifen. Conclusions: MDV3100 blocked both DHT- and E2-mediated growth of breast cancer cells, whereas bicalutamide enhanced E2-mediated proliferation. MDV3100 may have unique therapeutic utility in patients with AR+ breast cancer, regardless of ER status. Funding: DOD Breast Cancer Program Idea Award BC074403, Avon Foundation for Women, and University of Colorado Cancer Center pilot project funds to JKR.
New scoring system of IHC for p53 and high AgNOR index characterizes prognosis in SCC
Authors: Muhammad Munir, Mulazim Bukhari, Eyyadh Kamel
Journal: Clinical Cancer Research (2007)

A33  Aims:  To investigate the prognostic significance of the new IHC scoring in SCC and the relationship of AgNOR proliferative index  Materials and methods:  On 80 randomly selected patients with T0 to T4 skin SCC and 20 SCP. Sections from formalin-fixed, paraffin-embedded specimens were stained with AgNOR and immunohistochemically for p53 protein.  Results:  p53 expression was scored according to the new scoring criteria and correlated positively with mAgNOR and pAgNOR. IHC scores of p53 and AgNOR index were associated with grading and staging of SCC. This relationship indicated that tumors expressing high score of p53 and AgNOR index are more aggressive with poor prognosis when compared with SCP with low p53 expression and AgNOR index. Correlation between p53 expression and its scoring system revealed that it might be involved in several biologic processes including apoptosis and cell proliferation. The expression of p53 protein, particularly in combination with AgNOR index has definite prognostic value in SCC. This two-parameter, combination between p53 expression and AgNOR index revealed an enhanced prognostic potential when compared with single parameters.  Conclusion:  Our new method of p53 scoring is informative, reproducible and easy to perform on all types of biopsies received in any lab. It helps in differentiation, grading and staging of malignant neoplasms. It also helps to differentiate between benign and premalignant lesions of the skin and mucous membranes that sometimes creates a lot of problems on H&E sections. It will help oncologists to assess the prognosis of any malignancy and check the efficacy of their therapeutic modalities in the future.
Identification of New BMP6 Pro-Peptide Mutations in Patients with Unexplained Iron-Overload
Authors: Chiara Piubelli, Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
Journal: Blood (2016)
Psychosomatic Aspects of Patients on Hemodialysis
Authors: I Fukunishi
Journal: Psychotherapy and Psychosomatics (1990)

The relationship between quality of life (QOL) and alexithymia was examined in dialysis patients. Hemodialysis (HD) patients with diabetic nephropathy had poor QOL in medical dimension. Although they had good QOL in psychological and social dimensions, a high prevalence of alexithymia associated with self-control ability was observed. These results suggest that their inability to care for themselves was reflected in poor medical dimension, and that good psychological and social dimensions were merely an outward appearance. Therefore, identification of alexithymia in dialysis patients is important along with a three-dimensional evaluation of QOL. Multidisciplinary comprehensive assessment of QOL including alexithymia will lead to a real improvement of dialysis patients' QOL.
Elevated phosphorylated mammalian target of rapamycin (p-mtor) expression in human neoplasms
Authors: J. S. Ross, J. Qian, C. Sheehan, D. Jones, T. Jennings
Journal: Journal of Clinical Oncology (2007)

10571 Background: Mammalian target of rapamycin (mTOR) regulates several cell functions critical to tumorigenesis including proliferation, growth, mobility and survival. mTOR expression and dysregulation have been reported carcinomas of breast, head &amp; neck, liver and kidney, but have not yet been studied in non small cell lung cancers (NSCLC), colorectal adenocarcinomas (CRC), nor brain tumors including gemistocytic astrocytomas (GA) and glioblastomas (GBM). Methods: Formalin-fixed paraffin-embedded tissue sections from 121 NSCLC [45 squamous cell carcinomas (SCC), 45 pure adenocarcinomas (AC), and 31 bronchioloalveolar carcinomas (BAC) including both pure BAC and adenocarcinomas with BAC features], 108 CRC, 8 GA and 24 GBM were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using monoclonal rabbit anti-human p-mTOR antibody (Cell Signaling, Danvers, MA). Immunohistochemical assessment included intensity and percentage of positive cells in both benign and carcinomatous elements. Results were correlated with morphologic and prognostic variables in NSCLC and CRC and GBM. Results: Elevated p-mTOR expression was noted in 33% SCCs, 64% ACs, and 65% BAC, 78% CRC, 75% GA and 96% GBM. For NSCLC, increased expression of p-mTOR correlated with histologic subtype (p=0.004). Within SCC greater than 3 cm in size, only 20% had an increase in p-mTOR, while 53% of SCC ≤ 3 cm showed an increase in p-mTOR expression (p=0.03). 100% high grade vs. 43% low grade (p=0.05) and 100% advanced stage (p=0.037) vs. 54% low stage BAC showed an increase in p-mTOR. Consistently, 100% BACs with positive lymph node status vs. 54% node negative BACs showed an increased level of p-mTOR (p=0.037). For CRC, p-mTOR over-expression correlated with high tumor grade (80% Grade 3 vs 50% Grade 1 p=0.042). Majority of GA (6/8) and nearly all GBM (23/24) were positive for p-mTOR (p=0.135). Conclusions: Activated mTOR protein, defined by phosphorylation of mTOR at Serine-2448 (p-mTOR), is increased in NSCLC, CRC and both GA and GBM. These findings suggest a potential role for mTOR dysregulation in lung, colon and brain tumorigenesis and support the currently ongoing clinical trials investigating the therapeutic relevance of rapamycin analogs in the treatment of these tumors. No significant financial relationships to disclose.
Drug company Aspen faces probe over hiking generic prices
Authors: Nigel Hawkes
Journal: BMJ (2017)

The European Commission has launched an investigation into increased prices on cancer drugs imposed by Aspen, a South African company.

Aspen acquired five drugs from GlaxoSmithKline (GSK) in 2009 in a deal worth $2.2bn (then about £1.4bn) in cash and shares. Aspen increased the UK price of busulfan, a leukaemia drug, from £5.20 to £69.02 a pack. Chlorambucil, also used in leukaemia treatments, rose from £8.36 to £42.87.

Margrethe Vestager, the EU’s competition commissioner, said that people depended on drugs “to save or prolong our lives” and that, “when the price of a drug suddenly goes up by several hundred percent, this is something the commission may look at. More specifically, in this case we will be …
“Refractory” Eosinophilic Airway Inflammation in Severe Asthma
Authors: Anneke ten Brinke, Aeilko H. Zwinderman, Peter J. Sterk, Klaus F. Rabe, Elisabeth H. Bel
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

It has been suggested that patients with refractory eosinophilic airway inflammation represent a separate "eosinophilic" asthma phenotype associated with increased morbidity and a poor prognosis. To investigate whether persistent eosinophilia in these patients is a fixed feature or can still be modified by treatment, we investigated the effect of high-dose intramuscular corticosteroids on eosinophils in induced sputum. Twenty-two patients with stable severe asthma (15 women, aged 21-73 years) participated in this double-blind, placebo-controlled study. All were using inhaled corticosteroids (> or = 1,600 microg/day) or chronic oral prednisone. They were included if the percentage of eosinophils in induced sputum was above the upper limit of normal (> or = 2%). Two weeks after treatment with triamcinolone, but not placebo, sputum eosinophils almost completely disappeared from a median of 12.6-0.2% (p < 0.001). In 82% of patients, no eosinophils could be observed at all. In addition, the rescue medication score decreased from 1.4 to 0.8 (p = 0.01), and FEV1 improved from a median of 73.8-88.3% predicted (p = 0.001). We conclude that persistent sputum eosinophilia despite extensive antiasthma treatment is not a refractory phenomenon but is still sensitive to high-dose systemic corticosteroids. This implies that these patients with severe asthma need additional or alternative antiinflammatory treatment to combat the eosinophilia and associated poor prognosis.
Precision Psychiatry Meets Network Medicine
Authors: David Silbersweig, Joseph Loscalzo
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Emerging bronchoscopic treatments for chronic obstructive pulmonary disease
Authors: Wouter H. van Geffen, Huib A.M. Kerstjens, Dirk-Jan Slebos
Journal: Pharmacology & Therapeutics (2017)

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by pathophysiological factors including airflow limitation, hyperinflation and reduced gas exchange. Treatment consists of lifestyle changes, lung rehabilitation and pharmacological therapies such as long acting beta-2-agonists (LABA) and long acting muscarinic antagonists (LAMA). More recently bronchoscopic treatments are emerging for COPD. Among them endobronchial valves (EBV) and endobronchial coils (EBC), next to endobronchial stents, sclerosing agents, targeted lung denervation and liquid nitrogen metered cryospray. In this review we aim to summarize the new emerging bronchoscopic treatments and their effect sizes compared with lung rehabilitation and pharmacological therapies.
Intrastriatal injection of α-synuclein can lead to widespread synucleinopathy independent of neuroanatomic connectivity
Authors: Zachary A. Sorrentino, Mieu M.T. Brooks, Vincent Hudson, Nicola J. Rutherford, Todd E. Golde, Benoit I. Giasson, Paramita Chakrabarty
Journal: Molecular Neurodegeneration (2017)

Prionoid transmission of α-synuclein (αSyn) aggregates along neuroanatomically connected projections is posited to underlie disease progression in α-synucleinopathies. Here, we specifically wanted to study whether this prionoid progression occurs via direct inter-neuronal transfer and, if so, would intrastriatal injection of αSyn aggregates lead to nigral degeneration.To test prionoid transmission of αSyn aggregates along the nigro-striatal pathway, we injected amyloidogenic αSyn aggregates into two different regions of the striatum of adult human wild type αSyn transgenic mice (Line M20) or non-transgenic (NTG) mice and aged for 4 months.M20 mice injected in internal capsule (IC) or caudate putamen (CPu) regions of the striatum showed florid αSyn inclusion pathology distributed throughout the neuraxis, irrespective of anatomic connectivity. These αSyn inclusions were found in different cell types including neurons, astrocytes and even ependymal cells. On the other hand, intra-striatal injection of αSyn fibrils into NTG mice resulted in sparse αSyn pathology, mostly localized in the striatum and entorhinal cortex. Interestingly, NTG mice injected with preformed human αSyn fibrils showed no induction of αSyn inclusion pathology, suggesting the presence of a species barrier for αSyn fibrillar seeds. Modest levels of nigral dopaminergic (DA) neuronal loss was observed exclusively in substantia nigra (SN) of M20 cohorts injected in the IC, even in the absence of frank αSyn inclusions in DA neurons. None of the NTG mice or CPu-injected M20 mice showed DA neurodegeneration. Interestingly, the pattern and distribution of induced αSyn pathology corresponded with neuroinflammation especially in the SN of M20 cohorts. Hypermorphic reactive astrocytes laden with αSyn inclusions were abundantly present in the brains of M20 mice.Overall, our findings show that the pattern and extent of dissemination of αSyn pathology does not necessarily follow expected neuroanatomic connectivity. Further, the presence of intra-astrocytic αSyn pathology implies that glial cells participate in αSyn transmission and possibly have a role in non-cell autonomous disease modification.
FDG-PET/CT as a New Method for Diagnosis and Whole-Body Evaluation of Lemierre Syndrome
Authors: Jordy P. Pijl, Andor W.J. M. Glaudemans, Riemer H.J. A. Slart, Thomas C. Kwee
Journal: Clinical Nuclear Medicine (2017)

Lemierre syndrome is a rare disease that is defined by a pharyngeal infection, complicated by septicemia and internal jugular vein thrombosis followed by septic emboli. Because of its rarity, a delay in diagnosis is not uncommon. However, given the mortality rate of approximately 2%, prompt diagnosis and detection of septic emboli are essential to initiate prompt treatment, preventing organ damage and ongoing sepsis. We present 3 cases that demonstrate the value of FDG-PET/CT as a possible alternative or adjunct to conventional imaging methods for diagnosis and whole-body evaluation of Lemierre syndrome.
Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults
Authors: Dennis T. Villareal, Lina Aguirre, A. Burke Gurney, Debra L. Waters, David R. Sinacore, Elizabeth Colombo, Reina Armamento-Villareal, Clifford Qualls
Journal: New England Journal of Medicine (2017)

Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia.In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs - aerobic training, resistance training, or combined aerobic and resistance training - or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions.A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (P<0.001 for between-group comparisons). Peak oxygen consumption (milliliters per kilogram of body weight per minute) increased more in the combination and aerobic groups (17.2 to 20.3 [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons). Strength increased more in the combination and resistance groups (272 to 320 kg [18% increase] and 288 to 337 kg [19% increase], respectively) than in the aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body weight decreased by 9% in all exercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events included musculoskeletal injuries.Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults. (Funded by the National Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).
Ultra-Deep Targeted Sequencing Does Not Identify MM Patients with Different Prognosis: Results from a Randomized Phase II Clinical Trial
Authors: Yanira Ruiz-Heredia, Joaquín Martínez-López, Jose Carlos Martínez-Ávila, Beatriz Sanchez-Vega, Inmaculada Rapado, Cristina Jimenez, Esteban Braggio, Rafael Martinez, Laura Rosiñol, Enrique M. Ocio, M Asuncion Echeveste, Jaime Perez de Oteyza, Albert Oriol, Joan Bargay, Mercedes Gironella, Jesus Martin, Rosa M. Ayala, Joan Bladé, Keith Stewart, Maria-Victoria Mateos, Jesus San Miguel, Ramon Garcia-Sanz, Juan José Lahuerta, Xabier Aguirre
Journal: Blood (2016)
An oncogenetics consultation dedicated to children suffering from cancer.
Authors: Véronique Mari, Marie Amelie Met Domestici, Christine Soler, Anne Deville, Nicolas Sirvent, Maryline Poiree, Marc Frenay
Journal: Journal of Clinical Oncology (2012)

e20006 Background: When a child suffers from a cancer, parents worry about a probable hereditary cause. If a cancer occurs in the context of a genetic mutation, this can worsen the situation and make it more complicated. On the other hand, when the hereditary cause is rejected, the reinsurance for the family is clear. Methods: A partnership has been set between the Oncogenetics department in Centre Antoine Lacassagne Hospital in Nice and the Archet hospital in Nice (CHU) who takes in charge the children suffering from a cancer. Fifty little patients are seen every year in the paediatric oncology service at the Archet hospital (CHU). A consultation in oncogenetics is suggested to each family and insistently when a known syndrome is suspected. This consultation is also about to provide an other kind of care, in an other hospital, focused on the family with the aim to free of guilt the parents. Psychological care for families is in backdrop as they can express freely their questioning. Results: Twenty one families have been seen and fifteen different types of cancers recorded: mostly haematological cancers and neurological cancers. For each family, a pedigree was drawn. Data concerning the child’s disease and familial data were gathered. Most of the time, these information led to reassure the families. Therefore two Li and Fraumeni syndrome have been evoked. The first child suffered from a plexus choroid carcinoma and the second one had two distinct cancers: a nephroblastoma and a medulloblastoma. On the other hand, 2 children had had a LAL within a family with history of malignant haemopaties. Interestingly, 3 children with isolated LAL in the family where suggested to contribute to a research trial. Conclusions: This oncogenetic pediatric consultation allows to detect known hereditary predisposition syndromes and to contribute to researches in paediatric oncology. Above all, this strong bound between the oncogentics department and the pediatric oncology service permitted to reach an objective: offering families a specialised consultation with psychological support with a gap from disease.