tbuckley/cabot-search huggingface dataset:
Direct, indirect and total effects of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children in Navarra, Spain, 2001 to 2014: cohort and case–control study
Authors: Marcela Guevara, Aurelio Barricarte, Luis Torroba, Mercedes Herranz, Alberto Gil-Setas, Francisco Gil, Enrique Bernaola, Carmen Ezpeleta, Jesús Castilla
Journal: Eurosurveillance (2016)

We estimated the direct, indirect and total effects of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) in children. A population-based cohort study followed children aged between 2.5 and 59 months between 2001 and 2014 in Navarra, Spain. IPD incidence was compared by PCV status and period. All cases diagnosed from July 2010 to December 2014 and eight matched controls per case were analysed to estimate the adjusted direct effect of PCV13. A total of 120,980 children were followed and 206 IPD cases were detected. Compared with unvaccinated children in the baseline period (2001–2004), overall IPD incidence in 2011–2014 (76% average PCV coverage) declined equally in vaccinated (total effect: 76%; hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.14–0.40) and unvaccinated children (indirect effect: 78%; HR: 0.22; 95% CI: 0.09–0.55). IPD incidence from non-PCV13 serotypes increased among vaccinated children (HR: 2.84; 95% CI: 1.02–7.88). The direct effect of one or more doses of PCV13 against vaccine serotypes was 95% (odds ratio: 0.05; 95% CI: 0.01–0.55). PCV13 was highly effective in preventing vaccine-serotype IPD. The results suggest substantial and similar population-level vaccine benefits in vaccinated and unvaccinated children through strong total and indirect effects.
Heterogeneity Of CXCR4 Expression In Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Tomasz Szczepanski, Urszula Malek, Lukasz Sedek, Alicja Sonsala, Joanna Zawitkowska, Teresa Odoj, Iwona Malinowska, Joanna Trelinska, Ewa Niedzielska, Katarzyna Derwich, Wanda Badowska, Maciej Niedzwiecki, Grazyna Sobol-Milejska, Katarzyna Muszynska-Roslan, Mariusz Wysocki, Grazyna Karolczyk, Maria Wieczorek, Tomasz Urasinski, Jerzy R Kowalczyk
Journal: Blood (2013)
New Tests to Assess Lung Function
Authors: Peter T. Macklem, Peter T. Macklem
Journal: New England Journal of Medicine (1975)

IntroductionLUNG-FUNCTION testing has an important role in the assessment of patients with a variety of cardiorespiratory disorders. A number of tests are now performed routinely in most teaching hospitals. The commonest are measurements obtained by plotting expired lung volume against time during a determination of forced expiratory vital capacity. The resulting curve generates a number of indexes including the forced expiratory volume in one second (FEV1.0) and the ratio between this volume and the forced vital capacity (FEV1.0/FVC). Other routine tests include the subdivisions of lung volume, measurements of airway resistance and of diffusing capacity. . . .
A new class of anti-cancer drugs targeting the tyrosine kinase receptor ROR1 in CLL.
Authors: Hakan Mellstedt, Salam Khan, Mohammad Hojjat-Farsangi, Amir Hossein Daneshmanesh, Jan Vagberg, Styrbjorn Bystrom, Johan Schultz, Martin Norin, Elisabeth Olsson, Charlotte Lofberg, Carina Norstrom, Thomas Olin, Anders Österborg, Ali Moshfegh
Journal: Journal of Clinical Oncology (2015)

8556 Background: RTK families are attractive therapeutic candidates. One of the families is the ROR receptors. ROR1 is of importance during embryogenesis but down-regulated in most adult human tissues.ROR1 has been shown to be expressed in CLL as well as in other hematological malignancies and solid tumors and is constitutively phosphorylated. ROR1 siRNA transfection of CLL cells induced apoptosis. We have produced and explored the activity of a new class of compounds, acting as inhibitors of phosphorylation of the tyrosine kinase domain of ROR1 (ROR1-TKI). We describe for the first time the activity of a lead ROR-TKI, KAN0439834. Methods: ROR1 inhibitors were derived from a high-through-put screen (HTS) using HTRF assay based on recombinant intracellular kinase domain of ROR1. A chemical lead series was optimized for activity on target, in vitro ADME and in vivo pharmacokinetic properties. Results: KAN0439834 induced apoptosis in vitro of fresh CLL cells from patients with non-progressive and progressive disease as well as from patients with fludarabine resistant disease with and without 17p abnormalities (EC50 for CLL cells < 200 nM and for normal PBMC > 14 µM). In vitro incubation resulted in dephosphorylated ROR1, Src, PIKδ, AKT, mTOR and CREB. 6 h incubation was sufficient to induce full apoptosis at 24 h. In NOD-SCID mice xenografted with human CLL cells orally bioavailable KAN0439834 induced a significant reduction of ROR1+cells, dephosphorylated pROR1, downregulated Mcl-1 and upregulated cleaved PARP. PK analyses showed a blood concentration of KAN0439834 to be sufficient to induce apoptosis of CLL cells. Minimal animal toxicity could be noted. Conclusions: The RTK ROR1 is expressed in CLL cells and of importance for survival. Targeting ROR1 by a TKI induced a strong killing of leukemic cells in vitro. The drug dephosphorylated ROR1 as well as PI3K/AKT/mTOR. In an animal CLL model the lead ROR1 inhibitor compound significantly reduced xenotransplanted CLL cells with minimal animal toxicity. This is a first report of a novel class of candidate drugs targeting ROR1. The candidate drug will be further evaluated in preclinical in vivo efficacy and safety models before proceeding to clinical evaluation.
Depression in Chinese medical inpatients
Authors: L L Yang, C Y Zuo, L Y Su, M T Eaton
Journal: American Journal of Psychiatry (1987)

The authors studied depressive symptoms among 251 Chinese medical inpatients through the use of the Beck Depression Inventory. Assessment of 100 healthy Chinese volunteers validated the use of American score norms for Chinese subjects. A total of 47.8% of the 251 medical inpatients (N = 120) met the Beck scale criterion for depression. Beck scale scores varied with the occupation of patients and the severity of medical illness but did not vary with sex, age, marital status, duration of hospitalization, or medical diagnosis.
Case 10-2005
Authors: Howard M. Heller, Sam R. Telford, John A. Branda
Journal: New England Journal of Medicine (2005)

A 73-year-old man was admitted to the hospital because of three days of fever and pain and weakness in his leg muscles that caused difficulty walking. He had begun taking atorvastatin several months earlier and had recently traveled to Cape Cod and South Carolina. There was mild leukopenia and thrombocytopenia, with elevated levels of creatine kinase. A diagnostic procedure was performed.
Case 13-2006
Authors: Andrew X. Zhu, Alan D. D'Andrea, Dushyant V. Sahani, Robert P. Hasserjian
Journal: New England Journal of Medicine (2006)

A 50-year-old man was referred because of a painful lytic bone lesion of the right ulna and multiple hepatic masses that had been identified on computed tomography. Biopsy of the bone lesion disclosed adenocarcinoma. Fanconi's anemia had been diagnosed 10 years earlier, and squamous-cell carcinoma of the esophagus 4 years earlier. A diagnostic procedure was performed.
Laparoscopic General Surgery
Authors: Nathaniel J. Soper, L. Michael Brunt, Kurt Kerbl
Journal: New England Journal of Medicine (1994)

Over the past five years, a revolution has taken place in general surgery requiring the retraining of tens of thousands of surgeons and the retooling of their operating rooms. This startling change has come about because of the rapid acceptance of laparoscopic techniques for therapeutic intervention, particularly removal of the gallbladder. The term "laparoscopy" (from the Greek laparo, the flank, and skopein, to examine) refers to the visual examination of the abdominal cavity by means of an endoscope or telescope (the laparoscope). Laparoscopic surgery is a means of performing diagnostic and therapeutic procedures after gaining access to the abdominal cavity. . . .
Use of Separated Human Red Cells
Authors: John G. Gibson
Journal: New England Journal of Medicine (1954)

DURING the last decade the use of preserved whole blood has become accepted practice. The majority of hospitals now operate blood banks, obtaining blood from the American National Red Cross or by individual recruitment. The standard collecting solution is acid citrate dextrose (ACD),1 which has preservative qualities sufficient to permit safe usage of properly refrigerated whole blood up to twenty-one days.2 ACD blood differs significantly from the normal in several important respects. Since it is a diluted blood one must infuse a volume of 575 cc. to administer the components of 500 cc. of blood. The solution contains 16.8 milliequiv. . . .
The New York Court of Appeals Rules on the Rights of Incompetent Dying Patients
Authors: John J. Paris
Journal: New England Journal of Medicine (1981)

The Brother Fox case, known by the legal title Eichner v. Dillon,1 reached its conclusion in the New York Court of Appeals on March 31, 1981.2 The state's highest court decreed that the formulation of guidelines for decisions on termination of treatment belong to the legislature and not the courts. It vacated all the cumbersome and costly procedural demands instituted by the Appellate Division of the State Supreme Court and voided that court's acceptance of the "substituted judgment" standard for determining the intent of an incompetent terminally ill patient.Instead of accepting the argument that the constitutional right of . . .
Detection, Quantitation, and Characterization of the Major Internal Virion Antigen of the Bovine Leukemia Virus by Radioimmunoassay 2
Authors: Hugh C. McDonald, Jorge F. Ferrer
Journal: JNCI Journal of the National Cancer Institute (1976)

The major internal polypeptide of the bovine leukemia virus (BLV) was purified to homogeneity with the use of gel filtration and affinity chromatography. Like previous results, the protein had a molecular weight of 25,000 daltons as determined by electrophoresis in polyacrylamide gels with sodium dodecyl sulfate, More than 90% of the 125I-labeled protein was precipitated by bovine sera that reacted in immunofluorescence tests with acetone-fixed BLV-infected cells. In contrast, minimal precipitation (<5%) was observed with sera from 36 cattle in leukemia-free herds; these sera, negative by immunofluorescence, included six samples that had high titers of antibodies to the foamy-like bovine syncytia virus (BSV). Antisera prepared against several other oncornaviruses or the Mason-Pfizer monkey virus (M-PMV) did not bind the BLV p25 protein. Conversely, the labeled p30 polypeptides of several oncornaviruses tested did not react with bovine sera that had high titers of antibodies to BLV p25. Competitive radioimmunoassay(s) (RIA) also failed to detect cross-reactions between BLV p25 protein and the internal polypeptides of other mammalian and' avian oncornaviruses, M-PMV, or foamy-like BSV. The RIA for BLV p25 antigen was also highly sensitive and specific for the detection and quantitation of the antigen in virus preparations and cell homogenates.
Survival and Quality of Life Data from the Act One Randomised, Double-Blind, Placebo-Controlled, Phase Ii Study of Espindolol for the Treatment and Prevention of Cachexia in Patients with Stage III / Iv Non-Small Cell Lung Cancer or Colorectal Cancer
Authors: J. Beadle, A. Coats, G.F. Ho, K. Prabhash, S. von Haeling, R. Brown, S. Anker
Journal: Annals of Oncology (2014)
Use of the Urobilinogen Test for the Detection of Para-Aminosalicylic Acid in the Urine
Authors: George M. Lepehne
Journal: New England Journal of Medicine (1959)

DURING the course of an examination for urobilinogen in the urine, I recently noted that, after the addition of Ehrlich's paradimethylamidobenzaldehyde reagent, an immediate dark-red color appeared, followed by a heavy precipitate. For several months the patient had received an oral dose of 8 gm. of para-aminosalicylic acid and 300 mg. of isoniazid daily for treatment of pulmonary tuberculosis. To test the possibility that these drugs were responsible for the unusual reaction, each was tested with Ehrlich's reagent. The addition of 0.06 to 0.12 gm. (1 to 2 gr.) of para-aminosalicylic acid dissolved in water to Ehrlich's reagent resulted in . . .
NIMG-62USING A MULTI-COMPARTMENT DIFFUSION MODEL TO CHARACTERIZE EDEMA DIFFERENCES BETWEEN GBMS AND BRAIN METASTASES
Authors: Nickpreet Singh, Drew Parker, Lukasz Macyszyn, Donald M. O'Rourke, Steven Brem, Ragini Verma
Journal: Neuro-Oncology (2015)

The differential effects of brain metastases (MET) and glioblastoma multiforme (GBM) on the peritumoral edema are difficult to decipher based on conventional brain imaging, as they comprise of varying degrees of edema and infiltration. Diffusion tensor imaging (DTI) is a form of MRI used to characterize local structure of brain tissues based on water diffusivity patterns quantified using indices such as mean diffusivity (MD). Previous attempts to differentiate GBMs and METs based on peritumoral edema have led to conflicting results, due to variations in tumor location, type and confounds of traditional DTI measures. The aim of this study is to use new DTI-based measures to unambiguously differentiate METs and GBMs, based on peritumoral edema characteristics. We fitted a multi-compartment diffusion model to patients with METs (N = 16) and GBMs (N = 51). This model estimates two compartments, unrestricted diffusion (free water) as in edema and restricted diffusion as in white matter, in the peritumoral edema, which was extracted from these patients using our tumor segmentation software GLISTR. Two measures were computed in the peritumoral region: edema fraction (EF) and diffusion fraction (DF), which is the percent decrease in MD after applying free water correction. The former characterizes the water content of the tissue and the latter the effect of this content on MD values. The DF was smaller in GBMs (69%) compared to METs (77%), with a significant difference between tumor types (p = 0.014). Furthermore, the variance in DF was significantly higher in GBMs (p = 0.03). Additionally, there is increased variance in EF of GBMs (p = 0.0001). Together, these results demonstrate that peritumoral edema of GBMs is more heterogeneous, perhaps due to infiltration, whereas that of METs consists more homogeneously of water. Therefore, these measures of edema characterization, EF and DF, can be used as imaging markers for distinguishing GBMs from METs.
The Intestinal Microbiome and Estrogen Receptor–Positive Female Breast Cancer
Authors: Maryann Kwa, Claudia S. Plottel, Martin J. Blaser, Sylvia Adams
Journal: JNCI Journal of the National Cancer Institute (2016)

The huge communities of residential microbes, including bacteria, viruses, Archaea, and Eukaryotes, that colonize humans are increasingly recognized as playing important roles in health and disease. A complex populous ecosystem, the human gastrointestinal (GI) tract harbors up to 1011 bacterial cells per gram of luminal content, whose collective genome, the gut metagenome, contains a vastly greater number of individual genes than the human genome. In health, the function of the microbiome might be considered to be in dynamic equilibrium with the host, exerting both local and distant effects. However, 'disequilibrium' may contribute to the emergence of disease, including malignancy. In this review, we discuss how the intestinal bacterial microbiome and in particular how an 'estrobolome,' the aggregate of enteric bacterial genes capable of metabolizing estrogens, might affect women's risk of developing postmenopausal estrogen receptor–positive breast cancer. Estrobolome composition is impacted by factors that modulate its functional activity. Exploring variations in the composition and activities of the estrobolome in healthy individuals and in women with estrogen-driven breast cancer may lead to development of microbiome-based biomarkers and future targeted interventions to attenuate cancer risk.
BMET-12SURVIVAL IN BREAST CANCER PATIENTS WITH BRAIN METASTASES AFTER GAMMA KNIFE STEREOTACTIC RADIOSURGERY
Authors: Christopher Grubb, Ashish Jani, Cheng-Chia Wu, Shumaila Saad, Yasir H. Qureshi, Tavish Nanda, Andrew M. Yaeh, Tzlil Rozenblat, Michael B. Sisti, Jeffery Bruce, Guy M. McKhann, Jeraldine Lesser, Simon K. Cheng, Steven R. Isaacson, Eileen P. Connolly, Tony J. C. Wang
Journal: Neuro-Oncology (2015)

BACKGROUND: Recent studies have suggested a difference in outcome for breast cancer patients with brain metastases based on breast cancer subtype. These subtypes are defined as ER/PR+ and HER2- (luminal A), ER/PR+ and HER2+ (luminal B), ER/PR- and HER2- (triple-negative), and ER/PR- and HER2+ (HER2). The recently published modified Graded Prognostic Analysis (GPA) score for predicting overall survival (OS) in these patients includes subtype, number of CNS metastases, age, and performance status. We investigated whether this model was predictive of outcomes in these patients treated with Gamma Knife Stereotactic Radiosurgery (GKRS) at our institution and if any additional factors were predictive. METHODS: We reviewed all patients treated by GKRS for brain metastases from breast cancer at our institution from 2000 to 2014. Characteristics included subtype, age at breast cancer diagnosis, clinical stage, chemotherapy, age at diagnosis of brain metastases, Karnofsky Performance Status, years between breast cancer diagnosis and brain metastases, number of brain metastases, extracranial metastases, controlled primary tumor, type of treatment, and GPA score. OS was calculated using the Kaplan-Meier method and Cox regression analysis was performed to identify predictors. RESULTS: 61 patients were included. The majority of patients had luminal type. These patients were more likely to present with multiple metastases (p = 0.024). The median survival after treatment for the entire cohort was 16 months. We found no significant difference in survival based on subtype. According to GPA score, patients with the highest score had the best OS (p = 0.112). Multivariate analysis showed that stage II or III breast cancer at diagnosis, more than three brain metastases, and treatment with surgery and whole brain radiation for brain metastases were predictors for worse OS. CONCLUSION: In our cohort, breast cancer subtype is not a significant predictor for survival in these patients. The breast-cancer specific GPA was a good predictor of OS.
Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians
Authors: Matthew Nielsen, Amir Qaseem
Journal: Annals of Internal Medicine (2016)

Background: The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria. Methods: A narrative review of available clinical guidelines and other relevant studies on the evaluation of hematuria was conducted, with particular emphasis on considerations for urologic referral. High-Value Care Advice 1: Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria. High-Value Care Advice 2: Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults. High-Value Care Advice 3: Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults. High-Value Care Advice 4: Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited. High-Value Care Advice 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause. High-Value Care Advice 6: Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy. High-Value Care Advice 7: Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.
Randomized Controlled Trial of Family Therapy in Advanced Cancer Continued Into Bereavement
Authors: David W. Kissane, Talia I. Zaider, Yuelin Li, Shira Hichenberg, Tammy Schuler, Marguerite Lederberg, Lisa Lavelle, Rebecca Loeb, Francesca Del Gaudio
Journal: Journal of Clinical Oncology (2016)

Systematic family-centered cancer care is needed. We conducted a randomized controlled trial of family therapy, delivered to families identified by screening to be at risk from dysfunctional relationships when one of their relatives has advanced cancer.Eligible patients with advanced cancer and their family members screened above the cut-off on the Family Relationships Index. After screening 1,488 patients or relatives at Memorial Sloan Kettering Cancer Center or three related community hospice programs, 620 patients (42%) were recruited, which represented 170 families. Families were stratified by three levels of family dysfunction (low communicating, low involvement, and high conflict) and randomly assigned to one of three arms: standard care or 6 or 10 sessions of a manualized family intervention. Primary outcomes were the Complicated Grief Inventory-Abbreviated (CGI) and Beck Depression Inventory-II (BDI-II). Generalized estimating equations allowed for clustered data in an intention-to-treat analysis.On the CGI, a significant treatment effect (Wald χ(2) = 6.88; df = 2; P = .032) and treatment by family-type interaction was found (Wald χ(2) = 20.64; df = 4; P < .001), and better outcomes resulted from 10 sessions compared with standard care for low-communicating and high-conflict groups compared with low-involvement families. Low-communicating families improved by 6 months of bereavement. In the standard care arm, 15.5% of the bereaved developed a prolonged grief disorder at 13 months of bereavement compared with 3.3% of those who received 10 sessions of intervention (Wald χ(2) = 8.31; df = 2; P =.048). No significant treatment effects were found on the BDI-II.Family-focused therapy delivered to high-risk families during palliative care and continued into bereavement reduced the severity of complicated grief and the development of prolonged grief disorder.
Preliminary Observations on Mental Disturbances Occurring in Patients under Therapy with Cortisone and ACTH
Authors: Lincoln D. Clark, Walter Bauer, Stanley Cobb
Journal: New England Journal of Medicine (1952)

IT HAS become increasingly apparent, during the past year, that mental disturbances are a not uncommon complication of therapy with cortisone and ACTH. It was initially observed that mild euphoria was frequent in patients undergoing this form of treatment, and more recently a variety of other mental abnormalities have been reported.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 It is intended to describe in this paper a series of patients who developed varying degrees of mental disturbance while under treatment with these agents and to review briefly the possible etiologic factors and theoretical implications involved.The 10 cases histories to be presented are divided for descriptive purposes . . .
211P: Inflammatory cells characterization and localization in malignant pleural mesothelioma (MPM) tissue samples: Correlation with histologic subtype and prognosis
Authors: G. Pasello, L. Urso, V. Polo, L. Bonanno, N. Nannini, F. Lunardi, S.E. Vuljan, P.F. Conte, F. Rea, F. Calabrese
Journal: Journal of Thoracic Oncology (2016)