tbuckley/cabot-search huggingface dataset:
OP0064 Drug Survival and Reasons for Discontinuation of Biological Therapy in 1679 Polyarticular Juvenile Idiopathic Arthritis Patients:
Authors: G. Horneff, H.I. Huppertz, P. Haas, K. Tenbrock, K. Minden
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To determine long term drug adherence and reasons for treatment discontinuation. <h3>Methods</h3> Since 2001, JIA patients starting treatment with biologics have been followed by the <i>Biologika in der Kinderrheumatologie</i> (BIKER) registry. This database was screened for discontinuations of biological therapy. <h3>Results</h3> 1679 polyarticular JIA pts were identified, 1190 treated with Etanercept, 372 Adalimumab, 69 Tocilizumab and 48 Abatacept. 892 had RF neg. polyarthritis (RFnegPA), 228 RF pos. polyarthritis (RFposPA) and 556 extended oligoarthritis (extOA). Treatment was discontinued in 764 pts. The frequency of discontinuation in pts with RFnegPA (422; 47.3%) was comparable to extOA (259; 46.6%), while it was lower in RFposPA (83; 36.3%; p=0.0019; Odds 0.625) compared to RFnegPA. The most common reason for disc. was inefficacy (283; 16.9%), followed by remission (223; 13.3%), intolerance (62; 3.7%) and others (51; 3.0%). In 145 (8.6%) cases the reason was not reported. No difference was found regarding the rate of inefficacy in either RFnegPA (16.8%), RFposPA (18.2%) or extOA (16.9%) and intolerance (4.1%; 2.6% and 3.4%, respectively), however patients with RFposPA (6.1%) less frequently disc. for remission than pts with RFnegPA (14.1%; p=0.00005; Odds 0,324) or pts with extOA (14.9%; p=0.00069; Odds 0.373). Related to the total time of exposure, the rate of disc. was highest in extOA (14.4/100 patient-years [PY]) followed by RFnegPA (13.7/100 PY) and significantly lower in RFposPA (7.5/100 PY; p&lt;0.0001, RR 0.55). 597 (50.2) patients disc. ETA, compared to 141 (37.9%) who disc. ADA, 10 (14.5%) TOCI and 16 (33.3%) ABA. Related to the total time of exposure, the rate of disc. was lowest in the TOCI cohort (8.3/100 PY) followed by ETA (12.1/100 PY), ADA (16.9/100 PY) and ABA (17.2/100 PY). Compared to ETA, the disc. rate of ADA was significantly higher (p&lt;0.0005, RR 1.4). By Kaplan-Meier analysis drug survival of ETA, ADA and ABA was comparable but significantly prolonged for TOCI (p=0.01 compared to ETA, 0.007 to ADA. Remission led to disc. of ETA in 201 (16.9%), ADA in 21 (5.6%), TOCI in 1 (1.4%) and in none with ABA. Significantly more patients discontinued ETA in remission compared to other biologics (p=0.001; p=0.00068; and p=0.0003). Disc. rates of ADA due to inefficacy and intolerance was significantly higher compared to ETA. <h3>Conclusions</h3> Most common reasons for discontinuation of biologics are inefficacy as well as remission. Marked differences between JIA categories and biologics used are found. Lowest rate of discontinuation is observed in RFposPA. Etanercept is more frequently discontinued due to remission and less frequently due to inefficacy than other biologics. Discontinuation due to intolerance is rare with all biologics. <h3>Disclosure of Interest</h3> None declared
The International Endorsement of US Distress Screening and Psychosocial Guidelines in Oncology: A Model for Dissemination
Authors: Mark Lazenby
Journal: Journal of the National Comprehensive Cancer Network (2014)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Distress Management have, since 1997, called for routine screening of distress in patients with cancer. Following the example of pain as the fifth vital sign, the case for using the concept of distress as the sixth vital sign was made by leading psycho-oncologists in 2007. Cancer care organizations in Canada and the International Psycho-Oncology Society have adopted the NCCN Guidelines for Distress Management and have named distress screening as the sixth vital sign, thereby encouraging cancer care clinicians to think of screening for distress when they screen for pain and other vital signs. Using the evidence integration triangle, this article explores the dissemination of the notion of distress as the sixth vital sign in an international context. This exploration shows that NCCN and similar organizations can adopt the evidence integration triangle in its next phase of moving toward full implementation of the NCCN Guidelines for Distress Management.
Treatment of Chronic Hepatitis C with Recombinant Interferon Alfa
Authors: Gary L. Davis, Luis A. Balart, Eugene R. Schiff, Karen Lindsay, Henry C. Bodenheimer, Robert P. Perrillo, William Carey, Ira M. Jacobson, John Payne, Jules L. Dienstag, David H. VanThiel, Carlo Tamburro, Jay Lefkowitch, Janice Albrecht, Carlton Meschievitz, Terryl J. Ortego, Alexandra Gibas
Journal: New England Journal of Medicine (1989)

Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P<0.001) and 28 percent in those treated with 1 million units (P<0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common. (N Engl J Med 1989; 321: 1501–6.)
Rheumatoid Nodules Simulating Basal-Cell Carcinoma
Authors: Louis A. Healey, Kenneth R. Wilske, Richard W. Sagebiel
Journal: New England Journal of Medicine (1967)

Subcutaneous nodules occur in 20 to 25 per cent of all patients with rheumatoid arthritis and more often in those with the classic form of the disease. The pathogenesis of the nodule is not known, but several associations are recognized. The rheumatoid factor is always present in the serum when nodules are found. External pressure may lead to the formation of nodules, and hence they are more common over bony prominences. The characteristic location over the proximal ulna is attributed to the patients' habit of leaning on the forearms when sitting in a chair and using the forearms for leverage . . .
Subclinical Brain Swelling in Children during Treatment of Diabetic Ketoacidosis
Authors: Elliot J. Krane, Mark A. Rockoff, James K. Wallman, Joseph I. Wolfsdorf
Journal: New England Journal of Medicine (1985)

Clinically apparent cerebral edema is a rare and often fatal complication of diabetic ketoacidosis. To determine whether subclinical brain swelling occurs more commonly, we obtained cranial CT scans in six children with diabetic ketoacidosis treated with fluid resuscitation and continuous low-dose insulin therapy. Control scans were obtained before hospital discharge. Compared with the scans during convalescence, the early scans of all six children showed a narrowing of the brain's ventricular system, compatible with brain swelling. Average changes in diameter were 1.3 +/- 0.1 mm for the third ventricle and 3.7 +/- 0.8 mm for the lateral ventricles (P less than 0.01). In addition, a narrowing of the subarachnoid spaces was subjectively noted during a blind reading of the early scans. Although no single scan was overtly indicative of cerebral edema, the data suggest that subclinical brain swelling may be a common occurrence during treatment of diabetic ketoacidosis in children. Sequential CT scans of the brain may provide a means of evaluating modifications of standard therapy aimed at preventing cerebral edema.
Evaluation of “Virus-Like” Particles in the Plasmas of 255 Patients with Leukemia and Related Diseases
Authors: Guy R. Newell, Warren W. Harris, Kim O. Bowman, Charles W. Boone, Norman G. Anderson, T. W. Bartlett, Elizabeth L. Rutenberg
Journal: New England Journal of Medicine (1968)

Abstract The plasmas of 255 patients with neoplasms of the blood-forming organs and 44 controls were screened for virus-like particles. Plasma samples were banded by cesium chloride density-gradient centrifugation and negatively stained, and representative electron-microscope fields were photographed and particles counted. The number and distribution of particles were evaluated according to diagnosis, clinical status of the patient, white-cell count and platelet count. No relation between any of the classes of partides and clinical features were found. A large percentage of both control and disease groups had about the same numbers of particles. No common clinical characteristics of patients with extremely high particle counts were found. Virus-like particles seen by this technic in the plasmas of patients with leukemia and related disorders are considered to be unrelated to their disease. The importance of thin sectioning in future studies of this kind is emphasized.
P159 The use of omalizumab in severe asthma is associated with a decline in blood eosinophils
Authors: LJ Holmes, G Tavernier, S Fowler, K Hince, RM Niven
Journal: Thorax (2015)

<h3>Introduction/aim</h3> Omalizumab (Xolair) is a recombinant humanised monoclonal antibody licensed for the treatment of severe allergic asthma patients with IgE mediated disease. The mechanism of action of omalizumab is to bind to IgE preventing interaction with FCERI (high affinity receptors) upon the surface of mast cells and basophils, thereby reducing the activation of the inflammatory cascade and associated clinical symptoms. Although blood eosinophilia is a useful measure of airway inflammation, the correlation between blood eosinophils and omalizumab treatment has not been described outside clinical trial. Therefore, our aims were to identify whether the introduction of omalizumab is associated with a change in the blood eosinophil count within our cohort of patients with severe asthma. <h3>Methods</h3> We collected measurements of blood eosinophils in patients maintained on omalizumab for periods 12 months pre and post, and (where available) 24 months pre and post initiation of therapy. We also investigated any correlation between blood eosinophils pre and post treatment versus clinical parameters including total IgE and omalizumab dose. <h3>Results</h3> Complete data sets including 12-month blood eosinophil data were available for 49 of our current cohort of 92 patients on treatment. The mean blood eosinophil count dropped from 0.33 × 10<sup>9</sup>cells/l (IQR 0.37) × 10<sup>9</sup>cells/l pre-treatment to 0.22 × 10<sup>9</sup>cells/l (IQR 0.30) post treatment (<i>p</i> = &lt;0.001). Additionally, we widened the window to 24 months pre and post initiation of treatment, if blood eosinophil data was not available at 12 months. Data for 59 patients demonstrated similar significant reduction in mean blood eosinophil, 0.34 × 10<sup>9</sup>cells/l (IQR 0.34) pre-treatment to 0.23 × 10<sup>9</sup>cells/l (IQR 0.29) (<i> p = 0 </i>.003). No association was seen between the changes in mean blood eosinophil counts post treatment versus total monthly omalizumab dose and baseline total IgE. <h3>Conclusion</h3> Our data demonstrates a significant reduction in blood eosinophils in patients who are receiving omalizumab treatment when comparing blood eosinophils at 12 and 24 months pre and post treatment. Future work should investigate whether this is a direct result of omalizumab therapy, due to confounding by other treatment, or a marker of improved asthma control.
Hematopoietic Stem-Cell Transplantation for Systemic Lupus Erythematosus
Authors: Richard K. Burt, Ann Traynor, Rosalind Ramsey-Goldman
Journal: New England Journal of Medicine (1997)

Valvular Heart Disease Associated with Fenfluramine-PhentermineTo the Editor: Nineteen of the 24 patients described by Connolly et al. (Aug.28 issue) 1 in the primary report linking fenfluramine and phentermine with cardiac valvular abnormalities were identified in Fargo, North Dakota, a city with only 74,111 residents in 1990. 2 Twelve of the Fargo cases, and perhaps the association itself, were initially identified by an astute echocardiographic sonographer.This relation had not been discovered previously despite the fact that fenfluramine has been approved since 1973 and that 18 million prescriptions for these drugs were filled in 1996 alone. 1 Diagnosis of a cardiac abnormality in 18 of the 24 patients was based on echocardiographic findings of valvular insufficiency and "unusual valvular morphology." 1 The key unanswered question is whether these echocardiographic abnormalities have clinical import for the majority of patients using these drugs or whether they are simply a visual finding.The drugs are so widely used and these reports have prompted such widespread concern that all efforts should be taken to be certain that the association with important heart disease is real.On the other hand, if the incidence rate in Fargo is confirmed and if the echocardiographic abnormalities frequently lead to clinically significant disease, these drugs will be responsible for a major epidemic of valvular heart disease that could have been far worse if not detected by the echocardiographer.
Combined hedgehog and epidermal growth factor receptor (EGFR) inhibition in a direct patient tumor model (DPTM) of head and neck squamous cell cancer (HNSCC).
Authors: S. Keysar, R. Anderson, S. Takimoto, A. Tan, I. Deyneko, K. McGovern, R. W. Ross, J. Song, A. Jimeno
Journal: Journal of Clinical Oncology (2010)

5558 Background: A DPTM of HNSCC was established to optimally test novel therapies and the role of cancer stem cells (CSC) in relapses after therapy. This study examines the role of the Hedgehog pathway (HhP) in HNSCC and the effect of the smoothened (SMO) inhibitor IPI-926 alone and combined with the EGFR inhibitor cetuximab (Cet). Methods: Mouse models generated from implanted HNSCC surgical cases were optimized for a combination of factors (e.g. mouse strain, tumor location) yielding the most similar tumor to the parental cancer using morphologic, stroma invasion and gene expression analysis. Results: Tumor fragments from 25 cases were implanted with a 65% engraftment rate. An unbiased gene analysis comparing pathways enriched in 42 HNSCC and 14 head and neck normal tissues showed enrichment for the HhP in the cancers. IHC staining for the ligand sonic hedgehog (SHH) of a tissue array of 60 HNSCC and 20 normal tissues indicated that 65% were positive (++) or very positive (+++) and only 35% of the cancers were negative or faint (+), while 78% of normal tissues were negative for SHH. Samples from 3 DPTM and 3 cell line-derived xenografts were positive for SHH. Four DPTMs were treated in vivo with Cet, IPI-926, and the combination. IPI-926 had activity (T/C <40%) in two cases, and both Cet and the combination induced regressions in three. Whereas in all cases Cet-treated tumors re-grew 4-8 weeks post-therapy, combination- treated mice were relapse-free 3 months post-therapy. To test if Cet leads to CSC accumulation, putative CSC markers were measured by flow cytometry. CD24/44 and CD24/ALDH cells accumulated in Cet-treated tumors but decreased in combination-treated tumors. Implanted CD24/44 and CD24/ALDH positive cells generated tumors at a higher rate than negative cells despite a 100-fold cell dilution. These subgroups expressed SMO and GLI1 genes 200-fold and 700-fold higher than negative cells, respectively. Conclusions: The HhP is activated in HNSCC, with over-expression seen in the CSC subpopulation, where data suggests autologous signaling. When combined with Cet, HhP inhibition with IPI-926 diminishes CSC and prevents tumor relapse in a DPTM of HNSCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Infinity Infinity
Can We Really Teach Psychosomatic Medicine?
Authors: Don R. Lipsitt
Journal: Psychotherapy and Psychosomatics (1991)

Medicine, it seems, is lately in a state of perpetual crisis. Some would attribute the problem, at least in part, to the enduring heritage of Descartes, who imprinted dualistic notions of a separation of mind and body upon medical education and practice. The perspective of psychosomatic medicine has long been hailed as the remedy for flaws in the way medicine has been taught and practiced for at least five decades. If medicine as a humanistic endeavor is to take account of the whole individual, it must encompass biological, social and psychological dimensions of the person. Many attempts at curriculum reform and postgraduate education have had variable success in countering the dualism of medicine. This presentation will discuss the challenge, the problems and the future of psychosomatic teaching, with illustrations from a variety of educational experiments.
Jaundice of Hepatic Origin during the Course of Methyl-Testosterone Therapy
Authors: Irving B. Brick, Laurence H. Kyle
Journal: New England Journal of Medicine (1952)

THE occurrence of jaundice during methyl-testosterone therapy was recently reported by Kinsell1 and Werner, Hanger and Kritzler.2 In view of the apparent rarity of this toxic effect of a commonly used drug, as reflected by the sparsity of cases reported in the literature, and of the distinctive features of this type of liver disease, we are reporting two cases of jaundice that occurred during the sublingual use of methyl testosterone. Furthermore, widespread knowledge of this possibility may stimulate others to report and may serve as a warning that methyl-testosterone administration should be considered in the differential diagnosis of jaundice—especially in . . .
Johann Friedrich Blumenbach (1752 to 1840)
Authors: Frederick P. Bornstein
Journal: New England Journal of Medicine (1962)

WITHIN the span of the nineteenth century a number of ancient and long established phenomena disappeared from the scene of Western civilization such as cavalry officers, the Holy Roman Empire and the Universally Educated Man. To Goethe, whose influence is quite manifest in Blumenbach's writings, Johann Friedrich Blumenbach may already have been one of the deplorable specialists of the younger generation; to contemporary epigones it is a marvel that one man should have contributed to such diverse fields as geology, the classification of the mammoth and the history of medicine, and at the same time have given first proper stimulus . . .
Immune and Clinical Assessment in a Cohort of Pediatric Hispanic Patients with Partial Digeorge Syndrome: An Institutional Review
Authors: Hanadys Ale, Raquel Olavarrieta, Zaimat Beiro, William R. Blouin, Vivian P. Hernandez-Trujillo, Jose G. Calderon
Journal: Journal of Allergy and Clinical Immunology (2016)
P101 Peripheral blood type 2 innate lymphoid cell count in patients with severe eosinophilic asthma
Authors: B Hilvering, S Go, L Stoeger, K Borg, C Connelly, S Thulborn, S Pahlke, ID Pavord, L Xue
Journal: Thorax (2015)

<h3>Background</h3> A subgroup of patients with severe asthma have persistent eosinophilic airway inflammation despite treatment with high intensity corticosteroid treatment. One possible explanation for this pattern of disease is involvement of a type 2 innate lymphoid cells (ILC2s) dependant and relatively corticosteroid resistant pathway generating type 2 cytokines such as IL-5 and Il-13. The presence of high numbers of ILC2s in the nasal polyps commonly associated with severe eosinophilic asthma supports this view. We have carried out a cross-sectional study testing the hypothesis that ILC2 counts are increased in peripheral blood of patients with severe eosinophilic asthma. <h3>Methods</h3> Blood was taken from 9 controls and 33 patients with asthma, 23 of whom met the 2014 ERS/ATS guideline criteria for severe asthma and had historical evidence of eosinophilic airway inflammation as defined before (Pavord <i>et al</i>. Lancet 2012;380:651–9). ILC2 were measured as lineage- CD45<sup>+</sup>CD127<sup>+</sup>CRTH2+ by flow cytometry and numbers presented as total cell counts and% peripheral blood mononuclear cells. <h3>Results</h3> ILC2<b> c</b>ounts were repeatable within patients (ICC 0.97; n = 6). Mean ± SD ILC2 counts were 566 ± 379, 323 ± 224, 437 ± 628 and 429 ± 421cells/mL (Figure 1A) and 0.034 ± 0.022, 0.02 ± 0.017, 0.020 ± 0.028 and 0.019 ± 0.014% of total lymphocytes (Figure 1B) in normal controls (n = 9), patients with mild to moderate asthma (n = 10), patients with severe asthma at BTS step 4 (n = 12), and patients with severe asthma at BTS step 5 (n = 11) respectively. <h3>Conclusion</h3> Type 2 innate lymphoid cells are scarce in peripheral blood but can be measured consistently. We found no evidence of increased counts in peripheral blood from patients with severe eosinophilic asthma.
Cancer in Relatives of Children with Central-Nervous-System Neoplasms
Authors: Jacqueline Farwell, John T. Flannery
Journal: New England Journal of Medicine (1984)

We compared the occurrence of cancer in parents, siblings, and offspring of 643 patients who had central-nervous-system tumors in childhood (cases), as recorded in the Connecticut Tumor Registry, with the occurrence in parents, siblings, and offspring of 360 controls selected according to birth certificate and matched for sex, birth date, and birthplace. Overall cancer incidence was comparable in the two groups. However, 11 nervous-system tumors occurred in relatives of cases, whereas none occurred in relatives of controls (P = 0.0005). Nine relatives of cases but no relatives of controls had cancer of the hematopoietic-lymphatic system (P = 0.003). Nine siblings of cases but only one sibling of a control had cancer as children. Medulloblastoma and glioblastoma multiforme were overrepresented in the group of children whose relatives had central-nervous-system tumors. We compared the actual number of cancers of the central nervous system or hematopoietic-lymphatic system in relatives of cases with the number expected on the basis of known incidence rates and found a fivefold excess. We conclude that the occurrence of a brain tumor in a child is a marker for an increased likelihood of central-nervous-system tumors, leukemia, and childhood tumors in the family.
Pollutants and pesticides may be important
Authors: P. J Lewis
Journal: BMJ (1994)

We agree that there is no evidence to support the use of dexamethasone in meningococcal septicaemia.As previously highlighted, we did not find any evidence of benefit when it was used in meningococcal meningitis either.We reiterate that further clinical studies are urgently required to clarify these important issues.