tbuckley/cabot-search huggingface dataset:
How Far Should Blood Pressure Be Lowered?
Authors: Jane F. Desforges, Astrid E. Fletcher, Christopher J. Bulpitt
Journal: New England Journal of Medicine (1992)

WHEN doctors prescribe antihypertensive drugs they face a dilemma. They are well aware that the benefits of lowering blood pressure in patients with hypertension far outweigh the risks, yet they have been warned that at some level of lowered blood pressure the tables turn and the risks become dominant. The initial downward slope of the mortality rate and the subsequent upward slope when the blood pressure gets too low form the so-called J curve. Our argument, presented here, is not that the J curve does not exist, but rather that the putative cause- and-effect relation between the reduction in blood . . .
Case 17-2005
Authors: Benjamin D. Medoff, Jo-Anne O. Shepard, R. Neal Smith, Alexander Kratz
Journal: New England Journal of Medicine (2005)

A 22-year-old woman was transferred because of respiratory failure. She had a history of sickle cell anemia and had back and leg pain the day before she was admitted to another hospital, where respiratory failure developed while she was being treated for a sickle cell crisis. After transfer, assisted ventilation, nitric oxide, and exchange transfusion did not reverse the hypoxemia, and the patient died. An autopsy was performed.
ATNT-01ABT-414 MONO- OR COMBINATION THERAPY WITH TEMOZOLOMIDE (TMZ) RECHALLENGE IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM) AND AMPLIFIED EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR): A PHASE I STUDY
Authors: Hui K. Gan, Priya Kumthekar, Andrew B. Lassman, Ryan Merrell, Martin van den Bent, Kyriakos P. Papadopoulos, Andrew M. Scott, Erica Gomez, JuDee Fischer, Helen Mandich, Hao Xiong, Ho-Jin Lee, Wijith Munasinghe, Lisa Roberts-Rapp, Peter Ansell, Kyle Holen, Rose Lai, David A. Reardon
Journal: Neuro-Oncology (2015)

BACKGROUND: Aberrant EGFR signaling plays a vital role in GBM oncogenesis. ABT-414 is an antibody-drug conjugate with a toxic payload (monomethylauristatin F) linked to ABT-806, an antibody targeted to activated EGFR. This phase I, open-label, 3-arm study (NCT01800695) evaluates ABT-414 mono- or combination therapy with TMZ rechallenge in patients with GBM. Herein, we report outcomes in recurrent GBM. METHODS: Eligible patients (≥18 years) had recurrent supratentorial GBM and Karnofsky performance status ≥70. ABT-414 was given intravenously every 2 weeks with TMZ rechallenge (150-200 mg/m2 days 1-5 q28; Arm B) or as monotherapy (Arm C). ABT-414 dose escalation used a modified continual reassessment method. Primary objectives were to assess ABT-414 safety, maximum tolerated dose (MTD), and recommended phase II dose (RPTD); secondary objectives included antitumor activity evaluation. RESULTS: As of April 2015, 19 Arm B patients were treated in 4 dose groups (0.5-1.5 mg/kg), and 27 Arm C patients were treated at 1.25 mg/kg. In Arms B/C, 10/17 patients had amplified EGFR. Most common grade 3/4 treatment-emergent adverse events in either arm were keratitis (11%/19%), γ-glutamyltransferase increase (16%/0%), convulsions (11%/0%), fatigue (11%/0%), and thrombocytopenia (11%/4%). ABT-414 MTD was 1.5 mg/kg in Arm B and was not reached in Arm C; RPTD is 1.25 mg/kg for both arms. Best objective responses were complete response (CR) in 3 patients and a partial response (PR) in 1 patient in Arm B, and 1 CR and 1 PR in Arm C patients (all confirmed responses were observed in patients with EGFR amplification).Objective response rate among EGFR-amplified subjects was 22.2% (6/27). CONCLUSIONS: RPTD for ABT-414 is 1.25 mg/kg for both combination therapy with TMZ rechallenge and monotherapy. ABT-414 demonstrated a unique safety profile including ocular AEs, and appears to have antitumor activity in recurrent GBM with EGFR amplification.
An unusual presentation of body cavity lymphoma
Authors: N. Mankan, S. Madhunapantala, A. Maini
Journal: Journal of Clinical Oncology (2004)

6699 Background: BCL (Body Cavity Lymphoma) is an uncommon primary NHL (Non-Hodgkin's lymphoms) that proliferates within serous body cavities - pleural, pericardial or peritoneal, resulting in recurrent effusions. It is common in young to middle-aged HIV (Human Immunodeficiency Virus) positive homosexual males. In the absence of HIV infection, it almost universally develops in the background of HHV-8/KSHV (Human Herpes Virus-8/ Kaposi's Sarcoma Herpes Virus) infection with or without EBV (Epstein Barr Virus). Rare BCLs have been reported in elderly populations, which are both HIV negative and HHV-8 negative. We report an unusual case of BCL, which is HHV-8 negative and EBV positive. Abstract: 75 yrs old Immigrant Ashkenazi Jew from Russia was admitted with shortness of breath for 1 month and leg edema. No B-symptoms. His Karnofsky performance status was 80. He is heterosexual, monogamous, non-smoker and denied alcohol or intravenous drug abuse. Clinical examination revealed a right-sided pleural effusion only. Complete Blood Count showed mild normocytic normochromic anemia with hemoglobin -11.5 gm/dl. Total white count, differential, renal and liver function tests were normal. Serum LDH 200 U/L, serum β2 Microglobulin 2.8. Pleural fluid was frankly hemorrhagic with 80,000 RBC/cu mm, 16,800 WBC/ cu mm with 65% lymphocytes and 26% monocytes. Pleural fluid LDH 4500 U/L and cytology revealed Large cell lymphoma. CT scan of chest, abdomen and pelvis failed to demonstrate any lymphadenopathy or organomegaly. There was no pericardial effusion or ascites. Pleural fluid flow-cytometry demonstrated monoclonal lambda B-cell population lacking CD5 or CD10. The cells were positive for CD19, CD20, CD22 and CD45 and negative for CD2, CD3, CD4, CD5, CD7, CD9, CD10, CD11c and CD13/33. Bone marrow aspiration biopsy and flow-cytometry were negative for disease. Serum PCR for HHV-8, Human T Cell Leukemia Virus 1 and 2, Hepatitis C Virus negative, serum EBV IgG positive. CD4 count was 400 and CD8 was 300 with a ratio of 1.3. A diagnosis of BCL was made. He underwent therapeutic thoracentesis with relief of respiratory symptoms.Standard CHOP-like chemotherapy has been planned for this patient. No significant financial relationships to disclose.
High serum YKL-40, but not plasma VEGF and serum HER2, as a prognostic biomarker of short survival in patients with metastatic colorectal cancer
Authors: N. Nicolaisen, J. S. Johansen, P. Pfeiffer, I. J. Christensen, C. Qvortrup, S. E. Nielsen, B. Glimelius, N. Keldsen, T. Fokstuen, B. V. Jensen
Journal: Journal of Clinical Oncology (2007)

14517 Purpose: To evaluate the prognostic value of plasma VEGF, serum YKL-40 and HER2 before, during and after chemotherapy in patients with their first manifestation of metastatic colorectal cancer (mCRC). Patients and Methods: Prospective, longitudinal study of 105 patients (60 men and 45 women, median age 65, range 36–79 years, PS 0–2) from 7 centers referred with their first manifestation of mCRC. The patients were treated with Oxaliplatin 130 mg/m 2 day 1 and Capecitabine 2000 mg/m 2 days 1–14 every 3 weeks. Median follow-up was 1.8 years. 92 patients had progression and 62 died. The biomarkers were determined by ELISAs. Results: Pretreatment plasma VEGF (median 90 ng/l, range 3–2622, 37% had high level &gt;137 ng/l) and serum YKL-40 (102 μg/l, 28–692, 40% had higher level than the age-corrected 95th percentile in healthy individuals) were significantly (p&lt;0.001) elevated in the patients compared to normal levels. Serum HER2 was not elevated (7.90 μg/l, 3.6–92, 6% had high level &gt;15 μg/l). Pretreatment serum YKL-40 was higher in patients who died compared to those alive (115 vs. 75 μg/l, p=0.004). No differences in plasma VEGF (97 vs. 85 ng/l, p=0.27) and serum HER2 (8.0 vs. 7.4 μg/l, p=0.16) were found. Univariate Cox analysis showed that plasma VEGF and serum HER2 before treatment or during follow-up could not predict progression-free and overall survival. Pretreatment serum YKL-40 (log transformed, scored as a continuous variable) was in a univariate analysis a prognostic biomarker of overall survival (HR=1.8, 95% CI: 1.3–2.6, p=0.0006), but not of progression- free survival (p=0.81). Multivariate Cox analysis (age, sex, number of organs with metastasis, pretreatment serum YKL-40 (continuous variable)) showed that serum YKL-40 (HR=1.8, 95% CI: 1.3–2.6, p=0.001) and possible the number of organs with metastasis (p=0.06) were independent predictors of overall survival. During follow-up, a high serum YKL-40 (log transformed continuous variable and landmark time) predicted shorter time to progression (HR=1.5, 95% CI 1.1–2.1, p=0.01) and overall survival (HR=1.7, 95% CI 1.2–2.4, p=0.005). Conclusion: Serum YKL-40 is a prognostic biomarker of overall survival and during follow-up also of progression-free survival in patients with mCRC. No significant financial relationships to disclose.
Abstract 1591: Comprehensive molecular profiling of circulating tumor cells from metastatic breast cancer patients
Authors: Mark Jesus Mendoza Magbanua, Louai Hauranieh, Ritu Roy, Praveen Pendyala, Eduardo Sosa, Janet Scott, Hope Rugo, John Park
Journal: Cancer Research (2015)

Abstract Background: Recent enumeration studies on CTCs have demonstrated the clinical value of these cells. The molecular biology of CTCs, however, remains poorly understood. Methods: We performed RNA and DNA profiling of CTCs from metastatic breast cancer (MBC) patients. 244 blood samples from 162 MBC patients were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate highly pure CTCs. Microfluidic-based multiplex QPCR analysis was utilized to determine the expression levels of 64 cancer-related genes. Parallel genome-wide copy number analysis by array comparative genomic hybridization was also performed on CTCs isolated from the same enriched blood samples. Results: Transcriptional analysis of CTCs was successfully performed in 151 samples from 105 patients. We observed the up-regulation of several genes including CCND1, EPCAM, KRT7 and MUC1 and the down-regulation of hematopoietic-related genes including PTPRC (CD45) and CD68 (adjusted p &amp;lt;0.001) in CTCs. Clustering analysis of expression profiles revealed three CTC clusters, one containing both subtypes basal (ESR1-low) and normal-like (ESR1-low, CAV1/VIM-high) and two other clusters containing luminal subtype (ESR1-high). A subset of CTCs expressed epithelial-mesenchymal transition genes, however, genes for stem cellness were not generally expressed. Serial CTC expression profiling in 28 patients demonstrated changes in expression over time. Exploratory single CTC expression analysis revealed cell-to-cell heterogeneity. Parallel genome-wide copy number analysis in matched CTCs from 49 patients revealed gains (e.g. 1q and 8q), losses (e.g., 8p and 16q), and focal amplifications (e.g. on 8q and 11q including CCND1) that are frequently observed in primary breast cancers. We also observed three copy number clusters with varying levels of genomic aberrations. Up-regulation of CCND1 and ERBB2 in CTCs was associated with increased level of genomic instability. Conclusions: Parallel gene expression and copy number profiling provided novel insights on the biology of CTCs. Molecular characterization of CTCs may shed further light on the biology of metastasis and disease progression. Citation Format: Mark Jesus Mendoza Magbanua, Louai Hauranieh, Ritu Roy, Praveen Pendyala, Eduardo Sosa, Janet Scott, Hope Rugo, John Park. Comprehensive molecular profiling of circulating tumor cells from metastatic breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1591. doi:10.1158/1538-7445.AM2015-1591
A Corrective Shoe for Toe Drop
Authors: Charles A. Lamb
Journal: New England Journal of Medicine (1950)

PARALYSIS of the muscles below the knee is the most frequent residual defect following infantile paralysis. For this defect many surgical procedures are available, and many more various mechanical aids have been devised. The interest of this article is limited to the explanation of a mechanical aid for toe drop whether due to poliomyelitis or other nerve injuries.Some type of metal appliance is usually recommended, all of which have the same weaknesses. The chief disadvantage is that all create pressure points on the skin of the leg, producing tenderness by friction if the ankle is permitted to move. Another . . .
A phase 1b open-label multicenter study of AZD4547 in patients with advanced squamous cell lung cancers: Preliminary antitumor activity and pharmacodynamic data.
Authors: Paul K. Paik, Ronglai Shen, David Ferry, Jean-Charles Soria, Alastair Mathewson, Elaine Kilgour, Donal Landers, Paul Frewer, Nigel Brooks, Fabrice Andre
Journal: Journal of Clinical Oncology (2014)

8035 Background: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs. Prognosis is poor with few treatment options. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs and occurs in ~20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with activity in FGFR1 amplified SQCLC cell lines and patient-derived xenografts. Prior work identified a recommended dose of 80mg po bid. Methods: This was a multicentre Phase 1 expansion of AZD4547 in patients with previously treated stage IV FGFR1 amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8≥ 2) was confirmed through central FISH (N=13) or review of local results (N=2). Primary endpoint was safety/tolerability. Secondary endpoints were preliminary anti-tumor activity, PK, and PD. CT scans were performed at baseline and every 6 weeks. Results: 15 patients were treated. Median age=66 (48-72); female=46%; former/current smoker=100%; WHO restricted PS=69%. 8 patients had FISH ratios between 2-2.8 (low amplification). 7 patients had FISH ratios > 2.8 (high amplification). Mean relative dose intensity= 97%. The most common related AEs were GI and dermatologic. Grade ≥ 3 related AEs occurred in 3 patients (20%) (central serous retinopathy (CSR), hyponatremia, dehydration). Related SAEs occurred in 3 patients (CSR,dehydration, asthenia and dyspnea). There were 3 discontinuations due to AEs and no deaths due to drug. 14 patients were evaluable for tumor response assessment. There were: 1 PR, 4 SD, 9 PD (7 progressions and 2 deaths). The 1 PR was observed in a patient with high FGFR1amplification. Preliminary analysis found an increase in serum phosphate following treatment with AZD4547. Exon-sequencing of 283 cancer-related genes in 6 patient tumors, including 1 with a PR, showed no clear response modifiers. Conclusions: AZD4547 was well-tolerated in patients with FGFR1 amplified SQCLC but did not meet its pre-specified efficacy endpoint in terms of overall response rate for continuation. The increase in serum phosphate concentration observed in this study provides evidence that AZD4547 at this dose and schedule causes pharmacologic target inhibition. Clinical trial information: NCT00979134.
Case 18-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Donald N. Medearis, David L. Gang
Journal: New England Journal of Medicine (1978)

Presentation of CaseA four-year-old boy was admitted to the hospital because of circulatory collapse.He was well until seven days earlier, when fever, sore throat, lethargy and anorexia developed, and his mother noticed a rash. He was taken to another hospital, on Cape Cod, where examination revealed a non-petechial maculopapular rash on the trunk and extremities; the palms and soles were not affected, and there was no urticaria or vesiculation. The tympanic membranes were slightly red. The white-cell count was 4800, with 30 per cent neutrophils and 28 per cent band forms. A throat culture yielded no pathogenic micro-organisms. . . .
Primary Immunodeficiency Caused by Mutations in the Gene Encoding the CD3-γ Subunit of the T-Lymphocyte Receptor
Authors: Antonio Arnaiz-Villena, Marcos Timon, Alfredo Corell, Paloma Perez-Aciego, J. Manuel Martin-Villa, Jose R. Regueiro
Journal: New England Journal of Medicine (1992)

PRIMARY immunodeficiency diseases are a heterogeneous group of disorders resulting from intrinsic defects of the immune system.1 They are frequently associated with repeated bacterial, fungal, or v...
Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumor (GIST).
Authors: O. Oladeji, E. Wardelmann, U. Ronellenfitsch, D. Pink, P. Reichardt, P. Ströbel, P. Hohenberger
Journal: Journal of Clinical Oncology (2010)

10053 Background: It is often recommended to regard patients with a ruptured of GIST as having a very high risk for recurrence. Patients have been entered to phase III adjuvant trials of imatinib. However there are only case reports and a series on abdominal leiomyosarcoma available with real data. Methods: 554 pts. with histologically confirmed GIST were retrieved from our database. The written reports from surgical resection were reviewed in detail for circumstances of emergency, intraoperative findings, handling of the specimen, signs of tumor rupture, margins of clearance, and concordance with the pathology report. Review pathology and mutation analysis in genes encoding KIT and platelet-derived growth factor alpha (PDGFRA) was done in 61%. Median follow-up is 52 months. Results: We identified 27pts (17 f, 10 m; median age 51, range 26-69 yrs) with a documented tumor rupture: n=19 with spontaneous tumor perforation indicating laparotomy, n=2 with a ruptured tumor detected incidentally during operation for intra-abdominal hemorrhage after trauma, n=6 with rupture of the specimen during resection. Primary tumor location: stomach n=7, duodenum n=1, small bowel n=19. Median tumor size was 10.5 cm (range, 4-28 cm). According to the Miettinen & Lasota system the distribution of very low : low : intermediate : high risk tumors was 1:2:7:17. Of the 23 pts. without metastases at presentation, 18 remained untreated and all but one developed tumor recurrence. Median time to relapse (RFS) was 22 months (range, 5-83+ months, 95% CI: 8.5-35.4 mos). One patient remains free from disease at 83+ mos. The single most often detected mutation involved codon 557-558 in 11/24 pts: W557_558Kdel (n=5), other mutation types n=6. The RFS of this subgroup was 11 mos. vs. 26 mos. with mutations at other exons of KIT, PDGFRA or wt. Conclusions: Patients with a perforation or rupture of a GIST to the abdominal cavity have a close to 100% risk of tumor recurrence. Patients with deletion mutation of codons 557-558 show a less than 1 year RFS. This group of patients are clear candidates for adjunctive drug therapy even if size and mitotic count of the primary tumor would not make them eligible according to risk classification systems. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer Novartis, Pfizer Novartis Novartis
Randomized, double-blind and placebo-controlled study of the immunomodulatory effects of Lingzhi in children with cancers
Authors: M. K. Shing, T. F. Leung, Y. L. Chu, C. Y. Li, K. W. Chik, P. C. Leung, V. Lee, P. M. Yuen, C. K. Li
Journal: Journal of Clinical Oncology (2008)

14021 Background: Lingzhi (Ganoderma lucidum) is a traditional Chinese medicine which is widely used to 'strengthen immunity' among patients with cancers. However, there is no published randomized controlled trial on its efficacy and safety despite the many in vitro studies showing its anti-viral and anti-oxidative. Methods: This randomized, double-blind, placebo-controlled, parallel- group clinical trial recruited cancer patients aged 2–18 years from Children's Cancer Centre of a university-affiliated teaching hospital. These patients were recruited either during maintenance (for leukemias) or within weeks following (for solid tumors) chemotherapy. Stratified by underlying cancers, they were randomized to receive 4–6 capsules daily of Lingzhi or matched placebo, which were manufactured by our Institute of Chinese Medicine according to GMP standard, for 6 months. The changes in subjects' lymphoproliferative responses to mitogens during study were compared between Lingzhi and placebo groups. Results: 29 patients were assigned to each of Lingzhi or placebo groups, with mean (SD) age being 8.9 (4.4) years and 9.6 (5.2) years respectively (P=0.553). Sixteen subjects in Lingzhi group and 17 subjects in placebo group suffered from leukemias, and others had solid tumors (P=0.791). The mean (95% CI) changes in stimulation indices (SI) of purified peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were 364 (42–687) and 83 (44–121) for Lingzhi group and -134 (-580–311) and -1 (-56–54) for placebo (P=0.046 for PHA and 0.028 for PWM). The result for lymphoproliferative response to concanavalin A was marginally significant (P=0.074). None of the subjects had significant hematologic or biochemical derangement. Patients were followed for a median of 2.9 years (IQR 2.3–3.8 years), and 20 from Lingzhi group and 21 from placebo remained disease-free. Conclusions: A 6-month treatment with Lingzhi augments mitogen-induced lymphoproliferative responses in immunocompromized children with cancers. Funding: Hong Kong Children's Cancer Foundation Peter Nash Pediatric Oncology Research Grant. This trial is registered with FDA under clinical trial number NCT00575926. No significant financial relationships to disclose.
Observations on Neoplastic Spread
Authors: John W. Turner
Journal: New England Journal of Medicine (1953)

MANY patients with cancer have metastases when medical aid is first sought; in many others metastatic foci develop later. The earlier such metastases can be recognized, the greater the likelihood of significant palliation by application of the newer modes of therapy of the past two decades 1 2 3 4 5 and the improved older modes of treatment.6 7 8 9 10 Late symptoms produced by metastatic foci in organs and systems often remote from the primary site may lead patients to consult a neurologist, thoracic surgeon, orthopedist, internist or some other physician not involved in the earlier attempt to control the primary growth. Specialists in almost all fields . . .
Case 1-1996
Authors: R.P. Shannon, G.A. Rose, V. Nickeleit
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 69-year-old woman was admitted to the hospital because of severe, persistent congestive heart failure after treatment for bacteremia.The patient had been well until several months earlier, when chronic fatigue developed. Three weeks before admission symptoms of an upper respiratory tract infection appeared, with cough and weakness. The temperature ranged up to 38.9°C on several occasions. Fifteen days before admission she was taken to another hospital.There was a history of obesity, a calcified aortic valve, and non-insulin-dependent diabetes mellitus; the patient had been admitted to the same hospital eight months earlier because of a blood . . .
Better mental healthcare in England may have reduced suicides
Authors: Ingrid Torjesen
Journal: BMJ (2016)

Improvements to mental health services, such as greater availability of specialist community services, a smoother transition from child to adult mental health services, and better implementation of clinical guidelines, have been linked to significantly reduced suicide rates in mental health services, a study published in the Lancet Psychiatry has shown.1

The study also found that suicide rates were higher at mental health trusts with higher levels of staff turnover, suggesting that organisational factors are important in preventing suicide.

Some 19 248 people who died by suicide from 1997 to 2012, who were in contact with mental health services in the 12 months before they died, were included …