tbuckley/cabot-search huggingface dataset:
The Treatment of Acquired Hemolytic Anemia with Adrenocorticotrophic Hormone (ACTH)
Authors: William Dameshek, Martin C. Rosenthal, Lawrence I. Schwartz
Journal: New England Journal of Medicine (1951)

ACQUIRED hemolytic anemia, in contrast with the hereditary types, is usually due to an "extrinsic" mechanism acting upon normal red blood cells, injuring them and leading to an increased rate of destruction. In many cases, a fundamental pathologic process such as lymphosarcoma or leukemia can be found (symptomatic1 2 3 or secondary types), but most of the cases have no well defined etiology — that is, they are "idiopathic." Whether the anemia is symptomatic or idiopathic, an abnormal antibody can usually be found free in the blood or adsorbed to the red-cell surface. We have postulated that this antibody, which is ordinarily . . .
Case 9-1967
Authors: Earle W. Wilkins, Robert E. Scully
Journal: New England Journal of Medicine (1967)

Presentation of CaseA five-year-old girl was admitted to the hospital because of a mass under the scapula.Seven months previously x-ray films, taken because of scoliosis of the thoracic spine, revealed intact vertebras; mottled areas of consolidation were seen in the right lower lobe. Two months later a cough developed, but she remained afebrile. She was admitted to another hospital, where x-ray films of the chest (Fig. 1) showed consolidation of the right lower lobe, predominantly in the superior segment. Cultures of the sputum and throat were negative. Antibiotics were given for ten days, with symptomatic improvement, but a . . .
Imprime Pgg, a Novel Immune Modulator, in the 1St-Line Treatment of Stage Iv Nsclc: Results from a Randomized, Controlled, Multicenter Phase 2 Study
Authors: W. Engel-Riedel, F. Schneller, M. Wolf, W. Schuette, J. Lowe, P. Mattson, M. Gargano, M.L. Patchen, R.D. Huhn, A. Braun
Journal: Annals of Oncology (2014)
Women with bipolar illness: clinical and research issues
Authors: E Leibenluft
Journal: American Journal of Psychiatry (1996)

The purpose of this article is to review the literature concerning gender differences in the course of bipolar illness and discuss issues relevant to the treatment of women with the illness.The literature concerning the following topics is reviewed: gender differences in the course of bipolar illness; effects of the female reproductive cycle on the course of bipolar illness; special considerations in the treatment of bipolar women (focusing on the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes); and hypotheses to explain the greater prevalence of rapid cycling among bipolar women than among bipolar men.Data clearly indicate that rapid cycling is more common among bipolar women. Data also suggest that bipolar women may have more depressive episodes (and fewer manic episodes) and may be more likely to suffer from mixed (as opposed to pure) mania than bipolar men. While it is clear that bipolar women are at high risk for postpartum episodes, the effects of other reproductive system events (i.e., puberty, menstrual cycle, pregnancy, menopause, use of oral contraceptives or hormone replacement therapy) on the course or treatment of bipolar illness have received little systematic study. It is unclear whether women are at higher risk than men for developing lithium-induced hypothyroidism. Higher rates of hypothyroidism, greater use of antidepressants, and gonadal steroid effects are possible explanations for the greater prevalence of rapid cycling among bipolar women.Gender differences in bipolar illness and the effects of the female reproductive system on the course and treatment of the illness deserve more study. The importance of a longitudinal approach to these questions is emphasized.
Evidence of Sexual Transmission of Zika Virus
Authors: Eric D'Ortenzio, Sophie Matheron, Yazdan Yazdanpanah, Xavier de Lamballerie, Bruno Hubert, Géraldine Piorkowski, Marianne Maquart, Diane Descamps, Florence Damond, Isabelle Leparc-Goffart
Journal: New England Journal of Medicine (2016)

Zika virus is known to be transmitted by mosquitoes. The authors report the sexual transmission of Zika virus to a woman in Paris from a man who had recently traveled from Brazil.
Randomized, open‐label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma
Authors: Ann‐Lii Cheng, Sumitra Thongprasert, Ho Yeong Lim, Wattana Sukeepaisarnjaroen, Tsai‐Shen Yang, Cheng‐Chung Wu, Yee Chao, Stephen L. Chan, Masatoshi Kudo, Masafumi Ikeda, Yoon‐Koo Kang, Hongming Pan, Kazushi Numata, Guohong Han, Binaifer Balsara, Yong Zhang, Ana‐Marie Rodriguez, Yi Zhang, Yongyu Wang, Ronnie T. P. Poon
Journal: Hepatology (2016)

Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet‐derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis‐associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open‐label, randomized phase 2 study of Asian‐Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6‐9.1) months for dovitinib and 8.4 (5.4‐11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8‐4.2) months and 4.1 (2.8‐4.3) months for dovitinib and sorafenib, respectively. Common any‐cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar‐plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0‐13.8] and 5.7 [4.3‐7.0] months, respectively [ P = .0002]; HGF, 11.2 [8.9‐13.8] and 5.9 [5.0‐7.6] months, respectively [ P = 0.0002]). Conclusion : Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (H epatology 2016;64:774‐784)
Renin Release, Saralasin and the Vasodilator-Beta-Blocker Drug Interaction in Man
Authors: William A. Pettinger, Helen C. Mitchell
Journal: New England Journal of Medicine (1975)

Saralasin, an angiotensin antagonist, was used to study the role of renin-angiotensin in the vasodilator-beta-blocker drug interaction in hypertensive subjects. Plasma renin activity was elevated by withdrawal of propranolol in seven patients using minoxidil and propranolol. After propranolol withdrawal, saralasin caused hypotension (100/60 mm Hg or less) in five. Propranolol lowered blood pressure and plasma renin activity and diminished the hypotensive response to saralasin. Saralasin induced renin release in all patients, an effect blocked by propranolol. We conclude that angiotensin can be the major determinant of blood pressure in vasodilator-drug treated patients, that propranolol lowering of blood pressure in this vasodilator-beta-blocker drug interaction is related to suppression of renin release, and that the angiotensin feed-back-suppression mechanism for inhibiting renin release in functionally located proximal to beta-adrenergic receptors mediating renin release.
Treatment of Ethylene Glycol Poisoning with Intravenous 4-Methylpyrazole
Authors: Frédéric J. Baud, Martine Galliot, Alain Astier, Dang Vu Bien, Robert Garnier, Joseph Likforman, Chantal Bismuth
Journal: New England Journal of Medicine (1988)

THE toxic effects of ethylene glycol result from its metabolic conversion by alcohol dehydrogenase into glycolic acid — a process that causes metabolic acidosis. Glycolate is then metabolized to oxalate, the apparent cause of the renal toxicity of ethylene glycol. Ethanol and methanol are also metabolized by alcohol dehydrogenase, and it is the formaldehyde and formic acid produced through this pathway that cause the toxic effects of methanol. The activity of alcohol dehydrogenase is markedly inhibited by 4-methylpyrazole in vitro1 2 3 4 and in vivo in both animals5 and humans.6 7 8 9 10 11 In studies in animals, 4-methylpyrazole has been shown to reduce or eliminate . . .
Molecular Basis of Phenotypic Heterogeneity in Phenylketonuria
Authors: Yoshiyuki Okano, Randy C. Eisensmith, Flemming Güttler, Uta Lichter-Konecki, David S. Konecki, Friedrich K. Trefz, Mary Dasovich, Tao Wang, Karen Henriksen, Hans Lou, Savio L.C. Woo
Journal: New England Journal of Medicine (1991)

Phenylketonuria is a metabolic disorder that results from a deficiency of the hepatic enzyme phenylalanine hydroxylase. Its clinical phenotype varies widely, and to date more than 10 mutations in the phenylalanine hydroxylase gene have been identified in persons with the disorder. We attempted to relate the clinical phenotype of patients to their genotype.
Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML
Authors: Terrence N. Wong, Christopher A. Miller, Jeffery M. Klco, Allegra Petti, Ryan Demeter, Nichole M. Helton, Tiandao Li, Robert S. Fulton, Sharon E. Heath, Elaine R. Mardis, Peter Westervelt, John F. DiPersio, Matthew J. Walter, John S. Welch, Timothy A. Graubert, Richard K. Wilson, Timothy J. Ley, Daniel C. Link
Journal: Blood (2015)
S114 Feasibility study for a randomised controlled trial of Pseudomonas aeruginosa eradication treatment in patients with Bronchiectasis
Authors: HR Abo-Leyah, A Smith, M Clark, J Hill, TC Fardon, JD Chalmers
Journal: Thorax (2015)

<h3>Introduction</h3> Guidelines recommend Pseudomonas aeruginosa (PA) eradication treatment for new isolation of PA in bronchiectasis patients, but evidence is lacking. We performed a feasibility study to identify how many patients with new PA isolation would be eligible for a future randomised controlled trial (RCT). <h3>Methods</h3> For 12 months (2013–2014) we piloted a PA “alert” system that would notify the study team when PA was isolated in sputum samples. Patients were reviewed using electronic medical records to classify patients as 1- New PA, having never isolated PA before and therefore eligible for eradication, 2- Relapsed PA, patients having been free from PA and now isolating it again- therefore eligible for eradication, 3- Chronic PA, and therefore not eligible for eradication, 4- patients without HRCT confirmed bronchiectasis. Anti-PA IgG antibodies were measured in serum as a predictor of potential eradication success. <h3>Results</h3> There were 322 PA isolates from sputum over 12 months, in 156 patients. 22 patients presented new PA, 13 patients relapsed PA, 17 chronic PA and 104 patients did not have bronchiectasis (66%). The most frequent diagnoses in the non-bronchiectasis group was COPD. Overall, 35 patients would have been eligible for a trial of PA eradication on clinical grounds. Of these patients, clearance (negative PA culture at next follow-up sample) was demonstrated in 63%. PA IgG was positive in all of the patients with chronic PA, and identified those with successful clearance: sensitivity 93% and specificity 54%. A low antibody level was strongly associated with successful eradication (negative likelihood ratio 0.06, successful eradication in 92.3%). Mortality was very high in this patient group. 9%, 30% and 24% of patients died within 12 months follow-up in the 3 groups respectively. <h3>Conclusion</h3> This feasibility demonstrates that a future community based RCT of PA eradication would require a large number of centres, and be resource intensive. Major challenges in powering a future study include the low proportion of true first isolates and the high frequency of spontaneous PA clearance. Raised PA IgG was not sufficiently specific to exclude successful eradication, but a low PA IgG suggests a high likelihood of success.
Evaluating antivascular effects and antitumoral activity in patients with hepatocellular carcinoma treated with JX-594, a targeted multimechanistic oncolytic poxvirus, prior to sorafenib therapy.
Authors: J. Heo, D. H. Kirn, C. Breitbach, M. Cho, R. Patt, C. Kim, S. Kim, B. Rhee, J. C. Bell, T. Hwang
Journal: Journal of Clinical Oncology (2010)

e14564 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus granulocyte macrophage, colony stimulating factor (GM-CSF) expression stimulates acute tumor vascular shutdown and antitumoral immunity. JX-594 has been shown to be well tolerated by intravenous (IV) infusion and intratumoral (IT) injection and JX-594 is being developed as a novel therapy for patients with refractory hepatocellular carcinoma (HCC). Sorafenib is an antiangiogenic agent approved for patients with advanced HCC. Complementary antitumor effects are predicted with these two agents due to acute vascular disrupting effects of JX-594 and chronic antiangiogenic effects of sorafenib. Methods: Patients with confirmed treatment-refractory HCC were treated with JX-594 followed by standard sorafenib therapy. A subset of patients had previously received and failed sorafenib therapy. Patients were treated with three doses of JX-594 (IV and/or IT) and subsequently initiated standard sorafenib therapy. Results: As of January 10, 2010, seven patients have been treated with JX-594 followed by sorafenib. The sequential treatment regimen was well tolerated. Due to the different toxicity profiles of JX-594 and sorafenib, as well as the sequential dosing regimen, no drug interactions were expected. To date, five patients were evaluable for tumor response. Five (5) of 5 (100%) patients treated with both agents exhibited significantly decreased tumor blood flow and Choi responses (defined as > 15% reduction in density of tumor; range 68% - 125%). Choi responses occurred as early as 10 days post sorafenib initiation and have not been reported with sorafenib therapy alone. Conclusions: JX-594 shows promise as a novel agent for the treatment of refractory HCC. The complementary anticancer effects observed with subsequent sorafenib therapy warrant a randomized, controlled study of JX-594 followed by sorafenib versus placebo followed by sorafenib which will be initiated in 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Green Cross, Jennerex Biotherapeutics Jennerex Biotherapeutics Jennerex Biotherapeutics, Sillajen Green Cross, Jennerex Biotherapeutics, Sillajen
135O_PR: Plasma genotyping for predicting benefit from osimertinib in patients (pts) with advanced NSCLC
Authors: G.R. Oxnard, K.S. Thress, R.S. Alden, R. Lawrance, C.P. Paweletz, M. Cantarini, C. Barrett, J. Yang, P. Jänne
Journal: Journal of Thoracic Oncology (2016)
Case 10-2000
Authors: Louis R. Caplan, David N. Louis
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 63-year-old man was admitted to the hospital in early July because of rapidly progressive changes in behavior and ataxia.The patient had been well until 13 days earlier, when he began to have bifrontal headaches, with low-grade fever. Ibuprofen and acetaminophen were prescribed. Two days later, he was found to be disoriented and confused, with a stumbling gait, and was brought to another hospital. The white-cell count was 12,600 per cubic millimeter, with 88 percent neutrophils; the erythrocyte sedimentation rate was 55 mm per hour. The aspartate aminotransferase level was 91 U per liter, and the . . .
Elective Neck Dissection in Early Oral Cancer: Debate Resolved:
Authors: Charlie Schmidt
Journal: JNCI Journal of the National Cancer Institute (2015)

A debate over whether to remove lymph nodes from the neck during surgical treatment of early oral cancer has gone on for decades. Now findings from a randomized control trial reported last June at the American Society of Clinical Oncology’s (ASCO) annual meeting, in Chicago may finally put that controversy to rest. After just over 3 years of follow-up, 80% of 245 patients who had the nodes removed during surgical treatment of the primary tumor were still alive, compared with 67.5% of 255 patients randomized to a watch-and-wait policy who had the nodes removed only when metastases were suspected. “The elective node dissection (e.g., removal) prevented one death in every eight patients and one recurrence in every four patients who received it,” said Anil D’Cruz, M.D., chief of the department of head and neck surgery at the Tata Memorial Centre in Mumbai, India, and the study’s principal investigator. “[From] those results, I believe elective neck dissection should be the standard of care for all patients with early-stage, node-negative oral cancer.” Appearing most often on the tongue, or on skin membranes in the cheek, oral cancer results mainly from tobacco and alcohol abuse. It’s especially common among men in South Asian countries such as India, where betel nut chewing adds to the risk. Infection with the human papillomavirus 16 (HPV-16) virus is also a risk factor, especially among younger, nonsmoking women. The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program predicts that 47,000 people will be diagnosed with oral cancer in the United States in 2015. Since it rarely produces pain or other detectable symptoms before it metastasizes to the lymph nodes, and then typically to the lungs, oral cancer is usually diagnosed at late stages when 5-year survival rates rarely exceed 50%. By contrast, 5-year survival rates in early-stage oral cancers treated successfully with surgery can exceed 90%, but early detection of the primary tumor depends on access to health care. In India, where health care access is poor, only 10%–15% of oral cancer patients are diagnosed with early-stage disease, compared with about 25% in the United States.
Clinical and molecular characteristics of non-small cell lung cancer patients harboring PIK3CA mutations.
Authors: Sebastian Yves Friedrich Michels, Matthias Scheffler, Masyar Gardizi, Marc Christiaan Allardt Bos, Lucia Nogova, Katharina Koenig, Jana Fassunke, Carina Heydt, Ihle Michaela, Helen Kuenstlinger, Karin Toepelt, Frank Ueckeroth, Kerstin Albus, Monika Heidi Serke, Winfried Randerath, Walburga Engel-Riedel, Sabine Merkelbach-Bruse, Lukas Carl Heukamp, Reinhard Buettner, Juergen Wolf
Journal: Journal of Clinical Oncology (2014)

1527 Background: Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically. Methods: Tumor tissue collected consecutively from 1,144 NSCLC patients within a molecular screening network between March 2010 and March 2012 was analyzed for PIK3CA mutations using dideoxy-sequencing and next-generation sequencing (NGS). Clinical, pathological, and genetic characteristics of these patients are described and compared with a control group of PIK3CA-wildtype patients. Results: Among the total cohort of 1,144 patients we identified 42 (3.7%) patients with PIK3CA mutations in exon 9 and exon 20. These mutations were found with a significant higher frequency in sqamous cell carcinoma (8.9%) compared to adenocarcinoma (2.9%, p<0.001). Overall, they were significantly associated with smoking (p=0.012). The most common PIK3CA mutation was exon 9 E545K. The majority of patients (57.1%) had additional oncogenic driver aberrations. Further, PIK3CA-mutated patients had significantly higher incidence of malignancy prior to lung cancer (p<0.001). The median overall survival of these patients treated with systemic medication at stage IV was 9.5 months (95% CI, 2.3 – 16.8 months) and 32.1 months (95% CI, 17.9 – 46.3 months) for the local stages. Conclusions: Analysis of the largest cohort of PIK3CA-mutated NSCLCs described so far shows clinical and genetic heterogeneity of this subgroup in adenocarcinomas as well as in squamous cell carcinomas. In addition, we found that PIK3CA mutation positive lung cancer frequently develops in patients with prior malignancies.
Case 15-2008
Authors: Michael J. Barry, Donald S. Kaufman, Chin-Lee Wu
Journal: New England Journal of Medicine (2008)

A 55-year-old man was referred to this hospital for management of prostate cancer. An elevated serum prostate specific antigen (PSA) level was found during evaluation of urinary symptoms; core needle biopsies of the prostate disclosed adenocarcinoma, with a Gleason score of 6 out of 10. Examination and computed tomography showed a smoothly enlarged prostate and no lymphadenopathy. Options for management were discussed.
<i>KIR3DL1</i> Allelic Polymorphism and HLA-B Epitopes Modulate Response to Anti-GD2 Monoclonal Antibody in Patients With Neuroblastoma
Authors: Christopher J. Forlenza, Jeanette E. Boudreau, Junting Zheng, Jean-Benoît Le Luduec, Elizabeth Chamberlain, Glenn Heller, Nai-Kong V. Cheung, Katharine C. Hsu
Journal: Journal of Clinical Oncology (2016)

In patients with neuroblastoma (NB), treatment with anti-GD2 monoclonal antibody (mAb) directs natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cells. However, tumor cytotoxicity is attenuated by ligation of inhibitory killer immunoglobulin-like receptors (KIRs) by HLA class I molecules. KIR3DL1 polymorphism influences its ability to engage HLA-Bw4 ligands. We tested the hypothesis that poorly interacting combinations of KIR3DL1 and HLA ligands are more permissive of mAb-mediated antitumor effect.KIR3DL1 and HLA-B subtyping were performed with a multiplex intermediate-resolution polymerase chain reaction assay for a cohort of 245 patients who were treated with antibody 3F8 for high-risk NB. Patient outcomes were analyzed according to expected degree of interaction between KIR3DL1 and HLA-B subtypes and grouped as strong, weak, or noninteractors. A comparison of NK response to 3F8 mAb opsonized NB cells between strong- and noninteracting donors was performed by flow cytometry.KIR3DL1 and HLA-B subtype combinations associated with noninteraction as a result of lack of receptor expression [KIR3DL1(-)], failure of interaction with inhibitory ligands [KIR3DS1(+)], or absence of KIR ligands resulted in significantly improved overall and progression-free survival. Patients with KIR3DL1 and HLA-B subtype combinations that were predictive of weak interaction had superior outcomes compared with those that were predictive of strong interaction; however, both groups were inferior to those with noninteracting subtype combinations. In vitro analysis of 3F8-mediated ADCC showed that KIR3DL1(-) and 3DS1(+) NK cells were insensitive to inhibition by HLA-Bw4-expressing NB targets.We conclude that KIR3LD1 and HLA-B allele combinations can have a prognostic impact on patient survival after treatment with anti-GD2 mAb that relies on NK-ADCC. The survival advantage seen in noninteracting combinations supports the therapeutic disinhibition of individuals with strongly interacting KIR and ligand pairs.