tbuckley/cabot-search huggingface dataset:
Right-Sided Infective Endocarditis as a Consequence of Flow-Directed Pulmonary-Artery Catheterization
Authors: Katherine M. Rowley, K. Soni Clubb, G. J. Walker Smith, Henry S. Cabin
Journal: New England Journal of Medicine (1984)

We studied 142 consecutively autopsied patients prospectively to determine the frequency and clinical importance of right-sided endocardial lesions in patients who had undergone flow-directed pulmonary-artery catheterization within one month of death. Of the 55 catheterized patients, 29 (53 per cent) had one or more right-sided endocardial lesions: 12 (22 per cent) had subendocardial hemorrhage, 11 (20 per cent) sterile thrombus, 2 (4 per cent) hemorrhage and thrombus, and 4 (7 per cent) infective endocarditis. Of 41 lesions seen in the 29 patients, 23 (56 per cent) were located on the pulmonic valve, 6 (15 per cent) on the tricuspid valve, 6 (15 per cent) in the right atrium, 4 (10 per cent) in the right ventricle, and 2 (5 per cent) in the main pulmonary artery. All four patients with infective endocarditis had had positive antemortem blood cultures while the catheter was in place, but in only one had the diagnosis of endocarditis been suspected clinically. The unusual locations of the infected vegetations (on the pulmonic valve in three and in the right atrium in one) and the similar location of the uninfected lesions suggest that the infective endocarditis was a consequence of catheter-induced endocardial damage with concurrent or subsequent bacteremia. Among the 87 non-catheterized patients, there were two subendocardial hemorrhages and one resolving right atrial thrombus. We conclude that endocardial damage from flow-directed pulmonary-artery catheterization is common and that right-sided infective endocarditis should be suspected in bacteremic catheterized patients.
The Treatment of Esophageal Diverticulum by Inversion
Authors: Donald E. Coburn
Journal: New England Journal of Medicine (1951)

THE treatment of esophagopharyngeal diverticulum continues to be an interesting surgical problem. For the majority of practitioners interest in the subject arises out of the comparative rarity of the condition and the fact that the diverticulum may masquerade under the guise of chronic laryngeal disease or vague dysphagia for many years.The problems associated with the surgical treatment of esophagopharyngeal diverticulum are due to the fact that the esophagus withstands surgery poorly and that the location of the diverticulum allows any postoperative infection direct access to the mediastinum. These two factors have resulted in a careful and slow surgical evolution . . .
Case 18-1974
Authors: Edgar Sowton, Daniel A. Symonds
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 49-year-old man was admitted to the hospital because of bleeding per rectum.He was well until seven years previously, when there was the gradual onset of exertional dyspnea and occasional mild pain in the anterior part of the chest, for which he was admitted to the hospital. There was no history of hypertension, rheumatic fever, diabetes, excessive alcohol consumption or lipid disorder or family history of heart disease. Thyroid-function and blood lipid studies were negative. Serum enzyme determinations and electrocardiograms failed to document myocardial infarction, and he was discharged on digitalis therapy. Shortly after discharge a . . .
Case 27-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Stephen E. Goldfinger, Benjamin Castleman
Journal: New England Journal of Medicine (1971)

Presentation of Case First admission. A 73-year-old man was admitted to the hospital because of melena.For many years he had experienced nocturnal episodes of postprandial epigastric "pressure" and bloating, occurring only in recumbency and not relieved by the ingestion of milk or alkali. Twelve years before admission melena occurred. An upper gastrointestinal series disclosed a sliding hiatus hernia, 8 by 5 cm. After transthoracic repair of the hiatus hernia the gastrointestinal symptoms disappeared. Eleven years before entry he began to have substernal "pressure" on exertion, with radiation to the left arm and the jaw; relief was obtained by . . .
Phase II study of MGCD0103 in patients with relapsed follicular lymphoma (FL): Study reinitiation and update of clinical efficacy and safety.
Authors: R. E. Martell, A. Younes, S. E. Assouline, D. Rizzieri, S. Fox, M. A. Drouin, J. Wilhelm, M. Mehran, J. M. Besterman, R. H. Van Der Jagt
Journal: Journal of Clinical Oncology (2010)

8086 Background: MGCD0103 is an orally available selective inhibitor of histone deacetylases (HDACs). Methods: Trial 008 is a phase II, open-label study in relapsed or refractory lymphoma. Eligibility included: pathologic confirmation of relapsed or refractory diffuse large B-cell lymphoma or FL; ≥1 site of measurable disease (≥2.0 cm), ECOG 0 or 1. MGCD0103 was given 3x/week starting at 85 mg or 110 mg. This presentation focuses on the FL population (n=28). Results: The updated efficacy evaluation indicates that 3 patients experienced PR (11%). The most common toxicities grade (G) ≥3 were fatigue, neutropenia, anemia, nausea, anorexia and thrombocytopenia. In addition, 1 patient experienced a pericardial serious adverse event (SAE) (G2 pericarditis associated with a G1 pericardial effusion). Pericardial SAEs were observed in other MGCD0103 trials and hence the studies were voluntarily suspended for further investigation. In total, 437 patients have been treated with MGCD0103. There were 19 patients (4.3%) with a SAE where one of the listed terms involved the pericardium. Patients with Hodgkin Lymphoma were more likely (9.5%) to experience a pericardial SAE as compared to other diagnosis, while patients with solid tumors had an incidence of only 0.9%. Most pericardial SAEs (14) occurred during Cycle 1 of treatment. There were no clear relationships with the starting dose level, exposure, cumulative dose, drug lots, prior history of chest pain/arrhythmia or other cardiac diseases, prior therapies, prior mediastinal or thoracic radiotherapy, presence of mediastinal lesions, PD markers of HDAC activity or inflammation, low albumin levels at baseline, pneumonia, sepsis or infection. Statistically significant associations were found with patients who had a history of pericardial disease, presence of lung lesions, and on-study reports of chest pain or pleural effusion. Conclusions: Single agent activity has been observed in FL with MGCD0103. While the role of MGCD0103 in pericardial events cannot be ruled out, numerous confounding factors make the interpretation difficult. In concurence with the regulatory agencies, the study with FL patients has been re-opened to recruitment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MethylGene MethylGene MethylGene MethylGene
Abstract 4598: Low-frequency coding variants in BAT2, HIST1H1E and BPIFB1 are associated with lung cancer risk in Chinese populations
Authors: Guangfu Jin, Meng Zhu, Rong Yin, Wei Shen, Lin Xu, Zhibin Hu, Dongxin Lin, Hongbing Shen
Journal: Cancer Research (2015)

Abstract Objective: Genome-wide association studies have successfully identified a subset of common variants associated with lung cancer risk. However, these variants explain only a fraction of lung cancer heritability. Alternatively, it is proposed that uncommon variants may have strong effects and contribute to the missing heritability. The aim of the study was to evaluate the role of low-frequency or rare variants in lung cancer development. Methods: We analyzed exome chips with a total of 247,870 variants in 1,348 lung cancer cases and 1,998 controls in discovery stage and subsequently validated promising associations in additional 3,581 cases and 3,669 controls in replication stages. Single-variant and gene-based analyses were carried out in coding variants with minor allele frequency less than 0.05. Results: We identified three low-frequency missense variants in BAT2 (OR = 0.54, P = 1.02×10-9), HIST1H1E (OR = 0.49, P = 5.66×10-7) and BPIFB1 genes (OR = 1.79, P = 3.99×10-7) significantly associated with lung cancer risk. The risk allele of variant in BPIFB1 was also associated with early onset of lung cancer. BAT2 and HIST1H1E located at MHC III region across 6p22.2-6p21.31 and BPIFB1 at 20q11.21 were frequently associated with inflammation/immune-related diseases, and were found to be differentially expressed between lung tumors and paired normal tissues. In addition, down-regulation of BPIFB1 was significantly associated with poor prognosis of lung cancer patients. Conclusions: Our results highlight importance of uncommon variants in lung cancer susceptibility, and indicate potential biology of candidate genes at 6p22.2-6p21.31 and 20q11.21 in the process of lung carcinogenesis. Citation Format: Guangfu Jin, Meng Zhu, Rong Yin, Wei Shen, Lin Xu, Zhibin Hu, Dongxin Lin, Hongbing Shen. Low-frequency coding variants in BAT2, HIST1H1E and BPIFB1 are associated with lung cancer risk in Chinese populations. [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 4598. doi:10.1158/1538-7445.AM2015-4598
Case 13-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, B. Taylor Thompson, James F. Southern
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 63-year-old woman was admitted to the hospital because of a diagnosis of pneumonia of the right lower lobe, complicated by coronary artery disease, pulmonary edema, and cardiac arrest with ventricular fibrillation, trachel intubation, and cardiac resuscitation.There was a history of severe coronary artery disease, with multiple myocardial infarcts, poor left ventricular function, and chronic obstructive pulmonary disease. The patient was maintained on ethacrynic acid, supplemental potassium salts, isosorbide dinitrate, captopril, and diltiazem. She was in her customary state of health until about 10 days before entry, when she experienced the onset of a productive cough, . . .
Abstract POSTER-CTRL-1214: Systematic identification of high risk women for genetic counseling and surgical prevention of ovarian cancer
Authors: Robert Resta, Charles W. Drescher, David Beatty, M Robyn Andersen, Kate Watabayashi, Jason Thorpe, Hannah Purkey, Jessica Chubak, Nancy Hanson, Diana S.M. Buist, Nicole Urban
Journal: Clinical Cancer Research (2015)

Abstract Objectives: Information technology provides an opportunity for systematic identification of high-risk patients for appropriate referral. We conducted a randomized controlled trial to test whether routine identification of women at high risk for epithelial ovarian cancer using an electronic database and subsequent referral to genetic counseling would promote genetic testing and prophylactic surgery. Methods: Electronic data in a mammography reporting system from a large community hospital in Seattle was used to identify women at increased risk for ovarian cancer based on personal and family cancer history. Following secondary confirmation of eligibility and consent, women were randomly assigned to an intervention consisting of a genetic counseling referral, or to standard clinical care. Results: A total of 458 women were enrolled. Compared to standard clinical care systemic identification and referral of high risk women to genetic counseling increased the number of women who elect to undergo genetic testing (75 vs 20, p&amp;lt;0.005) and prophylactic surgery (OR: 3.5, p=0.05). Conclusions: Our results demonstrated that systematic identification of high-risk women for referral to genetic counseling is feasible and increases utilization of risk-appropriate prevention strategies. Citation Format: Robert Resta, MS CGC; Charles W. Drescher, MD; David Beatty, MD; M Robyn Andersen, PhD; Kate Watabayashi, BA; Jason Thorpe, MSc; Hannah Purkey, BS; Jessica Chubak, PhD; Nancy Hanson, MS CGC; Diana S.M. Buist, MPH PhD; Nicole Urban, ScD. Systematic identification of high risk women for genetic counseling and surgical prevention of ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1214.
p27 Is a Candidate Prognostic Biomarker and Metastatic Promoter in Osteosarcoma
Authors: Yiting Li, Manjula Nakka, Aaron J. Kelly, Ching C. Lau, Mark Krailo, Donald A. Barkauskas, John M. Hicks, Tsz-Kwong Man
Journal: Cancer Research (2016)

Metastatic progression is the major cause of death in osteosarcoma, the most common bone malignancy in children and young adults. However, prognostic biomarkers and efficacious targeted treatments for metastatic disease remain lacking. Using an immunoproteomic approach, we discovered that autoantibodies against the cell-cycle kinase inhibitor p27 (KIP1, CDKN1B) were elevated in plasma of high-risk osteosarcoma patients. Using a large cohort of serum samples from osteosarcoma patients (n = 233), we validated that a higher level of the p27 autoantibody significantly correlated with poor overall and event-free survival (P < 0.05). Immunohistochemical analysis also showed that p27 was mislocalized to the cytoplasm in the majority of osteosarcoma cases and in highly metastatic osteosarcoma cell lines. We demonstrated that ectopic expression of cytoplasmic p27 promoted migration and invasion of osteosarcoma cells, whereas shRNA-mediated gene silencing suppressed these effects. In addition, mutations at the p27 phosphorylation sites S10 or T198, but not T157, abolished the migratory and invasive phenotypes. Furthermore, the development of pulmonary metastases increased in mice injected with cells expressing cytoplasmic p27 compared with an empty vector control. Collectively, our findings support further investigation of p27 as a potential prognostic biomarker and therapeutic target in osteosarcoma cases exhibiting aberrant p27 subcellular localization. Cancer Res; 76(13); 4002-11. ©2016 AACR.
SAT0346 Risk Characterisation Methodology Enabling Safety Comparisons Between Tofacitinib and Tumour Necrosis Factor Inhibitors
Authors: J.R. Curtis, L. Klareskog, R. Zhang, S. Krishnaswami, A. Anisfeld, Y. Chen, J. Geier
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Tofacitinib is an oral JAK inhibitor for the treatment of RA. For new therapies, it is important to contextualise safety with established therapies such as TNF inhibitors (TNFi). Analyses were conducted based on the projected patient-years (PY) of accrual within the pooled Phase 2, Phase 3 and long-term extension (P2P3LTE) tofacitinib rheumatoid arthritis (RA) studies and external data for TNFi. <h3>Objectives</h3> To estimate the minimum threshold for detecting risk of specific adverse events (i.e., serious infections, all malignancies [excluding non-melanoma skin cancer (NMSC)], NMSC, major adverse cardiovascular endpoints [MACE], opportunistic infections [OI], lymphoma and gastrointestinal [GI] perforations) based on PY available for tofacitinib. <h3>Methods</h3> Power calculations were conducted based on a Poisson distribution to estimate the minimum PY of exposure needed to have 90% probability that the lower bound of the confidence interval (CI) for tofacitinib minus TNFi will be &gt;1, for true tofacitinib rates of 1.2×, 1.5× or 2.0× the comparator rates. Rates of events for TNFi were derived from sources (i.e., published clinical trials and observational studies) intended to optimise similarity to the tofacitinib clinical trial database in term of baseline characteristics, study duration and average patient follow-up time. <h3>Results</h3> Based on projections, approximately 18,000 PY of exposure to tofacitinib will be accrued within the RA BID clinical development programme; the majority of these data will come from patients treated for at least 3 years. Table 1 highlights the PY of exposure needed to detect an increased risk in safety events as compared with published TNFi rates. <h3>Conclusions</h3> The risk characterisation approach represents an indirect method to contextualise the safety profile of tofacitinib as compared with TNFi. Ongoing and planned prospective active surveillance complement the data generated from clinical trials. <h3>References</h3> Askling J, Baecklund E, Granath F, et al. Ann Rheum Dis 2009;68(5):648-53. Gout T, Ostör AJ, Nisar MK. Clin Rheumatol 2011;30(11):1471-4. Keystone EC, van der Heijde D, Kavanaugh A, et al. J Rheumatol, 2013. 40(9):1487-97. Mariette X, Matucci-Cerinic M, Pavelka K, et al. Ann Rheum Dis 2011. doi: 10.1136/ard.2010.149419. Winthrop KL. Rheum Dis Clin Am, 2012;38:727-645. <h3>Disclosure of Interest</h3> J. Curtis Grant/research support from: Pfizer, Inc., L. Klareskog: None declared, R. Zhang Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., S. Krishnaswami Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., A. Anisfeld Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., Y. Chen Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., J. Geier Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc.
The Development of Vancomycin Resistance in a Patient with Methicillin-Resistant<i>Staphylococcus aureus</i>Infection
Authors: Krzysztof Sieradzki, Richard B. Roberts, Stuart W. Haber, Alexander Tomasz
Journal: New England Journal of Medicine (1999)

Over the past two decades, vancomycin has been considered the antibiotic of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections. Indeed, multidrug-resistant clones of MRSA for which the only available effective antibacterial agent is vancomycin have recently been identified. Recent reports describing the therapeutic failure of vancomycin for MRSA infections have aroused considerable concern regarding the emergence of MRSA strains for which there will be no effective therapy.1–3 The mechanism of reduced susceptibility in these staphylococcal strains has not been identified, although data indicate that it is not the same as the vancomycin-resistance mechanism in enterococcal strains.4 We describe here . . .
GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease
Authors: Marilyn J. Telen, Ted Wun, Timothy L. McCavit, Laura M. De Castro, Lakshmanan Krishnamurti, Sophie Lanzkron, Lewis L. Hsu, Wally R. Smith, Seungshin Rhee, John L. Magnani, Helen Thackray
Journal: Blood (2013)
A Simultaneous Outbreak of Meningococcal and Influenza Infections
Authors: Lowell S. Young, F. Marc LaForce, J. James Head, James C. Feeley, John V. Bennett
Journal: New England Journal of Medicine (1972)

During a nine-day period in January, 1968, 11 cases of systemic Group B, sulfonamide-resistant Neisseria meningitidis infections with three deaths occurred among 55 elderly women confined to a single ward in a mental institution. Organisms were recovered from four patients and from five carriers. A fourfold increase in serum antibody activity to N. meningitidis antigens was found in all patients surviving systemic infection. A concurrent outbreak of A2 influenza affecting 50 per cent of this population was also documented. Serologic evidence of systemic infection or nasopharyngeal carriage of N. meningitidis, was found to be significantly associated with serologic evidence of influenza infection (p equal to 0.029). The most likely hypothesis is that influenza may enhance the acquisition of meningococci after exposure to these bacteria.
Recurrent Pericardial Effusion Secondary to Sarcoidosis of the Pericardium
Authors: Arthur D. Shiff, Charles J. Blatt, Charlotte Colp
Journal: New England Journal of Medicine (1969)

SARCOIDOSIS is a disease of unknown cause that has been reported to involve virtually every organ. Involvement of the pericardium, however, is an uncommon pathological finding, and, to date, there have been no well documented cases of a pericardial effusion secondary to pericardial sarcoidosis. The patient with generalized sarcoidosis described below underwent a thoracotomy and partial pericardiectomy for the diagnosis and treatment of recurrent pericardial effusion. This effusion was shown to be due to sarcoid involvement of the pericardium.Case ReportA 31-year-old Negro woman was hospitalized on July 4, 1966, with a 2-week history of weight loss, fever and . . .
Abstract 1436: The SxxSS motif of T-cell Factor-4 isoforms regulates Wnt5a expression and EMT in human liver cancer cells
Authors: Hironori Koga, Toru Nakamura, Mitsuhiko Abe, Yu Ikezono, Fumitaka Wada, Hirohisa Yano, Takuji Torimura
Journal: Cancer Research (2015)

Abstract Background: The T-cell factor (TCF)-4 is a key transcriptional protein activated by Wnt/β-catenin signaling. Previously we identified 14 TCF-4 isoforms derived from human HCC cell lines (Exp Cell Res 2011). The TCF-4J and K pair have been characterized based on the presence (K) or absence (J) of a SxxSS motif. TCF-4J-overexpressing HCC cells (J cells) exhibited high tumorigenic potential in contrast to TCF-4K-overexpressing cells (K cells) (PLoS ONE 2012). However, K cells often showed morphological alteration, reminiscent of epithelial-mesenchymal transition (EMT), which is involved in non-canonical Wnt signaling (BMC Cancer 2013). The finding suggested that the SxxSS motif had potential to regulate EMT through the non-canonical Wnt signaling pathway. Thus, the AIM of this study was to investigate whether the SxxSS motif modulated expression levels of EMT regulators and Wnt5a, a representative non-canonical Wnt ligand. Methods: The human HCC cell line HAK-1A (Hepatology 1993) was used. TCF-4K mutants (269A, 272A, and 273A) were prepared with conversion of serine (S) in the SxxSS motif to alanine (A) by site-directed mutagenesis. HAK-1A-derived stable clones overexpressing TCF-4J, K, and K-mutants (269A, 272A, and 273A cells, respectively) were established. Western blot analysis and real-time RT-PCR were employed to evaluate protein and mRNA expression levels, respectively. Sh-RNA was used to knockdown wnt5a gene expression. Results: The 269A-mutant cells robustly expressed Wnt5a in both protein and mRNA levels, while empty vector-transfected cells (control), J cells, or K cells did not. Of note, Wnt5a expression was coupled with SLUG expression and EMT-like cellular morphological change. Snail was hardly expressed in the cells examined in this study. When the Wnt5a expression was specifically silenced by using sh-RNA, the expression level of SLUG was clearly decreased. Conclusion: The findings in this study suggest that serine 269 (the first serine) of the SxxSS motif of TCF-4 is a major switch to control Wnt5a transcription, thereby modulating the expression level of the EMT-regulator SLUG in a human HCC cell line. Citation Format: Hironori Koga, Toru Nakamura, Mitsuhiko Abe, Yu Ikezono, Fumitaka Wada, Hirohisa Yano, Takuji Torimura. The SxxSS motif of T-cell Factor-4 isoforms regulates Wnt5a expression and EMT in human liver cancer cells. [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 1436. doi:10.1158/1538-7445.AM2015-1436