tbuckley/cabot-search huggingface dataset:
A Prospective Six Sigma Quality Improvement Trial to Optimize Universal Screening for Genetic Syndrome Among Patients With Young-Onset Colorectal Cancer
Authors: Sean Dineen, Patrick M. Lynch, Miguel A. Rodriguez-Bigas, Sarah Bannon, Melissa Taggart, Colleen Reeves, Cathy Modaro, Michael Overman, George J. Chang, John M. Skibber, Y. Nancy You
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: Improving the quality of health care is a national priority, and providing patient-centered care is one of the 6 key areas for quality improvement. In the setting of patients with young-onset colorectal cancer (CRC), appropriate genetic workup and testing for potential underlying inherited CRC syndromes is fundamental to patient-centered care. Lynch syndrome (LS) is the most common of these inherited syndromes, and current recommendations from the NCCN and other professional societies advocate universal screening for LS among young patients with CRC. However, practical implementation of these guidelines often falls short. Methods: We conducted a prospective quality improvement intervention trial to optimize universal screening for LS in young (age <50 years) patients, involving 356 eligible patients during the 12-month preintervention period and 299 patients during the postintervention. Results: Applying the Six Sigma conceptual framework, we demonstrated a significant increase in use of tumor-based molecular testing and subsequent confirmatory germline mutation testing for LS. This led to identification of more patients to be managed as having LS and of more first- and second-degree relatives to benefit from the testing results. Conclusions: This study demonstrated the successful application of a quality improvement conceptual framework for the universal adoption of molecular biomarker testing in patients with cancer, and for improving adherence to NCCN Clinical Practice Guidelines in Oncology for CRC Screening. As molecular and genetic testing is becoming increasingly common, we present a prototype study for improving the adoption of molecular studies and the provision of guideline-based patient-centered care.
The end of adjuvant chemotherapy (adCT) era with doxorubicin-based regimen in resected high-grade soft tissue sarcoma (STS): Pooled analysis of the two STBSG-EORTC phase III clinical trials
Authors: A. Le Cesne, M. Van Glabbeke, P. J. Woll, V. H. Bramwell, P. G. Casali, H. J. Hoekstra, P. Reichardt, P. C. Hogendoorn, P. Hohenberger, J. Y. Blay
Journal: Journal of Clinical Oncology (2008)

10525 Background: The EORTC STBSG has coordinated the two largest trials of adCT vs no adCT in localized high grade STS. In both studies adCT failed to demonstrate any benefit on overall survival (OS). The aim of this analysis was to identify subgroups of patients who benefit more from adjuvant CT than others. Methods: We pooled individual patient (pt) data from two EORTC trials comparing adCT (CYVADIC in 62771 and AI in 62931) to a control arm in completely resected STS (R0 or R1) to identify prognostic factors, by univariate and a multivariate analysis. The outcome of pts (OS or PFS) was subsequently compared between the two groups of pts according to each investigated factor. Results: A total of 819 pts were included, with a median follow-up of 8.2 years (62771 trial: 468 pts, 9.7 yrs; 62931 trial: 351 pts; 6.6 yrs). Large tumor size, high histologic grade and R1 resection are independent adverse prognostic factors for both PFS and OS. AdCT is an independent favourable prognostic factor for PFS but not for OS. A significant interaction between the benefit of adCT and age, sex and R1 resection was observed for both PFS and OS. Tumor size, histologic subtype and grade were not associated with any PFS or OS benefit for adCT. Males had a significantly better PFS but not OS in the adCT arms, pts older than 40 yrs had a significantly better PFS in the adCT (while adCT was associated with a marginally (p=0.08) worse OS in pts<40). Pts with R1 resection had a significantly better PFS and OS in the adCT arms. Conclusions: This study confirms previously documented prognostic factors in completely resected STS. Contrary to our initial hypothesis, adCT is not associated with a better outcome in young pts or any pathological subgroup. Quality of initial surgery is the most important prognostic and predictive factor for utility of adCT for PFS and OS. No significant financial relationships to disclose.
Value of Bed Rest in Patients with Rheumatoid Arthritis
Authors: John A. Mills, Robert S. Pinals, Marian W. Ropes, Charles L. Short, June Sutcliffe
Journal: New England Journal of Medicine (1971)

Abstract To determine the value of bed rest in the treatment of rheumatoid arthritis, a group of patients at the time of hospitalization for therapy were randomly assigned to one of two treatment p...
The Molecular Basis of Steroid 5α-Reductase Deficiency in a Large Dominican Kindred
Authors: Anice E. Thigpen, Daphne L. Davis, Teofilo Gautier, Julianne Imperato-McGinley, David W. Russell
Journal: New England Journal of Medicine (1992)

PSEUDOHERMAPHRODITISM in men is often caused by genetic deficiencies in the production or action of androgens.1 , 2 One form of this condition is a deficiency of steroid 5α-reductase, the enzyme that catalyzes the conversion of testosterone to dihydrotestosterone in androgen-sensitive tissues.3 , 4 Affected persons have 46,XY karyotypes. At birth, they have normal male structures derived from the wolffian duct, but defects in the external genitals ranging from simple hypospadias to a blind vaginal pouch and clitorislike phallus. The most common defect is a urogenital sinus with a blind vaginal pouch.1 2 3 4 During puberty, the affected boys undergo various degrees of virilization.3 Affected females . . .
Variations in the First Apical Sound Simulating the So-Called “Presystolic Murmur of Mitral Stenosis”
Authors: Mariano M. Alimurung, Maurice B. Rappaport, Howard B. Sprague
Journal: New England Journal of Medicine (1949)

ALTHOUGH Fauvel,1 in 1843, attributed the apical presystolic murmur to stenosis of the mitral valve, Duroziez's2 description — "ffout-tata-rou" — in 1862 has been considered as the classic auscultatory sign. Since then, numerous observations and studies have confirmed the original concepts, and modifications have been added.A few additional observations are herewith reported, with particular reference to the so-called "presystolic crescendo murmur." We have observed by means of the phonocardiographic technic that auscultatory presystolic murmurs may at times be an auscultatory illusion owing to certain variations in the first heart sound. Although our series is small, we consider these observations pertinent to . . .
Curcumin/cisplatin based radiotherapy: The new and effective method to treat cervical cancer
Authors: mayank singh, Neeta Singh
Journal: Clinical Cancer Research (2008)

A9  Back ground  Cervical cancer is the most common cancer in Indian females and is associated with excessive inlammation. The present treatment for cervical cancer is cisplatin based radiotherapy but it is associated with various side effects. Curcumin (Diferuloyl methane), a chemopreventive agent, is a natural compound extracted from Curcuma longa that allows suppression and retardation of carcinogenesis and effectively inhibits inflammation. The objective of this study was compare the existing therapy regime with a Curcumin/cisplatin based radiotherapy.   Methods  HeLa, SiHa and Ca Ski cells were cultured in DMEM and RPMI medium supplemented in 10% FBS in a humidified atmosphere of 95% air and 5% CO2 at 37oC and were treated with 50µM curcumin/ 10μg cisplatin and 10μg cisplatin alone for 24 hrs followed by 2G radiation dose from cobalt 16 source. Cells which were not sensitized with Curcumin/Cisplatin were also treated with variable radiation doses. Apoptosis was measured by flow cytometery, Protein expression was assessed using western blotting, Telomerase expression was monitored using PCR/ELISA while caspase activity was measured using synthetic substrates.   Results  Treatment of cervical cancer cells with Curcumin/cisplatin combination dose followed by radiation resulted in increased apoptosis in comparison to cisplatin based radiotherapy.  The combination therapy resulted in increased expression of proapoptotic Bax, p73 and decreased downregulation of antiapoptotic Bcl Xl, inflammatory Cox 2, Cyclin D1 and effective reduction in activity of Telomerase in comparison to cisplatin based radiotherapy. The combination therapy also resulted in increased activation of caspase -9 and -3.  Conclusion  The present study indicates that curcumin has the potential to make cervical cancer therapies more effective and safer with minimization of side effects which are associated with generation of excessive reactive oxygen species in present therapy regime. This study also indicates that in some cases curcumin can replace cisplatin as a chemotherapeutic drug.
Case 8-2008
Authors: Jeremy S. Abramson, Camille N. Kotton, Nahel Elias, Dushyant V. Sahani, Robert P. Hasserjian
Journal: New England Journal of Medicine (2008)

A 33-year-old man was admitted to the hospital with fever, abdominal pain, and pancytopenia 15 years after renal transplantation. Imaging studies disclosed hepatosplenomegaly. A diagnostic procedure was performed.
Prospective Study of 352 Young Patients with Chemical Diabetes
Authors: John B. O'Sullivan, Clare M. Mahan
Journal: New England Journal of Medicine (1968)

Three criteria for "chemical diabetes" were evaluated by determination of their accuracy in predicting the subsequent development of classic diabetes, as measured by decompensation of carbohydrate control. Three hundred and fifty-two subjects with the diagnosis of chemical diabetes made on the basis of these three criteria, were followed for a maximum of 12 years, and the data observed were analyzed by the life-table technic. Fifty-two per cent of the cases diagnosed according to the United States Public Health Service criteria (fasting blood sugar level of 110, one-hour levels of 170, two-hours levels of 120 and three-hours levels of 110 mg per 100 ml) progress to decompensation of carbohydrate control within 10 years of the diagnosis, as estimated by life-table analysis, whereas only 32 per cent diagnosed by the Fajans and Conn criteria, and 21 per cent diagnosed by the Mosenthal and Barry, show similar progression. Body weight and a family history of diabetes had no appreciable effect on these findings.
Completely endoscopic resection of glioblastomas using a transparent conduit: Proof of concept
Authors: J. Engh, A. Mintz, F. Lieberman, A. B. Kassam
Journal: Journal of Clinical Oncology (2008)

2066 Background: Completely endoscopic resection of high grade gliomas has not been reported in a neurosurgical case series. Methods: Using frameless image guidance, an 11.5 mm cylindrical transparent port (endoport) is established as a transcortical conduit into the lesion. The port is introduced through a small cortisectomy. Microsurgical instruments, suction, and bipolar cautery are all introduced through the port as needed to facilitate resection. Five patients (four female, one male) underwent tumor resection using the fully endoscopic method. Age varied from 37–74 years (mean 57.8 years). All patients presented with some degree of confusion (two with somnolence), two patients (40%) had significant headache, and 3 patients (60%) were hemiparetic at the time of evaluation. Three tumors were in the left frontal region, one tumor was a butterfly glioma, and one tumor was in the right centrum semiovale. Tumor size varied from 41 to 65 mm in greatest dimension (mean 51.4 mm). Results: All patients demonstrated pathologically confirmed glioblastomas. On post-operative MRI, one patient had a gross total resection, two patients had >95% radiographic resection, and two patients had subtotal resection. No patient demonstrated any radiographic evidence of injury to surrounding brain as a result of resection. No patient suffered a post-operative complication or a new neurological deficit. One patient was taken back to the operating room for tumor progression well after discharge. Conclusions: Fully endoscopic resection of high-grade gliomas through a minimal access port is feasible and may be a safe alternative to open surgical extirpation. The degree of underlying white matter injury and the size of the cortisectomy for tumor resection may be less than with conventional methods of tumor removal. Further studies are warranted to determine whether or not this technique is safer than a standard tumor resection in the setting of glioblastoma. No significant financial relationships to disclose.
Substrate-Product Relation of 1-Hydroxylase Activity in Primary Hyperparathyroidism
Authors: Vincenzo LoCascio, Silvano Adami, Guido Galvanini, Marcello Ferrari, Luciano Cominacini, Donata Tartarotti
Journal: New England Journal of Medicine (1985)

The synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D), is thought to be relatively insensitive to the serum concentration of its precursor, 25-hydroxyvitamin D (25-OH-D). We compared the effect of oral administration of 25-OH-D3 (50 micrograms per day for one month) on serum concentrations of calcium, phosphate, parathyroid hormone, 25-OH-D, and 1,25-(OH)2D in five healthy adults and in six patients with primary hyperparathyroidism. In normal adults the mean (+/- S.D.) serum level of 25-OH-D rose from 18 +/- 9 to 136 +/- 47 ng per milliliter; no significant changes were observed in the other serum levels. In contrast, comparable increases in the levels of circulating 25-OH-D in patients with primary hyperparathyroidism caused a consistent slight rise in serum calcium and phosphate levels, a partial suppression of parathyroid hormone, and a sharp increase in the level of 1,25-(OH)2D. During this period a significant positive correlation was found between serum concentrations of 25-OH-D and 1,25-(OH)2D (P less than 0.001). These results provide evidence that in patients with primary hyperparathyroidism, levels of circulating 1,25-(OH)2D may be more dependent on the prevailing serum concentrations of 25-OH-D than they are in normal adults.
Measurement of LV Volumes and Function Using Oxygen-15 Water-Gated PET and Comparison With CMR Imaging
Authors: Roel S. Driessen, Janna E. van Timmeren, Wijnand J. Stuijfzand, Mischa T. Rijnierse, Ibrahim Danad, Pieter G. Raijmakers, Aernout M. Beek, Albert C. van Rossum, Robin Nijveldt, Adriaan A. Lammertsma, Hendrik J. Harms, Marc C. Huisman, Paul Knaapen
Journal: JACC. Cardiovascular imaging (2016)
The Relation between Genotype and Phenotype in Cystic Fibrosis — Analysis of the Most Common Mutation (ΔF<sub>508</sub>)
Authors: Eitan Kerem, Mary Corey, Bat-sheva Kerem, Johanna Rommens, Danuta Markiewicz, Henry Levison, Lap-Chee Tsui, Peter Durie
Journal: New England Journal of Medicine (1990)

Both the clinical manifestations of cystic fibrosis and the genotypes of patients are heterogeneous, but the associations between the two are not known. We therefore studied blood samples from 293 patients with cystic fibrosis for the presence of the most common disease-causing mutation (ΔF508) on chromosome 7 and compared the results with the clinical manifestations of the disease.
Respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma
Authors: Kecia N. Carroll, Tebeb Gebretsadik, Gabriel J. Escobar, Pingsheng Wu, Sherian Xu Li, Eileen M. Walsh, Ed Mitchel, Chantel D. Sloan, William D. Dupont, Tina V. Hartert
Journal: Journal of Allergy and Clinical Immunology (2016)
S24 Lung parenchymal assessment in primary and secondary pneumothorax - A Case-Control Study
Authors: OJ Bintcliffe, AJ Edey, IS Negus, NA Maskell
Journal: Thorax (2015)

<h3>Introduction</h3> Primary pneumothorax has been defined as occurring in patients with no known lung disease but the assumption that the underlying lung is normal is increasingly contentious. The purpose of this case-control study is to evaluate lung structure and quantify the extent of any emphysema in patients with primary and secondary spontaneous pneumothorax compared with a control group without pneumothorax and to assess the influence of smoking on this process <h3>Methods</h3> 20 patients with primary pneumothorax (PSP), 20 patients with secondary pneumothorax (SSP) and 40 control patients with computed tomography scans suitable for quantitative analysis were evaluated. Demographics and smoking histories were collated. Quantitative evaluation of low attenuation areas of the lung was performed using semi-automated software. The percentage of segmented lung below the low attenuation threshold value of -950 Hounsfield units was calculated, based on a previously validated threshold.<sup>1</sup> The extent of emphysema-like destruction was also assessed visually by an experienced consultant chest radiologist. <h3>Results</h3> The extent of emphysema and percentage low attenuation area was greater in PSP patients compared with controls matched for age and smoking history (Median 0.25 vs 0.00, p = 0.019) and was also higher in SSP compared with PSP patients (16.15 vs 0.25, p &lt; 0.001). PSP patients who smoked had significantly greater low attenuation area than PSP non-smokers (0.7 vs 0.1, p = 0.034). No such difference was detected between smokers and non-smokers within the control group (0.0 vs 0.05, p = 0.798). <h3>Conclusions</h3> The majority of patients with PSP had quantifiable evidence of parenchymal destruction and emphysema. The presented data is supportive of the hypothesis that there is likely to be a spectrum of lung damage ranging from ‘normal patients’ through to patients with SSP, and rather than a clear distinction between PSP and SSP these conditions exist on a continuum. <h3>Reference</h3> 1 Heussel CP, Herth FJ, Kappes J, <i>et al.</i> Fully automatic quantitative assessment of emphysema in computed tomography: comparison with pulmonary function testing and normal values. <i>Eur Radiol</i>. 2009;<b>19</b>(10):2391-402
Case 1-1963
Journal: New England Journal of Medicine (1963)

Presentation of Case A fifty-three-year-old man was referred to the hospital because of pain in the chest. Five days before entry, after prolonged exposure to the sun, the patient had a shaking chill, followed by generalized malaise, a moderate loss of appetite and a sore throat. Two days later he struck his left ankle on a subway turnstile and was aware of swelling of the ankle and pain in the left calf thereafter. On the day before admission he became weak and experienced severe dyspnea on mild exertion, necessitating absence from his job as a dental technician. On the evening . . .
Termination of Restricted Diet in Children with Phenylketonuria: A Randomized Controlled Study
Authors: Neil A. Holtzman, Doris W. Welcher, E. David Mellits
Journal: New England Journal of Medicine (1975)

This study demonstrates the feasibility of a randomized controlled investigation of terminating the phenylalanine-restricted diet in four-year-old children with phenylketonuria. The parents of 14 of 16 children gave informed consent, knowing their children would be randomly assigned to either a diet-continuation or a diet-termination group. Compared with the continuation group, the mean serum phenylalanine of the termination group was 15.1 mg per dl higher (P <0.005) one year, and 9.2 mg per dl higher(P <0.025) two years after diet termination. Mean weight gain between four and six years of age was 3.4 kg greater in the terminated than in the continued group (P <0.01). There were no significant differences in mean head circumferences, height or performances on psychologic tests. At age six, mean I.Q. in the terminated group was 99.8, in those continuing the diet 103.6. Children in both groups showed some subtest scatter in memory and concentration. Thus, no harmful effects of diet termination were noted, but a longer period of observation in a larger number of subjects is needed. (N Engl J Med 293:1121–1124, 1975)
Computer-Assisted Digoxin Therapy
Authors: Carl C. Peck, Lewis B. Sheiner, Carrol M. Martin, Darrel T. Combs, Kenneth L. Melmon
Journal: New England Journal of Medicine (1973)

In 42 patients requiring digitalis, and randomly divided into two groups, the performance of a computer program using patient size and renal function to compute digoxin dosage was compared to that of unaided physician judgment. Serum digoxin concentrations were measured repeatedly. Efficacy was measured by changes in the manifestations of heart failure, and toxicity by electrocardiographic criteria. For each patient, physicians specified a desired serum digoxin concentration and predicted this concentration at each visit. For one group, the computer program suggested the dosage needed to achieve the desired digoxin concentration. Efficacy was the same in both groups, and there was no toxicity. Although the computer slightly outperformed the physicians, prediction and achievement errors were unacceptably large. Hence, much between-patient variability in serum digoxin concentrations remains unexplained after adjustments for dose, body size and renal function. This argues for measurement of digoxin concentrations and their use for feedback dosage adjustment. (N Engl J Med 289:441–446, 1973)
Case 36-2010
Authors: Konstantina M. Stankovic, Amy F. Juliano, Robert P. Hasserjian
Journal: New England Journal of Medicine (2010)

A 50-year-old woman had pain and hearing loss in the left ear. Examination revealed erythema, white debris, and a serous effusion. Treatment led to transient improvement in pain, but hearing loss persisted. Three months after the onset of symptoms, a mass was noted in the ear canal.
The Vitamin Content of Commercial Winter Goat's Milk
Authors: Arthur D. Holmes, Harry G. Lindquist, Carleton P. Jones, Anne W. Wertz, Katharine Esselen, Beula V. McKey, Evelyn Fuller
Journal: New England Journal of Medicine (1945)

IT HAS been estimated that the retail value of goat's milk produced in this country exceeds $100,000,000 annually. A large portion of fluid goat's milk is used for infants, for invalids and for consumption in the home of the producer.Various claims have been made for the superiority of goat's milk over cow's milk. Besley1 states that of the two, goat's milk has larger amounts of albumin and nonprotein nitrogen, greater quantities of vitamin B1, a softer curd and smaller fat globules. Richards2 reports "the fact that goat's milk is alkaline in its reaction while cow's milk is acid, . . .
Umbilical cord blood–derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect
Authors: Claudio G. Brunstein, Jeffrey S. Miller, David H. McKenna, Keli L. Hippen, Todd E. DeFor, Darin Sumstad, Julie Curtsinger, Michael R. Verneris, Margaret L. MacMillan, Bruce L. Levine, James L. Riley, Carl H. June, Chap Le, Daniel J. Weisdorf, Philip B. McGlave, Bruce R. Blazar, John E. Wagner
Journal: Blood (2015)