tbuckley/cabot-search huggingface dataset:
Prognostic value of 18F-FDG PET/CT metabolic tumor volume for complete pathologic response and clinical outcomes after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer.
Authors: Puja Venkat, Jasmine A Oliver, Will Jin, Joshua Dault, Jessica M. Frakes, Sarah E. Hoffe, Jose Mario Pimiento, Khaldoun Almhanna, Jacques Fontaine, Luis Pena, Kujtim Latifi
Journal: Journal of Clinical Oncology (2016)

150 Background: The prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has not yet been defined in locally advanced esophageal cancer (LAEC). This study aims to elucidate the prognostic role of PET/CT for patients treated with neoadjuvant chemoradiation (CRT) followed by esophagectomy. Methods: We retrospectively evaluated patients with LAEC treated from 2006 to 2014 with neoadjuvant CRT followed by esophagectomy. 86 patients had pre-CRT and post CRT PET/CT scans performed at our institution. These scans were imported into an image analysis program. PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), mean standardized uptake value (SUVmean), and peak standardized uptake value (SUVpeak) were recorded for both pre-CRT and post-CRT scans. MTV was defined using a previously described liver method. The correlation of these parameters with pathologic complete response (pCR) and clinical outcomes was analyzed using binomial logistic regression and cox regression. Results: Pre-CRT MTV &lt; 33.6 (median value) was significantly predictive of pCR (p = 0.019, OR = 3.064). An ROC curve was produced to determine a binary cutoff of 35.8, yielding a higher specificity (62.3% vs. 59%) and the same sensitivity (72.7%), increasing the significance to p = 0.010, OR = 3.378. The ratio of postMTV/preMTV (MTVr) was calculated. MTVr &gt; 0.2857 (median value) was significantly predictive of distant metastasis (DM) after esophagectomy (p = 0.018, OR = 3.680). An ROC curve was produced to determine a binary cutoff of 0.301, which increased specificity from 57.1% to 60.3%, and maintained the same sensitivity at 81.3%, increasing the significance to p = 0.014, OR = 3.815. SUVmax, mean and peak were not predictive. Conclusions: Pre CRT MTV was predictive of pCR and MTVr was predictive of DM. Our data suggests that MTV is superior to SUVmax, mean and peak in predicting for response to treatment in LAEC. Further study is needed to determine if Pre CRT MTV and change in MTV can help define which patients will most benefit from esophagectomy and/ or adjuvant chemotherapy.
NCCN Guidelines and Quality Cancer Care: Where Have We Come From, and Where Should We Be Going?
Authors: Daniel G. Coit
Journal: Journal of the National Comprehensive Cancer Network (2016)

I have a clear and vivid recollection of the initial meeting of our NCCN Melanoma Panel 20 years ago. Roughly 25 national experts in melanoma, all from NCIdesignated comprehensive cancer centers across the country, including surgeons, medical oncologists, dermatologists, radiologists, and pathologists, gathered together in a room in New York City, in a group chaired by Alan Houghton, MD, and overseen by Rodger Winn, MD. The stated mission of the then-fledgling organization, the National Comprehensive Cancer Network, was to “improve the quality, effectiveness, and efficiency of cancer care.” 1 Our panel’s charge sounded straightforward at the time: to derive a set of evidence-based or, when evidence was insufficient, consensus-based treatment guidelines for physicians treating patients with melanoma of all stages. We were to develop recommendations for the diagnosis, workup, initial treatment including adjuvant therapy, follow-up, and management of recurrent disease. Over the ensuing 2 decades, these guidelines have evolved substantially, in part in response to evolving new information (clinical trials of local, regional, and systemic therapy; newer imaging modalities; and seminal retrospective reviews, series, and meta-analyses), but also in large part in response to our continuously evolving understanding of the role of guidelines as they are applied to achieve quality in clinical cancer care. This evolving understanding involves several components, including the challenge of effectively defining quality care, the task of identifying which elements of a treatment guideline best support quality care, and determining how best to measure the impact of guidelines on quality care.
Protection of Jeopardized Ischemic Myocardium by Reduction of Ventricular Afterload
Authors: William E. Shell, Burton E. Sobel
Journal: New England Journal of Medicine (1974)

To determine whether reduction of ventricular afterload protects ischemic myocardium, we studied 38 patients with acute myocardial infarction. Serial serum creatine phosphokinase values were used to estimate ischemic myocardial injury (i.e., "infarct size"). In addition, "infarct size" was predicted by nonlinear least-squares approximation from creatine phosphokinase changes during the first seven hours after admission. In 10 hypertensive and 14 normotensive patients "infarct size" as actually observed and as predicted was virtually identical. Another group of 14 patients, hypertensive on admission, were given trimethaphan to lower blood pressure, decrease ventricular afterload, and presumably diminish myocardial oxygen requirements. In these patients, observed "infarct size" was 24 per cent less than that predicted (p<0.01). Mortality within one month was less in the treated than in untreated patients matched for predicted "infarct size." The results suggest that reduction of ventricular afterload in hypertensive patients with acute myocardial infarction protects ischemic myocardium. (N Engl J Med 291:481–486, 1974)
Endpiece: Poles apart?
Authors: Fred Charatan
Journal: BMJ (2003)

The young have aspirations that never come to pass, the old have reminiscences of what never happened.

Saki (Hector Hugh Monro, 1870-1916),

Reginald at the Carlton: Reginald, 1904.

Scottish writer of humorous, ironic, and macabre short stories, killed in action in the first world war
Interaction of Chronic Hypoxia of Moderate Altitude on Pulmonary Hypertension Complicating Defect of the Atrial Septum
Authors: James E. Dalen, Robert A. Bruce, Leonard A. Cobb
Journal: New England Journal of Medicine (1962)

PULMONARY hypertension is a serious and relatively frequent complication of the ostiumsecundum type of defect of the atrial septum.1 2 3 4 It increases the symptoms and disability of cardio-respiratory impairment and substantially raises the mortality for surgical correction of this defect. Recent evidence indicates that prolonged hypoxia of high altitude elevates pulmonary arterial pressure in man and other mammals5 6 7; the possibility that even slight hypoxia, associated with exposure to moderate altitude, affects pulmonary arterial pressures has not been systematically investigated to our knowledge. Because pulmonary hypertension, under acute hypoxic conditions, probably represents the consequences of vasoconstriction, and because pulmonary vascular engorgement . . .
Renal Oxalosis and Azotemia after Methoxyflurane Anesthesia
Authors: Joseph A. Frascino, Parker Vanamee, P. Peter Rosen
Journal: New England Journal of Medicine (1970)

Renal biopsies performed in seven patients after methoxyflurane anesthesia followed by renal failure disclosed a striking degree of oxalate precipitation. The extent of the precipitation paralleled, but could not fully account for, the corresponding degree of azotemia. Urinary oxalate, determined in six patients, was elevated (96 to 480 mg per 24 hours). Methoxyflurane thus appears to cause secondary hyperoxaluria, and intrarenal oxalate precipitation may occur when renal function is compromised for any reason during or immediately after surgery. Oxalate deposition, when extensive, may contribute to the severity of the renal failure.
Long-Term Follow-up of Idiopathic Chronic Pericardial Effusion
Authors: Jaume Sagristà-Sauleda, Juan Angel, Gaietà Permanyer-Miralda, Jordi Soler-Soler
Journal: New England Journal of Medicine (1999)

A large idiopathic chronic pericardial effusion can be defined as a collection of pericardial fluid that persists for more than three months and has no apparent cause. We conducted a prospective study of the natural history and treatment of this disorder.Between 1977 and 1992, we prospectively evaluated and enrolled patients with large idiopathic chronic pericardial effusion. We performed pericardiocentesis in most of the patients. We performed pericardiectomy when large pericardial effusion reappeared after pericardiocentesis. Follow-up ranged from 18 months to 20 years (median, 7 years).During the study period, we evaluated a total of 1108 patients with pericarditis, 461 of whom had large pericardial effusion. Twenty-eight of these patients (age range, 7 to 85 years; median, 61) had large idiopathic chronic effusion and were included in the study. The duration of effusion ranged from 6 months to 15 years (median, 3 years). At the initial evaluation, 13 patients were asymptomatic. Overt tamponade was found in eight patients (29 percent). Therapeutic pericardiocentesis, performed in 24 patients, was followed by the disappearance of or marked reduction in the effusion in 8. Five of the 24 patients underwent early pericardiectomy, and in 11 large pericardial effusion reappeared. Cardiac catheterization, performed in 16 patients, showed elevated intrapericardial pressure (4.75+/-3.79 mm Hg) and reduced transmural pressure (1.0+/-2.50 mm Hg) before pericardiocentesis. Both of these abnormalities in pressure improved significantly after pericardiocentesis. Pericardiectomy, performed in 20 patients, yielded excellent long-term results. At the end of the follow-up period, 10 patients had died, but none had died from pericardial disease.Large idiopathic chronic pericardial effusion is well tolerated for long periods in most patients, but severe tamponade can develop unexpectedly at any time. Pericardiocentesis alone frequently results in the resolution of large effusions, but recurrence is common and pericardiectomy should be considered whenever a large effusion recurs after pericardiocentesis.
P88 The evaluation of Exophiala in paediatric cystic fibrosis
Authors: LB Patel, J Panickar, A Shawcross, S Wilkinson
Journal: Thorax (2015)

<h3>Introduction</h3> The increasing prevalence of fungal pathogens in paediatric cystic fibrosis (CF) is challenging current practice. Whilst respiratory growth and colonisation with <i>Exophiala</i>, a saprophytic fungus is documented; the susceptibility, clinical manifestation and management is unclear. <h3>Aim</h3> To evaluate the clinical manifestation of <i>Exophiala</i> and the role of antifungal therapies in paediatric CF. <h3>Setting</h3> Royal Manchester Children’s Hospital provides tertiary care for 182 patients and shared care for 170 patients encompassing a diverse range of genotypes. <h3>Population</h3> Fifteen patients have yielded <i>Exophiala</i> positive sputum swabs on routine screening over 24 months. <h3>Measures</h3> Objective measures of disease severity and demographics; age, gender, BMI (Z-score), lung function, hospital admissions are assessed against <i>Exophiala</i> growth and co-existing pathogens. Antifungal treatment regimens are described and compared. <h3>Analysis</h3> Significant clinical manifestation of <i>Exophiala</i> and evidence of eradiation in this population is described. <h3>Results</h3> Data reveals no significant difference in sex ratio 8:7 (♂:♀) though distribution is skewed towards older patients 46.7% (n = 7) &gt;15 years, 26.6% 12–14 years, 12.5% 10 years, 12.5% 5–7 years. Two distinct categories of carriage are evident; sporadic growth (n = 9) and colonisation (n = 6). All positive sputa contained ≥2 organisms’ suggesting coexisting colonisation. 73.3% of all patients and 100% percent of patients colonising <i>Exophiala </i>had coexisting colonisation of <i>Candida albicans</i>. 100% of patients colonising <i>Exophiala</i> also had a drop in BMI and Z-score from diagnosis to date of study. They also had a rate of &gt;9 admissions/year. Lung function tests revealed variation independent of carriage. Symptomatic carriage of <i>Exophiala</i> was treated with triazoles; voriconazole, itraconazole and posaconazole though 50% of blood triazole levels were below therapeutic range. One patient cleared <i>Exophiala</i> without antifungal treatment. No further growth was noted following itraconazole treatment on initial growth in another patient. Colonisation was treated successfully with intravenous voriconazole, though re-colonised 4 months later. Colonisation was evident in 2 patients despite 6–12 months of oral voriconazole but was eradicated on switching to oral posaconazole. <h3>Conclusion</h3> Data from this single centre study suggests that some paediatric CF patients may be more susceptible to fungal infections. <i>Exophiala carriage</i> manifestation varies and may affect height and weight. <i>Exophiala </i>eradication can be achieved.
An Evaluation of the Anterior Resection of the Rectum and Low Sigmoid
Authors: Frank C. Wheelock, Giles Toll, Leland S. McKittrick
Journal: New England Journal of Medicine (1959)

CARCINOMA of the rectosigmoid area of the colon is of common occurrence and fortunately is productive of early symptoms. Carcinomas in this location account for 60 per cent of all cases in the colon.1 Resection with anastomosis for certain of these cases, rather than a combined abdominoperineal resection or an anterior resection with a permanent colostomy, has tempted surgeons for years. In 1920 Crile2 reported 38 anterior resections with no mortality — an excellent result not duplicated by others. Interest was further stimulated by the thorough monograph on this subject by d'Allaines et al.3 in 1948. Until recent years wide . . .
A 380-gene meta-signature of active tuberculosis compared with healthy controls
Authors: Simon Blankley, Christine M. Graham, Joe Levin, Jacob Turner, Matthew P.R. Berry, Chloe I. Bloom, Zhaohui Xu, Virgina Pascual, Jacques Banchereau, Damien Chaussabel, Ronan Breen, George Santis, Derek M. Blankenship, Marc Lipman, Anne O'Garra
Journal: European Respiratory Journal (2016)

Mycobacterium tuberculosis is estimated to have infected one third of the world's population and continues to be a significant cause of mortality and morbidity [1]. There is a need for new and improved diagnostics or treatment-monitoring tools and blood-based mRNA diagnostics are a potential solution [2]. Gene expression microarray analysis of human blood has been widely used to profile the host transcriptional response in active tuberculosis (TB) to identify potential biomarkers and better understand the host immune response [2]. So far, there has been a relative lack of concordance in the actual genes being identified from the published studies [2, 3], although there has been agreement in some of the pathways identified. Interferon (IFN) signalling has been identified as a dominant signature in many of the individual studies [2, 4]; however, when significant gene lists were combined from eight publicly available TB datasets, TREM1 (triggering receptor expressed on myeloid cells 1) signalling became the most significant pathway [5]. Modular and meta-profiling identify a common transcriptional response of patients with TB versus healthy controls <http://ow.ly/YvEP7>
New Tests to Assess Lung Function
Authors: J. Milic-Emili, W.A. Whitelaw, J. Ph. Derenne
Journal: New England Journal of Medicine (1975)

IN recent years two clinically applicable, simple and rapid methods for measuring the ventilatory response to carbon dioxide and hypoxia have been described.1,2 Neither of these methods, however, is capable of differentiating patients who will not breathe because of central or neuromuscular inadequacy from those who cannot breathe because of mechanical abnormalities of the chest, such as airways obstruction and decreased compliance of the respiratory system. Measurement of inspiratory mechanical work,3,4 oxygen cost of breathing5 and diaphragmatic electromyography6 have been used in the past to separate patients who will not from those who cannot breathe. These measurements, however, take time, . . .
Case 2-1997
Authors: George A. Jacoby, C. Mhorag Hay
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 38-year-old schizophrenic man was admitted to the hospital because of digital clubbing and a cardiac murmur.The patient had been well until about one year earlier, when he began to have swelling of the fingers and toes. Eleven months before admission, an evaluation elsewhere showed a grade 2 systolic murmur at the lower left sternal border. One month before admission, he underwent a dental extraction and took ampicillin prophylactically for two days. On the day of admission, examination of the patient in the medical clinic revealed two loud murmurs. A cardiac ultrasonographic examination showed severe mitral . . .
Adrenocortical Function in Anorexia Nervosa before and after Lobotomy
Authors: Mark D. Altschule
Journal: New England Journal of Medicine (1953)

CLINICAL differences between anorexia nervosa and panhypopituitarism are usually so striking that differentiation of these two disorders is not difficult.1 There are also important physiologic differences. Nevertheless, the idea persists in some quarters that the physical manifestations of anorexia nervosa are partly due to secondary hypoadrenalism and that ACTH (adrenocorticotrophic hormone) should have a specific, beneficial effect. Observations on adrenocortical function in anorexia nervosa made at this hospital and elsewhere may be of interest in this connection.Material and MethodsA nineteen-year-old girl with anorexia nervosa was studied at McLean Hospital; the clinical manifestations of her disorder have already been . . .
RARE-19CASE REPORT OF THE NATURAL HISTORY OF INCIDENTALLY FOUND MEDULLOBLASTOMA FOLLOWED RADIOGRAPHICALLY IN A YOUNG ADULT WITH CHRONIC HEADACHES
Authors: Nicholas Pytel, Mariah Bashir, Shahriar Salamat, Rishi Lulla, Neha Patel, Diane Puccetti
Journal: Neuro-Oncology (2015)

Medulloblastoma is a malignant tumor diagnosed in 12-25% of pediatric brain tumors, 77% before the age of 19. In adulthood, the rate sharply declines with increasing age to be only diagnosed in 0.4-1% of adult brain tumors. These tumors are diagnosed typically after symptoms are noted consistent with increased intracranial pressure. We present a case of a young adult who was followed with serial MRI scans due to history of headaches and over time developed a lesion in the cerebellum that was later diagnosed as a medulloblastoma. We present this case as a natural history of medulloblastoma and will include a review of the literature. Patient AG had the original MRI brain scan for chronic headaches yielding only a right posterior fossa arachnoid cyst. Four years later, persistent headaches warranted another scan showing a new lesion with T2 FLAIR hyperintensity in the left cerebellar hemisphere. Serial scans over two years showed progression in size and complexity of this new lesion originally thought benign. AG underwent craniotomy with mass resection that resulted in cytoplasmic beta-catenin positive medulloblastoma without anaplasia on neuropathology. It was also without metastasis or CSF involvement. Post-operative imaging showed a small suspicious area near the resection cavity which biopsies later proved positive for residual medulloblastoma greater than 1.5 cm, thus placing this patient into the high-risk treatment category. AG elected proton therapy (36 in the craniospinal region with posterior fossa boost) with vincristine following protocol ACNS0331 with maintenance therapy afterward. AG has since been followed with serial MRI scans without evidence of residual disease. After reviewing the literature, low occurrences of incidental CNS tumors have been found in trauma and research cases. It is rare to have radiographic evidence of the onset of a malignant brain tumor. We present our case and literature review of this entity.
Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients
Authors: Lisa Pieri, Patrizia Bonadonna, Chiara Elena, Cristina Papayannidis, Federica Irene Grifoni, Michela Rondoni, Stefania Girlanda, Marina Mauro, Diomira Magliacane, Elena Maria Elli, Maria Loredana Iorno, Fabio Almerigogna, Federica Scarfì, Roberto Salerno, Tiziana Fanelli, Francesca Gesullo, Giuditta Corbizi Fattori, Massimiliano Bonifacio, Omar Perbellini, Anna Artuso, Simona Soverini, Caterina De Benedittis, Simona Muratori, Valerio Pravettoni, Vittoria Cova, Gabriele Cortellini, Fabio Ciceri, Agostino Cortelezzi, Giovanni Martinelli, Massimo Triggiani, Serena Merante, Alessandro Maria Vannucchi, Roberta Zanotti
Journal: American Journal of Hematology (2016)

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a “real‐life” setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with ( n = 255) and without ( n = 165) skin lesions, smouldering ( n = 20), aggressive ( n = 28), associated with other hematological diseases mastocytosis ( n = 21) and mast cell leukemia ( n = 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis &gt;60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease‐associated manifestations. Am. J. Hematol. 91:692–699, 2016. © 2016 Wiley Periodicals, Inc.
Oral Anticoagulant Drugs
Authors: John A. Oates, Alastair J.J. Wood, Jack Hirsh
Journal: New England Journal of Medicine (1991)

The vitamin K-antagonist drugs were reviewed in the Journal in the early 1970s.1 , 2 Since then, there has been considerable progress in research at both a basic and an applied level. The mode of action of coumarins has been clarified; their role in the management of thromboembolic disorders has been more clearly defined; a system has been developed to standardize the measurement of their anticoagulant effect3; and their safety has been improved for a number of indications without compromising efficacy, through the use of a lower degree of anticoagulation than formerly in North America.4 Warfarin (a 4-hydroxycoumarin compound) is the . . .
Intrauterine Diagnosis of the Hurler and Hunter Syndromes
Authors: Joseph C. Fratantoni, Elizabeth F. Neufeld, B. William Uhlendorf, Cecil B. Jacobson
Journal: New England Journal of Medicine (1969)

Prenatal diagnosis was accomplished for two women who had previously borne children affected with genetic disorders of mucopolysaccharide metabolism — the Hurler syndrome (autosomal recessive) in one case and the Hunter syndrome (X-linked recessive) in the other. Amniotic fluid, which contains fetal cells, was obtained by transabdominal amniocentesis. After culture in vitro, the amniotic fluid cells displayed two characteristics (a distinctive kinetic pattern of radioactive sulfate incorporation into mucopolysaccharide and metachromatic staining with toluidine blue) that are also exhibited by cultured skin fibroblasts derived from patients with these metabolic disorders.