tbuckley/cabot-search huggingface dataset:
Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis
Authors: T Barbui, J Thiele, A M Vannucchi, A Tefferi
Journal: Blood Cancer Journal (2015)

The 2001/2008 World Health Organization (WHO)-based diagnostic criteria for polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) were recently revised to accomodate new information on disease-specific mutations and underscore distinguishing morphologic features. In this context, it seems to be reasonable to compare first major diagnostic criteria of the former WHO classifications for myeloproliferative neoplasm (MPN) and then to focus on details that have been discussed and will be proposed for the upcoming revision of diagnostic guidelines. In PV, a characteristic bone marrow (BM) morphology was added as one of three major diagnostic criteria, which allowed lowering of the hemoglobin/hematocrit threshold for diagnosis, which is another major criterion, to 16.5 g/dl/49% in men and 16 g/dl/48% in women. The presence of a JAK2 mutation remains the third major diagnostic criterion in PV. Subnormal serum erythropoietin level is now the only minor criterion in PV and is used to capture JAK2-unmutated cases. In ET and PMF, mutations that are considered to confirm clonality and specific diagnosis now include CALR, in addition to JAK2 and MPL. Also in the 2015 discussed revision, overtly fibrotic PMF is clearly distinguished from early/prefibrotic PMF and each PMF variant now includes a separate list of diagnostic criteria. The main rationale for these changes was to enhance the distinction between so-called masked PV and JAK2-mutated ET and between ET and prefibrotic early PMF. The proposed changes also underscore the complementary role, as well as limitations of mutation analysis in morphologic diagnosis. On the other hand, discovery of new biological markers may probably be expected in the future to enhance discrimination of the different MPN subtypes in accordance with the histological BM patterns and corresponding clinical features.
Abstract 271: Outcomes of Extracorporeal Membrane Oxygenation in Adult Patients With Refractory Shock and Cardiac Arrest
Authors: Eisuke Kagawa, Keigo Dote, Masaya Kato, Shota Sasaki, Yoshinori Nakano, Masato Kajikawa, Akifumi Higashi, Kiho Itakura, Akihiko Sera, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani
Journal: Circulation (2010)

Introduction: Extracorporeal membrane oxygenation (ECMO) could rapidly provide temporary circulatory assistance for patients complicated with shock or cardiac arrest. However, the relation between ...
Relationship of circulating soluble urokinase plasminogen activator receptor (suPAR) levels to disease control in asthma and asthmatic pregnancy
Authors: István Ivancsó, Gergely Toldi, Anikó Bohács, Noémi Eszes, Veronika Müller, János Rigó, Barna Vásárhelyi, György Losonczy, Lilla Tamási
Journal: European Respiratory Journal (2014)

Asthma may frequently complicate pregnancy, posing a risk for pregnancy outcomes. Elevated plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is related to a worse prognosis in many conditions; however its value in asthma and asthmatic pregnancy is unknown.  The present study aimed to investigate the suPAR, CRP and IL-6 levels in asthma (asthmatic non-pregnant, ANP; N=38; female N=27) and asthmatic pregnancy (AP; N=15), compared to healthy non-pregnant controls (HNP; N=29; female N=19) and to healthy pregnant women (HP; N=58). The relationship between suPAR levels and asthma control was also evaluated. The diagnostic efficacy of suPAR in asthma control was analyzed using ROC analysis.  IL-6 and CRP levels were comparable in all study groups. Circulating suPAR levels were lower in HP and AP than in HNP and ANP subjects, respectively (2.01 [1.81-2.38] and 2.39 [2.07-2.69] vs. 2.60 [1.82-3.49] and 2.84 [2.33-3.72] ng/mL, respectively, p=0.0001). suPAR and airway resistance correlated in ANP (r=0.47, p=0.004). ROC analysis of suPAR values in ANP patients with PEF above and below 80% yielded an AUC of 0.75 (95% CI: 0.57-0.92, p=0.023) and with ACT total score above and below 20 an AUC of 0.80 (95% CI: 0.64-0.95, p=0.006). The cut-off value of suPAR to discriminate between controlled and not controlled AP and ANP was 4.04 ng/mL.  suPAR may help objective assessment of asthma control, since it correlates with airway resistance and has good sensitivity in detection of impaired control. Decreased levels both in healthy and asthmatic pregnant women presumably represents pregnancy induced immune tolerance.
Osteoporosis in Men
Authors: Gordana M Prelevic
Journal: Journal of the Royal Society of Medicine (2001)

Osteoporosis is one of the most common metabolic bone diseases, and its prevalence will rise as our population grows older. Although osteoporosis is less common in men than in women its morbidity and mortality seem to be even greater. Furthermore the incidence of osteoporosis in men may well be underestimated, since men are far less likely than women to have a bone density scan.

Epidemiological studies suggest that, in the USA, about 1.5 million men over 65 years of age have osteoporosis and another 8-13 million have osteopenia1. The calculated lifetime risk of fracture for men is 13.5% at the age of 50 years and 25.6% at the age of 601.

The prevalence in men of fractures of the spine or hip is about one-third that in women2. There seems to be a lag period such that an exponential increase in fracture incidence begins 10 years later in men than in women3, coinciding with the phase of accelerated bone loss after the age of 704.

Although women have a higher overall prevalence of fracture, the increase in fracture risk for each standard deviation decrease in bone mineral density (BMD) seems to be higher in men. Moreover, mortality associated with hip fracture is two to three times higher in men than in women5,6,7,8. Strict criteria for the diagnosis of osteoporosis in men are still lacking: the World Health Organization definition, based on a T score greater than -2.5, relates to Caucasian women. The underlying mechanisms, risk factors and natural history of osteoporosis in men are now attracting much research attention.
Secondary gain from illness leading to prolonged weaning failure
Authors: Abdel Hakim Bayarassou, Wolfram Windisch, Jan Hendrik Storre
Journal: European Respiratory Journal (2012)

Objective:  For some patients prolonged weaning from invasive ventilation comes along with a temporary transfer to home mechanical ventilation. This is associated with a high logistic support, infrastructure of staff and costs for health insurance. Here, patients9 physical abilities for weaning needed to be monitored closely to avoid mismanagement of patients.   Methods:  Tracheotomised COPD-patients on home mechanical ventilation were analysed during readmission for a follow-up visit and possible decannulation.   Results:  Three COPD-patients were identified. All patients showed clear evidence to perform weaning from invasive positive pressure ventilation. However, one homeless patient (50years/male) refused to be weaned due to anxiety loosing his new established home environment. A second patient (64years/male) refused to be weaned based on fear loosing the financial support given from the health insurance to patient9s family for nursing. A third patient (65years/female) was successfully weaned to noninvasive ventilation, but called for re-tracheostomy due to fear loosing infrastructure of staff at home.   Conclusion:  Prolonged weaning and establishment of invasive home mechanical ventilation can lead to secondary gain from illness. Following, the goal of self-determined living can be contrary to prospective medical therapy.
MENTAL HYGIENE FOR THE TRAINEE
Authors: R. ROBERT COHEN
Journal: American Journal of Psychiatry (1943)

A. This program for mental hygiene appears to have definite practical value in creating rapid normal military adjustment by building up good morale in new trainees. B. Through a reduction in psychosomatic complaints, 122 to 531 man-hours of training time have been saved during the basic training period of a single company; and in a total of 5 companies tested, 996 man-hours were saved during the basic period training time. If comparable results were obtained by such a program throughout the entire Army, the saving of training time would be enormous. On January 21, 1943, this program was approved for trial conversion into films. C. This method improved morale not only in the clinical psychosomatic cases but also in the subclinical potential psychosomatic cases, who do not appear for medical relief. This trend was shown by the greater number of Sunday sick calls, smaller number of total sick calls for all causes, less time lost by AWOL's, better grades in training, and by the appreciative responses to the questionnaire in the conditioned experimental groups. D. This method has produced men who should continue to adjust themselves normally to situations they may meet in the future. E. By the same token, men in the control groups who were not given the benefit of this conditioning may possibly break down later on. F. The application of this mental hygiene program should be particularly beneficial to the incoming 18-and 19-year-old inductees. The facilitation of military adjustment through such a program should have a favorable influence on civilian morale as reflected by the letters from these men to their parents.
Clinical Relevance of Expression of the CIP/KIP Cell-Cycle Inhibitors p21 and p27 in Laryngeal Cancer
Authors: Giancarlo Pruneri, Lorenzo Pignataro, Nadia Carboni, Roberto Buffa, Devrim Di Finizio, Bruno Mario Cesana, Antonino Neri
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS: We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had ≤ 10% of p21 and ≤ 50% of p27 immunoreactive neoplastic cells. RESULTS: In 41 cases (31.1%), p21 was expressed in ≤ 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1–positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1 + /p27 − phenotype had the poorest disease-free and overall survival rates. CONCLUSION: Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.
Bronchial brush-biopsies cells in dependence on infectional agent species at COPD exacerbation
Authors: Sofya Nesterovich, Ekaterina Bukreeva
Journal: European Respiratory Journal (2011)

Inflammatory process at COPD exacerbation result in high growth activity and injured effects of bronchial epitheliocytes.

To define bronchial brush-biopsies cytogramms peculiarities in dependence on infectional agent species associated with COPD exacerbation.

46 COPD exacerbation patients were examined. Cytological research of brush-biopsies were taken at bronchoscopy was made; the quantitative bacteriological sputum research, definition of diagnostic main IgG, IgM levels to Ch.pneumoniae, M.pneumoniae in serum by means immuno-assay method, in sputum by means of PCR method were made.

Infectional character of COPD exacerbation was confirmed at 36 patients. Typical ciliated epithelial cells count was low in H.influenzae, Ch.pneumoniae, M.pneumoniae 14.6±2.2%, 15.1±2.5%, 15.5±3.0%, (p<0.05), than in S.pneumoniae, M.catarrhalis agents (32.7±3.6%, 37.1±5.1%). Reserved cells count was high (p<0.05) in M.pneumoniae (12.0±2.7%), than S.pneumoniae, H.influenzae, Ch.pneumoniae, M.catarrhalis agents (5.3±1.1%, 8.4±1.5%, 8.9±1.9%, 5.1±2.3%). Squamous metaplased cells was high (p<0.05) in H.influenzae, Ch.pneumoniae, M.pneumoniae (6.3±1.2%, 7.5±1.2%, 7.4±1.6%), than in S.pneumoniae, M.catarrhalis agents (2.5±0.9%, 2.2±0.7%). Dystrophical epithelial cells count was high (p<0.05) in H.influenzae, Ch.pneumoniae (56.6±2.1%, 54.9±2.8%), than S.pneumoniae, M.pneumoniae M.catarrhalis agents (46.9±3.0%, 44.7±3.5%, 38.9±4.3%).

Neutrophiles count was high (p<0.05) in H.influenzae, Ch.pneumoniae (50.2±4.4%, 56.5±4.2%) than at S.pneumoniae, M.pneumoniae M.catarrhalis agents (36.0±4.0%, 30.8±4.6%, 34.8±4.6%).

H.influenzae, Ch.pneumoniae have more injured effects, but M.pneumoniae result in high growth activity.
Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control
Authors: Mathieu Molimard, Vincent Le Gros, Isabelle Bourdeix
Journal: European Respiratory Journal (2012)

Evolution of severe asthma after discontinuation of omalizumab (OMA) (Xolair®) for good asthma control is still not very well known. This study provides real-life data in this situation.   Methods:  Observational, descriptive, cross-sectional, retrospective study in which 24 pulmonologists recorded data on patient and asthma characteristics during OMA treatment prescribed in patients with severe persistent allergic asthma uncontrolled despite best available therapies, and after OMA discontinuation (minimal follow up required = 6 months), for all their patients in who OMA had been discontinued due to achievement of good asthma control.   Results:  Data from 61 patients were collected [characteristics at OMA initiation: females 65.6%; mean age 40.7 yrs (min 6, max 82); mean asthma duration 22.3 yrs]. Mean duration of OMA treatment was 22.7 months (CI 95% : 19.4-26.0). Mean duration of good asthma control before discontinuation was 11.8 months (CI 95% : 12.0-18.1). Mean change in FEV 1  under OMA was +13%. After OMA discontinuation, median follow up duration was 9.26 months, loss of control was observed in 34 patients (55.7%) for who median time to loss of control was 13 months (CI 95% : 8.2-28.1). The % of patients with an observed loss of control were 69.2%, 59.1% & 45.7% after respectively  2 years of OMA treatment. OMA was reintroduced in 20 out of the 34 patients with loss of control: 14 were responders (70%), 4 not responders (20%) & 2 not yet evaluable (10%).   Conclusion:  Proportion of observed loss of control depended on prior treatment duration. Most of patients were still responders after OMA reintroduction.  Funded by: Novartis Pharma SAS.
Bioengineering Human Myocardium on Native Extracellular Matrix
Authors: Jacques P. Guyette, Jonathan M. Charest, Robert W. Mills, Bernhard J. Jank, Philipp T. Moser, Sarah E. Gilpin, Joshua R. Gershlak, Tatsuya Okamoto, Gabriel Gonzalez, David J. Milan, Glenn R. Gaudette, Harald C. Ott
Journal: Circulation Research (2015)

Rationale: More than 25 million individuals have heart failure worldwide, with ≈4000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only ≈2500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective: The objective of this study is to translate previous work to human scale and clinically relevant cells for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human induced pluripotent stem cell–derived cardiomyocytes. Methods and Results: To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiomyocytes derived from nontransgenic human induced pluripotent stem cells and generated tissues of increasing 3-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole-heart scaffolds with human induced pluripotent stem cell–derived cardiomyocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions: Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human induced pluripotent stem cell–derived cardiomyocytes and enable the bioengineering of functional human myocardial-like tissue of multiple complexities.
Phase III controlled evaluation of sucralfate to alleviate stomatitis in patients receiving fluorouracil-based chemotherapy.
Authors: C L Loprinzi, C Ghosh, J Camoriano, J Sloan, P D Steen, J C Michalak, P L Schaefer, P J Novotny, J B Gerstner, D F White, A K Hatfield, S K Quella
Journal: Journal of Clinical Oncology (1997)

Stomatitis is a major dose-limiting toxicity of bolus fluorouracil (5FU)-based chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data that suggested a sucralfate oral solution could alleviate chemotherapy-induced oral mucositis, we developed a prospective trial to test this contention.A phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered onto the study at the time of the first cycle of 5FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5FU. In addition, each patient was randomized to receive either a sucralfate solution or a placebo solution to be used if they developed mouth tenderness or mouth sores. The study solution was to be used four times daily for 7 days starting on the first day of mouth tenderness or mouth sores. Stomatitis scores were determined by health care providers and by patients themselves.There was a total of 131 assessable patients entered onto this trial, 50 of whom developed mucositis and used the study medication (27 sucralfate and 23 placebo). There was no suggestion of any difference in stomatitis severity or duration on either protocol arm.The resultant data from this clinical trial did not support the prestudy hypothesis that sucralfate would be beneficial for the treatment of 5FU-induced stomatitis.
Adverse Effects of Cigarette and Noncigarette Smoke Exposure on the Autonomic Nervous System
Authors: Holly R. Middlekauff, Jeanie Park, Roya S. Moheimani
Journal: Journal of the American College of Cardiology (2014)

This review summarizes the detrimental effects of cigarette and noncigarette emission exposure on autonomic function, with particular emphasis on the mechanisms of acute and chronic modulation of the sympathetic nervous system. We propose that the nicotine and fine particulate matter in tobacco smoke lead to increased sympathetic nerve activity, which becomes persistent via a positive feedback loop between sympathetic nerve activity and reactive oxidative species. Furthermore, we propose that baroreflex suppression of sympathetic activation is attenuated in habitual smokers; that is, the baroreflex plays a permissive role, allowing sympathoexcitation to occur without restraint in the setting of increased pressor response. This model is also applicable to other nontobacco cigarette emission exposures (e.g., marijuana, waterpipes [hookahs], electronic cigarettes, and even air pollution). Fortunately, emerging data suggest that baroreflex sensitivity and autonomic function may be restored after smoking cessation, providing further evidence in support of the health benefits of smoking cessation.
Ethical Obligations and Counseling Challenges in Cancer Genetics
Authors: Wylie Burke, Nancy Press
Journal: Journal of the National Comprehensive Cancer Network (2006)

Cancer genetics is creating new practice opportunities in medical genetics, oncology, and primary care. The ethical and counseling challenges of this new area of practice are not unique but sometimes take new form in the context of genetic risk. This article uses cases to explore the issues associated with shared family risk, including competing concerns of family members, duty to warn relatives of genetic risk, and testing of children and other relatives. The ethical obligations of clinicians start with the need to maintain competence in the face of rapidly evolving science. Clinicians should be able to identify patients within their practice who are candidates for genetic testing. When genetic susceptibility to cancer is identified, patients should be offered counseling and follow-up, with referral as appropriate, to ensure delivery of care consistent with current standards. When patients experience barriers to needed health care, clinicians should advocate for their needs. Clinicians must ensure the autonomy and informed decision-making of all members of cancer-prone families. Clinicians must also provide emotional support and accurate information about cancer risks and cancer risk reduction measures, including uncertainties. Teamwork among different specialties is important in addressing these challenges.