tbuckley/cabot-search huggingface dataset:
Prognostic Score Including Gene Mutations in Chronic Myelomonocytic Leukemia
Authors: Raphaël Itzykson, Olivier Kosmider, Aline Renneville, Véronique Gelsi-Boyer, Manja Meggendorfer, Margot Morabito, Céline Berthon, Lionel Adès, Pierre Fenaux, Odile Beyne-Rauzy, Norbert Vey, Thorsten Braun, Torsten Haferlach, François Dreyfus, Nicholas C.P. Cross, Claude Preudhomme, Olivier A. Bernard, Michaela Fontenay, William Vainchenker, Susanne Schnittger, Daniel Birnbaum, Nathalie Droin, Eric Solary
Journal: Journal of Clinical Oncology (2013)

Purpose Several prognostic scoring systems have been proposed for chronic myelomonocytic leukemia (CMML), a disease in which some gene mutations—including ASXL1—have been associated with poor prognosis in univariable analyses. We developed and validated a prognostic score for overall survival (OS) based on mutational status and standard clinical variables. Patients and Methods We genotyped ASXL1 and up to 18 other genes including epigenetic (TET2, EZH2, IDH1, IDH2, DNMT3A), splicing (SF3B1, SRSF2, ZRSF2, U2AF1), transcription (RUNX1, NPM1, TP53), and signaling (NRAS, KRAS, CBL, JAK2, FLT3) regulators in 312 patients with CMML. Genotypes and clinical variables were included in a multivariable Cox model of OS validated by bootstrapping. A scoring system was developed using regression coefficients from this model. Results ASXL1 mutations (P &lt; .0001) and, to a lesser extent, SRSF2 (P = .03), CBL (P = .003), and IDH2 (P = .03) mutations predicted inferior OS in univariable analysis. The retained independent prognostic factors included ASXL1 mutations, age older than 65 years, WBC count greater than 15 ×10 9 /L, platelet count less than 100 ×10 9 /L, and anemia (hemoglobin &lt; 10 g/dL in female patients, &lt; 11g/dL in male patients). The resulting five-parameter prognostic score delineated three groups of patients with median OS not reached, 38.5 months, and 14.4 months, respectively (P &lt; .0001), and was validated in an independent cohort of 165 patients (P &lt; .0001). Conclusion A new prognostic score including ASXL1 status, age, hemoglobin, WBC, and platelet counts defines three groups of CMML patients with distinct outcomes. Based on concordance analysis, this score appears more discriminative than those based solely on clinical parameters.
Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non–Small-Cell Lung Cancer: KCSG-LU05-04
Authors: Jin Seok Ahn, Yong Chan Ahn, Joo-Hang Kim, Chang Geol Lee, Eun Kyung Cho, Kyu Chan Lee, Ming Chen, Dong-Wan Kim, Hoon-Kyo Kim, Young Joo Min, Jin-Hyoung Kang, Jin-Hyuck Choi, Sang-We Kim, Guangying Zhu, Yi-Long Wu, Sung Rok Kim, Kyung Hee Lee, Hong Suk Song, Yoon-La Choi, Jong-Mu Sun, Sin-Ho Jung, Myung-Ju Ahn, Keunchil Park
Journal: Journal of Clinical Oncology (2015)

To determine the efficacy of consolidation chemotherapy (CC) with docetaxel and cisplatin (DP) after concurrent chemoradiotherapy (CCRT) with the same agents in locally advanced non-small-cell lung cancer (LA-NSCLC).Patients were randomly assigned to either CCRT alone (observation arm) or CCRT followed by CC (consolidation arm). CCRT with docetaxel (20 mg/m(2)) and cisplatin (20 mg/m(2)) was administered every week for 6 weeks with a total dose of 66 Gy of thoracic radiotherapy in 33 fractions. In the consolidation arm, patients were further treated with three cycles of DP (35 mg/m(2) each on days 1 and 8, every 3 weeks). The primary end point was 40% improvement in progression-free survival (PFS) compared with observation.From October 2005 to April 2011, 437 patients were randomly assigned. Seventeen patients did not start CCRT as a result of consent withdrawal or ineligibility reasons after random assignment, leaving 420 patients for this analysis (n = 211 for observation; n = 209 for consolidation). Patient characteristics were similar in both arms. In the consolidation arm, 143 patients (68%) received CC, of whom 88 (62%) completed three planned cycles. The median PFS was 8.1 months in the observation arm and 9.1 months in the consolidation arm (hazard ratio, 0.91; 95% CI, 0.73 to 1.12; P = .36). Median overall survival times were 20.6 and 21.8 months in the observation and consolidation arms, respectively (HR, 0.91; 95% CI, 0.72 to 1.25; P = .44).CC with DP after CCRT with weekly DP in LA-NSCLC failed to further prolong PFS. CCRT alone should remain the standard of care.
Anti-Stunning and Anti-Infarct Effects of Adenosine-Enhanced Ischemic Preconditioning
Authors: Y Toyoda, V Di Gregorio, R A Parker, S Levitsky, J D McCully
Journal: Circulation (2000)

Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing post-ischemic functional recovery. In this study, the anti-infarct effects and the anti-stunning effects of APC in contributing to enhanced post-ischemic functional recovery were determined and compared with IPC.Sheep (n=96) were subjected to 15, 30, 45, or 60 minutes of regional ischemia and 120 minutes of reperfusion. IPC hearts received 5 minutes of regional ischemia and 5 minutes of reperfusion before ischemia/reperfusion. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine hearts (ADO) received a bolus injection of adenosine before ischemia/reperfusion. Regional ischemia (RI) hearts received no pretreatment. Infarct size/area at risk was determined by tetrazolium staining. Regional myocardial function was determined by sonomicrometry. Segment shortening after 15 minutes of ischemia in which no infarct was incurred was 32. 1+/-10.6% in RI, 70.6+/-8.5% in IPC, and 77.4+/-6.0% in APC hearts. Segment shortening after 30 minutes of ischemia was 60.7+/-6.3% in APC hearts (P:<0.05 versus RI, ADO, IPC) but was <37% in all other groups. Infarct size/area at risk after 30 and 60 minutes of ischemia was, respectively, 25.8+/-5.7% and 49.8+/-6.0% in RI, 12. 9+/-3.0% and 29.2+/-5.0% in ADO, 11.6+/-2.4% and 24.6+/-2.7% in IPC, and 5.1+/-1.6% and 12.4+/-2.0% in APC hearts (P:<0.05 versus RI, ADO, IPC).APC and IPC exhibit anti-infarct and anti-stunning effects in the ovine heart, but these effects are rapidly diminished with IPC. APC significantly extends these effects, providing for significantly enhanced infarct size reduction and post-ischemic functional recovery (P:<0.05 versus IPC).
Oral administration of an immunodominant T-cell epitope downregulates Th1/Th2 cytokines and prevents experimental myasthenia gravis
Authors: Fulvio Baggi, Francesca Andreetta, Elisabetta Caspani, Monica Milani, Renato Longhi, Renato Mantegazza, Ferdinando Cornelio, Carlo Antozzi
Journal: Journal of Clinical Investigation (1999)

The mucosal administration of the native antigen or peptide fragments corresponding to immunodominant regions is effective in preventing or treating several T cell–dependent models of autoimmune disease. No data are yet available on oral tolerance with immunodominant T-cell peptides in experimental autoimmune myasthenia gravis (EAMG), an animal model of B cell–dependent disease. We report that oral administration of the T-cell epitope α146-162 of the Torpedo californica acetylcholine receptor (TAChR) α-subunit suppressed T-cell responses to AChR and ameliorated the disease in C57Bl/6 (B6) mice. Protection from EAMG was associated with reduced serum Ab’s to mouse AChR and reduced AChR loss in muscle. The effect of Tα146-162 feeding was specific; treatment with a control peptide did not affect EAMG manifestations. The protective effect induced by peptide Tα146-162 was mediated by reduced production of IFN-γ, IL-2, and IL-10 by TAChR-reactive cells, suggesting T-cell anergy. TGF-β–secreting Th3 cells did not seem to be involved in tolerance induction. We therefore demonstrate that feeding a single immunodominant epitope can prevent an Ab-mediated experimental model of autoimmune disease.
Oxaliplatin plus irinotecan and leucovorin-modulated5-fluorouracil triplet regimen every other week:a dose-finding study in patients with advanced gastrointestinal malignancies
Authors: P. Comella, R. Casaretti, V. De Rosa, A. Avallone, F. Izzo, F. Fiore, L. Lapenta, G. Comella
Journal: Annals of Oncology (2002)
Effects of tracheotomy on respiratory mechanics in spontaneously breathing patients
Authors: V. Moscovici da Cruz, S.E. Demarzo, J.B.B. Sobrinho, M.B.P. Amato, L.P. Kowalski, D. Deheinzelin
Journal: European Respiratory Journal (2002)

Tracheotomy is a method of intubating the trachea, which is employed in several clinical settings, including the treatment of head and neck neoplasms. Tracheotomy is believed to facilitate weaning through changes in respiratory mechanics. Existing information concerning functional changes associated with tracheotomy are limited to comparisons with orotracheal intubation. In this study, respiratory mechanics were monitored in seven spontaneously breathing patients, before and after an elective tracheotomy was performed for surgical treatment of cancer. Campbell diagrams were constructed by plotting pressure, obtained with an oesophageal balloon catheter, against volume, obtained from a pneumotachograph placed at the airway opening. Work of breathing was calculated as the internal area of the Campbell diagram and was partitioned into its elastic and inspiratory and expiratory resistive components. Oesophageal pressure was also used to quantify intrinsic positive end-expiratory pressure (PEEPi) and the pressure-time product (PTP), which is considered to be proportional to the oxygen cost of breathing. PTP was divided into its resistive and elastic components. Inspiratory resistive work, PEEPi, inspiratory PTP, as well as its resistive and elastic components were significantly reduced by tracheotomy. Tracheotomy significantly reduces work of breathing and pressure-time product in spontaneously breathing patients.
Pedicled Flap Reconstruction for Patients With Pressure Ulcers
Authors: Jun Tashiro, David J. Gerth, Seth R. Thaller
Journal: JAMA Surgery (2015)

flap loss (OR, 7.53 [95% CI,).Trochanteric ulcers had higher total charges (OR, 3.47 [95% CI,).Discussion | Pressure ulcers involving the gluteal region, while least common among the sites analyzed, were associated with the lowest resource utilization and complication rates.In addition, demographic factors, such as sex, race, and socioeconomic status, affected complication rates and resource utilization in our analysis.Renal failure was associated with higher complication rates and longer lengths of stay.Pneumonia was associated with higher cost.Owing to the retrospective nature of the National Inpatient Sample database, however, chronological or causal relationships between diagnoses cannot be concluded.As health care resource allocations continue to be a challenge, our findings may assist plastic surgeons by defining groups of patients at high risk for complications or higher resource utilization related to pedicled flap reconstruction, such as comorbid diagnoses or variation by ulcer site.Other adjunctive management options, such as the use of a vacuum-assisted closure device or skin grafting, may be more appropriate therapeutic approaches.Future research should focus on subpopulations of patients at high risk for postoperative complications that are directly associated with resource utilization.
Psychiatric morbidity and skin disease: what dermatologists think they see
Authors: None Humphreys, None Humphreys
Journal: British Journal of Dermatology (1998)

It has been suggested that skin disease and psychological disturbance may be linked. Recent work has focused on the fatal outcome associated with some dermatological disorders as a result of suicide. The impressions of dermatologists about how much psychological or psychiatric morbidity they see related to dermatological disease has not been addressed. The survey reported here revealed that most dermatologists recognized the relationship and demonstrated the perceived need for clinical psychology and psychiatric services for patients with dermatological disorders. It confirmed the impression that in a small number of cases, skin complaints are associated with attempted or completed suicide.
Can Survival be Increased by Postoperative Irradiation Following Radical Mastectomy?
Authors: Thomas A. Watson
Journal: JAMA (1967)

The operation of radical mastectomy is widely, and in my opinion, properly employed in the management of patients with stage II cancer of the breast. If the axillary nodes are found to be negative on microscopic examination, and if the primary tumor is small and confined to the outer aspect of the breast, the most common site, then radiotherapy is not indicated. If, however, the primary tumor is situated in the inner aspect of the breast or centrally or if the tumor is large or the axillary nodes are found by the pathologist to contain metastases, then the question immediately arises as to whether the tumor has already spread beyond the limits of the operation. If such is the case then it would seem logical to supplement surgery by some form of treatment which has a chance of being curative. Undoubtedly the most important therapeutic measure in moderately advanced carcinoma
Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature
Authors: Juehua Gao, Ryan D Gentzler, Andrew E Timms, Marshall S Horwitz, Olga Frankfurt, Jessica K Altman, LoAnn C Peterson
Journal: Journal of Hematology & Oncology (2014)

A 50-year-old woman was diagnosed with acute myeloid leukemia (AML). She has history of thrombocytopenia for 25 years and a significant family history of thrombocytopenia, affecting her mother, siblings and their children, as well as her own children. Both her mother and maternal aunt died from myelodysplastic syndrome (MDS). Additional genetic analysis was performed and identified two heterozygous missence mutations in the second zinc finger domain of GATA2 gene (p.Thr358Lys, and p.Leu359Val), occurring in cis on the same allele. Given the patient's family history and clinical manifestation, this was interpreted as an acute myeloid leukemia with heritable GATA2 mutations associated with familial AML-MDS. Germline GATA2 mutations are involved in a group of complex syndromes with overlapping clinical features of immune deficiency, lymphedema and propensity to acute myeloid leukemia or myelodysplastic syndrome (AML-MDS). Here we reported a case of familial AML-MDS with two novel GATA2 mutations. This case illustrates the importance of recognizing the clinical features for this rare category of AML-MDS and performing the appropriate molecular testing. The diagnosis of heritable gene mutations associated familial AML-MDS has significant clinical implication for the patients and affected families. Clinical trials are available to further investigate the role of allogeneic hematopoietic stem cell transplant in managing these patients.
Randomized Phase II Study of Gefitinib Compared With Placebo in Chemotherapy-Naive Patients With Advanced Non–Small-Cell Lung Cancer and Poor Performance Status
Authors: Glenwood Goss, David Ferry, Rafal Wierzbicki, Scott A. Laurie, Joyce Thompson, Bonne Biesma, Fred R. Hirsch, Marileila Varella-Garcia, Emma Duffield, Ozlem U. Ataman, Marc Zarenda, Alison A. Armour
Journal: Journal of Clinical Oncology (2009)

To compare gefitinib with placebo in chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status.
RETRACTED: Non-steroidal anti-inflammatory drugs and the risk of oral cancer: a nested case-control study
Authors: J Sudbø, JJ Lee, SM Lippman, J Mork, S Sagen, N Flatner, A Ristimäki, A Sudbø, L Mao, X Zhou, W Kildal, JF Evensen, A Reith, AJ Dannenberg
Journal: The Lancet (2005)
The effects of unsaturated dietary fats on absorption, excretion, synthesis, and distribution of cholesterol in man
Authors: Scott M. Grundy, E. H. Ahrens
Journal: Journal of Clinical Investigation (1970)

Cholesterol balance studies were carried out in 11 patients with various types of hyperlipoproteinemia to determine the mechanism by which unsaturated fats lower plasma cholesterol. Unsaturated fats produced no increase in fecal endogenous neutral steroids in 10 of 11 patients and no decrease in absorption of exogenous cholesterol in 5 patients who received cholesterol in the diet. In 8 of 11 patients no changes occurred in excretion of bile acids during the period on unsaturated fat when plasma cholesterol was declining. However, in 3 of 11 patients small but significant increases in bile acid excretion were found during this transitional period; in 2 others increases also occurred after plasma cholesterol had become constant at lower levels on unsaturated fat.Since the majority of patients showed no change in cholesterol or bile acid excretions during the transitional period, we propose that when excretion changes did occur they were probably not the cause of the plasma cholesterol change. Furthermore, turnover data and specific activity curves suggested that cholesterol synthesis was not influenced by exchange of dietary fats. Thus, excluding changes in excretion and synthesis, we conclude that it is most likely that unsaturated fats cause plasma cholesterol to be redistributed into tissue pools. We have also examined the possibility that cholesterol which is redistributed into tissues could be secondarily excreted as neutral steroids or bile acids. In at least 5 of 11 patients excretion patterns were consistent with this explanation. However, we cannot rule out that excretion changes may have been due to alterations in transit time, to changes in bacterial flora, or to transitory changes in absorption or synthesis of cholesterol or bile acids. Our conclusion that unsaturated fats cause a redistribution of cholesterol between plasma and tissue pools points to the necessity in future to explore where cholesterol is stored, to what extent stored cholesterol can be mobilized, and to define the factors governing these fluxes.
Epidemiology of spontaneous pneumothorax: gender-related differences
Authors: A. Bobbio, A. Dechartres, S. Bouam, D. Damotte, A. Rabbat, J.-F. Regnard, N. Roche, M. Alifano
Journal: Thorax (2015)

<h3>Background</h3> Epidemiology of spontaneous pneumothorax has been scantily studied. We aimed to assess the incidence of spontaneous pneumothorax and describe patients' characteristics with respect to age, sex, seasonal occurrence, primary or secondary character, surgical management and rehospitalisations on a large-scale database. <h3>Methods</h3> Data from all patients aged ≥14 years and hospitalised with a diagnosis of non-traumatic pneumothorax in France from 2008 to 2011 were retrieved from the National Hospitalisation Database. <h3>Results</h3> There were 59 637 hospital stays corresponding to 42 595 patients. Twenty-eight per cent of patients were rehospitalised at least once during the 4-year period. Annual rate of pneumothorax could be estimated at 22.7 (95% CI 22.4 to 23.0) cases for 100 000 habitants. The women to men ratio was 1:3.3. Mean age was significantly higher in women than in men (41±19 vs 37±19 years, p&lt;0.0001). No seasonal variation was observed. A surgical procedure was performed in 14 352 hospital stays (24%). In the group of patients aged &lt;30 years, there was no statistical difference between men and women with regard to type of pneumothorax (primary or secondary), type of hospitalisation unit (surgery vs medicine), treatment modality (surgery or not), intensive care unit (ICU) admission and hospital stay duration. Rehospitalisation was more frequent in women than in men (56% vs 52%, p&lt;0.0001). In the 30–49 years age group, surgery and rehospitalisation were more frequent in women than in men (each, p&lt;0.001). In the 50–64 years age group, surgical procedures and rehospitalisations were more frequent in men than in women (p=0.002 and p&lt;0.0001, respectively). <h3>Conclusions</h3> Sex and age are determinant factors in the course of spontaneous pneumothorax.
Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion
Authors: Caterina Di Cosmo, Xiao-Hui Liao, Alexandra M. Dumitrescu, Nancy J. Philp, Roy E. Weiss, Samuel Refetoff
Journal: Journal of Clinical Investigation (2010)

The mechanism of thyroid hormone (TH) secretion from the thyroid gland into blood is unknown. Humans and mice deficient in monocarboxylate transporter 8 (MCT8) have low serum thyroxine (T4) levels that cannot be fully explained by increased deiodination. Here, we have shown that Mct8 is localized at the basolateral membrane of thyrocytes and that the serum TH concentration is reduced in Mct8-KO mice early after being taken off a treatment that almost completely depleted the thyroid gland of TH. Thyroid glands in Mct8-KO mice contained more non-thyroglobulin-associated T4 and triiodothyronine than did those in wild-type mice, independent of deiodination. In addition, depletion of thyroidal TH content was slower during iodine deficiency. After administration of 125I, the rate of both its secretion from the thyroid gland and its appearance in the serum as trichloroacetic acid-precipitable radioactivity was greatly reduced in Mct8-KO mice. Similarly, the secretion of T4 induced by injection of thyrotropin was reduced in Mct8-KO in which endogenous TSH and T4 were suppressed by administration of triiodothyronine. To our knowledge, this study is the first to demonstrate that Mct8 is involved in the secretion of TH from the thyroid gland and contributes, in part, to the low serum T4 level observed in MCT8-deficient patients.
Differentiation of CD8 memory T cells depends on Foxo1
Authors: Rodrigo Hess Michelini, Andrew L. Doedens, Ananda W. Goldrath, Stephen M. Hedrick
Journal: The Journal of Experimental Medicine (2013)

The forkhead O transcription factors (FOXO) integrate a range of extracellular signals, including growth factor signaling, inflammation, oxidative stress, and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many yet to be unraveled cell type–specific responses. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure. In addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. Using lymphocytic choriomeningitis virus Armstrong to probe the response to infection, we found that Foxo1−/− CD8+ T cells expand normally with no defects in effector differentiation, but continue to exhibit characteristics of effector T cells long after antigen clearance. The KLRG1lo CD8+ T cells that are normally enriched for memory-precursor cells retain Granzyme B and CD69 expression, and fail to up-regulate TCF7, EOMES, and other memory signature genes. As a correlate, Foxo1−/− CD8+ T cells were virtually unable to expand upon secondary infection. Collectively, these results demonstrate an intrinsic role for FOXO1 in establishing the post-effector memory program that is essential to forming long-lived memory cells capable of immune reactivation.
Moderate and chronic hemodynamic overload of sheep atria induces reversible cellular electrophysiologic abnormalities and atrial vulnerability
Authors: Edith Deroubaix, Thierry Folliguet, Catherine Rücker-Martin, Sylvie Dinanian, Christophe Boixel, Pierre Validire, Pierre Daniel, André Capderou, Stéphane N. Hatem
Journal: Journal of the American College of Cardiology (2004)