tbuckley/cabot-search huggingface dataset:
Pulmonary platelet thrombi and vascular pathology in acute chest syndrome in patients with sickle cell disease
Authors: Ciprian B. Anea, Matthew Lyon, Itia A. Lee, Joyce N. Gonzales, Amidat Adeyemi, Greer Falls, Abdullah Kutlar, Julia E. Brittain
Journal: American Journal of Hematology (2015)

A growing body of evidence suggests a role for platelets in sickle cell disease (SCD). Despite the proinflammatory, occlusive nature of platelets, a role for platelets in acute chest syndrome (ACS), however, remains understudied. To provide evidence and potentially describe contributory factors for a putative link between ACS and platelets, we performed an autopsy study of 20 SCD cases-10 of whom died from ACS and 10 whose deaths were not ACS-related. Pulmonary histopathology and case history were collected. We discovered that disseminated pulmonary platelet thrombi were present in 3 out of 10 of cases with ACS, but none of the matched cases without ACS. Those cases with detected thrombi were associated with significant deposition of endothelial vWF and detection of large vWF aggregates adhered to endothelium. Potential clinical risk factors were younger age and higher platelet count at presentation. However, we also noted a sharp and significant decline in platelet count prior to death in each case with platelet thrombi in the lungs. In this study, neither hydroxyurea use nor perimortem transfusion was associated with platelet thrombi. Surprisingly, in all cases, there was profound pulmonary artery remodeling with both thrombotic and proliferative pulmonary plexiform lesions. The severity of remodeling was not associated with a severe history of ACS, or hydroxyurea use, but was inversely correlated with age. We thus provide evidence of undocumented presence of platelet thrombi in cases of fatal ACS and describe clinical correlates. We also provide novel correlates of pulmonary remodeling in SCD.
Abstract 195: Impairment of Carotid Artery Blood Flow by Supraglottic Airway Use in a Swine Model of Cardiac Arrest
Authors: Nicolas Segal, Demetris Yannopoulos, Brian D Mahoney, Ralph J Frascone, Colin G Cowles, Scott H McKnite, David G Chase
Journal: Circulation (2011)

Objective: Supraglottic airway devices (SGDs) can be inserted ‘blindly’ without stopping compressions during cardiopulmonary resuscitation (CPR) and are therefore often used instead of endotracheal tubes (ETT). These devices utilize pressurized balloons to direct air to the trachea and prevent esophagus insufflation. We hypothesize that the use of a SGD will compress the carotid artery and decrease carotid blood flow (CBF) during CPR. Methods: Ventricular fibrillation was induced in 9 female pigs (32±1Kg) anesthetized with isoflurane. Four minutes later CPR was then performed continuously for 3 six-minute epochs. During each epoch, an ETT was used for the first 3 minutes, followed by 3 minutes of each SGD (King LTS-D, LMA Flexible, or Combitube in a random order. The primary endpoint was mean CBF (ml/min). Statistical comparisons among the 4 airway devices were performed by Wilcoxon Rank test. Post mortem carotid arteriograms were obtained. Results: CBF (mean ml/minute ± SD) was significantly lower with each SGD [King (168 ± 42), LMA (106 ± 89), and Combitube (99 ± 128)] versus ETT (209 ± 134) (p&lt;0.05 for each SGD compared with ETT; figure). Arteriograms showed that each SGD compressed the internal and external carotid vessels. Conclusion: The use of 3 different SGDs during CPR significantly decreased CBF in a porcine cardiac arrest model. While these data are limited to pigs, they may impact clinical decision making. Figure: real time tracing during 1 experiment. Pink: Carotid blood flow (CBF); Blue: Thoracic aortic pressure (AO pressure); Green: Airway pressure. The figure shows that every time a SGD is used CBF significantly decreases without any differences in AO pressure.
Abstract 2295: Abnormal Myocardial Strains in Hypertrophic Cardiomyopathy Patients Despite Preserved Ejection Fraction and Absence of Myocardial Fibrosis
Authors: Zoran B Popovic, Deborah H Kwon, Micky Mishra, Teck Hwa Goh, Neil L Greenberg, Maran Thamilarasan, James D Thomas, Harry M Lever, Milind Y Desai
Journal: Circulation (2007)
Spontaneous changes of airway hyperresponsiveness in bronchial asthma
Authors: H Magnussen, D Nowak
Journal: European Respiratory Journal (1988)

In patients with bronchial asthma, changes of airway hyperresponsiveness may spontaneously occur with time or may be precipitated by a variety of factors, e.g.respiratory tract infections, allergen exposure, occupational hazards or atmospheric pollutants. Changes of airway responsiveness with timeChanges of airway responsiveness with time can be interpreted according to the period of observation.Changes within one day may reflect a circadian rhythm, changes within several days may be taken in order to estimate reproducibility, and changes within months or years may reflect the prognosis of the disease. Changes within one day RACHIELE et al.[1) reported on stable asthmatics in whom two histamine inhalation tests were carried out on six different days at 8, 16 and 22 h.In seven out of fifteen asthmatic subjects significant diurnal rhythms with a time range of least excitability between 9.8 and 23.1 h could be demonstrated.Diurnal changes of airway responsiveness may, therefore, be important in some patients with bronchial asthma. Changes within days or weeksSeveral authors have measured airway responsiveness repeatedly within days or weeks in order to estimate reproducibility.CocKROFT [22) reported on 58 subjects in whom the provocative concentration of agonist causing a 20% fall in forced expiratory volume in one second (PC 20 FEV 1 ) for histamine had been determined twice within one week.For all subjects PC 20 FEV 1 was reproducible •Knnkenhaw Grosshansdorf, Zentrum fllr Pneumolgie and Thoraxchixurgie LV A Freie und Hansestadt Hamburg.
Abstract 1879: Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies
Authors: Anna W. Ma, Ruzanna Atoyan, Anas Younes, Ian W. Flinn, Yasuhiro Oki, Amanda Copeland, Jesus G. Berdeja, Robert Laliberte, Jaye Viner, Maria Elena S. Samson, Steven Dellarocca, Ling Yi, Mylissa Borek, Brian Zifcak, Guangxin Xu, Jing Wang
Journal: Cancer Research (2014)

Abstract Histone deacetylases (HDACs) and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway are promising therapeutic targets in hematologic cancers and evidence of synergistic anti-cancer activity has recently emerged. CUDC-907, a small molecule drug candidate that is designed to target HDACs and PI3Ks in a single chemical entity, is currently in Phase 1 clinical testing for the treatment of patients with lymphoma or multiple myeloma. Preclinically, CUDC-907 has been shown to inhibit activation of PI3K/AKT, JAK/STAT and MAPK pathways in hematologic cancer cell lines such as Hodgkin's lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. In this study, we report that in the setting of hematological malignancies, CUDC-907 targets not only the cancer cells but also the tumor microenvironment. Cytotoxicity against primary CLL cells was independent of the protective effects provided by stromal cells when primary CLL cells were co-cultured with nurse-like cells. CUDC-907 was shown in vitro to impair cytokine and chemokine production by immune cells in the tumor microenvironment and by Hodgkin's lymphoma cells. The ongoing first-in-human Phase 1 clinical study of CUDC-907 has yielded preliminary evidence of anti-cancer activity and impact on the tumor microenvironment as measured by cytokine and chemokine levels (e.g., thymus and activation regulated chemokine [TARC]). Ongoing analyses are probing the potential utility of selected cytokine and chemokine as predictive markers of CUDC-907 activity. Citation Format: Anna W. Ma, Ruzanna Atoyan, Anas Younes, Ian W. Flinn, Yasuhiro Oki, Amanda Copeland, Jesus G. Berdeja, Robert Laliberte, Jaye Viner, Maria Elena S. Samson, Steven Dellarocca, Ling Yi, Mylissa Borek, Brian Zifcak, Guangxin Xu, Jing Wang. Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1879. doi:10.1158/1538-7445.AM2014-1879
Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells.
Authors: J Connor, R Bannerji, S Saito, W Heston, W Fair, E Gilboa
Journal: The Journal of Experimental Medicine (1993)

This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN-gamma genes were introduced and expressed in MBT-2 cells. The tumor-forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL-2- or IFN-gamma-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine-secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL-2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL-2-secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL-2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the "cured" mice.
Web-based telehome monitoring of nocturnal pulse oximetry (NPO) desaturation is a feasible tool to determine timing of non-invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS)
Authors: Anna Porcu, Maurizio Moretti
Journal: European Respiratory Journal (2014)

Introduction  Progression of respiratory failure in ALS requires a closer follow-up process to determine the timing of application of NIV. Nocturnal hypoventilation (NH) generally precedes daytime hypercapnia.  Aim  To test telehome monitoring (THM) of NPO to detect early NH.  Methods  ALS patients without daytime hypoxemia and FVC > 80% pred received a THM device which acquires signals from an internal pulse oximeter and connects to modem by bluetooth technology. In a Web-page, oxygen saturation percentages calculated and displayed on a graphical user interface is accessed.  Mean time spent with a saturation below 90% (TB90%) for ≥5% of night time was calculated on 5 consecutive monitorings per patients. Measurements were repeated every 6 months over 2 yrs follow-up.  Results  14 ALS patients were studied. Mean TB90 ≥5% was detected in 5 subjects (35%) out of 14 when FVC was ≥70%pred and in the remaining 9 patients when FVC was between 69-55% pred. Arterial hypercapnia (PaC0 2  >45 mmHg) was detected only in 1 patient with FVC>60% pred. Patients started NIV when early NH was detected; nocturnal NIV was well tolerated and no patient developed acute hypercapnic crises over 2 year follow-up.  Conclusions  THM of NPO in ALS was more sensitive than usual FVC or daytime arterial blood gases in detecting early NH; 5 consecutive nocturnal monitorings reduced the intraindividual variability of the test.  If early detection of NH determines the timing of application of nocturnal NIV, the frequency of acute hypercapnic crises provoking hospital admission may be reduced.  Supported by Fondazione Cassa di Risparmio di Carrara.
Loss of SMAD4 Promotes Colorectal Cancer Progression by Accumulation of Myeloid-Derived Suppressor Cells through the CCL15–CCR1 Chemokine Axis
Authors: Susumu Inamoto, Yoshiro Itatani, Takamasa Yamamoto, Sachiko Minamiguchi, Hideyo Hirai, Masayoshi Iwamoto, Suguru Hasegawa, Makoto Mark Taketo, Yoshiharu Sakai, Kenji Kawada
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We previously reported that loss of SMAD4 promotes chemokine CCL15 expression to recruit CCR1+ myeloid cells via the CCL15–CCR1 axis, which facilitates metastasis of colorectal cancer to the liver. The purposes of this study were to investigate whether essentially the same mechanism works in tumor invasion of the primary colorectal cancer and to evaluate the clinical importance of CCL15 expression and CCR1+ cell accumulation. Experimental Design: Using human colorectal cancer cell lines with reduced expression of SMAD4 or CCL15, we investigated tumor growth activities in vivo. We used immunohistochemistry (IHC) to investigate expression of SMAD4, CCL15, and CCR1 with 333 clinical specimens of primary colorectal cancer. We next characterized the CCR1+ cells using double immunofluorescence staining with several specific cell-type markers. Finally, we determined the serum CCL15 levels in 132 colorectal cancer patients. Results: In an orthotopic xenograft model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, resulting in aggressive tumor growth. IHC indicated that loss of SMAD4 was significantly associated with CCL15 expression, and that CCL15-positive primary colorectal cancers recruited approximately 2.2 times more numbers of CCR1+ cells at their invasion front than CCL15-negative colorectal cancers. Importantly, these CCR1+ cells were of the myeloid-derived suppressor cell (MDSC) phenotype (CD11b+, CD33+, and HLA-DR−). Most CCR1+ cells showed the granulocytic-MDSC phenotype (CD15+), whereas some showed the monocytic-MDSC phenotype (CD14+). Serum CCL15 levels in colorectal cancer patients were significantly higher than in controls. Conclusions: Blocking the recruitment of CCR1+ MDSCs may represent a novel molecular-targeted therapy, and serum CCL15 concentration can be a novel biomarker for colorectal cancer. Clin Cancer Res; 22(2); 492–501. ©2015 AACR.
Twelve-minute walking distance predicts COPD mortality
Authors: R. Harpa Arnardóttir, Christer Janson, Hans Hedenström, Margareta Emtner
Journal: European Respiratory Journal (2012)

Background:  Patients in pulmonary rehabilitation (PR) suffer from poor lung function, exercise capacity and health-related quality of life (HRQoL). Some of these factors have been shown to relate to mortality in COPD. Drop-out from clinical PR-studies is often high and might indicate worse prognosis in that group.   Aims:  To measure the five-year survival of 89 COPD-patients enrolled in a four-month PR at Uppsala University Hospital and investigate if the 12 min walking distance (12MWD), peak exercise capacity (Wpeak), HRQoL and being able to fulfill the training period had prognostic value for survival.   Methods:  Lung function (FEV 1 , VC), 12MWD, Wpeak and HRQoL (SF-36) were measured at baseline. Of 89 included patients, 53 fulfilled the PR-program.   Results:  Mean baseline FEV 1  was 34 ± 12 (% pred.) and most patients had GOLD stages III or IV. Mean follow-up time was 1732 ± 324 days. Twenty patients (22%) died during follow-up. Causes of death were cancer (n=9), COPD (n=6) and cardiovascular diseases (n=5). Survival among drop-outs and fulfillers (mortality 31% and 17%, respectively) did not differ significantly (p=0.06). At baseline, survivors were younger than non-survivors (p=0.01) and had higher values of FEV 1  (p=0.01), Wpeak (p=0.03) and 12MWD (p=0.0003), but HRQoL was similiar in both groups. Cox proportional hazard analysis including age, FEV 1 , Wpeak, 12MWD and the factor “drop-outs/ fulfillers”, revealed low 12MWD (p=0.008) as the only significant mortality predictor in the model, with HR= 0.82 (95% CI: 0.7-0.95), per 50 m increase. With 12MWD    Conclusion:  12MWD is a strong predictor of survival in patients with COPD.
Key factors associated with readmission in COPD patients
Authors: Debbie Macfie, Christine Norton, Yvonne Goddard, Sarah Elkin
Journal: European Respiratory Journal (2013)

The aim of this study was to identify which factors are associated with readmission after an exacerbation of COPD.  Patients who had more that one admission in a year were identified from a COPD discharge database. Information was collected on smoking status, FEV1 %, co morbidities including congestive cardiac failure, diabetes, cognitive impairment, anxiety and social factors.  332 /951 patients had more than one re admission over 24 months. This project concentrated on 150 randomly chosen patients. The average age of patients was 73 yrs. 79 (53%) female. 60% had very severe(21/150) or severe copd.( 69/150).66(44%)were current smokers, 68 (45%)had anxiety, 21/150 (14%)had cognitive impairment. For patients with cardiac failure (38/150) the average number of admissions was 4, cardiac risks, including MI (52/150) 5, diabetes (10/150) 4. Patients with cognitive deficits and/or anxiety experienced 5.8 and 5.1 admissions respectively. 24% of readmissions were in those who lived alone, 40% had a package of care (POC), 12% lived with family with no POC, 8% live with family with a POC, 6% in residential homes.  The average LOS for COPD in our trust is 4.6 days. In COPD patients with identified cardiac failure it was 9.9 days, cardiac risks (including MI) 7.9 days, diabetes 6.6 days, cognitive deficits 7.7 days and anxiety 8.3 days.  Readmission seems to be driven by myriad causes. Key factors, anxiety and having more than one additional co morbidity and occur more in current smokers. The LOS for patients with cognitive or anxiety issues was equal or greater than other co morbidities. These factors warrant further discharge planning pathways involving social work, mental health facilitators, psychologist and other specialist teams.
Temozolomide-loaded photopolymerizable PEG-DMA-based hydrogel for the treatment of glioblastoma
Authors: Thibaut Fourniols, Luc D Randolph, Aurélie Staub, Kevin Vanvarenberg, Julian G Leprince, Véronique Préat, Anne des Rieux, Fabienne Danhier
Journal: Journal of Controlled Release (2015)
Predictions about new long-stay patients: were they valid?
Authors: R L Okin, D Pearsall, T Athearn
Journal: American Journal of Psychiatry (1990)

During 1979-1989, the long-stay population in Massachusetts state psychiatric hospitals declined and then moderately increased, although to far below its initial 1979 level. The increase toward the end of the period was due to a growing number of patients admitted, an increase in the proportion of these new patients who were retained for 1 year or longer, and a decrease in discharges of long-stay patients, especially those hospitalized for 20 or more years. The last factor was particularly important and was due to the fact that the number of these very-long-stay patients had become so small by 1983 that the effect of their continued discharge on the total long-stay population was minimal. The authors point out that more community services, not more hospital beds, may be needed. They recommend that states assess the clinical needs of the long-stay population before determining how to allocate their resources to address this phenomenon.
Prioritization and burden analysis of rare variants in 208 candidate genes suggest they do not play a major role in CAKUT
Authors: Nayia Nicolaou, Sara L. Pulit, Isaac J. Nijman, Glen R. Monroe, Wout F.J. Feitz, Michiel F. Schreuder, Albertien M. van Eerde, Tom P.V.M. de Jong, Jacques C. Giltay, Bert van der Zwaag, Marlies R. Havenith, Susan Zwakenberg, Loes F.M. van der Zanden, Geert Poelmans, Elisabeth A.M. Cornelissen, Marc R. Lilien, Barbara Franke, Nel Roeleveld, Iris A.L.M. van Rooij, Edwin Cuppen, Ernie M.H.F. Bongers, Rachel H. Giles, Nine V.A.M. Knoers, Kirsten Y. Renkema
Journal: Kidney International (2015)
Twice-weekly dapsone for primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infection: efficacy, safety and pharmacokinetic data
Authors: M. Cruciani, E. Bertazzoni Minelli, M. Mirandola, R. Luzzati, M. Merighi, L. Lazzarini, G. Gatti, S. Vento, R. Mazzi, M. Malena, A. Benini, A. Cazzadori, G. Piemonte, D. Bassetti, E. Concia
Journal: Clinical Microbiology and Infection (1996)
Left ventricle diastolic dysfuntion in severe COPD and exercise tolerance
Authors: Marta Lόpez, Mariana Muñoz, Rosa Planas, Eduard Claver, Maria José Manuel, Federico Manresa, Jordi Dorca, Salud Santos
Journal: European Respiratory Journal (2011)

COPD patients with similar airflow obstruction could have different degree of dyspnea and exercise tolerance. Actually it is unknown why this happens. The aim of our study was to evaluate the prevalence of left ventricle diastolic dysfunction (LVDD) in stable severe COPD patients, analyzing its implication in exercise tolerance and the relationship with specific functional and analytical parameters.   Methods:  We evaluated 75 consecutive outpatients with FEV 1  between 30-50%. Twenty five (33%) were excluded because of previous heart disease, atrial fibrillation or Charlson score > 5. Pulmonary function test, 6-minute walking test (6MWT), arterial gases, NTproBNP, inflammatory markers (CRP, leukocytes) and echocardiographic DD parameters were performed in all patients.   Results:  Patients were 67±6 y/o, 92% men, tobacco consumption 58±24 p/y. Prevalence of risk factors was: hypertension 44%, DM 26% and dyslipidemia 32%. The functional data showed: FEV 1  39±5%, FVC 76±16%, TLC 129±24%, RV 228±87%, PaO 2  67±10, BMI 28±5, dyspnea MRC scale I-II (72%) and III (28%), 6MWT distance 367±87 m, BODE between 2-7.  LVDD prevalence was 98% (type I 85%, type II 15%). No relationship was found between 6MWT distance or dyspnea and DD parameters (E/A ratio, pulmonary vein flow, E/E 9  ratio), hyperinflation or laboratory tests. LVDD did not correlate to hyperinflation, inflammation or right ventricle overload.   Conclusions:  Prevalence of LVDD in severe COPD patients is very high however it does not seem this condition determines their exercise tolerance. In our study, high prevalence of LVDD is not related to air trapping, inflammation or interventricular dependence so other factors should be studied.  Funded SOCAP 2010