tbuckley/cabot-search huggingface dataset:
P232 Communication and End of Life Care (EoLC) in People with Respiratory Disease
Authors: C Hodgekiss, A Edwards, IJ Clifton
Journal: Thorax (2012)

<h3>Background</h3> Leeds Teaching Hospitals Trust (LTHT) is a flagship trust for the National End of Life Care (EoLC) strategy. Key areas of improvement in EoLC have been identified, including identification of people approaching end of life and communication of this to the individual, family and primary care colleagues. The Gold Standards Framework is a national systematic evidence based approach to optimising EoLC. This retrospective study reviewed all deaths during in-patient stay and within 28 days of discharge from respiratory medicine. <h3>Methods</h3> All in-patient deaths or deaths within 28 days of discharge from hospital under the care of a respiratory physician at LTHT between April and September 2011 were reviewed. All communication with primary care in the preceding 12 months was reviewed. <h3>Results</h3> 144 individuals died on respiratory wards, median (range) age of 76 (18–96) years with the majority having a length of stay over 8 days. 42 individuals died within 28 days of discharge from a respiratory ward, median (range) age of 71 (42–87) years. The commonest cause of death was pneumonia and lung malignancy for in-patient and post-discharge deaths respectively. 23.8% and 83% of in-patient and post-discharge deaths respectively had documented communication with primary care about a palliative intent to care, the majority of these had a diagnosis of thoracic malignancy. Within the 12 months pre-death all patients had evidence that EoLC may have been appropriate to consider. <h3>Conclusions</h3> Palliative communication with primary care was made for some individuals, mostly with lung malignancy. This probably reflects more predictable disease trajectory and MDT decisions of "best supportive care". Lack of confidence around predicting terminal disease in other respiratory conditions, particularly those such as COPD which are prone to exacerbations, may account for the differences in rates of communication of palliative care approaches in these disease groups. A key driver for the implementation of high quality EoLC for patients with respiratory disease is recognition of patients approaching the end of life and communication with the individual, family and primary care to ensure that the patient's wishes for EoLC are identified and supported.
NICE recommends exercise and not acupuncture for low back pain
Authors: Jacqui Wise
Journal: BMJ (2016)

Acupuncture is no longer recommended for the management of non-specific low back pain with or without sciatica because evidence shows that it is no better than sham treatment, says new draft guidance from the National Institute for Health and Care Excellence (NICE).1

The guideline recommends exercise such as stretching, yoga, or aerobic exercise as the first step in managing low back pain, and people should also be encouraged to continue with normal activities as much as possible. It recommends that manipulation, mobilisation, and massage should be used only …
SAT0136 Sarilumab, a Fully Human Mab Against IL-6R Alpha, Subcutaneously-Administered Shows Significant Improvement in Ra Patients as Early as 2 Weeks: A Time to Event Analysis for Acr50 and Eular Good Response
Authors: R. Fleischmann, S. Fiore, C. Fan, D. Thompson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sarilumab (SAR) is a fully human mAb directed against IL-6Rα. <h3>Objectives</h3> Evaluate the temporal pattern of cumulative incidence of ACR50 and EULAR (good+moderate) responses during the MOBILITY Part A study. <h3>Methods</h3> Adults with active, moderate-to-severe RA and an inadequate response to treatment with MTX were randomized to 6 groups: SAR 100mg every other week (q2w), 150mg q2w, 100mg weekly (qw), 20 mg q2w, 150mg qw, or placebo (Pbo). All patients (pts) were on background MTX. Kaplan-Meier and proportional hazards methods were used to evaluate cumulative incidence of pts achieving ACR50 response during first 12 wks. Similar analyses were conducted for EULAR responses based on proportion by week and time to event comparing EULAR good+moderate response for all 6 groups. <h3>Results</h3> Baseline demographic and disease characteristics were similar across treatment groups (n=306): 79% women; mean age 52 yrs; disease duration 8 yrs; RF+ 79.7%; tender joint count 27; swollen joint count 17; hsCRP 2.8mg/dL; HAQ-DI 1.6. In contrast to Pbo and 100 q2w groups, 4 SAR doses showed a response to treatment by wk 2. The 25<sup>th</sup> percentile was achieved on or before wk 8 in 150 and 200mg q2w groups and in 100 and 150 qw groups. Table 1 shows relative hazards for achieving ACR50 response in sari vs Pbo. EULAR response results confirm ACR 50 response with 4 SAR groups (all except 100mg q2w) achieving significantly higher proportions of EULAR good and EULAR good+moderate responses vs Pbo by wk 2. Observed AEs were similar to those reported with other IL-6 inhibitors. <h3>Image/graph</h3> <h3>Conclusions</h3> The effect of SAR in reducing signs and symptoms by the ACR50 response and EULAR good and good+moderate criteria was seen early. Pts treated with 150 or 200mg q2w or 100 or 150mg qw were &gt;2 times as likely as Pbo to achieve ACR50 response after 12 wks. A significant improvement in the proportion of EULAR responders was also observed for 4 SAR groups starting at wk 2. These proportional hazard methods support Phase 3 study of 150 and 200mg q2w regimens that provide high hurdle ACR and EULAR clinical responses. <h3>Acknowledgements</h3> Funded by Sanofi and Regeneron. <h3>Disclosure of Interest</h3> R. Fleischmann Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron, S. Fiore Employee of: Sanofi, C. Fan Employee of: Sanofi, D. Thompson Employee of: Regeneron
Abstract PD03-09: Metformin Induces Apoptosis in Triple Negative Breast Cancer Cells Via Inhibition of Stat3 Activity
Authors: XS Deng, S Wang, A Deng, B Liu, SM Edgerton, AD. Thor
Journal: Cancer Research (2010)

Abstract Background: Metformin inhibits breast cancer cell proliferation and colony formation, with S phase arrest and the induction of apoptosis in triple negative breast cancer cells in vitro. In these cells, metformin down-regulates Cyclin D1 and Cyclin E, as well as EGFR, p-EGFR, p-AKT, p-MAPK, p-Src and p-mTOR, whereas it up-regulates p-AMPK (Liu, et al. Cell Cycle, 2009). Non-triple negative breast cancer cells are resistant to metformin induced apoptosis, although they show similar changes in p-AMPK induction with metformin (Alimova, et al. Cell Cycle, 2009). We hypothesized that there are unique signaling intermediates associated with metformin responsivity in triple negative cells and have identified the signal transducer and activator of transcription 3 (Stat3) as a potential target. Stat3 is constitutively activated in a wide range of tumors, including breast cancer (up to 60%). It reportedly promotes cancer cell proliferation and survival. Methods: Human triple negative breast cancer cell lines (MDA-468, MDA-231, BT20 and HCC70) were used to evaluate interactions between metformin and Stat3 signaling. Activation of Stat3 was examined by Western blot analysis with phosphorylation-specific antibodies. Cell proliferation was determined by MTS assay. Apoptosis was quantitated by an apoptosis ELISA assay and Western blots for PARP and caspase cleavage. In these 4 cell lines, Stat3-over-expressing clones were obtained via transfection of a constitutive active (CA) construct of Stat3. Specific knock-down of Stat3 expression was achieved by using a lentiviral system containing Stat3 small hairpin RNA. Results: In a dose and time dependent manner, metformin inhibits Stat3 phosphorylation at sites Tyr705 and Ser727, Cyclin D1 and E protein expression, cleavage of PARP and the pro-caspases 3, 8, and 9. Overexpression of the CA-Stat3 attenuates the aforementioned meformin-associated PARP and caspase cleavage as well as apoptosis, and it suppresses metformin induced cell cycle arrest and changes in cyclin D1 and E. In contrast, specific knock-down of Stat3 expression sensitizes the triple negative breast cancer cells to metformin-mediated apoptosis and cell cycle arrest, enhancing the signaling changes we describe above. Conclusion: These data indicate that Stat3 is a critical intermediary for metformin action in triple negative breast cancer cells. Our studies suggest that targeting Stat3 activation may be a useful strategy to treat breast cancer patients with triple negative phenotype. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD03-09.
Endoscopic intracavitary pull-through vacuum treatment of an insufficient pancreaticogastrostomy
Authors: Andreas Fischer, Hans Richter-Schrag, Jens Hoeppner, Alexander Braun, Stefan Utzolino
Journal: Endoscopy (2014)

A 73-year-old patient underwent pylorus-preserving pancreatic head resection due to a branch-duct type intraductal papillary mucinous neoplasm. At Day 7, repeat laparotomy was performed because of elevated amylase concentrations in the abdominal drains. During the procedure, signs of pancreatitis were observed but no pancreaticogastrostomy leak was seen. Drains provided continuous irrigation. At Day 9 gastric liquid was observed in the drains and 5 days later a computed tomography scan confirmed insufficiency of the pancreaticogastrostomy. As the patient was in a stable clinical condition, continuous irrigation was continued. On endoscopic placement of a jejunal feeding tube at Day 40, broad pancreaticogastrostomy insufficiency with an infected cavity was seen, with visible abdominal drainage ([Fig. 1]).
The Sugar-Water Test for Paroxysmal Nocturnal Hemoglobinuria
Authors: Robert C. Hartmann, David E. Jenkins
Journal: New England Journal of Medicine (1966)

THE diagnosis of paroxysmal nocturnal heinoglobinuria is relatively easy in patients who give the classic story of hemoglobinuria on arising, with subsequent clearing during the day. In many patients, however, the presenting symptoms are less dramatic, and the hemoglobinuria either is not recognized or is truly occult. In such patients there may be considerable delay in diagnosis. Thus, paroxysmal nocturnal hemoglobinuria should probably be considered in any patient with a puzzling anemia, particularly if reticulocytosis, pancytopenia or a history of repeated transfusion reactions is present.1 The diagnostic acid hemolysis and thrombin tests are not technically difficult but may present problems . . .
Rectal Biopsy as an Aid in the Diagnosis of Hirschsprung's Disease
Authors: Orvar Swenson, John Herbert Fisher, H. Edward MacMahon
Journal: New England Journal of Medicine (1955)

THE diagnosis of Hirschsprung's disease is not always easy. The patient presenting a typical history of chronic constipation, with physical signs of a distended abdomen and an empty rectal ampulla, who has a widely dilated colon with a narrow distal segment on barium-enema examination constitutes no diagnostic problem. However, in cases in which part of the diagnostic criteria are absent or inconclusive, the problem of diagnosis is particularly difficult. Rectal biopsy is offered as an aid in the diagnosis of these cases.In the study of 169 patients with congenital megacolon several indications for rectal biopsy have occurred. One of . . .
Epidemic Typhus (<i>Rickettsia prowazekii</i>) in Massachusetts: Evidence of Infection
Authors: Pearl K. Russo, David C. Mendelson, Paul H. Etkind, Max Garber, Victor P. Berardi, Robert F. Gilfillan
Journal: New England Journal of Medicine (1981)

All sickness arrives on wings and departs limpingly. — French proverbMassachusetts has been free of louse-borne typhus (epidemic typhus) for more than three decades. According to the Centers for Disease Control (CDC), the last known case of epidemic typhus in the United States was reported in 1950. The patient had contracted the disease in Mexico.1 The Centers' Virology Division of the Bureau of Laboratories described case histories of eight persons who had serologic reactions that indicated recent infection with Rickettsia prowazekii, the etiologic agent of epidemic typhus.2 The serum samples had been selected from specimens from 1575 persons . . .
530 HIGH EFFICACY AND SAFETY OF TENOFOVIR DF IN 441 NAIVE AND NUC-EXPERIENCED CHRONIC HEPATITIS B PATIENTS: A REAL LIFE MULTICENTER PROSPECTIVE COHORT STUDY
Authors: P. Marcellin, F. Zoulim, X. Causse, C. Hézode, D. Larrey, G. Pageaux, B. Roche, R. Truchi, D. Ouzan, A. Pauwels, J. Dumortier, C. Stern, O. Libert, J.-F. Cadranel, J.-P. Zarski
Journal: Journal of Hepatology (2012)
Abstract LB-232: MEK2 signaling pathway alone is sufficient but not necessary for melanoma cell proliferation
Authors: Chih-Shia Lee, Karl J. Dykema, Danielle M. Hawkins, Kyle A. Furge, Nicholas S. Duesbery
Journal: Cancer Research (2010)

Abstract The Raf-MEK-ERK signaling pathway plays a critical role in survival of many types of cancers, including melanoma. Targeting this pathway by using MEK inhibitors is a rational therapeutic strategy for melanoma treatment. Despite their success in pre-clinical studies, MEK inhibitors have failed to obtain satisfactory responses in clinical cancer trials. An improved understanding of MEK signaling in melanoma survival will facilitate the design of more effective therapeutics. There are two isoforms of MEK; MEK1 and MEK2. Although they are thought to be functionally redundant, recent studies have suggested that these two signaling molecules have non-overlapping cellular functions. To test this we developed a novel experimental system to allow signaling through individual MEK pathway in human melanoma SK-MEL-28 cells. In this system, multiple MEK/MKK pathways are inhibited by anthrax lethal toxin (LeTx), a Bacillus anthracis-secreted toxin which specifically and proteolytically inhibits members of MEK/MKK proteins. MEK1 or MEK2 signaling is rescued by expressing a cleavage-resistant MEK mutant (MEK1cr or MEK2cr) able to actively signal in the presence of LeTx. Using this approach, we determined that MEK2 signaling, and not MEK1, is sufficient for melanoma cell proliferation and anchorage-independent growth. To explain this we hypothesized that MEK1 and MEK2 signaling differentially regulate downstream effectors to control cell survival. To test this and to identify the non-overlapping effectors downstream to MEK1 and MEK2, we compared gene expression profiles using Agilent 60-mer Whole Human Genome Microarrays. We found that global suppression of MKK signaling by LeTx treatment significantly altered expression of 20% of represented genes. These mainly include genes involved in survival pathways such as the pathways of DNA replication, E2F transcription factors, rRNA processing, and cell proliferation, as well as oncogenic pathways such as Myc and Ras. Of these genes, approximately half were rescued by expression of one of MEK1cr or MEK2cr. Whereas MEK2cr had a more pronounced effect on expression and predominantly rescued signaling associated with cell proliferation, MEK1cr rescued signaling normally associated with epithelial to mesenchymal transition. Our findings demonstrate that MEK1 and MEK2 have non-redundant cellular functions and differentially regulate downstream effectors in SK-MEL-28 cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-232.
Treatment of the Idiopathic Respiratory-Distress Syndrome with Continuous Positive Airway Pressure
Authors: George A. Gregory, Joseph A. Kitterman, Roderic H. Phibbs, William H. Tooley, William K. Hamilton
Journal: New England Journal of Medicine (1971)

Abstract We applied a continuous positive airway pressure to 20 infants (birth weight 930 to 3800 g) severely ill with the idiopathic respiratory-distress syndrome. They breathed spontaneously. Pressure, up to 12 mm of mercury, was delivered through an endotracheal tube to 18 infants and via a pressure chamber around the infant's head to two. Arterial oxygen tension rose in all, permitting us to lower the inspired oxygen an average of 37.5 per cent within 12 hours. Minute ventilation decreased with increased continuous positive airway pressure, but this had little effect on arterial carbon dioxide tension, pH, arterial blood pressure and lung compliance. Sixteen infants survived, including seven of 10 weighing less than 1500 g at birth.
Abstract 4397: Bioavailability of substituted quinoline, a gap junction enhancer
Authors: Ying Ding, Keshar Prasain, Duy H. Hua, Thu Annelise Nguyen
Journal: Cancer Research (2011)

Abstract Breast cancer is one of the most malignant diseases that threaten the health of women all over the world, especially in western countries. It ranks the second leading cause of cancer deaths among women in the United States. Several drugs have been discovered to target different pathways of breast cancer cells; however, drug resistance and side effects have increasingly become a major concern. One of the effective methods is combinational treatment of different drugs. Loss of gap junctional intercellular communication (GJIC) is thought as one of the important hallmarks of cancer. It is believed that restoration of GJIC in cancer cells is related to reduction of tumorigenesis and increase of drug sensitivity. Gap junctions are intercellular channels connecting adjacent cells, allowing cells to transport small molecules (&amp;lt; 1.2kDa) from one cell to the next. This ordination of communication keeps cells at homeostasis. Previous report showed that combinational treatment of substituted quinoline (PQ1, a gap junction enhancer) and tamoxifen (a common used chemotherapeutic agent for breast cancers) can lower the concentration of tamoxifen in T47D breast cancer cells. It was also reported that PQ1 could increase 70% GJIC in T47D cells, whereas had no effect on GJIC in normal human mammary epithelial cells (HMECs) in vitro. However, the toxicity of PQ1 in vivo is still unknown. In this study, bioavailability of PQ1 was studied in mice. Twenty-five micrograms/kg body weight of PQ1 was administered orally to 5 week old mice. After 1, 12, or 24 hours of treatment, mice were sacrificed, and amounts of PQ1 in different organs were tested by HPLC and mass spectrometry. Expressions of connexin 43 and different protein markers (survivin, caspase-8, cleaved caspase-3, and aryl hydrocarbon receptor (AhR)) in organs were tested by western blot analysis. Hematoxylin and eosin staining was performed. Our results showed that compared to control, the expression of Cx43 in normal organs of the mice treated with PQ1 decreased, which is contrary to the effect of PQ1 on cancer cells. We also found that PQ1 can increase the expression of survivin and decrease the expression of caspase-8 and cleaved caspase-3 in nearly all the tested organs. Expression of AhR in liver was directly related with PQ1 amount, which means PQ1 is mediated through AhR and can be metabolized by liver. Histological results of the liver implied that PQ1 is not toxic to the tissue structure. Our studies demonstrate that PQ1 is a promising anti-cancer drug as well as in combinational treatment with other antineoplastic drugs with high specificity to cancer cells and low toxicity to normal organs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4397. doi:10.1158/1538-7445.AM2011-4397
EFFICACY AND SAFETY OUTCOMES OF VARIOUS RATE CONTROL STRATEGIES FOR PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE WITH REDUCED EJECTION FRACTION AND ATRIAL FIBRILLATION OR FLUTTER WITH RAPID VENTRICULAR RESPONSE
Authors: Siva Krothapalli, Lee Joseph, Omer Iqbal, Olurotimi Mesubi, Hardik Doshi, Nicole Worden, Jayasheel Eshcol, Musab Alqasrawi, Prashant Bhave, Michael Giudici
Journal: Journal of the American College of Cardiology (2015)
TM-13 * DIMINISHED PROGRESSION OF GLIOBLASTOMA WITH A SUPPLEMENTED HIGH-FAT LOW-CARBOHYDRATE DIET
Authors: R. T. Martuscello, L. P. Deleyrolle, C. D. Louviere, D. J. McCarthy, C. L. Skinner, M. A. Jundi, B. A. Reynolds
Journal: Neuro-Oncology (2014)

Glioblastoma [GB] is the deadliest and most malignant type of brain tumor, with a median survival less than 12 months. Research into tumor metabolism and the Warburg Effect have shed new light on an idea that puts energy disparities at the forefront for new and innovative treatment options for patients. Tumor cells have an established dependence on glucose that plays a significant role in growth and survival. The human body retains secondary energy sources that can be utilized in times of starvation and glucose deprivation. By exchanging ketones (β-hydroxybutyrate) for glucose as the primary energy source in the body we can slow the progression of glioblastoma's. Conventional methods for entering ketosis, such as the ketogenic diet (KD), have been tested clinically with variable success due to high rates of side effects and low diet palatability, reducing compliance. Therefore, we have created a supplemented high-fat low-carbohydrate (sHFLC) Diet [10%C;60%F(30%MCT);30%P] that induces the two key physiological features of the KD but is more nutritionally sound and palatable. Dietary effectiveness was tested in vitro using patient derived GB neurosphere cell lines and in vivo using NOD/SCID xenografts. In culture, individually reducing glucose and increasing ketones resulted in a significant reduction in tumor cell viability that was enhanced by the combination of low glucose and elevated ketones. In vivo we demonstrate that animals fed the sHFLC exhibited a significant decline in circulating glucose (96.01mg/dL ±14.25 vs 165.1mg/dL ±20.87, p < .0001) and elevation in circulating ketones (1.798mmol ±1.121 vs .400mmol ±.115, p < .0001), slowed tumor progression (390.18mm3 ±133 vs 1020.69mm3 ±368.9, p < .0001; at 28 days post-implant) and increased survival (46.5 ±13.16 days vs 34.5 ±4.2 days, p < .0001) compared to normal fed controls. Additionally the sHFLC better maintained animal body weight as well as overall appearance when compared to the KD (28.78g ±1.812 vs 24.45g ±5.999, p < .001).