tbuckley/cabot-search huggingface dataset:
Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study
Authors: Michael R. Rickels, Katrina J. Ruedy, Nicole C. Foster, Claude A. Piché, Hélène Dulude, Jennifer L. Sherr, William V. Tamborlane, Kathleen E. Bethin, Linda A. DiMeglio, R. Paul Wadwa, Andrew J. Ahmann, Michael J. Haller, Brandon M. Nathan, Santica M. Marcovina, Emmanouil Rampakakis, Linyan Meng, Roy W. Beck
Journal: Diabetes Care (2015)

OBJECTIVE Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS At eight clinical centers, a randomized crossover noninferiority trial was conducted involving 75 adults with type 1 diabetes (mean age, 33 ± 12 years; median diabetes duration, 18 years) to compare intranasal (3 mg) versus intramuscular (1 mg) glucagon for treatment of hypoglycemia induced by intravenous insulin. Success was defined as an increase in plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the glucose nadir within 30 min after receiving glucagon. RESULTS Mean plasma glucose at time of glucagon administration was 48 ± 8 and 49 ± 8 mg/dL at the intranasal and intramuscular visits, respectively. Success criteria were met at all but one intranasal visit and at all intramuscular visits (98.7% vs. 100%; difference 1.3%, upper end of 1-sided 97.5% CI 4.0%). Mean time to success was 16 min for intranasal and 13 min for intramuscular (P &amp;lt; 0.001). Head/facial discomfort was reported during 25% of intranasal and 9% of intramuscular dosing visits; nausea (with or without vomiting) occurred with 35% and 38% of visits, respectively. CONCLUSIONS Intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. Although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response.
Ventilatory support of patients with sepsis or septic shock in resource-limited settings
Authors: Ary Serpa Neto, Marcus J. Schultz, Emir Festic
Journal: Intensive Care Medicine (2015)

In this chapter we discuss recommendations on the identification of patients with acute respiratory distress syndrome (ARDS), indications for mechanical ventilation, and strategies for lung-protective ventilation in resource-limited settings. Where blood gas analyzers are unavailable, it can be replaced by the plethysmographic oxygen saturation/fractional inspirational oxygen concentration (SpO2/FiO2) gradient. Bedside lung ultrasound is a valuable diagnostic tool assessing pulmonary edema and other pathologies. A number of recommendations for safe and lung-protective mechanical ventilation in patients with sepsis and respiratory failure are provided. However, many of these have not been trialed specifically in resource-limited settings. These recommendations include an elevated head-of-bed position and a minimum level of positive end-expiratory pressure (PEEP) of 5 cm H2O only to be in patients with moderate or severe ARDS. In addition, low FiO2 and low oxygenation goals are suggested, using PEEP/FiO2 tables. Recruitment maneuvers are indicated in refractory hypoxia, but require experienced staff. Low tidal volumes (5–7 ml/kg predicted body weight, avoiding >10 ml/kg) are recommended and if at all possible in combination with end-tidal carbon dioxide (CO2) monitoring for recognition of dislodgement of the endotracheal tube and under- or overventilation. “Volume-controlled” modes could be safer than “pressure-controlled” modes, and we recommend to check regularly whether a patient tolerates a “support” mode; we also suggest to perform spontaneous breathing trials to timely identify patients who are ready for extubation, but also to plan extubating patients when sufficient staff is around to guarantee safe re-intubation.
Effect of perfluorotributylamine-enriched alginate on nucleus pulposus cell: Implications for intervertebral disc regeneration
Authors: Zhen Sun, Beier Luo, Zhongyang Liu, Liangliang Huang, Bing Liu, Teng Ma, Bo Gao, Zhi-Heng Liu, Yu-Fei Chen, Jing-Hui Huang, Zhuojing Luo
Journal: Biomaterials (2015)
Phase Ib dose-escalation study of Pexa-Vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia virus, administered by intravenous (IV) infusions in patients with metastatic colorectal carcinoma (mCRC).
Authors: Jeeyun Lee, Young Suk Park, James Burke, Ho Yeong Lim, Jihye Lee, Won Ki Kang, Joon Oh Park, Adina Pelusio, Caroline Breitbach, David H. Kirn
Journal: Journal of Clinical Oncology (2013)

3608^ Background: Pexa-Vec is an EGFR-targeted vaccinia virus engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF), thereby stimulating direct oncolysis, tumor vascular disruption and anti-tumor immunity (Nat Rev Cancer 2009). Dose-dependent IV Pexa-Vec delivery was defined previously (Nature2011). This study was designed to assess the safety, maximal tolerated dose and anti-tumor activity of Pexa-Vec administered IV in patients with mCRC after failure of standard therapies. Methods: Nine patients were treated at 1 of 3 dose levels (10 6 , 10 7 or 3x10 7 pfu/kg IV every 2 weeks x 4) in a standard 3+3 dose-escalation design; 6 additional patients were enrolled at the MFD. Anti-tumor activity according to RECIST was determined using serial CT scans. Pharmacokinetic studies were also performed. Data summarized prior to database lock. Results: 15 patients with mCRC refractory to irinotecan, oxaliplatin, and 5-FU were treated (median lines of therapy 5; range 2-7); 13 of 15 received prior anti-angiogenic agents, and 11 of 12 KRAS WT tumors failed cetuximab. Adverse events were generally grade 1/2 and included: fever (93%), chills (93%), headache (60%), nausea (60%), and hypotension (40%). No dose-limiting toxicities or grade 3/4 events were reported. Only patients treated at high-dose (Cohort 3 &amp; Expansion) exhibited a pustular rash (n=9; 78%). Pexa-Vec genomes detected in blood acutely were above the dose threshold for systemic delivery. Notably, clearance was not more rapid with repeated IV treatments despite the induction of humoral immunity. Furthermore, patients at the top dose level exhibited increased disease stabilization at Week 4 (89% high-dose (n= 9) versus 33% low-dose (n=6)). A trend (p=0.16) towards increased overall survival at high vs low-dose Pexa-Vec was observed with 78% high-dose patients still alive between 5 and 13 mos. Conclusions: Repeat IV Pexa-Vec was well-tolerated with transient flu-like symptoms. Dose-dependent safety, pharmacokinetics and anti-tumor activity were described in treatment-refractory mCRC patients. Clinical trial information: NCT01380600.
Alternating Hepatic Arterial Infusion and Systemic Chemotherapy for Liver Metastases From Colorectal Cancer: A Phase II Trial Using Intermittent Percutaneous Hepatic Arterial Access
Authors: M. Sitki Copur, Mary Capadano, James Lynch, Timothy Goertzen, Timothy McCowan, Randall Brand, Margaret Tempero
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the objective response to a short course of hepatic arterial infusion (HAI) using temporary, percutaneously placed catheters alternating with systemic prolonged continuous infusion fluorouracil (ci 5-FU) and daily oral leucovorin (L). PATIENTS AND METHODS: Eligible patients were previously untreated (except for adjuvant therapy) adults with liver-predominant metastases, with Eastern Cooperative Oncology Group performance status of 0 to 2. Treatment regimen included HAI with fluorodeoxyuridine (FUDR) 60 mg/m 2 /d and L 15 mg/m 2 /d continuously infused daily for 4 days. After a 1-week rest, ci 5-FU was administered through a central venous access device using a dose of 180 mg/m 2 /d with a fixed dose of oral L at 5 mg/m 2 /d for 21 out of 28 days. Cycles were repeated every 6 weeks. After four cycles of therapy, patients were maintained on ci 5-FU and daily oral L until evidence of progression. RESULTS: Forty-three patients were enrolled onto this trial. One patient was ineligible. The objective response rate for all patients (17 partial, zero complete) was 41% (95% confidence interval [CI], 26% to 56%). Five patients were not able to receive at least one complete cycle of HAI. Among patients who received at least one complete cycle of HAI, the response rate was 46% (95% CI, 30% to 62%). Five patients underwent a liver resection after enrolling onto the protocol. At the time of analysis, estimated median time to progression was 6 months, and estimated median overall survival was 13 months. CONCLUSION: The objective response rate was comparable to that achieved with more prolonged and more frequent HAI using FUDR. This approach should be studied as an acceptable alternative to surgically placed hepatic arterial catheters/pumps and may have a role as neoadjuvant therapy for liver metastases that are unresectable, as well as an adjuvant role for patients with resected hepatic metastatic colorectal cancer.
Multimodality Approaches to Localized Gastric Cancer
Authors: Prajnan Das, Yixing Jiang, Jeffrey H. Lee, Manoop S. Bhutani, William A. Ross, Paul F. Mansfield, Jaffer A. Ajani
Journal: Journal of the National Comprehensive Cancer Network (2010)

Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.
A survey on cases of tick-borne encephalitis in European countries
Authors: O Donoso Mantke, R Schädler, M Niedrig
Journal: Eurosurveillance (2008)

The European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) is finalising a project to improve the diagnostic and monitoring of encephalitis viruses in Europe. Part of this study was to analyse the present surveillance situation for tick-borne encephalitis (TBE), which is the most important flavivirus infection of the central nervous system in the European Union (EU) and Russia. A questionnaire was mailed to contact points in all Member States of the EU and three non-EU countries (Norway, Russia and Switzerland) to summarise their TBE surveillance and prevention activities. Information was requested on case definition, type of laboratory tests for TBE diagnostics, investigations regarding tick-transmitted diseases, mapping of endemic foci, vaccination programmes, and recommendations for travellers. The survey gives an overview of the existing epidemiological and laboratory sources of information and the number of TBE cases from 2004 until 2007, but also showed that, in particular, case definitions, diagnostic assays for confirmation, and methods/indicators for mapping risk areas differ widely across the participating countries. The data will help to develop recommendations for the standardisation and quality control or TBE surveillance and diagnostics.
Lack of publication bias in randomized clinical trials (RCTs) sponsored by the National Cancer Institute (NCI) and performed by Cooperative Oncology Groups (COGs)
Authors: H. P. Soares, A. Kumar, S. Daniels, D. J. Sargent, J. C. Buckner, S. Swann, R. E. Smith, A. Khyatat, R. J. Wells, B. Djulbegovic
Journal: Journal of Clinical Oncology (2004)

6004 Background: Failure to publish clinical research carries important scientific and ethical consequences. Scientifically, publication of only positive results leads to an overestimation of the true efficacy of a new therapy. Ethically, failure to publish constitutes a breach of contract with the public, patients and sponsors who expect dissemination of the results. Previous studies have estimated that 7–51% of completed studies in medicine are not published (AIDS Edu Prev 1997;9:15–21). The publication rate of the NCI COGs is, however, not known. Methods: Eight COGs sponsored by the NCI have conducted and completed more than 30 RCTs each. We obtained a list of all completed phase III RCTs with details of their publication status from the main protocol office of the NCI, principal investigators and statistical offices from 4 of the COGs (table 1). We used the NCI definition of completed studies in the determination of the publication rate: studies that met their primary objectives, were closed to accrual and in which all patients have completed therapy. Studies that were initiated but were closed early due to poor accrual were excluded. Results: The number of trials included in this analysis range from 30 to 81 RCTs per COG. The publication rate ranged from 95 to 100% (table 1). Of 240 published studies, 98% were published as manuscripts while 2% were published as an abstract only. Conclusions: The publication rate of the NCI sponsored trials is high. The Cooperative Oncology Groups, which are sponsored by the NCI and publicly funded, have an outstanding publication record for their trials. This record minimizes publication bias, and ensures dissemination of the knowledge gained through the performance of clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration US NIH (grant# R01 NS044417–01)
Unevaluated or inefficient approaches are hard to justify
Authors: I Marks
Journal: BMJ (1994)

The limited resources available for health make it important that money is spent in the best interests of patients. If money is spent on inefficient treatments there is less available for good care, so routine methods should have had their value proved in randomised controlled trials. This ideal is hard to attain. Randomised controlled trials cost time and money and only a minority of medical treatments have been evaluated in this way. To draw firm conclusions several randomised controlled trials in varying circumstances are usually needed and, for chronic conditions, follow up is essential to show that gains last. Finally, treatments which work in randomised controlled trials must be shown to be helpful in audit of routine care.

Given our imperfect knowledge, which are efficient psychotherapies and which not? Which have been well evaluated, for which problems in which circumstances, at what cost, and who can deliver them? Such questions can be answered firmly for some clinical problems, with less confidence for others, and hardly at all for many. Most successful psychotherapies are brief (five to 15 sessions) and focused.

Randomised controlled trials have shown exposure therapy to be …
Hematopoietic Potential and Retroviral Transduction of CD34+Thy-1+ Peripheral Blood Stem Cells From Asymptomatic Human Immunodeficiency Virus Type-1–Infected Individuals Mobilized With Granulocyte Colony-Stimulating Factor
Authors: Uwe Junker, James J. Moon, Creton S. Kalfoglou, Irena Sniecinski, Stephen J. Forman, John A. Zaia, Hideto Kaneshima, Ernst Böhnlein
Journal: Blood (1997)
Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals
Authors: J.M. Fitzpatrick, J.S. Biswas, J.D. Edgeworth, J. Islam, N. Jenkins, R. Judge, A.J. Lavery, M. Melzer, S. Morris-Jones, E.F. Nsutebu, J. Peters, D.G. Pillay, F. Pink, J.R. Price, M. Scarborough, G.E. Thwaites, R. Tilley, A.S. Walker, M.J. Llewelyn, Mark Melzer, Frederick Pink, Jennifer Fitzpatrick, Gill Jones, Martin Llewelyn, Joanna Peters, Jason Biswas, Jonathan Edgeworth, Lucy Guile, Antonio Querol-Rubiera, Abid Hussain, Neil Jenkins, Ed Moran, Devedas Pillay, Matthew Scarborough, Tom Rawlinson, Ryan Judge, Robert Tilley, Anita Lavery, Stephen Morris-Jones, James Price, Emmanuel Nsutebu
Journal: Clinical Microbiology and Infection (2015)
Surfactant protein expression at various COPD Gold stages
Authors: Sophie Seehase, Henrik Watz, Christian Kugler, Ekkehard Vollmer, Torsten Goldmann
Journal: European Respiratory Journal (2014)

An imbalance of the pulmonary surfactant systems is suggested to be involved in developing chronic obstructive pulmonary disease (COPD). Up to date, there is no detailed knowledge about the expression of surfactant proteins (SP) within the various COPD GOLD stages.  Archived HOPE- as well as formalin-fixed paraffin embedded tumor free lung tissues from 37 subjects (GOLD I: 16, GOLD II: 16, GOLD III: 5) were investigated by immunohistochemistry (IHC). From each, single sections were performed and stained for 6 different proteins involved in the surfactant system – SP-A, proSP-B, SP-C, SP-D, haptoglobin, ABCA3. Ten pictures of each IHC stained section were randomly taken avoiding the regions in proximity of the edges of the specimen as well as of larger airways. Quantitative assessment of the IHC staining in the lung tissue was performed. IHC-positive area per total area were correlated with the respective GOLD stages.  No differences of proSP-B, SP-D and haptoglobin were detectable in lungs of GOLD stages I to III. The amount of positive area of ABCA3 and SP-A was increased between GOLD I and GOLD III, but not statistically significant. The amount of positive stained SP-C area was significantly increased in lungs GOLD III, compared to GOLD I.  Our data revealed that a correlation of surfactant and ABCA3 protein expression in lung tissue of COPD patients is not of clinical relevance. Thus, we will establish a COPD-score considering grade of emphysema and numbers of inflammatory cells, since this appears to be more likely to characterize the relationship of histopathological hallmarks and clinical symptoms in patients suffering from COPD.
LO8 : Daclatasvir, sofosbuvir, and ribavirin combination for HCV patients with advanced cirrhosis or posttransplant recurrence: Phase 3 ALLY-1 study
Authors: F. Poordad, E.R. Schiff, J.M. Vierling, C. Landis, R.J. Fontana, R. Yang, F. McPhee, E. Hughes, S. Noviello, E.S. Swenson
Journal: Journal of Hepatology (2015)
Changes in Subtype Diagnosis of Schizophrenia: 1920-1966
Authors: JAMES R. MORRISON
Journal: American Journal of Psychiatry (1974)

A review of admissions to a general psychiatric hospital over a 47-year period revealed that the diagnoses of catatonic and hebephrenic schizophrenia decreased markedly, that paranoid schizophrenia, with some variation, remained approximately the same, and that there was a great increase in chronic undifferentiated schizophrenia. Possible causes for these findings include changes in definitions and in hospital admission practices; the more effective use of therapy, the degree and type of drug abuse, and the waning interest of psychiatrists in clinical diagnoses may provide other reasons.
REMOVAL OF THIRTY DENTICLES FROM ONE BICUSPID SOCKET
Authors: Bundy Allen
Journal: JAMA (1918)

May 29, 1917, a woman, aged 23, called my attention to a slight prominence of the gum buccally to the upper right bicuspid region which had not produced any symptoms other than the elevation of the tissue. Figure 1 is a roentgenogram of the upper right bicuspid region showing the presence of a collection of denticles. The patient was referred to Dr. John Voss of Iowa City, Iowa, who extracted thirty denticles from the first bicuspid socket (Fig. 2). All teeth were present, and occlusion was perfect, excepting for the third molars, which had not erupted. <h3>Child Labor Standards.</h3> —To secure ideal standards, national or local, we must presuppose ideal citizens, educated, alert, knowing what they want and organized to demand efficiency of their public servants.—Lindsay,<i>Child Labor Bulletin</i>.
Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance
Authors: Douglas C. Palmer, Geoffrey C. Guittard, Zulmarie Franco, Joseph G. Crompton, Robert L. Eil, Shashank J. Patel, Yun Ji, Nicholas Van Panhuys, Christopher A. Klebanoff, Madhusudhanan Sukumar, David Clever, Anna Chichura, Rahul Roychoudhuri, Rajat Varma, Ena Wang, Luca Gattinoni, Francesco M. Marincola, Lakshmi Balagopalan, Lawrence E. Samelson, Nicholas P. Restifo
Journal: The Journal of Experimental Medicine (2015)

Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the suppressor of cytokine signaling (SOCS) family, is induced by TCR stimulation in CD8+ T cells and inhibits their functional avidity against tumors. Genetic deletion of Cish in CD8+ T cells enhances their expansion, functional avidity, and cytokine polyfunctionality, resulting in pronounced and durable regression of established tumors. Although Cish is commonly thought to block STAT5 activation, we found that the primary molecular basis of Cish suppression is through inhibition of TCR signaling. Cish physically interacts with the TCR intermediate PLC-γ1, targeting it for proteasomal degradation after TCR stimulation. These findings establish a novel targetable interaction that regulates the functional avidity of tumor-specific CD8+ T cells and can be manipulated to improve adoptive cancer immunotherapy.
Refugees in the eastern Mediterranean region
Authors: Kamel Aljouni, Yagob Y Al-Mazrou, Walid S Ammar, Abdallah S Daar, Nils Daulaire, Majid Ezzati, Mahmoud Fathalla, Didier P Houssin, Ilona Kickbusch, Abdelhay Mechbal, Hoda M Rashad, Belgacem Sabri
Journal: The Lancet (2015)
Microembolization During Carotid Artery Stenting in Patients With High-Risk, Lipid-Rich Plaque
Authors: Piero Montorsi, Luigi Caputi, Stefano Galli, Elisa Ciceri, Giovanni Ballerini, Marco Agrifoglio, Paolo Ravagnani, Daniela Trabattoni, Gianluca Pontone, Franco Fabbiocchi, Alessandro Loaldi, Eugenio Parati, Daniele Andreini, Fabrizio Veglia, Antonio L. Bartorelli
Journal: Journal of the American College of Cardiology (2011)
Lack of autophagy induces steroid-resistant airway inflammation
Authors: Yuzo Suzuki, Hadi Maazi, Ishwarya Sankaranarayanan, Jonathan Lam, Bryant Khoo, Pejman Soroosh, Richard G. Barbers, J.-H. James Ou, Jae U. Jung, Omid Akbari
Journal: Journal of Allergy and Clinical Immunology (2015)