tbuckley/cabot-search huggingface dataset:
Randomized phase II trial of two sequential schedules of docetaxel (D) and cisplatin (C) followed by gemcitabine (G) in patients with advanced non-small cell lung cancer
Authors: E. Galligioni, V. Gebbia, G. Cartenì, T. Gamucci, F. Grossi, F. Ferraù, M. Nardi, C. Pollera, S. Rossi, F. De Marinis
Journal: Journal of Clinical Oncology (2007)

18154 Background: C based doublets remain the cornerstone for first line treatment of advanced NSCLC but the role of sequential use of chemotherapy is still investigational. Aim of this study was to assess the activity and toxicity of 3 courses of C and D followed by 3 courses of single agent G, to reduce C exposure and sequentially administer 2 second generation cytotoxic drugs. The weekly D/C schedule was further investigated, to reduce toxicity. Methods: Chemotherapy naive stage IIIB or IV measurable NSCLC pts, aged 18–70 and PS 0–1, were stratified by stage (IIIB vs IV) and randomized, after local ethic committee approval and signed informed consent, to D and C (both 75 mg/m 2 on day 1) q21 days for 3 cycles (Arm A), or to D and C (both 25 mg/m 2 on days 1, 8, 15) q28 days for 3 (Arm B). Responding or stable pts of each arm, were treated with 3 additional cycles of G (1,200 mg/m 2 on days 1, 8) q 21 days. Primary endpoint of the study was response rate (RECIST). Sample size was calculated of 42 pts per arm, considering worthy of further investigation a regimen with =14 objective responses. Results: Between May 2005 and October 2006, 88 pts were enrolled (Arm A/B: 43/45), with 69 evaluable so far (median age 63 yrs, median PS 0, and M/F ratio 53/16). Toxicity (NCI-CTG criteria) after 3 cycles, evaluable on 67 (32/35) pts, was mainly hematological, with grade 3/4 neutropenia in 17 pts (17/0), neutropenic fever in 1 (arm A), infections in 2 (arm B), grade 3/4 thrombocytopenia in 3 (1/2) and grade 3/4 anemia in 2 (arm A). Non-hematological grade 3/4 toxicity consisted of fatigue (4/1), diarrhea (4/1), pulmonary toxicity (1/4), pain (2/3), stomatitis (1/2) and alopecia (2/0). Fifty one pts (A/B: 29/22) are evaluable for response after 3 cycles, with 16 PR (55%) and 7NC in arm A and 1CR+6PR (32%) and 7NC in arm B. Objective responses after 6 cycles, available only in few pts so far, show 1CR+10PR in arm A and 2PR in arm B. At a median FU of 6.5 months, 60/85 pts are alive (33/27) and 25 are dead (8/17), with 3 pts, never treated, lost to f. up. Conclusions: From these preliminary results, CD combination appears active and manageable while the activity of G, cannot be defined yet. Data collection is continuing and analysis will be completed and mature, by the time of the meeting. [Table: see text]
A phase II trial of sunitinib in patients with recurrent high-grade glioma
Authors: C. Chaskis, J. Sadones, A. Michotte, M. Dujardin, H. Everaert, B. Neyns
Journal: Journal of Clinical Oncology (2008)

13001 Background: High-grade gliomas (HGG) are characterized by neoangiogenesis and disruption of the blood-brain barrier. KIT, PDGFR-α and VEGFR2 are commonly amplified in HGG and represent an attractive therapeutic target. Sunitinib is a small molecule that inhibits the VEGFRs, FLT1, FLK1/KDR, PDGFR-a and -b, c-Kit, the FLT3 and RET kinases. We evaluated the effect of sunitinib in patients (pts) with recurrent HGG. Methods: Pts received a continuous oral daily dose of 37.5 mg sunitinib. Glioma dimensions, CNS edema and tumor perfusion were assessed by T2 and T1w(±Gd) MRI images. Cerebral blood flow (CBF) in the glioma and contralateral white and grey matter was assessed by T1-DCE- and T2*-DSC-based perfusion; lesion-to-normal-white matter CBF ratios (CBFr) were obtained. Uptake of 2- 18F-Fluoromethyl-L-Phenylalanine was assessed by PET (FMP-PET). Results: Twelve pts have been enrolled since 1 July 2007 (median age 46 (range 36–71), M/F 10/2, KPS 90–80: 6 pts, 70–60: 6 pts). All pts had recurrent disease following surgery, radiation therapy and temozolomide. Initial diagnosis was low-grade glioma in 4 pts, anaplastic oligo-astrocytoma in 1 pt and glioblastoma in 7 pts. A total of 50 treatment weeks (range 2–15; 10 pts) were evaluated for toxicity. Worse toxicity per pt included febrile neutropenia (gr3, n=1; gr4, n=1), afebrile neutropenia (gr2, n=1), fatigue (gr2, n=2), thrombocytopenia (gr2, n=2; gr3, n=1), lymphopenia (gr3, n=1; gr4, n=1), elevated AP and GGT (gr2, n= 1), and hypertension (gr2, n=3). Hematological toxicity necessitated a dose reduction to 25 mg/day in all 3 pts who continued treatment beyond 4 wks. Nine pts were evaluable for response. One pt experiencd neurological improvement, regression on MRI with reduced activity on FMP-PET and remains on treatment after 15 weeks. Two pts have SD after 4w and continued therapy. Six pts had PD within the first 4 weeks of treatment. CBFr was reduced in 4 out of 6 pts that were evaluated at present. Conclusions: Sunitinib 37.5 mg on a continuous daily basis reduces the CBFr in a majority of patients with recurrent high-grade gliomas. Tumor regression is less frequently observed. Hematological toxicity necessitated a dose reduction to 25 mg/day in a significant proportion of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Merck, Schering-Plough, Wyeth Pfizer, Schering-Plough, Wyeth
Transfusion-Induced Immunologic Abnormalities Not Related to AIDS Virus
Authors: J Kaplan, S Sarnaik, J Levy
Journal: New England Journal of Medicine (1985)

Immunologic abnormalities characteristic of AIDS including the lowering or inversion of the ratio of helper to suppressor T lymphocytes and diminished natural-killer-cell activity have been detected in otherwise healthy subjects with hemophilia who receive clotting factor and in subjects with congenital anemias who receive repeated blood transfusions.  Because both groups are known to be at risk of infection with the blood-borne virus responsible for AIDS the question arises whether the immunologic abnormalities detected in these subjects developed as a result of infection with the AIDS-associated retrovirus or as a consequence of repeated transfusion.  To address this issue serum samples obtained from 23 subjects with sickle cell anemia who had received repeated transfusions were tested for the presence of antibody to AIDS-associated retrovirus.  As shown in Table 1 peripheral-blood lymphocytes obtained from these subjects were found to have diminished helper/suppressor ratios and natural-killer-cell activity as compared with lymphocytes obtained from normal control subjects and from patients with sickle cell anemia who had not received repeated transfusions.  However at the time of this study 10 months later none of the subjects given transfusions had detectable levels of antibody to AIDS-Associated retrovirus.  This observation strongly suggests that the diminished helper/suppressor ratios and natural-killer-cell activity previously detected in these subjects were not due to infection with the AIDS retrovirus but to other factors associated with repeated transfusion.  Only a small proportion of those infected with the AIDS retrovirus acquire full-blown AIDS and some may have no evidence of immunologic abnormalities.  This finding indicates that host factors including the status of the immune system influence the outcome of such an infection.  The components of the immune system that may be involved have yet to be established but may well include the natural killer cells since such cells appear to be important in controlling the outcome of other viral infections.  Repeated transfusions therefore carry not only the risk of infection with the AIDS retrovirus but also the risk of producing immunologic abnormalities that may increase the likelihood that full-blown AIDS will develop after such an infection.  (full text)
Modification of the percutaneous approach to peritoneal dialysis catheter placement under peritoneoscopic visualization
Authors: N S Nahman, D F Middendorf, W H Bay, R McElligott, S Powell, J Anderson
Journal: Journal of the American Society of Nephrology (1992)

The placement of percutaneous peritoneal dialysis catheters under direct peritoneoscopic visualization is a relatively new technique for establishing peritoneal dialysis access. In this study, in which a modification of the Seldinger technique was used to facilitate the placement of the peritoneoscope, the experience with 82 consecutive catheterization procedures in 78 patients is reported. In 2 (2.4%) of 82 catheterization procedures, we were unable to enter the peritoneal cavity but experienced no other complications unique to the percutaneous approach. Of the 80 successful catheterization procedures, 76 represented first-time catheter placement and constituted a population subjected to life-table analysis examining catheter survival rates, the time to first cutaneous exit site or s.c. tunnel infection, and the time to first episode of peritonitis. After a follow-up period of 50.1 patient yr, 11 catheters were lost because of catheter dysfunction. Other clinical complications included peritoneal fluid leaks at the cutaneous exit site in 11 instances (0.22/patient yr), cutaneous exit site infection in 7 instances (0.14/patient yr), s.c. tunnel infection in 2 instances (0.04/patient yr), and 34 episodes of peritonitis (0.68/patient yr). The results of this study demonstrate that the suggested modification of the percutaneous placement of peritoneal dialysis catheters, under peritoneoscopic visualization, is a viable method for establishing peritoneal access.
Discussing: the Bhopal saga: causes and consequences of the world's largest industrial disaster
Authors: Carol S. Wood
Journal: Environmental Health Perspectives (2005)

After 20 years, victims, health care workers, and governments are still trying to comprehend what has been called the world's worst industrial accident. The Bhopal Saga is an attempt to bring order from the chaos of events before, during, and after the methyl isocyanate (MIC) release. Not a scientific analysis, the book summarizes events leading up to the accident of December 1984 and the relief work in the ensuing two decades.
Abstract 360: MiR-133 Modulates the Beta1-Adrenergic Receptor Transduction Cascade
Authors: Alessandra Castaldi, Tania Zaglia, Vittoria Di Mauro, Pierluigi Carullo, Giacomo Viggiani, Giulia Borile, Barbara Di Stefano, Gabriele Giacomo Schiattarella, Maria Giovanna Gualazzi, Leonardo Elia, Giuliano Giuseppe Stirparo, Gianluigi Pironti, Paolo Kunderfranco, Maria Luisa Colorito, Giovanni Esposito, Marie-Louise Bang, Marco Mongillo, Gianluigi Condorelli, Daniele Catalucci
Journal: Circulation Research (2014)

Rationale: The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, over-activation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors (βARs) in cardiomyocytes (CMs) and lead to increased heart rate and cardiac contractility. However, chronic stimulation of βARs leads to impaired cardiac function and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MiR-133 is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of mRNA translation/stability. Objective: To determine whether miR-133 affects βAR signaling during progression to heart failure. Methods and Results: Based on bioinformatic analysis, β1AR and other components of the β1AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A (PKA), were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult CMs following selective β1AR stimulation. Furthermore, gain- and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β1AR stimulation. This was confirmed in vivo using a novel cardiacspecific TetON-miR-133 inducible transgenic mouse model (Tg133). When subjected to transaortic constriction, Tg133 mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared to control mice. Conclusions: MiR-133 controls multiple components of the β1AR transduction cascade and is cardioprotective during heart failure.
Abstract 14685: Re Expression of Isl-1, a Transcription Factor Mastering Embryonic Cardiogenesis, in Acute Myocardial Infarction Patients
Authors: Aya Barzelay, Ilana Gofman, Michal Entin-Meer, Sofia Mysel Auslander, Jeremy Ben-Shoshan, Shmuel Banai, Arik Finkelstein, Gad Keren
Journal: Circulation (2012)
Prevalence and Cost of Office Visits Prior to Colonoscopy for Colon Cancer Screening
Authors: Kevin R. Riggs, Jodi B. Segal, Eun Ji Shin, Craig Evan Pollack
Journal: JAMA (2016)

This study uses employer-sponsored private insurance claims data to determine the proportion of colonoscopies for colon cancer screening and polyp surveillance that were preceded by office visits and the associated insurance payments for those visits between 2010 and 2013.
A phase II trial of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for patients with refractory or relapsed non-Hodgkin's lymphoma
Authors: B. Park, W. Kim, H. Eom, J. Kim, S. Oh, C. Suh
Journal: Journal of Clinical Oncology (2009)

8559 Background: Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in salvage setting. However, this regimen has the modest response with severe nephrotoxcity and neurotoxicity, especially to heavily treated patients. We investigated the response rate and toxicity of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOx) for recurrent or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), looking for the more effective and less toxic therapy. Methods: Patients with recurrent or refractory diffuse large B-cell NHL or mantle cell lymphoma, measurable disease, and more than one previous chemotherapy regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m 2 intravenously (i.v.) on Days 1 and 8, ifosfamide 2000 mg/m 2 i.v. on Day 1, dexamethasone 40 mg orally on Days 1–4, and oxaliplatin 130mg/m 2 i.v. on Day 2, every 21 days. The primary end point was a response after three cycles. Patients could then proceed to stem cell transplantation (SCT) or receive up to six treatment cycles. Results: Twenty-seven eligible patients were evaluable for toxicity and response. The median age of the patients was 54 years (range, 18–75 years) and most had diffuse large-cell lymphoma. After 3 cycles, there were 4 complete responses (CR; 15%) and 10 partial responses (PR; 37%). There was an overall response rate (RR) of 52%. The RR after completion of all protocol chemotherapy including SCT was 44% (10 CR, 2 PR). In total 88 cycles of GIDOx, grade 3 and 4 neutropenia occurred in 33% and 16% of cycles, respectively. Grade 3 and 4 thrombocytopenia occurred in 14% and 16% of cycles, respectively. Tow patients (2%) experienced febrile neutropenia. Seven patients (26%) proceeded to SCT. Conclusions: GIDOx is an active salvage regimen in aggressive B-cell NHL and can be administered with acceptable toxicity. No significant financial relationships to disclose.
IL-22 capacitates dermal fibroblast responses to TNF in scleroderma
Authors: Nicolò Costantino Brembilla, Aleksandra Maria Dufour, Montserrat Alvarez, Stéphanie Hugues, Elisa Montanari, Marie-Elise Truchetet, Paola Lonati, Lionel Fontao, Armando Gabrielli, Serena Vettori, Gabriele Valentini, Wolf-Henning Boehncke, Pierluigi Meroni, Carlo Chizzolini
Journal: Annals of the Rheumatic Diseases (2015)

Interleukin (IL) 22 mRNA in systemic sclerosis (SSc) skin and Th22 cells in SSc peripheral blood are increased, but the role of IL-22 in fibrosis development remains poorly understood.Biopsies were obtained from the involved skin of 15 SSc, 4 morphea and 8 healthy donors (HD). The presence of IL-22+ cells in the skin was determined by immunostaining. The in vitro response of HD and SSc fibroblasts to IL-22, IL-22 in conjunction with tumour necrosis factor (TNF) or keratinocyte conditioned medium was assessed by ELISA, radioimmunoassay (RIA), real-time PCR and western blot. The in vivo response in mice was assessed by histomorphometry.IL-22+ cells were over-represented in the dermis and epidermis of morphea and in the epidermis of SSc compared with HD. The majority of dermal IL-22+ cells were T cells. Dermal fibroblasts expressed both IL-22 receptor subunits IL-10RB and IL-22RA, expression of which was enhanced by TNF and reduced by transforming growth factor (TGF)-β. IL-22 induced rapid phosphorylation of p38 and ERK1/2 in fibroblasts, but failed to induce the synthesis of chemokines and extracellular matrix components. However, IL-22 enhanced the production of monocyte chemotactic protein 1, IL-8 and matrix metalloproteinase 1 induced by TNF. Fibroblast responses were maximal in the presence of conditioned medium from keratinocytes activated by IL-22 in conjunction with TNF. Dermal thickness was maximal in mice injected simultaneously with IL-22 and TNF.IL-22 capacitates fibroblast responses to TNF and promotes a proinflammatory fibroblast phenotype by favouring TNF-induced keratinocyte activation. These results define a novel role for keratinocyte-fibroblast interactions in the context of skin fibrosis.
解读《高血压防治基层实用规范》（二）
Authors: 严晓伟
Journal: BMJ (2004)

(上接2003年第6期第349页) 三、基层医生应如何掌握高血压的药物治疗? 高血压的药物治疗是基层医生在高血压治疗中的一个难点.尽管很多基层医生很重视降血压药物的应用,但面对众多的药物种类,常常觉得无所适从.如在初步的治疗用药后,如果血压下降不满意,如何寻找影响药物疗效的因素,并进行药物的调整;在血压达到满意控制后,如何巩固降血压治疗的成果,等等.为给予患者正确的药物治疗,在获得满意的降血压疗效的同时,减少药物引起的不良反应,现从以下几个方面就基层医生对高血压药物治疗的理解进行讨论.
Outcomes for APBI with strut-based brachytherapy: First 100 accrued patients (5-year median follow-up).
Authors: Robert R. Kuske, Coral Quiet, Margaret B. Snyder, Maureen Lyden, Deanna J. Attai, Lydia T. Komarnicky, Jay E. Reiff, Constantine Mantz, Steven E. Finkelstein, Daniel Scanderbeg, Catheryn M. Yashar
Journal: Journal of Clinical Oncology (2014)

114 Background: The SAVI Collaborative Research Group (SCRG), was created to study the long-term outcomes of women receiving accelerated partial breast irradiation (APBI) using strut-based applicators. The outcomes for the first 100 accrued patients in the study are reported. Methods: Patients for this subset analysis weretaken as the initial 100 treated across all participating sites. Median follow-up of this cohort was 56.3 months at the time of the abstract. Patients were treated with APBI using the strut-based brachytherapy device with conventional dose and fractionation (3.4 Gy x 10 fx, BID). Treatment planning goals for the planning target volume were a V90&gt;90%, V150&lt;50 cc, and V200&lt;20 cc. Patients were followed regularly by their radiation oncologist and outcomes were graded based on the CTCAE v3.0 (common terminology criteria for adverse events, version 3.0). Recurrence (raw and actuarial) rates were also calculated based on the follow up. Cosmesis was graded using the Harvard Scale. Results: 75 patients had invasive disease and 25 had ductal carcinoma in situ. The median age was 60.5 yrs (range 40-85 yrs), with 84% post-menopausal. Median tumor size was 10.0 mm (range 0.7-35 mm) with 92% being estrogen receptor positive. 65% of patients had at least one round of hormone therapy and 7% had chemotherapy. All patients completed APBI as planned with no serious adverse events. All patients met the dosimetric criteria. Good/excellent cosmesis was seen in &gt;94% of subjects at all times of follow up (6-60 months). The 5-yr actuarial rates for TR/MM were 2.2%, 1.5% and 4.2% for all subjects, invasive and DCIS subgroups, respectively. The 5-yr actuarial rates for IBTR were 3.3%, 3.0% and 4.2% for all subjects, invasive and DCIS subgroups, respectively. Conclusions: For these initially treated 100 patients with a median 5 years of follow up, strut-based brachytherapy appears to be a well-tolerated, effective treatment with low rates of toxicities and local control as good as other brachytherapy APBI methods.
Abstract 13003: MicroRNA-133 Promotes Direct Cardiac Reprogramming by Snai1 Repression and Silencing Fibroblast Signatures
Authors: Naoto Muraoka, Hiroyuki Yamakawa, Kazutaka Miyamoto, Taketaro Sadahiro, Kohei Inagawa, Rie Wada, Tomohiko Umei, Takahiko Nishiyama, Ruri Kaneda, Toru Fukuda, Shu Takeda, Tomoyuki Suzuki, Shugo Tohyama, Hisayuki Hashimoto, Keiichi Fukuda, Masaki Ieda
Journal: Circulation (2013)

Naoto Muraoka, 2013 Finalist and Presenting Author
Abstract 15393: High Quality CPR With Optimized Rescuer-Dispatcher Teamwork
Authors: Tonje S Birkenes, Helge Myklebust, Andres Neset, Jo Kramer-Johansen
Journal: Circulation (2013)

Background: Calling the emergency phone number and starting CPR initiates the chain of survival for sudden cardiac arrest outside hospital. Traditional CPR courses teach to call for help and to per...
Abstract 13252: The Effects of Pre-LVAD Diabetes on Post-LVAD Outcomes
Authors: Burhan Mohamedali, Gardner Yost, Geetha Bhat
Journal: Circulation (2014)

Introduction: Diabetes Mellitus (DM) is a major risk factor for adverse cardiovascular (CV) outcomes. In this study, we investigated the effects of DM on post HeartMate II left ventricular assist device (LVAD) outcomes. Methods: In this retrospective study, 244 patients (Pts) were enrolled. Pts were stratified based on the presence or absence of pre-LVAD DM. DM was defined as a pre-existing history of DM requiring insulin or oral hypoglycemic medications or a new diagnosis of DM based on HgbA1C&gt; 7mg/DL. Baseline information and post adverse outcomes were tabulated. Results: The cohort comprised of 108 diabetics and 136 non-diabetics. DM pts had a slightly worse baseline medical profile than non-DM. DM pts were more likely to be obese, had worse creatinine, and higher systolic and mean arterial blood pressure. DM pts also had a higher prevalence of atrial fibrillation, obstructive sleep apnea, and renal insufficiency. HgbAIC profiles revealed sub-optimal diabetic control at baseline (Table1). Post-LVAD, other than a higher incidence of hemolysis in the diabetic pts (12% vs 4%; p= 0.03), there were no differences between the two groups. Post LVAD HgbA1C was statistically significantly better (7.2 vs 6.1 P-value &lt;0.001). Conclusions: Although DM is a poor risk factor for many adverse CV outcomes, there are no differences in adverse events in our pts post-LVAD placement compared to non-diabetic pts. This may be a result of improved access to care for diabetics, improvement in hemodynamics and biochemical derangements after normalization of cardiac output, or increased pancreatic blood flow. Our results indicate that diabetic pts who receive LVAD therapy are overall not at higher risk for adverse outcomes compared to non-diabetics. Further larger prospective studies are needed to validate our findings.