tbuckley/cabot-search huggingface dataset:
Pitfalls of Single-Electrocardiogram Lead Monitoring
Authors: Arvind Nishtala, Nora Goldschlager
Journal: JAMA Internal Medicine (2017)

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Effectiveness of foot orthoses for the prevention of lower limb overuse injuries in naval recruits: a randomised controlled trial
Authors: Daniel R Bonanno, George S Murley, Shannon E Munteanu, Karl B Landorf, Hylton B Menz
Journal: British Journal of Sports Medicine (2017)

Objectives To evaluate the effectiveness of prefabricated foot orthoses for the prevention of lower limb overuse injuries in naval recruits. Methods This study was a participant-blinded and assessor-blinded, parallel-group randomised controlled trial. Three-hundred and six participants aged 17–50 years who undertook 11 weeks of initial defence training at the Royal Australian Navy Recruit School (Cerberus, Australia) were randomised to a control group (flat insoles, n=153) or an intervention group (contoured, prefabricated foot orthoses, n=153). The combined incidence of medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain during the 11-week training period were compared using incidence rate ratios (IRR). Data were analysed using the intention-to-treat principle. Results Sixty-seven injuries (21.9%) were recorded. The control and intervention group sustained 40 (26.1%) and 27 (17.6%) injuries, respectively (IRR 0.66, 95% CI 0.39 to 1.11, p=0.098). This corresponds to a 34% reduction in risk of developing medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy or plantar fasciitis/plantar heel for the intervention group compared with the control group. Participants in the prefabricated orthoses group were more likely to report at least one adverse event (20.3% vs 12.4%; relative risk (RR) 1.63, 95% CI 0.96 to 2.76; p=0.068; number needed to harm 13, 95% CI 6 to 253). The most common adverse events were foot blisters (n=20, 6.6%), arch pain (n=10, 3.3%) and shin pain (n=8, 2.6%). Conclusion Prefabricated foot orthoses may be beneficial for reducing the incidence of lower limb injury in naval recruits undertaking defence training. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12615000024549.
Belimumab for the Treatment of Early Diffuse Systemic Sclerosis
Authors: Jessica K. Gordon, Viktor Martyanov, Jennifer M. Franks, Elana J. Bernstein, Jackie Szymonifka, Cynthia Magro, Horatio F. Wildman, Tammara A. Wood, Michael L. Whitfield, Robert F. Spiera
Journal: Arthritis & Rheumatology (2017)

To assess the safety and efficacy of treatment with belimumab in patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with background mycophenolate mofetil (MMF).In this 52-week, investigator-initiated, single-center, double-blind, placebo-controlled, pilot study, 20 patients with dcSSc recently started on MMF were randomized 1:1 to additionally receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety, efficacy, and differential gene expression.In the belimumab group, the median modified Rodnan skin thickness score (MRSS) decreased from 27 (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25) (P = 0.023). The median change in MRSS was -10 (IQR -13, -9) in the belimumab group and -3.0 (IQR -15, -1) in the placebo group (P = 0.411). There were no significant differences between the groups in the number of adverse events (AEs). A significant decrease in expression of B cell signaling and profibrotic genes and pathways was observed in patients with improved MRSS in the belimumab group but not in the placebo group.Patients in both treatment groups experienced significant improvements in MRSS. The median difference was greater in the belimumab group but did not achieve statistical significance in this small pilot study. AEs were similar between the groups. Changes in gene expression were consistent with mechanism of action and showed that clinical response to treatment with belimumab is associated with a significant decrease in profibrotic genes and pathways. Additional studies are needed to determine the role of belimumab in the treatment of dcSSc.
Abstract 20591: Vascular and Bleeding Complications in Nonagenarians Remain High in the Modern Era of PCI
Authors: Shawn X Li, Hannah I Chaudry, Bruce W Andrus, Theodore B Curran, Shelia M Conley, Nicholas I Buss, James T DeVries
Journal: Circulation (2016)

Introduction:  Despite a trend in modern PCI towards reduced bleeding and vascular complications, little is known about the absolute incidence of vascular complications in the very elderly. With older patients routinely being offered PCI, it is important to understand these risks to help guide decision making in this population.   Hypothesis:  Nonagenarians have higher vascular complications and bleeding than younger patients following PCI.   Methods:  The Dartmouth Dynamic Registry was queried for all PCI’s between 2000 and 2015. Patients were divided into 2 groups based on age (>89 and    Results:  Between 2000-2015, 16,395 patients under 90 years old and 175 nonagenarians underwent PCI (Table 1). In general, nonagenarians had fewer comorbid conditions than younger patients. More nonagenarians had transfemoral access versus radial access. Bleeding requiring transfusion was four-fold higher in nonagenarians and vascular complications were at least twice as likely when compared to younger patients (Table 2).   Conclusion:  The overall number of nonagenarians undergoing PCI remains small. However, nonagenarians have significantly higher rates of bleeding and vascular injury when compared to younger patients.
Phase II trial of bevacizumab in patients with surgery and radiation refractory progressive meningioma.
Authors: Sean Aaron Grimm, Priya Kumthekar, Marc C. Chamberlain, David Schiff, Patrick Y. Wen, Fabio Massaiti Iwamoto, David A. Reardon, Benjamin Purow, Jeffrey J. Raizer
Journal: Journal of Clinical Oncology (2015)

2055 Background: Systemic treatment options are limited for meningiomas that progress following surgery and radiotherapy. VEGF is associated with neovascularization, tumor growth, and edema in meningioma. This prospective phase II study was undertaken to determine the efficacy of bevacizumab (BEV), a VEGF ligand binding monoclonal antibody, in patients with progressive benign (BM), atypical (AM), and malignant meningioma (MM) as measured by median 6-month progression free survival (PFS-6). Secondary endpoints included median progression free survival (mPFS), median overall survival (mOS), and radiographic response rate. Methods: Patients with histologically confirmed BM, AM, or MM with radiographic progression were eligible. There was no limit on prior therapies. BEV was administered 10 mg/kg intravenously every two weeks. After 6 months of therapy, stable patients were eligible to switch to an every 3-week schedule of BEV (15 mg/kg). Clinical examination and imaging were performed every 4 and 8 weeks respectively for the first 6 months then every 6-12 weeks. Responses were graded using the Macdonald criteria. Results: 40 patients were treated: 15 BM, 22 AM, and 13 MM. Median KPS was 80. Median age was 54 (23-81) years. Median number of BEV infusions was 16 (2-62). Grade 3 toxicities included hypertension (10), proteinuria (2), hyponatremia (2), fatigue (1), bruising (1), nausea/vomiting (1), epistaxis (1), pancreatitis (1), perianal infection (1), ataxia (1), and thrombus/embolism (1). Grade 4 toxicities included anemia (1), wound infection (1), elevated lipase (1), and weakness (1). Best responses were stable disease (BM: 100%; AM: 85%; MM: 82%); partial response (BM: 0%; AM: 5%; MM: 0%); progressive disease (BM: 0%; AM: 10%; MM:18%). PFS-6, mPFS, and mOS were 87%, 22.5 months, 35.6 months for BM; 77%, 15.3 months, not reached for AM, and 46%, 3.7 months, 12.4 months for MM. Conclusions: Treatment of progressive meningioma with BEV commonly leads to disease stabilization. The results are promising compared to a contemporary meta-analysis, in which PFS6 was 29% and 27% for BM and AM/MM respectively, but require confirmation. Toxicity was minimal and expected for BEV notwithstanding prolonged drug exposure. Clinical trial information: NCT01125046.
Abstract #926: Pharmacokinetics and safety evaluation of chamomile
Authors: Janmejai Srivastava, Sanjay Gupta
Journal: Cancer Research (2009)

Chamomile is the oldest, best known and practiced plant in traditional medicine for its diversified healing and curative properties. In recent times it became more popular as tea and approximately million cups of chamomile tea is consumed everyday throughout the world. Earlier, we demonstrated the anticancer properties of chamomile extracts against various human cancer cell lines (J Agri Food Chem 55:9470-78, 2007). Chamomile extract contains 50-60% apigenin-7-O-glucoside (A7G) along with 1-1.2% free apigenin. Further development of chamomile as anticancer agent requires in vivo pharmacokinetic and toxicity evaluation. We preceded studying safety, stability, bio-distribution and systemic clearance of dried methanolic extract of chamomile in male albino mice. 22-25 g male albino mice received per oral supplementation of chamomile at single doses of 5, 10, 15, 20 and 25g/kg body weight suspended in 0.2ml of a vehicle consisting of 0.5% methyl cellulose and 0.025% Tween 20. Animals were kept under close observation for 24h for any adverse reaction and/or mortality. The maximum tolerable dose was recorded to be >25g/kg body weight, and the LD50 determined to be15g/kg body weight. During observation no apparent adverse symptoms like diarrhea, vomiting, lachrymal secretion, irritability, apathy to food and water were observed. Safety evaluations during long term chamomile supplementation with a dose of 10mg/mouse/day for 75 days exhibited no significant changes in the body weight of these mice, compared to control group. Histopathological enumeration of liver, kidney, spleen of chamomile supplemented animals did not exhibit any lesions or cellular infiltrations. In another pharmacokinetic study, per oral administration of 50mg/mouse chamomile extract exhibited the presence of A7G as early as 3 h in the plasma which peaked at 24h post-administration. A7G was detected in the liver, spleen and kidneys as early as 24h post administration and was traced up to 48h in the liver and intestine. Surprisingly, prostate showed a substantial peak of apigenin at 48h along with A7G peak at 72h post chamomile supplementation. Biological and physiochemical stability of chamomile extract evaluated at -20 degree centigrade, 4 degree centigrade and room temperature for 120 days demonstrated it to be highly stable in aqueous medium. Furthermore, ex-vivo experiments conducted on mouse intestine and liver demonstrated the conversion of A7G to apigenin. Taken together, the abundance of plant availability, with promising anticancer efficacy, accompanied by minimal toxicity will prompt us to move forward with the developmental work to establish chamomile as an anticancer agent.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 926.
Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of Uterine Leiomyoma
Authors: Xin Wu, Vanida A. Serna, Justin Thomas, Wenan Qiang, Michael L. Blumenfeld, Takeshi Kurita
Journal: Cancer Research (2017)

Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here, we report the elucidation of the biological characteristics of the two most prevalent uterine leiomyoma subtypes, MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas. Because each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-uterine leiomyoma were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF). Paradoxically, TAF carried no mutations in MED12, suggesting an interaction between SMC and TAF to coordinate their growth. The higher amount of extracellular matrix in MED12-LM than HMGA2-LM was partially due to the high concentration of collagen-producing TAF. SMC growth in a xenograft assay was driven by progesterone in both uterine leiomyoma subtypes. In contrast, TAF in MED12-LM proliferated in response to estradiol, whereas progesterone had no effect. The high concentration of estrogen-responsive TAF in MED12-LM explains the inconsistent discoveries between in vivo and in vitro studies on the mitogenic effect of estrogen and raises questions regarding the accuracy of previous studies utilizing MED12-LM cell culture. In addition, the differential effects of estradiol and progesterone on these uterine leiomyoma subtypes emphasize the importance of subtypes and genotypes in designing nonsurgical therapeutic strategies for uterine leiomyoma. Cancer Res; 77(24); 6891-901. ©2017 AACR.
[18F]fluorothymidine PET Informs the Synergistic Efficacy of Capecitabine and Trifluridine/Tipiracil in Colon Cancer
Authors: Seog-Young Kim, Jin Hwa Jung, Haeng Jung Lee, Hyunsu Soh, Sang Ju Lee, Seung Jun Oh, Sun Young Chae, Jai Hyuen Lee, Seung Jin Lee, Yong Sang Hong, Tae Won Kim, Dae Hyuk Moon
Journal: Cancer Research (2017)

Abstract In cancer therapy, enhanced thymidine uptake by the salvage pathway can bypass dTMP depletion, thereby conferring resistance to thymidylate synthase inhibition. We investigated whether sequential combination therapy of capecitabine and trifluridine/tipiracil (TAS-102) could synergistically enhance antitumor efficacy in colon cancer xenograft models. We also examined 3'-deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET as a means to predict therapeutic response to a sequential combination of capecitabine and trifluridine/tipiracil. [3H]FLT uptake after 5-fluorouracil treatment in vitro and [18F]FLT uptake after capecitabine (360 mg/kg/day) in athymic nude mice (Balb/c-nu) with xenografts (n = 10–12 per group) were measured using eight human colon cancer cell lines. We determined the synergistic effects of sequential combinations of 5-fluorouracil and trifluridine in vitro as well as the sequential combination of oral capecitabine (30–360 mg/kg) and trifluridine/tipiracil (trifluridine 75 or 150 mg/kg with tipiracil) in six xenograft models (n = 6–10 per group). We observed significant increases in [3H]FLT uptake in all cell lines and [18F]FLT uptake in five xenograft models after 5-fluorouracil and capecitabine treatment, respectively. Increased [18F]FLT uptake after capecitabine followed by extinction of uptake correlated strongly with tumor growth inhibition (ρ = −0.81, P = 0.02). The effects of these combinations were synergistic in vitro. A synergy for sequential capecitabine and trifluridine/tipiracil was found only in mouse xenograft models showing increased [18F]FLT uptake after capecitabine. Our results suggest that the sequential combination of capecitabine and trifluridine/tipiracil is synergistic in tumors with an activated salvage pathway after capecitabine treatment in mice, and [18F]FLT PET imaging may predict the response to capecitabine and the synergistic antitumor efficacy of a sequential combination of capecitabine and trifluridine/tipiracil. Cancer Res; 77(24); 7120–30. ©2017 AACR.
Phase II study of bavituximab plus docetaxel in patients with locally advanced or metastatic breast cancer
Authors: D. Tabagari, G. Nemsadze, M. Jincharadze, M. Janjalia, J. S. Shan
Journal: Journal of Clinical Oncology (2009)

3005 Background: Phosphatidylserine (PS) is an anionic phospholipid normally present on the inside surface of cell membranes. PS becomes exposed on the outside surface of tumor endolethial cells. Bavituximab (B) is a novel anti-PS monoclonal antibody and has demonstrated preclinical synergistic antitumor activity when used in combination with docetaxel. Methods: This Simon 2-stage trial is designed to determine the overall response rate (CR+PR) in patients with locally advanced or metastatic breast cancer to a combination of weekly bavituximab (3 mg/kg) plus docetaxel (35 mg/m2) on days 1, 8, 15 of a 28-day cycle for up to 6 cycles. Following completion of docetaxel, weekly bavituximab is continued until progression or toxicity. If ≥ 6 responses are observed in the 15 pt enrolled to Stage A, an additional 31 pts will be enrolled to Stage B. Secondary objectives include time to tumor progression, duration of response, overall survival, and safety. Results: Data are available for the 15 female pts enrolled in Stage A of the trial. Median age was 49 years;13 had stage IV and 2 had recurrent/progressive stage III breast cancer at study entry. All patients received prior chemotherapy, 13 had surgery, 7 had hormone therapy and 5 had prior radiotherapy. Patients received a median of 6 cycles of treatment. All patients reported at least one AE, to date. The most common AEs (regardless of severity or causality) were alopecia, epistaxis, fatigue, back pain, diarrhea, nasal dryness, infusion related reaction, arthralgia, pyrexia, stomatitis and nail bed bleeding. Grade 3 drug-related AEs were back pain, headache, DVT (discontinued study treatment at week 3) and chest pain (SAE) starting during a docetaxel infusion, which recurred after completion of bavituximab, reported in one patient each. Using RECIST, the overall response rate in these 15 pt is 67% (95% confidence interval, 38–88%) for the intent-to-treat group and 71% (95% CI, 42–92%) for the 14 evaluable patients. All responses were confirmed at least 4 weeks later. Conclusions: Bavituximab plus docetaxel achieved an encouraging response rate in advanced/metastatic breast cancer in Stage A of this study. Enrollment in Stage B of the trial is expected to be completed with preliminary results available by the annual meeting. [Table: see text]
The current agonists and positive allosteric modulators of α 7 nAChR for CNS indications in clinical trials
Authors: Taoyi Yang, Ting Xiao, Qi Sun, Kewei Wang
Journal: Acta Pharmaceutica Sinica B (2017)

The alpha-7 nicotinic acetylcholine receptor (α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.
TCT-498 Clinical characteristics, predictors of complications and successful recanalization in patients with coronary chronic occlusions undergoing percutaneous revascularization: Results from the multicenter Iberian Registry
Authors: Ignacio Amat-Santos, Victoria Martin Yuste, Jose Antonio Fernandez Diaz, Javier Martin-Moreiras, Pablo Salinas, Beatriz Vaquerizo, Laura Pardo, Julio Núñez Villota, Fernando Rivero, Juan Caballero-Borrego, Jose de la Torre Hernandez, Itziar Gomez
Journal: Journal of the American College of Cardiology (2017)
TCT-417 Comparative efficacy of two paclitaxel-coated balloons with different excipient coatings in patients with coronary in-stent restenosis
Authors: Roisin Colleran, Sebastian Kufner, Michael Joner, Janika Bohner, Felix Altevogt, Franz-Josef Neumann, Christian Valina, Mohamed Abdel-Wahab, Gert Richardt, Salvatore Cassese, Tareq Ibrahim, Heribert Schunkert, Karl-Ludwig Laugwitz, Adnan Kastrati, Robert Byrne
Journal: Journal of the American College of Cardiology (2017)
Cas groupés de Leptospirose à Rochefort, juin 2001
Authors: A Perra, V Servas, G Terrier, D Postic, G Baranton, G André-Fontaine, V Vaillant, I Capek
Journal: Eurosurveillance (2002)

Cinq cas groupes de leptospirose ont ete diagnostiques pres de Rochefort en juin 2001, chez des adolescents qui se sont baignes dans le canal Genouille. Les signes cliniques incluaient fievre, cephalees, douleurs abdominales et vomissements, frissons et myalgies. Trois des cas ont ete confirmes par PCR et serologie. La duree moyenne cumulee des baignades etait significativement superieure chez les cas (23,8 heures) compares aux temoins (14,4 heures). Aucun autre facteur de risque particulier n’a ete mis en evidence. L’enquete environnementale a revele la presence de rongeurs excreteurs de leptospires aux alentours du lieu de baignade. La prevalence des rongeurs seropositifs etait de 30,8% tous antigenes confondus, avec une predominance pour le serogroupe L. icterohaemorrhagiae (23,1%).
Image Gallery: Unilaterally dominant acrokeratoelastoidosis (punctate palmoplantar keratoderma type 3)
Authors: T. Taki, Y. Ogawa, A. Sakakibara, M. Kono, M. Akiyama
Journal: British Journal of Dermatology (2017)

Funding sources: no external funding. Conflicts of interest: none to declare. A 59‐year‐old man presented with dozens of asymptomatic, depressed keratotic papules on his hands and feet, which were refractory to treatments of a urea‐containing cream and cryotherapy. These papules were strikingly more numerous on the right side (Fig. 1a–f). He had no family history. No AAGAB mutation was found. A skin biopsy showed thick orthohyperkeratosis (Fig. 1g: haematoxylin and eosin stain) and degeneration of the elastic fibres (Fig. 1h: orcein stain). Although patients with unilateral acrokeratoelastoidosis have been reported,1,2 the present case is unique in that the lesions are distributed bilaterally but show marked predominance in one side of the body.
Prévalence d’anticorps anti-hépatite A chez des handicapés mentaux en Irlande
Authors: G Sayers, S Dooley, A Staines, J Lane, L Thornton, M Staines, S Brennan, P Kelly, F Finlay
Journal: Eurosurveillance (2007)

L’objectif de l’article suivant est de determiner la prevalence des anticorps anti-VHA (virus de l’hepatite A) et les facteurs de risque de cette infection chez des patients sejournant dans trois services d’handicapes mentaux de Dublin (Irlande) par une etude croisee. Six-cent trente-six personnes âgees de quatre et 78 ans et suivies dans l’un des trois services de sante mentale, ont participe a cette etude. L’unite de mesure principale a ete la mesure des anticorps anti-VHA (IgG) dans des prelevements salivaires par la methode de capture d’anticorps EIA (enzyme immunoassay). Les informations sur les facteurs de risque ont ete obtenues par le biais d’un questionnaire extrait du dossier medical personnel.