tbuckley/cabot-search huggingface dataset:
Safe Use of Therapeutic-Dose Oral Isotretinoin in Patients With a History of Pseudotumor Cerebri
Authors: Suzanne J. Tintle, Julie C. Harper, Guy F. Webster, Grace K. Kim, Diane M. Thiboutot
Journal: JAMA Dermatology (2015)

tissue culture, and from a papule for hematoxylin-eosin staining.Within an hour of obtaining the specimens, the pathologist reported frozen section findings of small organisms within the vasculature suggestive of either fungal spores, likely histoplasmosis, or staphylococcal bacteria.Permanent sections revealed a large neutrophilic pustule with inflammation extending throughout the dermis and prominent necrosis with basophilic structures filling necrotic vascular spaces (Figure 2A).Tissue Gram staining confirmed gram-positive cocci in the vessels (Figure 2B).Tissue culture, blood culture, bronchial washings, and fluid from bilateral empyemas all grew CA-MRSA.Results from transthoracic echocardiogram and bone scans were negative.Magnetic resonance images of the brain showed multifocal lesions, likely septic emboli.Findings from workup for possible immunodeficiency were negative.The patient was sent to a rehabilitation facility to complete a 6-week course of intravenous vancomycin.Discussion | The original classifications of CA-MRSA and hospital-acquired MRSA are no longer distinct: CA-MRSA now causes infections in health care settings, and hospitalacquired MRSA spreads in the community. 1In a study on disseminated Staphylococcus in children, MRSA was the causative agent in all cases.Children aged 5 to 12 years were most vulnerable, and trauma was found to be a common precipitating factor. 2 Septic vasculitis caused by septicemia from Staphylococci is an immune-complex negative, small-vessel neutrophilic vasculitis. 3Clinical lesions of septic vasculitis are characterized by retiform purpura, petechiae and ecchymoses, vesiculopustules, hemorrhagic bullae, and ulceration. 4n cases of septic emboli without evidence of vasculitis, some prefer the term septic vasculopathy.One study 5 compared 32 patients with bacterial sepsis, cutaneous lesions, and biopsy-proven septic vasculopathy.Cutaneous lesions were an early finding of sepsis in most patients (91%; n = 29).Most cases (n = 18) involved the development of lesions simultaneously or within the first 24 hours of sepsis that were disseminated rather than localized.Most lesions presented as purpuric papules and plaques, followed by petechiae, vesicles and bullae, pustules, distal ischemia, and nodules. 4Septic vasculopathy had a mortality rate of 20% in this study, 5 making early recognition and treatment essential.In addition to cutaneous findings, staphylococcal sepsis can involve the lung, heart, kidneys, brain, bone, and joints, 6 and it is important to evaluate for these potential sites of involvement.As this case report highlights, consulting dermatologists can play a role in identifying disseminated infections by recognizing the diverse skin manifestations and performing appropriate biopsies for analysis by frozen section, permanent section, and tissue culture.
Multicenter, randomized phase III study of adjuvant chemotherapy for axillary positive breast cancer (APBC) comparing 6 cycles (cy) of FEC vs 4 cy of FEC followed by 8 weekly paclitaxel (T) administrations: Safety analysis of GEICAM 9906 trial
Authors: A. Rodriguez-Lescure, M. Martin, A. Ruiz, E. Alba, L. Calvo, M. Ruiz-Borrego, B. Munarriz, J. M. Lopez-Vega, C. A. Rodriguez
Journal: Journal of Clinical Oncology (2004)

596 Background: Role of weekly T in adjuvant treatment of breast cancer is presently under evaluation in several studies like GEICAM 9906. Objective: This study compared differences in toxicity profile between arms. Methods: Patients (pt) with operable APBC, age: 18–70, Karnofsky ≥ 90, adequate bone marrow, renal and hepatic function, were randomized to receive 6 FEC cy (Fluorouracil 600 mg/m2 [F], Epirubicin 90 mg/m2 [E], Cyclophosphamide 600 mg/m2 [C]) day 1 every 3 weeks (Arm A) or 4 cy of the same schedule followed by 8 weekly doses of T 100 mg/m2 (Arm B). 1.249 pt were recruited in 30 months. 633 pt in arm A and 610 pt in arm B were analyzed for toxicity. Study was conducted as per GCP/ICH with 100% source data verification. Results: Median age was 50.4 years (Arm A) vs 50.2 (Arm B). Median number of FEC cy (A vs B) and T doses were 6 (range 1–6) vs 4 (range 1–4) and 8 (range 1–8), respectively. No statistical differences were found between relative dose-intensities (RDI) of E (98.8 vs 98.8%) and C (99.1 vs 99.1%). Median RDI of T was 99.5%. FEC administration: febrile neutropenia (FN) rate was statistically higher in arm A (9.3 vs 5.1% pt; p=0.004). Statistical differences were observed in (% pt): G3/4 neutropenia (30 vs 20.5%), G3 leukopenia (10.6 vs 7.4%) and G3 mucositis (5.4 vs 3%). No statistical differences were observed in (% pt): G3 nausea (5.8 vs 5.4%) and G3 vomiting (9.6 vs 7.4%). T administration: 0.5% of pt had FN. G3/4 neutropenia/ leukopenia occurred in 12.1% of pt. G2 neuropathy (sensory) and asthenia were present in 21.3 and 23.4% of pt, respectively. One sudden death (0.2%) occurred in Am A and 4 (0.7%) in arm B (2 of them late events) (p=0.294). Conclusions: Analysis of 1243 pt suggests treatment with FEC x 4 followed by T is associated with less severe neutropenia and FN events, but induces more peripheral neuropathy and asthenia. No significant financial relationships to disclose.
Problems with study on secondhand smoke and children’s tooth enamel
Authors: Hayato Yamana, Sachiko Ono, Hideo Yasunaga
Journal: BMJ (2015)

Using data from municipal health check-ups in Japan, Tanaka and colleagues found an association between secondhand smoke and dental caries in children.1 However, several factors should be considered.

The authors used numerous variables to calculate the propensity score—the probability of an infant being exposed to secondhand smoke at 4 months. However, this model was inadequate for distinguishing the exposed from the unexposed. The discriminatory ability of the logistic regression model …
Abstract MP71: The Association of Vascular Endothelial Tone and Function by Digital Peripheral Arterial Tonometry with Left Ventricular Structure and Function by Cardiac MRI
Authors: Avnish Tripathi, Solomon K Musani, Emelia Benjamin, Koby Sheffy, Ramachandran S Vasan, Herman A Taylor, Ervin R Fox
Journal: Circulation (2014)

Objectives: Higher vascular endothelial tone and impaired endothelial function as assessed by digital peripheral arterial tonometry (PAT) have been associated with increased cardiovascular morbidity and mortality. However, their relation to left ventricular mass (LVM), geometry and systolic function is not known. We examined this relation in a community-based cohort of African Americans. Methods: This study included participants of the Jackson Heart Study who had digital PAT and cardiac magnetic resonance imaging (CMRI) evaluated between 2007- 2013. LVM was adjusted for body size by indexing to height2.7 (LVMI). LVMI was log-transformed within sex and used in the analyses. Age- and sex-adjusted Pearson’s correlations were used to relate baseline pulse amplitude (BPA) and reactive hyperemia index (RHI) (markers of endothelial tone and endothelial function respectively) to LVMI, LV systolic and diastolic volumes (LVSV and LVDV), and stroke volume (SV) by CMRI. Using multivariable adjusted stepwise linear regression with age and sex forced into the model, the relation of PAT parameters to CMRI LV structure and function was evaluated adjusting for body mass index, systolic blood pressure, diabetes mellitus, and total cholesterol: HDL ratio. Results: The study population consisted of 440 participants [mean age 59 ± 10 years, 263 (60%) women]. Higher BPA (increased endothelial tone) was significantly and positively correlated with log-LVMI (0.272; p &lt;0.001). Higher RHI (improved endothelial function) was significantly and negatively correlated with log-LVMI (-0.114; p &lt;0.018). In age-sex adjusted models both higher BPA (β = 0.064, SE = 0.011, p &lt; 0.001) and lower RHI (β = -0.069, SE = 0.029, p = 0.018) were significantly related to higher log-LVMI. In the multivariable analyses higher BPA (β = 0.022, SE = 0.010, p = 0.023) but not RHI (p &gt; 0.05) was significantly associated with higher log-LVMI. BPA explained approximately 11% of the total variation of log-LVMI. PAT parameters were not significantly associated with LV volumes or cardiac function parameters in the multivariable analysis. Conclusions: In a community-based sample of African Americans higher endothelial tone measured by digital PAT was significantly associated with higher LVMI by CMRI after adjusting for traditional risk factors. Better endothelial function was correlated with lower LVMI and was significantly associated with lower LVMI in the age-sex adjusted model but not the fully adjusted model. These findings suggest that endothelial tone may be one of the potential determinants of LV hypertrophy in African Americans.
Abstract 12363: Tracking of Central and Upper Limb Systolic Pressure Over the Normal Human Lifespan
Authors: Audrey Adji, Michael F O’Rourke, Alberto Avolio
Journal: Circulation (2014)

Recent studies address the tracking of brachial cuff Systolic Pressure (SP) over segments of life and separately in pediatric populations to age 18 and adult populations from age 25 to 75+ years. There has been no attempt to link the two populations and sporadic studies only on central aortic pressure over long spans, and no explanation on the curious changes in brachial pressures in childhood, adolescence and young adult life. In this study, we attempt to describe changes in brachial and central aortic SP over the entire life span, to account for the changes and seek their cause and underlying mechanism. We considered 2 studies of brachial SP in children [1,2], and 3 in adults [3-5], linking pediatric and adult populations with another [6], and children with neonates in another [7]. Central aortic SP was generated by subtracting estimated amplification at different ages from the peak of upper limb SP using the methods of two commercial systems (use of transfer function in adults [5], SphygmoCor, and dete...
Reduced and Full-Preparation CT Colonography, Fecal Immunochemical Test, and Colonoscopy for Population Screening of Colorectal Cancer: A Randomized Trial
Authors: Lapo Sali, Mario Mascalchi, Massimo Falchini, Leonardo Ventura, Francesca Carozzi, Guido Castiglione, Silvia Delsanto, Beatrice Mallardi, Paola Mantellini, Stefano Milani, Marco Zappa, Grazia Grazzini
Journal: JNCI Journal of the National Cancer Institute (2015)

Population screening for colorectal cancer (CRC) is widely adopted, but the preferred strategy is still under debate. We aimed to compare reduced (r-CTC) and full cathartic preparation CT colonography (f-CTC), fecal immunochemical test (FIT), and optical colonoscopy (OC) as primary screening tests for CRC.
Combination therapy of an IL-15 superagonist complex, ALT-803, and a tumor targeting monoclonal antibody promotes direct antitumor activity and protective vaccinal effect in a syngenic mouse melanoma model
Authors: Xiaoyue Chen, Bai Liu, Kaiping Han, Lin Kong, Terra Noel, Emily K Jeng, Sarah Alter, Mark Rubinstein, Peter R Rhode, Hing C Wong
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Cytokine-based and antibody-targeted immunotherapies have both been important approaches in the treatment of malignant cancers. However, combinational therapies of cytokines and tumor-targeting antibodies remain to be further explored, especially in advanced solid tumors. In this
Abstract 19549: Aging Mice Maintain LV Function and Exhibit Less Remodeling, Dilation and Mortality in Pressure Overload Cardiomyopathy via Adaptive Extracellular Matrix Changes and Induction of Autophagy
Authors: Brianna M Coulter, Xiaoyong Geng, Joy Hwang, Jiangin Ye, Rich Sievers, Yerem Yeghiazarians, Randall Lee, Andrew Boyle
Journal: Circulation (2014)

Introduction:  Prior studies suggesting worse outcomes with aging after transverse aortic constriction (TAC) have not corrected for differences in aortic size between young and aging mice. Creating the same surgical TAC in young and aging mice causes a disproportionately greater degree of constriction in aging mice, resulting in bias against the aging mice.   Methods and Results:  Ascending aortic cross-sectional area (CSA) was 28% larger in aging mice (18-month old; 2.22±0.22 mm2) than in young mice (3-month old; 1.73±0.13 mm2:p   Conclusions:  Young mice exhibit exaggerated LV remodeling, inability to augment systolic function and increased mortality following TAC compared to aging mice. Greater baseline fibrosis or induction of adaptive cellular and matrix changes may protect the aging mice from LV dilation and death.
Transforming Growth Factor-β Is a Potent Inhibitor of Extracellular Matrix Degradation by Cultured Human Mesangial Cells
Authors: WILLIAM H. BARICOS, SHIRLEY L. CORTEZ, MICHAEL DEBOISBLANC, SHI XIN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Accumulation of the glomerular extracellular matrix (ECM) is a pivotal event in the progression from acute glomerular injury to end-stage renal disease. Although enhanced ECM synthesis has been demonstrated to contribute to ECM accumulation, the role of decreased ECM degradation is largely unknown. It was previously shown that glomerular ECM degradation is mediated by a plasminogen activator (PA)/plasmin/matrix metalloproteinase 2 (MMP-2) cascade. However, little information is available regarding the factors that regulate the activity of this degradative cascade in normal or pathologic states. Transforming growth factor-β1 (TGF-β1) is shown here to be a potent inhibitor of ECM degradation by cultured human mesangial cells. Using human mesangial cells grown on thin films of 125 I-labeled Matrigel, dose-dependent inhibition of ECM degradation in the presence of TGF-β1 was observed, reaching &gt;90% inhibition with 0.4 ng/ml TGF-β1. Addition of anti-TGF-β antibodies (4 μg/ml) in the absence of exogenous TGF-β increased ECM degradation (1.8 ± 0.2-fold versus controls, P &lt; 0.05). In contrast, platelet-derived growth factor, at concentrations up to 10 ng/ml, had no effect on ECM degradation. TGF-β completely blocked the conversion of plasminogen to plasmin and markedly reduced the conversion of latent MMP-2 to active MMP-2. TGF-β did not significantly alter the levels of tissue PA, total MMP-2, or tissue inhibitor of metalloproteinase-1, but did increase the levels of PA inhibitor-1 (1.8-fold, P &lt; 0.05), the major physiologic inhibitor of PA. These data document that TGF-β is a potent inhibitor of ECM degradation by cultured human mesangial cells, and they suggest that decreased mesangial matrix degradation, caused by TGF-β-mediated decreases in the activity of the PA/plasmin/MMP-2 cascade, may contribute to the glomerular matrix accumulation that occurs in progressive renal disease.
Stimulation of Tumor Induction by an Inhibitor of Cell Glycolysis
Authors: Herbert G. Crabtree
Journal: Cancer Research (1941)

In another communication (3) evidence was given that substances which reversibly inhibit the glycolytic process of cells also inhibit the rate of tumor induction by chemical carcinogens. By using a series of nonhydrolyzing chlor-compounds soluble in fat and water, it was shown that their power of inhibiting the rate of glycolysis ran parallel to their power of inhibiting the rate of tumor induction in mice by 3,4-benzpyrene and x,2,5,6-dibenzanthracene. The most potent of the substances used was mono-chloracetone, and this substance has been used exclusively in the experimenis described in this paper. In the experiments already reported this chlorcompound had been applied in a concentration and at time intervals arbitrarily chosen; viz., o. 3 per cent thrice weekly. The question arose whether the degree of inhibition of the rate of tumor induction was a function of these factors and might be modified by their variation. It is certainly true that higher concentrations increase the rate of glycolytic checking in vitro, and, if pushed too far, inflict irreversible damage on cells, but such simple relations could not be assumed for the inhibitory effect on tumor induction in vivo. In fact, Experiments I and II show that higher concentrations and more frequent applications of the chlor-compound tend to annul the inhibitory effect, and even suggest that some slight degree of stimulation can be effected. More clear-cut evidence for a stimulatory effect is given in Experiments III and IV, in which the chlorcompound was applied after discontinuing a preliminary treatment with the carcinogen. Considering the experiments as a whole, it has been demonstrated that the same substance, a simple inhibitor of cell glycolysis, can, under differentexperimental conditions, either retard or stimulate the rate of ininduction of tumors. Experiment L -E f f ec t o/ increased amounts o/ mono-chloracetone on the rate o/ tumor induct ion.-One hundred and twenty mice of mixed stock were epilated in the interscapular region 2 days before the experiment was begun, but not subsequently. Sixty of these mice were treated twice weekly with o. 3 per cent 3,4-benzpyrene and 6o similarly with o.[ per
Influence of skin color in the development of erlotinib-induced rash: A report from the SERIES clinic
Authors: S. E. Lai, L. Minnelly, P. O'Keeffe, A. Rademaker, J. Patel, C. L. Bennett, M. E. Lacouture
Journal: Journal of Clinical Oncology (2007)

9127 Background: A papulopustular reaction occurs in 68–75% of patients undergoing treatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib, necessitating dose modification or interruption in 14% and 12% of patients, respectively. Based on preclinical data showing that EGFR inhibition in the skin may potentiate the harmful effects of ultraviolet radiation (UVR) exposure, sun protection is generally advocated. Because the level of melanin, a biological pigment in the epidermis, correlates with increased intrinsic protection against the harmful effects of UVR, we hypothesized that lower levels of skin pigmentation would be associated with higher frequency and severity of erlotinib rash. Methods: We conducted a retrospective chart review of 42 patients undergoing erlotinib therapy to characterize the relationship between skin sensitivity to UVR and severity of EGFR inhibitor rash. Skin sensitivity to UVR was categorized using the Fitzpatrick skin phototype (SPT) classification scheme, and individuals were grouped in phototypes I/II, III/IV, and V/VI. Grading of rash was performed using the NCI-CTC criteria version 2.0 and 3.0. Results: Patients with SPT I/II developed rash grades 0 (6%), 1/2 (31%), and 3/4 (63%), whereas patients with skin phototype III/IV had rash grade 0 (26%), 1/2 (68%), and 3/4 (5%). Patients with SPT V/VI had rash grade 0 (43%), 1/2 (57%), and 3/4 (0%). Lower skin phototypes had higher grade rash (p=0.0006 by Fisher's exact test). Conclusions: Management of cutaneous side effects from EGFR inhibitors is important in order to achieve maximal patient compliance and anti-cancer therapeutic benefit, and the correlation between rash and survival underscores maintaining patients on therapy. The results of this study suggest that SPT may be an independent predictive factor for EGFR inhibitor-induced skin toxicities, thus impacting pre-therapy counseling and early intervention. [Table: see text]
Favorable Impact on LDL Particle Size in Response to Treatment With Pioglitazone is Associated With Less Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes
Authors: Preethi Mani, Kiyoko Uno, Julie St. John, Stuart Kupfer, Alfonso Perez, E. Murat Tuzcu, Stanley L. Hazen, Steven E. Nissen, Stephen J. Nicholls
Journal: Journal of the American College of Cardiology (2015)
Tissue factor-targeted immunotherapy of melanoma and triple negative breast cancer using a second generation ICON
Authors: Zhiwei Hu, Elizabeth McMichael, Amanda Campbell, Cheryl A London, William E Carson
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Hu and colleagues have identified tissue factor (TF-the primary initiator of coagulation and a modulator of angiogenesis) as a common yet specific biomarker and therapeutic target on a variety of cancer cells and angiogenic tumor vascular endothelial cells [1-3]. He has co-
Why does pre-clinical success in cardioprotection fail at the bedside?
Authors: Isabella Tritto, Giuseppe Ambrosio
Journal: Cardiovascular Research (2015)

This editorial refers to ‘Translational failure of anti-inflammatory compounds for myocardial infarction: a meta-analysis of large animal models’ by G.P.J. van Hout et al. , pp. 240–248. 

Translating findings from experimental studies into effective treatments for patients is never an easy task. Hurdles are particularly high when one tries to reproduce at the bedside the positive effects of cardioprotective interventions obtained in animal models of ischaemia/reperfusion injury. Despite the wealth of successful cardioprotective interventions in animals, none of the subsequent clinical trials has yet fulfilled this goal or changed clinical practice. Some small ‘proof-of-concept’ clinical studies have shown encouraging results, only to be negated later by larger trials.1

Controversy and frustration are evident in the reviews2,3 and position papers4–6 that have been written on this topic; however, these documents have done little to allay doubts. One possible explanation for the difficulty in translating pre-clinical findings into clinically useful therapies may have to do with the design of experimental studies. Van Hout et al .7 address this matter by undertaking a meta-analysis of the experimental studies, i.e. by carrying out a systematic review of the available evidence as it is typically done in the clinical settings. By using this approach, they point out some potential weaknesses …
Phase II study of RAD001 (everolimus) in previously treated small cell lung cancer (SCLC)
Authors: A. P. Kotsakis, A. Tarhini, D. Petro, R. Flaugh, G. Vallabhaneni, C. P. Belani, D. Friedland, A. Argiris
Journal: Journal of Clinical Oncology (2009)

8107 Background: Everolimus (E) is an oral inhibitor of mammalian target of rapamycin (mTOR), a novel target for anti-cancer therapy that plays a central role in the PI3K/AKT signaling pathway and other pathways that mediate tumor growth, proliferation, and angiogenesis. E has shown preclinical activity in SCLC cell lines and xenograft models. Methods: Eligibility included SCLC with disease progression after up to 2 prior chemotherapy regimens, ECOG performance status (PS) 0–2, and adequate bone marrow, liver, and kidney function. Patients (pts) were treated with E 10 mg, orally, once daily. Primary endpoint was the disease control rate (DCR), i.e. complete response (CR), partial response (PR) and stable disease (SD), after 2 cycles of E (6 weeks) in pts who received at least 1 cycle. A 2-stage design was followed. PI3K/AKT signaling pathway molecular biomarkers (AKT, pAKT, PTEN, P-S6, p-4E- BP1) will be evaluated on baseline tumor tissue. Results: 40 pts were enrolled; 14 males/26 females; median age 64 years (44–80); PS 0: 17, PS 1: 23; prior chemotherapy status: 1 prior regimen/sensitive relapse (i.e. relapse &gt;60 days from completion of first-line chemotherapy): 23 pts; 1 prior regimen/refractory: 4 pts; 2 prior regimens: 13 pts. 28 pts (70%) received ≥ 2 cycles of E, 7 (18%) 1 cycle and 5 (12%) did not complete the first cycle of E due to adverse events or early progression. Best response in 35 evaluable patients: 1 (3%) PR, 8 (23%) SD and 26 (74%) progression; DCR at 6 weeks was 26% with a duration of disease control of 2.7–6.3 months; median progression-free survival 1.4 months; and median overall survival 5.5 months. No grade 4 toxicity was seen. Grade 3 toxicities included thrombocytopenia (2), neutropenia (2), infection (1), pneumonitis (1), fatigue (1), elevated transaminases (1), hyperglycemia (1), diarrhea (1), and acute renal failure due to dehydration from diarrhea and poor oral intake (1). Conclusions: E is well tolerated but has limited single-agent antitumor activity in unselected patients with pretreated SCLC. [Table: see text]