tbuckley/cabot-search huggingface dataset:
NICE calls for more research on ELISA tests for Crohn’s disease
Authors: Jacqui Wise
Journal: BMJ (2016)

Enzyme linked immunosorbent assay (ELISA) kits show real promise in guiding treatment for people with Crohn’s disease, but the National Institute for Health and Care Excellence (NICE) warns that evidence is insufficient to recommend their routine use in the NHS.1

Tumour necrosis factor alpha (TNF-α) inhibitors, such as infliximab and adalimumab, help to stop inflammatory responses in the gut that are characteristic of Crohn’s disease. Although TNF-α inhibitors can help many people with Crohn’s, some do …
High-Dose Chemotherapy for Breast Cancer: “How Do You Know?”
Authors: Larry Norton
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.11.2769 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11387346 High-Dose Chemotherapy for Breast Cancer: "How Do You Know?" Larry Norton, MDxLarry NortonSearch for articles by this author https://doi.org/10.1200/JCO.2001.19.11.2769 Full Text PDF Figures and Tables "High-Dose Chemotherapy for Breast Cancer: "How Do You Know?"." Journal of Clinical Oncology, 19(11), pp. 2769–2770© 2001 by American Society of Clinical Oncology
Abstract 18830: Increase in Platelet Reactivity After Red Blood Cell Transfusion in Coronary and Non-coronary Patients: Results from the Transfusion-2 Study
Authors: Johanne Silvain, Jeremie Abtan, Rejane Martin, Mathieu Kerneis, Stephen A O'Connor, Delphine Brugier, Olivier Barthelemy, Farzin Beygui, Jean-Philippe Collet, Gilles Montalescot
Journal: Circulation (2012)

BACKGROUND: Red blood cell (RBC) transfusion increases platelet activation and aggregation in vitro in healthy volunteers. This provides a possible mechanism for the increase in recurrent ischemic events and mortality reported after RBC transfusion in acute coronary syndrome (ACS) patients. The aim of the study was to replicate these findings in coronary and non-coronary patients exposed to RBC transfusion. METHODS: Platelet reactivity was measured before and 12 hours after RBC transfusion using light transmission aggregometry with four different agonists and Vasodilatator-Stimulated Phosphoprotein Platelet Reactivity Index (VASP-PRI) by flow cytometry. Consecutive and unselected patients were considered. Relative changes in maximum platelet aggregation (MPA) and in residual platelet aggregation assessed 6 minutes after initiation were considered as well as VASP-PRI. RESULTS: Our study population consisted of 53 patients (45% of coronary patients) of whom 25 were on dual antiplatelet therapy (DAPT) (20 with clopidogrel and 5 with prasugrel) and 11 on aspirin alone. Transfusion led to a significant increase in MPA irrespective of the agonists used: 8.8% with ADP (52.1 ± 3.1 vs. 56.7 ± 2.8 p=0.03) and 12.5% with TRAP (46.8 ± 22 vs. 53.7 ± 24, p=0.02). A similar trend was observed with arachidonic acid and with the VASP PRI index (13.0 ± 23 vs. 16.5 ± 25, p = 0.2 and 46.3 ± 31 vs. 50.2 ± 27, p=0.3 respectively), although the difference was not significant. The impact of transfusion was more pronounced in patients exposed to DAPT (coronary patients) although P2Y12 Inhibitors provided lower levels of baseline platelet aggregation (Relative changes of +13.8%, p=0.02 with ADP, +24.5%, p=0.01 with TRAP, and +10%, p = 0.6 for the VASP-PRI). CONCLUSION: Red blood cell transfusion increase platelet reactivity in patients. This effect is more pronounced among patients treated with P2Y12 inhibitors and may account for the detrimental effect of RBC in the context of ACS.
Abstract 146: Glucagon-like Peptide-1 Receptor Activation Promotes Dual Benefits For Reversing Microvasculopathy And Mitochondrial Damage In Diabetic Heart.
Authors: Akio Monji, Yasuko K Bando, Toko Mitsui, Morihiko Aoyama, Hiroya Kawase, Toyoaki Murohara
Journal: Circulation Research (2013)

PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex4) is a remedy for type 2 diabetes mellitus (T2DM). Ex4 ameliorates cardiac dysfunction in preclinical and clinical settings. However, it remains unclear whether the impact of Ex4 on cardiac remodeling in diabetic cardiomyopathy (DMC), of which primary characteristics are microvasculopathy and mitochondrial damage. Methods and Results: Diet-induced T2DM (DIO) mice and age- and gender-matched lean control mice were allocated into EX4 (24 nmole/kg/day for 40 days; DIO-Ex4 and LEAN-Ex4) and vehicle groups (DIO-veh and LEAN-veh). We first confirmed the GLP-1R expression in every single chamber of mouse heart by immunoblotting and PCR. Ex4 treatment ameliorated both systemic and cardiac insulin resistance without affecting body weight in DIO. Cardiac capillary density of DIO-veh was reduced compared to those LEAN-veh, which were reversed by Ex4 treatment. Tube formation assay and immunoblot analysis using culture endothelial cells revealed that Ex4 directly enhanced in vitro angiogenesis in a PKA/eNOS-dependent fashion. Systolic and diastolic left-ventricular (LV) dysfunctions observed in DIO-veh were restored by Ex4 with decline in LV wall thickening. Myocardial fibrosis detected using sirius-red staining and tissue oxidative stress detected by a fluorescence indicator DHE were attenuated in DIO-Ex4. Of note, analyses using transmission electron microscopy and a fluorescence indicator for damaged mitochondria (mitotracker red) revealed that Ex4 treatment reversed cardiac mitochondrial remodeling and increased healthy mitochondria. Ex4 treatment modulated cardiac oxidative stress balance by upregulating antioxidative molecules (SOD, thioredoxin, glutathione peroxidase) and reduction of NOX4 level; whereas it had no influence on NOX2 level. Conclusions: Ex4 enhances cardiac angiogenesis via GLP-1R-mediated activation of PKA/eNOS axis and accelerates reverses remodeling of myocardial mitochondria, at least in part, via its facilitating effects on antioxidative defense.
Lanreotide depot/autogel (LAN) in patients with neuroendocrine tumors (NETs) aged ≤65 vs. &gt;65 years: Subgroup analyses from the CLARINET study.
Authors: A. Dasari, Alexandria T. Phan, Martyn E. Caplin, Marianne E. Pavel, Jaroslaw B Cwikla, Markus Raderer, Eva Sedlackova, Guillaume Cadiot, Edward M. Wolin, Jaume Capdevila, Lucy Wall, Guido Rindi, Alison Langley, Edda Gomez-Panzani, Philippe B. Ruszniewski
Journal: Journal of Clinical Oncology (2015)

e15177 Background: The somatostatin analog LAN 120 mg significantly prolonged progression-free survival (PFS) vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 <10%) nonfunctioning intestinal and pancreatic NETs (hazard ratio [HR] for progressive disease [PD]/death: 0.47 [95% CI: 0.30, 0. 73]). This large trial (n=204) allows the examination of treatment effects within subgroups of interest. We now compare PFS and safety data for patients aged ≤65 years vs. aged >65 years. Methods: In this 96-week randomized double-blind trial, patients received LAN 120 mg or PBO every 4 weeks by deep subcutaneous injection (NCT00353496). Subgroup analyses were undertaken to investigate only the consistency of treatment effects, the study was not designed or powered for such analyses. Results: Median age (range) was 57 years (30–65 years) for those ≤65 years old, and 71 years (66–92 years) for those >65 years old. Other baseline characteristics were similar between groups, including tumor origins (≤65 years: pancreatic 43%, midgut 34%; >65 years: pancreatic 46%, midgut 38%) and hepatic tumor loads (>25%: 30% and 37% for ≤65 and >65 years, respectively). Disease was predominantly stable at baseline (94% vs. 98%, respectively). Therapeutic effects of LAN 120 mg on PFS were similar for the two groups and there were no consistent differences in tolerability (Table). Overall, the most common adverse event was diarrhea (≤65 years: LAN 36%, PBO 32%; >65 years: LAN 33%, PBO 40%). Conclusions: Treatment effect with LAN 120 mg in terms of PFS was consistent across age groups. LAN tolerability/safety was favorable. Clinical trial information: NCT00353496. ≤65 years (n=115) >65 years (n=89) LAN PBO LAN PBO PFS Median [95% CI] PFS, months NR 18.1 [13.0, 24.0] NR 12.1 [9.4, 24.0] HR for PD/death [95% CI] 0.51 [0.29, 0.90] 0.38 [0.19, 0.74] Any AE 48 (87) 52 (87) 41 (89) 41 (95) Treatment-related AEs 31 (56) 18 (30) 19 (41) 11 (26) Serious AEs 13 (24) 14 (23) 12 (26) 18 (42) Withdrawals due to AEs 1 (2) 0 2 (4) 3 (7) Data are n (%) unless stated otherwise. AE, adverse event; HR, hazard ratio; NR, not reached; PD, progressive disease; PFS, progression-free survival .
Hunt for the culprit of cardiovascular injury in kidney disease: Figure 1
Authors: Christian Faul, Myles Wolf
Journal: Cardiovascular Research (2015)

This editorial refers to ‘Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue’ by R. Mencke et al. , pp. 220–231. 

Disordered phosphate homeostasis is thought to contribute mechanistically to the high rates of cardiovascular disease encountered in patients with chronic kidney disease (CKD), but how this occurs is uncertain. As the most recently discovered regulators of phosphate homeostasis, α-klotho, and fibroblast growth factor 23 (FGF23) have seized the investigative spotlight as candidate cardiovascular culprits.

α-Klotho is a transmembrane receptor that is most heavily expressed in the kidney tubules,1 whereas FGF23 is an endocrine hormone secreted primarily by osteocytes.2 FGF23 stimulates renal phosphate excretion and lowers circulating levels of calcitriol, which secondarily reduces the efficiency of dietary phosphate absorption in the gastrointestinal tract.3 These effects are mediated by FGF23 binding to and activating heterodimeric complexes of FGF receptors and α-klotho co-receptors in the kidney.4 A circulating soluble form of α-klotho that is derived from cleavage of its extracellular domain may also possess endocrine effects, including FGF23-independent phosphaturia.5 Highlighting their shared roles in regulating total body phosphate economy, deficiency of either α-klotho or FGF23 results in impaired renal phosphate excretion, endogenous calcitriol toxicity, and syndromes of accelerated aging marked by extensive arterial calcification among numerous other manifestations.6,7

Since renal excretion is the only means of phosphate egress from the body, CKD is a prototypical human condition of impaired phosphate excretion. Afflicting millions of people worldwide, it is also the most common. In CKD, renal expression of α-klotho progressively declines and circulating levels of FGF23 progressively increase.3 Enabled by assays that can reliably measure FGF23 in stored …
Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762)
Authors: CA Westbrook, AL Hooberman, C Spino, RK Dodge, RA Larson, F Davey, DH Wurster- Hill, RE Sobol, C Schiffer, CD Bloomfield
Journal: Blood (1992)
A phase II trial of the use of 4,4’-dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone (A-007) topical gel in the treatment of high-grade squamous intraepithelial lesions (HSIL) of the cervix
Authors: D. Muñoz, D. Cantu, A. Gonzalez, A. Meneses, A. Mohar, H. Astudillo-de la Vega, B. Nguyen
Journal: Journal of Clinical Oncology (2007)

5593 Background: The incidence of cervical cancer is highly correlated with cervical high grade squamous intraepithelial lesions (HSIL [CIN2/3]) and human papillomavirus (HPV) infection in men and women. Approximately 70 - 80% of sexually active adolescents and adults will become infected with HPV during their lifetime. In 2003 alone, there were 50 million cases of HPV infections in the United States. Our main objective is to determine the pathological response (complete and partial, based on independent review panel of two patho the uterine cervix of women with HSIL [CIN 2/3]. Materials and Methods: Following colposcopy, pap smear and biopsy confirmation of HSIL (CIN 2/3) and HPV infection status, women are treated with gel applied to the cervix via an intravaginal applicator once daily for 5 consecutive days of a 28-day cycle for 2 cycles. At month 4 post enrollment into the trial, all women undergo the loop electrosurgical excision procedure (LEEP) procedure and repeated virology assessment. Results: 65 patients were enrolled at 2 centers and completed treatment with A-007 and 100% (65/65) were HPV positive (81.5% by Hibrid Capture II for High Risk and 100% PCR positive). All baseline and LEEP pathological specimens will be blinded read by a panel of two independent expert pathologists. A subject will be considered a complete pathological responder (CR) when the patient has regression of HSIL (CIN 2/3) without pathological evidence of HSIL, and a partial pathological responder (PR) when she has regression of HSIL (CIN 2/3) to LSIL (CIN 1). Overall response rate is defined as the percentage of patients with CR and PR. To date, no serious adverse events (SAE) has been reported during treatment in all enrolled patients, only has been reported a moderate local and transitory itching/burning sensation during the first 5–20 minutes after application in 18% (12/65) of the cases. At this moment LEEP procedures are being scheduled for all patients and the pathological response rate as well as the HPV response rate will be available and presented at the conference. [Table: see text]
Complications of rhinosinusitis
Authors: Stephen L Ball, Sean Carrie
Journal: BMJ (2016)

A 65 year old man was initially referred to plastic surgery because of a recurrent abscess on the forehead, and headache. He was subsequently referred to ear, nose, and throat surgery for definitive management of his sinus complication. What is the diagnosis?



A subperiosteal abscess secondary to frontal sinusitis and osteomyelitis (Pott’s puffy tumour) that has spontaneously burst.

### Discussion

Frontal sinusitis with osteomyelitis (Pott’s puffy tumour) may present with headache, swelling, and sometimes a discharging frontal sinus fistula (fig 2⇓). It arises as a complication of frontal sinusitis and can spread intracranially, with complications from erosion of the posterior table, or more likely by septic thrombophlebitis through …
Abstract MP77: Projected Impact of Shifting Population Distributions of Blood Pressure on Rates of Coronary Heart Disease, Heart Failure and Stroke: The Atherosclerosis Risk in Communities Study
Authors: Shakia T Hardy, Laura R Loehr, Kenneth R Butler, Patricia P Chang, Aaron R Folsom, Gerardo Heiss, Richard F MacLehose, Kunihiro Matsushita, Christy L Avery
Journal: Circulation (2013)

Introduction: Rates of cerebrovascular disease, heart failure (HF), and coronary heart disease (CHD), increase progressively as blood pressure rises. Several authors have estimated the theoretical effects of shifting the population distribution of blood pressure; however few studies have examined the degree to which modest decrements in blood pressure affect HF incidence, or included a racially diverse population. Methods: Incident HF was identified by a first hospitalization with discharge diagnosis code of 428.X. Incident hospitalized (definite or probable) CHD and stroke were classified according to protocol. We used multivariable regression to estimate incidence rate differences (IRD) for HF, CHD, and stroke that could be associated with a two mm Hg reduction in systolic blood pressure (SBP) in 15,744 participants from the Atherosclerosis Risk in Communities Study. Results: Over a mean of 18.3 years of follow up, age-adjusted incidence rates for HF, CHD, and stroke were higher among African American than Caucasians (Table 1). After adjusting for antihypertensive use, gender, and age, a two mm Hg decrement in SBP across the total population was associated with an estimated 24/100,000 person-years (PY) and 39/100,000 PY fewer incident HF events in Caucasians and African Americans, respectively. The projected disease reductions were of smaller absolute magnitude for incident CHD and incident stroke. Extrapolation to the African American and Caucasian U.S. populations age greater than 45 years suggests that a two mmHg decrement in SBP could result in approximately 22,000 fewer incident HF events, 15,000 fewer incident CHD events, and 5,000 fewer incident stroke events annually. Conclusion: Our results suggest that modest shifts in SBP, consistent with what could theoretically be achieved through population level lifestyle interventions, could substantially decrease the incidence of HF, stroke, and CHD in the United States, especially among African American populations.
Durability of HBeAg seroconversion following adefovir dipivoxil treatment for chronic hepatitis B
Authors: Ting-Tsung Chang, M.L. Shiffman, M. Tong, Y.E. Liaw, P. Komolmit, J. Sorbel, S. Arterburn, E. Mondou, S. Chuck, P. Marcellin
Journal: Journal of Hepatology (2006)
Lack of differences in nephrotoxicity of intravenous bisphosphonates in metastatic breast cancer.
Authors: D. W. Luedders, M. K. Bohlmann, J. Steinhoff, A. Hornemann, K. Diedrich, M. Thill
Journal: Journal of Clinical Oncology (2010)

1122 Background: More than 50% of patients (pts) with advanced breast cancer develop bone metastases that may lead to multiple complications such as pathological fractures, bone pain, or hypercalcaemia. The standard treatment besides endocrine, targeted or chemotherapy is the use of bisphosphonates. However, one of its main adverse side-effects is bisphosphonate- induced nephrotoxicity. The mechanism by which the latter occurs is not well understood, although emerging evidence suggests that the effect of bisphosphonates on the kidney may differ between agents. Methods: Aim of the evaluation was to compare the renal toxicity of ibandronat 6mg i.v. (n=17) versus zoledronic acid 4mg i.v. (n=17) over a period of 6 months in pts with breast cancer with bone metastases. A prospective randomized trial was to examine specific kidney and other parameters (α1- and β2-microglobulin, albumin, α2-macroglobulin, IgG, and CRP) generated from spontaneous urine samples before treatment and after day 2, 4, and 6 in both groups. Results: We were unable to show any significant difference between the two treatment groups with regard to renal toxicity. All pts showed independently of the applied bisphosphonate only temporary renal dysfunction without any evidence of irreversible damage in terms of acute nephrotoxicity during the study period. The elevation rate of α1- microglobulin, a marker for proximal tubular damage, was especially not significantly different between the two groups. Conclusions: Both applied bisphosphonates are well tolerated and safe with regard to renal toxicity during a 6-months treatment in pts with advanced breast cancer and bone metastases. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Karyometry in the Estimation of Nuclear Population in Pulmonary Carcinomas2
Authors: P. Switzer, B. Gerstl, J. Greenspoon
Journal: JNCI Journal of the National Cancer Institute (1974)

A method including a computer program was developed for calculation of ellipsoid nuclei in pulmonary carcinomas. The method was based on replicate measurements of nuclear diameters, numbers of nuclei/unit area, thickness of microscopic sections, and the separate mean numbers of oblate and prolate nuclei/unit volume. Significant differences in cell population between individual epidermoid carcinomas were revealed. These were augmented when the karyometric results were calculated on the basis of morphometric data. Correlation of these data with survival time, and calculation of nucleic acid content based on them were discussed.
Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial
Authors: E. E. Vokes, J. E. Herndon, M. J. Kelley, D. Watson, M. G. Cicchetti, M. R. Green
Journal: Journal of Clinical Oncology (2004)

7005 Background: Standard therapy for unresectable stage III NSCLC includes concomitant chemoradiotherapy. In CALGB 39801, we evaluated whether the addition of induction chemotherapy prior to CT/XRT would result in improved survival. Methods: Between 10/1998 and 5/2002, 366 stage III patients (pts) were randomized to either immediate CT/XRT [carboplatin AUC of 2 and paclitaxel 50 mg/m2 each given weekly during 66 Gy chest XRT to; arm 1 (182 pts)] or two cycles of carboplatin AUC 6 and paclitaxel 200 mg/m2 given q 21 days x 2 cycles followed by identical CT/XRT; arm 2 (184 pts). The accrual goal was 360 patients. 290 deaths were required to have 80% power to detect a 40% increase in median survival assuming a one-tailed log-rank test conducted at the 0.025 level of significance. Results: 34% of pts were female, 66% male and 63% were age 60 or older. Grade 3 or 4 toxicities during induction chemotherapy consisted mainly of neutropenia (17%/21%). During CT/XRT, grade 3/4 neutropenia was noted in 11%/4% (arm 1) versus 21%/6% (arm 2), grade 3 anemia was 5% vs 11%, grade 3/4 fatigue 16%/1% vs 16%/4%, esophagitis 30%/1% vs 28%/7%, and dyspnea 9%/3% vs 15%/4%. Overall, 4 toxicities were experienced by 24% of patients on arm 1 versus 41% on arm 2 (p=0.001). With 254 of 290 targeted deaths, median survival on arm 1 is 11.4 months versus 14 months on arm 2 (p=0.154). One year survival estimates are 48% (41%–57%) and 54% (47%–62%) respectively. Conclusion: The median survival achieved in each of the treatment groups is low compared to other recent experiences in the literature. The reason(s) for this are uncertain. The addition of induction chemotherapy to immediate concurrent CT/XRT is associated with a 2.6 month increase in median survival. However these findings are not sufficient to reject the null hypothesis of no treatment difference between the two study arms. Further follow up of this data set is required. Our results do not support the use of induction chemotherapy followed by CT/XRT as evidence based standard of care for patients with unresectable stage III NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Oncology Aventis Aventis
Marrow Transplantation for Chronic Myeloid Leukemia: The Influence of Plasma Busulfan Levels on the Outcome of Transplantation
Authors: J.T. Slattery, R.A. Clift, C.D. Buckner, J. Radich, B. Storer, W.I. Bensinger, E. Soll, C. Anasetti, R. Bowden, E. Bryant, T. Chauncey, H.J. Deeg, K.C. Doney, M. Flowers, T. Gooley, J.A. Hansen, P.J. Martin, G.B. McDonald, R. Nash, E.W. Petersdorf, J.E. Sanders, G. Schoch, P. Stewart, R. Storb, K.M. Sullivan, E.D. Thomas, R.P. Witherspoon, F.R. Appelbaum
Journal: Blood (1997)
Enabling patients to drive is also important
Authors: D. O'Neill
Journal: BMJ (1995)

Data from transnational study of oral contraceptives have been misusedEDITOR,-The unpublished data from the transnational study of oral contraceptives have been misused and misinterpreted in Britain because of inexplicable haste and urgency not thought necessary by other major regulatory agencies.My col- leagues and I do not agree that our findings justify the drastic actions taken in Britian, whereby a "Dear Doctor" letter was sent to doctors, warning that oral contraceptives containing desogestrel and gestodene are associated with an increased risk of thromboembolism (pp 1112, 1117, and 1172).1 Doctors should be vigilant but not stampeded.