tbuckley/cabot-search huggingface dataset:
Bevacizumab effectiveness and tumor vessel subtypes in metastatic colorectal cancer patients.
Authors: Wen-zhuo He, Chang Jiang, Qiong Yang, Fang-xin Liao, Wan-ming Hu, Liang-ping Xia
Journal: Journal of Clinical Oncology (2016)

e23012 Background: Published papers reported that pericyte could promote endothelial cell survival. The aim of this study was to assess whether the pericyte coverage was a predictor for bevacizumab effectiveness in metastatic colorectal cancer (mCRC). Methods: From 2007 to 2014, 59 patients with mCRC who underwent chemotherapy combined with bevacizumab (CT + B group) and 131 patients who underwent chemotherapy alone (CT group) as first-line treatment were included into this study from Sun Yat-sen university cancer center. Paraffin-embedded tumor samples were sectioned and double stained immunohistochemistry for the pericyte marker a-smooth muscle actin (a-SMA) and endothelial cell marker CD31 were conducted to characterize the intratumoral vasculature. The perimeter and area of vessels were studied using Image Pro Plus software (five hotspots for each slice). The primary outcome was overall survival (OS). Student’s t test was used for the determination of significance between groups. Kaplan-Meier curves with log-rank tests were used to compare survival. Results: Vessels with pericyte (a-SMA+/CD31+) and without pericyte coverage (a-SMA-/CD31+) were identified. The median proportion of a-SMA-/CD31+ vessel was 15%. The a-SMA+/CD31+ vessels showed significantly increase in perimeter (131 ¦Ìm versus 62 ¦Ìm, p<0.001) and area (324 ¦Ìm2 versus 86 ¦Ìm2, p<0.001) in comparison with the a-SMA-/CD31+ vessels. The median percentage of a-SMA-/CD31+ vessel was higher in patients with left-sided colon cancer than those with right-sided colon cancer (18% versus 10%, p=0.037). For patients with a-SMA-/CD31+ vessels more than 15%, significantly longer OS were observed in CT + B than CT group (26.85 versus 22.60 months, P = 0.007). For patients with a-SMA-/CD31+ vessels less than or equal to 15%, no survival difference was observed between CT + B and CT group (23.36 versus 23.56 months, P = 0.591). Conclusions: Our data suggested that pericyte coverage was a predictor for bevacizumab benefit. Further data from randomized trials are needed to test our hypothesis. Percentage of a-SMA-/CD31 + vessel No. of patients OS events No. (%) Median OS, months (range) P CT CT + B CT CT + B ¡Ü15 82 36 81 (68.6) 23.36 23.56 0.519 >15 49 23 53 (73.6) 22.60 26.85 0.007
Understanding the Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use of GLP-1 RA and DPP-4 Therapies in Patients With Type 2 Diabetes
Authors: Ginger S. Carls, Edward Tuttle, Ruo-Ding Tan, Johnny Huynh, John Yee, Steven V. Edelman, William H. Polonsky
Journal: Diabetes Care (2017)

OBJECTIVE The objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide 1 receptor agonist (GLP-1 RA) or dipeptidyl peptidase 4 (DPP-4) inhibitor with published findings from randomized controlled trials (RCTs) evaluating these drugs. Selected RW patients were similar to RCT patients, and regression analysis was used in the RW data to adjust for differences between poorly adherent and adherent patients to explain why RCT and RW findings may differ. RESULTS RW patients initiating a GLP-1 RA (n = 221) or a DPP-4 (n = 652) experienced smaller reductions in HbA1c (GLP-1 RA: −0.52% [−6 mmol/mol], DPP-4: −0.51% [−6 mmol/mol])than reported in RCTs (−1.30% [−14 mmol/mol] from seven GLP-1 RA RCTs, n = 2,600; −0.68% [−8 mmol/mol] from four DPP-4 RCTs, n = 1,889). Baseline HbA1c, additional medications, and adherence were significant explanatory factors in the RW HbA1c change. Modeled estimates of RCT efficacy (−1.04% GLP-1 RA [−12 mmol/mol], −0.69% DPP-4 [−8 mmol/mol]) were within the RCTs’ reported range (GLP-1 RA: −0.84% to −1.60% [−9 to −18 mmol/mol], DPP-4: −0.47% to −0.90% [−5 to −10 mmol/mol]). Poor medication adherence accounted for approximately three-fourths of the gap between RW and expected RCT results (gap = 0.51% [6 mmol/mol] GLP-1 RA; 0.18% [3 mmol/mol] DPP-4). CONCLUSIONS Poor medication adherence is primarily why RW effectiveness is significantly less than RCT efficacy, suggesting an urgent need to effectively address adherence among patients with type 2 diabetes.
Impact de la video capsule dans la prise en charge et l’histoire naturelle des saignements digestifs inexpliqués: Suivi à 11 mois d’une population de 50 patients
Authors: O Favre, P Jacob, J Daudet
Journal: Endoscopy (2004)

Introduction: L’exploration par vidéo capsule Given Imaging® est la plus performante dans les saignements digestifs inexpliqués en terme de lésions diagnostiquées sur l’intestin grêle, mais on connaît mal son impact dans la prise en charge des patients et l’histoire naturelle des saignements. Patients et Méthodes: Ce travail rétrospectif a porté sur une série de 53 patients consécutifs explorés par vidéo capsule pour saignement digestif extériorisé (20) ou anémie ferriprive (33) inexpliqués par bilan endoscopique gastrique et colique, afin d’établir avec un suivi médian de 11 mois (3–17):
High Dose Cytarabine Is Superior to Intermediate Dose Cytarabine As Post-Remission Therapy for Younger Patients with Favorable Risk Acute Myeloid Leukemia
Authors: Nurul Aidah Abdul Halim, Gee Chuan Wong, Ho YL Aloysius, William YK Hwang, Yeh Ching Linn, Zhentang Lao
Journal: Blood (2016)
THE ROLE OF PLANTAR CUTANEOUS SENSATION AND THE PROXIMAL JOINT POSTURAL CONTROL STRATEGY TO MAINTAIN BALANCE IN CAI PATIENTS
Authors: Tae Kyu Kang, Jung Yeon Woo, Jae Seung Chang, Sae Yong Lee
Journal: British Journal of Sports Medicine (2017)

Background Previous studies revealed that the patient with chronic ankle instability (CAI) has postural control deficit. However, it is unclear that if CAI patients rely more on plantar cutaneous sensation or other compensation strategy such as proximal joint postural control strategy. Objective To investigate the alteration of lower extremity movement pattern to maintain balance in CAI patients as compared to healthy group with and without plantar cutaneous sensation (PCS). Design Case controlled study. Setting Laboratory. Patients (or Participants) Nine healthy subjects (age: 23.75±1.98 years; height: 164.10±6.90 cm; weight: 57.76±9.14 kg) and 10 CAI patients (age: 23.57±2.72 years; height: 166.14±7.74 cm; weight: 67.84±12.60 kg) with normal foot arch type (5 mm∼9 mm; 5.78±2.44 mm) were recruited. Interventions (or Assessment of Risk Factors) Subjects immersed both feet in an ice water for 10 minutes and performed three trials of a single-leg stance balance test with their eyes closed on a force plate for 10 s. Main Outcome Measurements Three-dimensional lower extremity kinematics (Vicon Inc, Oxford, UK) were analysed. The kinematic data were analysed by ensemble curves and 95% confidential interval (CI). Group (healthy and CAI) by time (plantar sensation) mixed model two-way repeated measures of ANOVA was performed to analyse differences of maximum joint kinematics. Results With diminished PCS, CAI group showed greater knee internal rotation (mean difference=−9.21±0.39°) and greater hip external rotation (mean difference=15.89±0.27°) throughout 10 seconds balance task. However, there were no significant main effects and interactions between group and time. Conclusions Since PCS is intact before ice immersion, CAI patients rely more on PCS in order to maintain balance and revealed similar joint kinematics. However, once PCS diminished CAI patients utilize proximal joint compensatory mechanism such as leaning toward the injured side at the hip joint through external rotation of the hip joint and internally rotating the knee joint to prevent inversion at the ankle joint.
Characterization and Correction of Olfactory Deficits in Kidney Disease
Authors: Sagar U. Nigwekar, Jeremy M. Weiser, Sahir Kalim, Dihua Xu, Joshua L. Wibecan, Sarah M. Dougherty, Laurence Mercier-Lafond, Kristin M. Corapi, Nwamaka D. Eneanya, Eric H. Holbrook, Dennis Brown, Ravi I. Thadhani, Teodor G. Păunescu
Journal: Journal of the American Society of Nephrology (2017)

Patients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort ( n =161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P =0.02) and ESRD (66.8%±15.1%; P &lt;0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial.
Abstract P264: Interaction of Collecting Duct-Derived Prorenin and Soluble Prorenin Receptor Increases Intraluminal Renin Activity and Augments Intratubular Angiotensin II Formation in Ang II-Dependent Hypertensive Rats
Authors: Minolfa C Prieto, Liu Liu, Alexis A Gonzalez, Dale M Seth, L Gabriel Navar
Journal: Circulation Research (2011)

Upregulation of collecting duct (CD)-derived renin (CD renin) in angiotensin II (Ang II)-dependent hypertension may provide a pathway for intratubular Ang II formation by acting on angiotensinogen (AGT) delivered from proximal tubule segments. Recently, a prorenin/renin receptor (PRR) has been cloned and shown to enhance renin and prorenin activation. The soluble form of the PRR (sPRR) is augmented in the renal inner medulla of chronic Ang II-infused rats. The present study was performed to determine if renin is secreted into the lumen by the CD cells in chronic Ang II-infused rats and to establish the functional contribution of sPRR to the enhanced renin activity in distal nephron segments. Accordingly, urinary levels of renin ( uRen ) and Ang II ( uAngII ) were measured by RIA in chronic Ang II-infused male Sprague-Dawley rats [80 ng/min, SC minipumps for 14 d, n=10] and sham-operated rats [n=10]. Systolic blood pressure increased in the Ang II rats by Day 5 and continued to increase throughout the study (Day 13; Ang II: 175±10 vs. sham: 116±2 mmHg; p &lt;0.05). Although plasma renin activity (PRA) was suppressed in the Ang II-infused rats, renal medullary renin content was significantly augmented (12,605±1,343 vs. 7,956±765 ng Ang I/h/mg; p &lt;0.05). The excretion of uAngII was also increased (3,813±431 vs. 2,080±361 fmol/day; p &lt;0.05). In addition, renin and prorenin excretion rates increased progressively and were markedly augmented by Day 13 of Ang II infusion [renin (8.6±1.5 vs. 2.8±0.5x10 -6 Enzyme Units Excreted (EUE) /day; prorenin: 15.8 ± 2.8 vs. 2.6 ± 0.7x10 -3 EUE /day, p &lt;0.05). Renin and prorenin protein levels examined by Western Blot in the urine were similarly increased. Importantly, the incubation of urine samples of Ang II-infused rats with recombinant human prorenin showed increased Ang I formation compared to sham-operated rats. In conclusion, in chronic Ang II-infused rats, the presence of sPRR in the urine reflects augmented enzymatic activity of prorenin secreted by the principal cells of the CD, which increase intratubular Ang II de novo formation in the distal nephron segments thus contributing to enhanced sodium reabsorption during Ang II-dependent hypertension.
Colorectal cancer with mutation in BRAF, KRAS and wild-type with respect to both oncogenes showing different patterns of DNA methylation
Authors: Hiromi Sasamoto, Takeshi Nagasaka, Kenji Notohara, Masanori Takeda, Keigo Kimura, Takeshi Kambara, Tatsuhiro Ishii, Atsuki Nagao, Takuyuki Uchida, Nagahide Matsubara, Noriaki Tanaka
Journal: Cancer Research (2005)

853   Purpose. BRAF mutations are common in sporadic colorectal cancers (CRCs) with a DNA mismatch repair (MMR) deficiency that results from promoter methylation of hMLH1, whereas KRAS mutations are common in MMR proficient CRCs associated with promoter methylation of MGMT. The aim of this study was to further investigate the link between genetic alterations in the RAS/RAF/ERK pathway and an underlying epigenetic disorder. Patients and Methods. Activating mutations of BRAF and KRAS were identified and correlated with promoter methylation of 11 loci, including MINT1, MINT2, MINT31, CACNA1G, p16INK4a, p14ARF, COX2, DAPK, MGMT, and the two regions in hMLH1 in 468 CRCs and matched normal mucosa. Results. BRAF V599E mutations were identified in 21 (9%) of 234 CRCs, and KRAS mutations were identified in 72 (31%) of 234 CRCs. Mutations in BRAF and KRAS were never found in the same tumor. CRCs with BRAF mutations showed high-level promoter methylation in multiple loci, with a mean number of methylated loci of 7.2 (95% CI, 6.6 to 7.9) among 11 loci examined (P
SAT0259 Three-dimensional (3-d) measurement of shoulder movement patterns in patients with a frozen shoulder
Authors: HM Vermeulen, M Stokdijk, PH Eilers, CG Meskers, PM Rozing, TP Vliet Vlieland
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> 3-D movement analysis with electromagnetic tracking systems proved to be a reliable tool in measuring range of motion (ROM) in healthy shoulders. 3-D analysis of movement patterns in subjects with pain and movement limitations of the shoulder has not yet been performed. <h3>Objectives</h3> To investigate 3-D movement patterns of the affected and non-affected shoulder in patients with a frozen shoulder before and after physical therapy. <h3>Methods</h3> Patients with a unilateral frozen shoulder were assessed before and after 3 months of intensive passive end-range of motion mobilisation techniques. 3-D movement analysis was performed with the ?Flock of Birds®? electromagnetic tracking device while the patient elevated the arms in 3 directions. Using segmented linear regression, the characteristic slope of the upward part of the curves of glenohumeral elevation angle (x-axis) versus scapular laterorotation angle (y-axis) was approximated. Within this analysis determining the turning point of the curve was essential. Additional measures included ROM with a goniometer and a VAS(0–100 mm) for shoulder pain. Mean differences between affected and non-affected side and mean changes of the slope of the regression line before and after 3 months were studied by paired t-tests. <h3>Results</h3> Eight women and 2 men with a unilateral frozen shoulder were included. Mean age was 49.1(sd 5.6) yrs, mean duration of complaints 11.4(sd 8.2) months. Mean active ROM in forward flexion, abduction and external rotation of the frozen shoulder before treatment was 97°(sd 17),75°(sd 21) and 22°(sd 13). Mean scores for pain during movement was 63(sd 25). Mean slopes of the curves of the scapular laterorotation angle in forward flexion, scapular abduction and abduction were 0.725, 0.719 and 0.958 for the affected side and 0.458, 0.504 and 0.494 for the unaffected side, respectively (p &lt; 0.005). After 3 months mean active ROM in the affected shoulder increased to 127°(sd 21) in forward flexion, 127°(sd 33) in abduction and 37°(sd 14) in external rotation (all p &lt; 0.005). Mean pain score decreased to 37 mm (sd 12)(p = 0.013). Mean changes of the slopes were 0.063(p = 0.202), 0.048(p = 0.169) and 0.264(p = 0.008) for forward flexion, scapular abduction and abduction, respectively. <h3>Conclusion</h3> This study shows that with a 3-D electromagnetic tracking system the abnormal movement pattern of a frozen shoulder, characterised by the earlier laterorotation of the scapula during shoulder elevation, can be described and quantified. Moreover, the system was sensitive to clinical improvements. Therefore, the system may be a useful tool for the evaluation of treatment of the frozen shoulder. Its value in other shoulder disorders remains to be established.
05.15 Altering peripheral cd8<sup>+</sup> t-cell function in ra through metabolic modulation with small molecule agents 3-bromopyruvate, fx-11 and cpi-613
Authors: André P. Meyer, Rui A Carvalho, H-M Lorenz, Margarida Souto-Carneiro
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> RA CD8<sup>+</sup> T cells (CD8s) present a pro-inflammatory, cytotoxic effector phenotype and may, therefore, play a major role in disease pathogenesis. The presence of such effector CD8s in the blood and synovial fluid suggests that they must adapt their metabolism to sustain their functional energetic demands. Thus, we hypothesised that modulation of CD8s-metabolism, by blocking essential glycolytic and citric acid cycle enzymes, might alter their phenotype and function. The ultimate goal was to explore the potential of this metabolic modulation as novel therapeutic opportunity in RA. <h3>Materials and methods</h3> 35 RA patients and 16 age and gender matched healthy controls (HC) were recruited at the Heidelberg University Hospital. Blood CD8s were purified by negative magnetic separation selection and CFSE labelled. Anti-human CD28/CD3 stimulated CD8s were cultured <i>in vitro</i> for 3 days in medium containing [1,6-<sup>13</sup>C] glucose. After 24 hours, enzyme blockers were added in non-toxic concentrations. Proliferation, subset distribution, CD57, CD147, CD25, CD137, TIM-3 and PD-1 expression were assessed by FACS. Cytokines were quantified by cytometric bead array. Changes in lactate production were monitored by<sup>1</sup>H-NMR spectroscopy. <h3>Results</h3> Upon inhibition of hexokinase II (3-Bromopzruvate, 3 BP), LDHA (FX11) and pyruvate dehydrogenase complex (CPI-613) both RA and HC CD8s significantly lost proliferative activity. We observed a loss of activity and cytotoxicity marker CD137, the effector function marker (CD25) and the exhaustion marker PD-1. The matrix metalloproteinase inductor and regulator of transmembrane monocarboxylate transport basigin (CD147) showed a strong downregulation. Interestingly, the lactate-dehydrogenase A (LDHA) blocker FX11, induced the strongest down-modulation of these surface molecules in RA CD8s. Metabolic interference also lead to changes in cytokine production. Concentrations of proinflammatory proteins IL-17 α, IL-6, IFN-γ, TNF-α, Perforin and VEGF were lower in the presence of 3 BP, FX11 and CPI-613. <sup>1</sup>H-NMR spectroscopy showed diminished newly-synthesised lactate levels in cell supernatants. <h3>Conclusions</h3> Metabolically altered CD8s presented a less proliferative, less pro-inflammatory and cytotoxic profile with lower <i>de novo</i> synthesis of lactate. Moreover, RA CD8s seemed to be more susceptible upon LDHA blockage than HC. This might indicate that CD8s metabolism, especially glycolytic pathways present a possible anti-inflammatory therapeutic target.
Glomus Tumor of the Neck Detected With 99mTc EDDA HYNIC-TOC
Authors: Neva Girotto, Tatjana Bogović-Crnčić, Svjetlana Grbac-Ivanković, Petra Valković-Zujić
Journal: Clinical Nuclear Medicine (2017)

A 54-year-old woman was referred to thyroid evaluation because of a lump on the left side of the neck. Ultrasound exam did not show any thyroid abnormality, but highly perfused nodule at the left common carotid artery bifurcation was found. Because of the specific location, somatostatin receptor scintigraphy with 99mTc EDDA HYNIC-TOC was performed, starting with perfusion images and followed with SPECT/CT imaging at 2 and 4 hours. Well-perfused nodule with intensive accumulation and no other visible pathology in the body raised suspicion of a glomus tumor, consistent with MR exam performed later. Subsequent surgical removal confirmed carotid paraganglioma.
Ex Vivo T Cell-Depleted Haploidentical HCT for Children with Acute Leukemia after a Reduced-Intensity Preparative Regimen Containing Low-Dose TBI
Authors: Yeon Jung Lim, Ho Joon Im, Sung Han Kang, Hyery Kim, Kyung-Nam Koh, Eun Seok Choi, Jong Jin Seo, Jin Kyung Suh
Journal: Blood (2016)
La naso gastroscopie induit moins de désaturation artérielle en oxygène que la fibroscopie oeso-gastro-duodénale par voie buccale sans sédation
Authors: E Nguyen-Khac, N Gournay, T Thevenot, D Masset, L Lurka, E Quinville, B Carlier, D Capron
Journal: Endoscopy (2004)

Introduction: La fibroscopie éso gastro duodénale (FOGD) peut induire une désaturation artérielle en oxygène [1]. La naso gastroscopie (NG) est un examen mieux toléré par le patient [2]. Cette meilleure tolérance s’accompagne t-elle aussi d’une moindre désaturation? Le but de notre étude prospective a été d’évaluer la NG en terme de désaturation artérielle en O2 par rapport à la FOGD. Patients et Méthodes: De janvier à juin 2003, tous les patients adressés pour une endoscopie éso gastro duodénale ont eu leur examen soit par un vidéo endoscope classique de 9 mm de diamètre par voie buccale (FOGD), soit par un naso vidéo endoscope de 6 mm par voie nasale (NG). Le choix était fait selon la disponibilité des appareils, en excluant les patients ayant une hémorragie digestive haute avec extériorisation hémorragique. Une anesthésie locale était réalisée par gel buccal et spray nasal à la lidocaïne. Un oxymètre de pouls permettait de recueillir la saturation en O2 (Sao2) avant puis pendant l’examen en retenant le chiffre le plus bas. L’importance de la désaturation était définie d’une part par la différence Sao2 initiale-Sao2 minimale (moyenne ± DS) et d’autre part par le rapport Sao2 minimale sur Sao2 initiale, répartie en 3 groupes: désaturation minime (> 95%), modérée (94 à 90%) et sévère (< 90%). Tous les examens étaient réalisés par le même opérateur. Résultats: La NG était réalisée avec succès par les narines dans 93,5% des cas. L’ensemble des résultats était identique avec ou sans la prise en compte des 5 NG réalisées par la bouche (Tableau 1). Enfin il n’y avait aucune corrélation entre l’âge, le score ASA et la désaturation. Conclusion: 1) La NG induit moins souvent de désaturation artérielle en oxygène. 2) La désaturation lorsqu’elle survient avec la NG, est moins profonde. Ces résultats confortent les études rapportant une meilleure tolérance clinique de la NG, avec ici un critère objectif de jugement. La NG pourrait être proposée en première intention chez les patients ayant les critères prédictifs d’une désaturation.