tbuckley/cabot-search huggingface dataset:
Does CT/MRI fusion improve volume delineation in the treatment planning for nasopharyngeal carcinoma?
Authors: P.-A. Gfeller, F. Sheehan
Journal: Journal of Clinical Oncology (2005)

5538 Background: Optimal radiotherapy relies on the accurate identification of target volumes. This is important in the nasopharynx, a tumour site with close proximity to multiple critical structures. CT and MRI are imaging modalities used in treatment planning for the nasopharynx. Fusion of CT/MRI images may optimize planning. The purpose of this study is to compare CT with CT/MRI fusion and its impact on target volume delineation. Methods: Patients with nasopharyngeal carcinoma treated with CT/MRI fusion between February and November 2003 were identified. Patients had undergone CT and MRI simulation on the same day. Images were co-registered to produce fusion images. Two 3-D image sets were prepared for each patient using CT and CT/MRI images. Four radiation oncologists independently contoured the primary tumour and grossly involved nodes on each data set. There was a minimum 1 week break between contouring on data sets. Volumes were analyzed for inter-observer and intra-observer variability. A survey (linear analog rating scale) was completed by the oncologists after contouring each data set. Results: 11 patients with stage IIb or Stage III undifferentiated nasopharyngeal carcinoma were identified. 88 image sets were created. The mean nodal volumes were 50% larger on CT/MRI fusion images then CT alone. The mean CT nodal volumes were 8.98 cc (range 2.94–20.89 cc) compared to CT/MRI volumes of 14.08 cc (3.75–34.73 cc) (p=0.001). There was no difference in the mean gross tumour volumes (GTV) for either modality. The mean CT GTV was 19.95cc (range 2.88–64.26cc) and CT/MRI GTV was 23.07cc (2.09–74.54 cc) (p=ns). The interobserver variation was larger for contoured GTVs compared to nodal volumes. Intra-observer variation was the same for both modalities. Radiation oncologists consistently rated their ability to delineate tumour and nodal volumes higher with CT/MRI fusion images. Conclusions: Modern radiotherapy techniques for nasopharyngeal carcinoma rely on accurate imaging to delineate target structures. This study clearly shows that with CT images alone nodal volumes may be underestimated or unidentified. CT/MRI fusion improves the delineation of target volumes in the planning of nasopharyngeal carcinoma. No significant financial relationships to disclose.
Hemostatic Effectiveness of Platelets Stored at 22°C
Authors: R. I. Handin, C. R. Valeri
Journal: New England Journal of Medicine (1971)

Storage of platelets at 22 rather than 4°C improves both 51Cr recovery and platelet life-span measurements. The functional state of such platelets after transfusion was studied in normal volunteers treated with aspirin to prolong bleeding time and impair platelet aggregation. Transfusion of fresh platelets to equal more than 10 per cent of the total immediately shortened the bleeding time and restored the platelet aggregation patterns to normal. The aggregation patterns of platelets deteriorated during storage in bags at 22°C. Within 24 hours after transfusion of platelets previously stored for 24 to 48 hours at 22°C, both bleeding time and aggregation patterns were restored toward normal. The observation that after transfusion to aspirin-treated volunteers normal aggregation returned suggests improvement in platelet function after transfusion. Return of normal aggregation in vivo was better for platelets stored at 22°C for only 24 hours than for platelets stored at 22°C for 48 hours.
Grade 1 Chondrosarcoma of Bone: A Diagnostic and Treatment Dilemma
Authors: R. Lor Randall, William Gowski
Journal: Journal of the National Comprehensive Cancer Network (2005)

Cartilaginous lesions of bone are relatively common and cover a large spectrum from latent enchondroma to aggressive dedifferentiated chondrosarcoma. Differentiating among these lesions, particularly benign enchondroma and low-grade chondrosarcoma, can be challenging. Differentiating involves assimilation and interpretation of clinical, radiographic, and histologic criteria. Molecular techniques to assist in distinguishing among the various subtypes are being developed, but these techniques have not yielded any clinically significant contribution. As a result of an imperfect diagnostic schema, a consensus on treatment algorithms has been elusive. This review highlights the specific clinical, radiographic, and histologic criteria currently used clinically to differentiate between benign enchondroma and low-grade chondrosarcoma. We discuss the promise of emerging molecular technologies. Finally, we provide a review of the available literature on treatment outcomes, along with a discussion of our own particular preferences.
Diazoxide in the Treatment of Infantile Hypoglycemia
Authors: Tullio R. Mereu, Aaron Kassoff, A. David Goodman
Journal: New England Journal of Medicine (1966)

IN the majority of infants with chronic hypoglycemia the specific origin of the disorder cannot be identified. Regardless of etiology, correction of the hypoglycemia is essential to prevent mental retardation. Except in the rare case of islet-cell adenoma pancreatic surgery in infants with hypoglycemic states has given disappointing results. Attempts to elevate the blood glucose with ACTH,1 glucocorticoids,2 , 3 long acting epinephrine,4 zinc glucagon,5 6 7 glutamic acid,8 human growth hormone9 10 11 and a low-leucine diet12 have yielded variable results. Of these methods it appears that only human growth hormone affords continuous control of blood glucose, but its limited availability has restricted its use. . . .
OC-092 Gut peptide hormone and neuro-endocrine responses to satiation during emotional modulation
Authors: U Marreddygari, S Surguy, K Seong, Q Aziz
Journal: Gut (2010)

<h3>Introduction</h3> Negative emotions are associated with increased and decreased food intake. The mechanisms for these contrasting behaviours are not known. The influence of stress and negative emotion on satiation is likely to occur through multiple physiological mechanisms. Our aim was to evaluate the affect of anxiety on gastric myoelectrical activity (GMA), autonomic nervous system (ANS) gut endocrine and stress neuroendocrine responses to a test meal. <h3>Methods</h3> 30 healthy volunteers (26±9 years, 17 M and 13 F) received a 10 min nutrient challenge (50 ml/min, 1.5 kcal/ml) during either neutral or anxiogenic stimuli (electric shock threat) in a randomised order. Satiation symptoms were assessed before and after the challenge. Anxiety VAS scores, ANS, GMA (dominant power, DP, tachygastria), cortisol, gut hormones (ghrelin, glucagon-like peptide (GLP-1) and pancreatic polypeptide (PP)) responses were monitored. <h3>Results</h3> Increased anxiety scores confirmed anxiety induction (p=&lt;0.01). During neutral vs anxiety emotion induction (N vs AN), symptom scores for discomfort (1.54±0.37 vs 2.8±0.46 p=&lt;0.05), fullness (5.2±0.5 vs 6.3±0.5, p=&lt;0.05) and belching 1.4±0.4 vs 2.7±0.5, p=&lt;0.01) were significantly higher during anxiety state. The test meal caused increase in prandial and postprandial sympathetic activity compared to baseline (cardiac sympathetic index (CSI) 1.7±0.1 vs 2.3±0.1, and 1.7±0.1 vs 2.4±0.1) and parasympathetic activity to decrease (cardiac vagal tone (CVT) 12.3±1.01 vs 8.4±0.6, 12.3±1.018 vs 7.6±0.6), these changes were more pronounced after anxiety induction compared with neutral state (CSI- p=0.02 and 0.05 and CVT-p=0.001 and 0.01). GMA dominant power increase was blunted (N vs AN, 5.05±0.9 vs −1.4±1.1, p=0.0001) with increased tachygastria (N vs AN, 22.6±17.4 vs 25.2±10.66 p=0.02) during the anxiety state. Anxiety state increased cortisol secretion compared with neutral (%13.71±5.5 vs −9.06±6.19, p=0.003). The test meal increased satiation hormones, GLP-1 and PP (p=0.001 and 0.001), with no differences between the two emotional states. Ghrelin levels decreased after the nutrient challenge, moreover, the degree of drop was more marked during anxiety state (N vs AN, per cent change −59.8±21.2 vs −454.7±169.2 (p=&lt;0.05). Ghrelin levels correlated with CVT (r=0.5, p=0.03) and cortisol responses (r=0.5 and p=0.02). <h3>Conclusion</h3> Our results suggest that heightened meal sensations are induced by negative emotional state and result from interplay between autonomic reactivity and gastric myoelctrical responses through interaction with gut hormone responses. Further studies are now required to study the role of these psycho-physiological factors in patients with obesity.
S83 Calcineurin inhibition impairs phenotypic maturation of dendritic cells in a<i>in vitro</i>model of invasive aspergillosis in lung transplant recipients
Authors: AG Adlakha, DPH Armstrong-James, B Lenhard
Journal: Thorax (2015)

<h3>Introduction</h3> Invasive aspergillosis in lung transplant recipients on immunosuppression is associated with high morbidity and mortality. The calcineurin inhibitor tacrolimus (FK506) inhibits the calcineurin-NFAT axis, which impairs the innate response to fungal infection.<sup>1</sup> Dendritic cells (DC’s) play a pivotal role in signalling to the adaptive immune system in infection – immature DC’s phagocytose antigen, leading to maturation into DC’s capable of stimulating T-cells. We investigated the effect of FK506 on DC function in invasive aspergillosis by assessing phenotypic maturation of DC’s in response to <i>Aspergillus fumigatus</i> (AF) infection. <h3>Methods</h3> Healthy volunteer PBMC’s negatively isolated by Ficoll® gradient were differentiated into DC’s with GM-CSF and IL-4. Day 5 cells were matured with IFN-γ. Day 7 cells were treated with FK506 and/or inoculated with swollen conidia of <i>A.fumigatus </i>(MOI 1:1). Cells were then stained with PE-bound anti-CD83 (a late maturation marker) and PerCP-Cy5.5-bound anti-CD-209 (a DC-specific marker) and analysed by the ImageStream® imaging flow cytometer. Statistical analysis was performed with Graphpad Prism v6.0, using unpaired t-tests with Welch correction. <h3>Results</h3> 5000 cells/condition were analysed. DC’s were subsetted by gating for CD-209 positivity. FK506 was not toxic to cells (similar cell viability between groups). We demonstrated up-regulation of CD83 (measured by mean fluorescent intensity) with IFN-γ stimulation of DC’s (12534 ± 799.3 vs. 26228 ± 1462, p &lt; 0.0001; mean fluorescent units +/-SEM), AF infection of unstimulated DC’s (12534 ± 799.3 vs. 29888 ± 1393, p &lt; 0.0001) and for AF infection of IFN-γ-stimulated DC’s (26228 ± 1462 vs. 36778 ± 1356, p &lt; 0.0001). CD83 mean fluorescent intensity was reduced with FK506 treatment of IFN-γ-stimulated DC’s (26228 ± 1462, vs. 20219 ± 846.0, p = 0.0004), AF-infected unstimulated DC’s (29888 ± 1393 vs. 24289 ± 1253, p = 0.0028), and AF-infected, IFN-γ-stimulated DC’s (36778 ± 1356 vs. 30159 ± 1279, p = 0.0004), but unchanged for unstimulated, un-infected DC’s (12534 ± 799.3, vs. 11942 ± 762.5, p = 0.5921). <h3>Conclusion</h3> Both<i> A.fumigatus</i> infection and IFN-γ stimulation promote phenotypic maturation of DC’s <i>in vitro</i>, and treatment with FK506 inhibits maturation in this context. This suggests an inhibitory effect of FK506 on innate antigen presentation to T-cells and may impair the adaptive immune response to invasive aspergillosis in lung transplants recipients. <h3>Reference</h3> 1 Herbst S, Shah A, Mazon Moya M, <i>et al</i>.<i> EMBO Mol Med</i>. 2015;<b>7</b>(3):240–58
SAT0041 The Course of Bone Marrow Edema in Early Undifferentiated and Rheumatoid Arthritis; A Longitudinal MRI Study on Bone Level
Authors: W.P. Nieuwenhuis, H.W. van Steenbergen, W. Stomp, T. Stijnen, T.W. Huizinga, J.L. Bloem, D. van der Heijde, M. Reijnierse, A.H. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> In rheumatoid arthritis (RA) patients, bone marrow edema (BME)-scores are associated with development of erosions. However, little is known on the course and outcome of BME at bone level. Therefore this study determined the association of BME and MRI-synovitis in the same bone longitudinally. <h3>Objectives</h3> This study was aimed to determine the course of BME and MRI-synovitis at bone level. Furthermore the association between the course of BME and local synovitis and the development of erosions in the same bone was studied. <h3>Methods</h3> 1,947 bones of MCP, wrist and MTP-joints of 59 patients presenting with rheumatoid or undifferentiated arthritis were studied using 1.5T MRI at baseline, after four and twelve months. Scanning and scoring of BME, synovitis and erosions were performed according to RAMRIS. The relation of the course of BME and synovitis to erosive progression at bone level during 1-year was evaluated. <h3>Results</h3> Of the bones showing BME at baseline (n=203), BME persisted in 56%, disappeared in 39%, and disappeared-reappeared seldom (5%). Stratified analyses at baseline revealed that BME was associated with erosive progression, in presence and in absence of local synovitis (ORs 7.5 95%CI 3.8-14.9 and 6.9 95%CI 1.9-25.6). Local synovitis, however, was not associated with erosive progression (OR 2.0 95%CI 0.6-7.0 in presence of BME and 1.9 95%CI 0.8-4.1 in the absence of BME). In multivariable GEE-analyses, persistent BME was strongly associated with erosive progression (OR 60 95%CI 17-318), in contrast to persistent synovitis (OR 1.4 95%CI 0.4-5.3). <h3>Conclusions</h3> BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independent of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for the comprehension on the development of erosions in RA. <h3>Disclosure of Interest</h3> None declared
Variceal Hemorrhage in a Patient With Hepatitis C Virus Cirrhosis in Whom Liver Synthetic Function had Normalized After Viral Elimination
Authors: Jordan Sack, Guadalupe Garcia‐Tsao
Journal: Hepatology (2016)

1Department of Internal MedicineYale University School of MedicineNew HavenCT 2Section of Digestive DiseasesYale University School of MedicineNew HavenCT 3Section of Digestive DiseasesVA‐CT Healthcare SystemWest HavenCT *ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO:Guadalupe Garcia‐Tsao, M.D.Section of Digestive DiseasesYale University School of Medicine333 Cedar Street1080 LMPP.O. Box 208019New Haven, CT 06520‐8019E‐mail: [email protected]
A Comparison of Childhood and Adult Type I Diabetes Mellitus
Authors: Jukka Karjalainen, Pasi Salmela, Jorma Ilonen, Heljä-Marja Surcel, Mikael Knip
Journal: New England Journal of Medicine (1989)

The incidence rate of insulin-dependent (Type I) diabetes mellitus is bimodal: one peak occurs close to puberty, and the other in the fifth decade. To evaluate possible differences in these forms of the disease, we examined the clinical, biochemical, autoimmune, and genetic features of 82 children and adolescents (1.3 to 18.2 years old) and 44 adults (20.0 to 55.8 years old) when they presented with Type I diabetes. The mean (±SEM) duration of symptoms before diagnosis was longer in the adults (7.5±1.0 vs. 3.9±0.4 weeks; P<0.001), and their serum C-peptide concentrations at diagnosis were higher (0.29±0.03 vs. 0.17±0.01 nmol per liter; P<0.001), suggesting that they had more residual beta-cell function. There were no significant differences between the two groups in sex ratio, blood glucose levels, hemoglobin A1 values, degree of metabolic decompensation, or frequency of Type I diabetes in first-degree relatives. Thirty-four of 80 children tested (42.5 percent) were positive for insulin autoantibodies, as compared with only 1 of 26 adults (3.8 percent; P<0.001). However, the frequencies of islet-cell autoantibodies were similar in the adults and children (conventional autoantibodies, both 81 percent; complement-fixing autoantibodies, 46.2 percent and 60 percent). More children than adults were heterozygous for both HLA-Dw3/4 antigens (26.6 percent vs. 9.8 percent; P<0.05) and HLA-DR3/4 antigens (36.6 percent vs. 12.5 percent; P<0.05). We conclude that Type I diabetes that begins in adulthood is characterized by a longer symptomatic period before diagnosis, better preservation of residual beta-cell function, and lower frequencies of insulin autoantibodies and HLA-D3/D4 heterozygosity than Type I diabetes that begins in childhood or adolescence. (N Engl J Med 1989; 320:881–6.)
PTH-045 Minimally invasive proctocolectomy and ileal pouch-anal anastomosis: an attractive management option for patients with ulcerative colitis
Authors: J Ahmed, S Stefan, N Goh, K Flashman, J Khan, A Parvaiz
Journal: Gut (2015)

<h3>Introduction</h3> Restorative proctocolectomy and Ileal pouch-anal anastomosis (IPAA) is the standard procedure for patients with ulcerative colitis (UC), refractory to medical treatment. Recently, there has been increased interest in the use of laparoscopy and robotic approaches for the management of these patients, due to associated benefits of minimal access techniques. Minimally invasive 2 or 3 stage restorative proctocolectomy and IPAA is technically challenging and performed in specialised centres. Aim of this study was to assess the feasibility and short term outcomes of this procedure in a specialist unit. <h3>Method</h3> Prospectively collected data related to 52 consecutive patients who underwent restorative proctocolectomy and IPAA, from June 2008 to February 2015, was analysed. <h3>Results</h3> Male were 32 (61%) and median age was 37 years (range – 18–68) with median BMI of 25 (range –17–38). 39 (75%) patients had previous surgery. 15 (28%) underwent panproctocolectomy and IPAA, whereas 37 (78%) patients had a 3-stage procedure. Median operating time was 220 (range – 135–480) minutes. 4 (2.8%) cases were performed with robotic approach whilst one case (1.9%) was converted to open in laparoscopic group. No intra-operative complication was recorded. All patients had a defunctioning ileostomy fashioned to protect pouch anal anastomosis. Median length of stay was 7 (range – 3–38) days. 30 days mortality, reoperation and anastomotic leak was none however 13 (25%) patients had readmission within 30days. The most common causes for readmission were abdominal pain and high stoma output. <h3>Conclusion</h3> Minimally invasive restorative proctocolectomy and IPAA is safe and attractive option. It has shown good short term outcomes, and offers the benefit of better cosmesis and short hospital stay. <h3>Disclosure of interest</h3> None Declared.
ATNT-10DOES VALPROIC ACID IMPROVE SURVIVAL IN GLIOBLASTOMA? A META-ANALYSIS OF RANDOMIZED TRIALS IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Caroline Happold, Thierry Gorlia, Olivier Chinot, Mark Gilbert, Burt Nabors, Wolfgang Wick, Stephanie L. Pugh, Monika Hegi, Timothy Cloughesy, Patrick Roth, David Reardon, James R. Perry, Minesh Mehta, Roger Stupp, Michael Weller
Journal: Neuro-Oncology (2015)

Several small uncontrolled retrospective case series as well as a post-hoc analysis of the registration trial for temozolomide in newly diagnosed glioblastoma (Weller et al., 2011) have indicated an association between valproic acid (VPA) use and improved outcome in patients with newly diagnosed glioblastoma. To confirm the hypothesis generated based on the analysis of the temozolomide registration trial, we performed a combined analysis of a survival association of AED use at the start of chemoradiotherapy with temozolomide in the pooled patient cohort (n = 1869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (NCT00943826), RTOG-0825 (NCT00884741), CENTRIC (NCT00689221) and CORE (NCT00813943). Progression-free (PFS) and overall survival (OS) were compared between (i) VPA versus no AED, (ii) VPA versus enzyme-inducing (EI)-AED, or (iii) VPA versus other non-EI-AED (without VPA). Results of Cox regression models stratified by trial and adjusted baseline prognostic factors including O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status were interpreted. The same analyses were performed with levetiracetam (LEV). VPA use at the start of chemoradiotherapy was not associated with improved PFS or OS compared with patients receiving no AED (PFS: hazard ratio (HR) = 0.92, 95% confidence interval (CI) 0.75-1.13, p = 0.41; OS: HR = 1.00, 95% CI 0.80-1.25, p = 0.95), EI-AED (PFS: HR = 0.95, 95% CI 0.74-1.21, p = 0.62; OS: HR = 1.02, 95% CI 0.0.77-1.33, p = 0.93) or non-EI-AED (PFS: HR = 1.02, 95% CI 0.80-1.3, p = 0.92; OS: HR = 1.06, 95% CI 0.83-1.35, p = 0.67). Similarly, no association with outcome was seen for LEV use. This pooled analysis did not validate an association of VPA or LEV use with improved survival, challenging the need for a full phase III trial exploring the repurposing of VPA or LEV as add-on to the standard of care treatment of newly diagnosed glioblastoma.
Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle
Authors: Megha H. Talati, Evan L. Brittain, Joshua P. Fessel, Niki Penner, James Atkinson, Mitch Funke, Carrie Grueter, W. Gray Jerome, Michael Freeman, John H. Newman, James West, Anna R. Hemnes
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: In heritable pulmonary arterial hypertension with germline mutation in the bone morphogenetic protein receptor type 2 (BMPR2) gene, right ventricle (RV) dysfunction is associated with RV lipotoxicity; however, the underlying mechanism for lipid accumulation is not known.Objectives: We hypothesized that lipid accumulation in cardiomyocytes with BMPR2 mutation occurs owing to alterations in lipid transport and impaired fatty acid oxidation (FAO), which is exacerbated by a high-lipid (Western) diet (WD).Methods: We used a transgenic mouse model of pulmonary arterial hypertension with mutant BMPR2 and generated a cardiomyocyte cell line with BMPR2 mutation. Electron microscopy and metabolomic analysis were performed on mouse RVs.Measurements and Main Results: By metabolomics analysis, we found an increase in long-chain fatty acids in BMPR2 mutant mouse RVs compared with controls, which correlated with cardiac index. BMPR2-mutant cardiomyocytes had increased lipid compared with controls. Direct measurement of FAO in the WD-fed BMPR2-mutant RV showed impaired palmitate-linked oxygen consumption, and metabolomics analysis showed reduced indices of FAO. Using both mutant BMPR2 mouse RVs and cardiomyocytes, we found an increase in the uptake of 14C-palmitate and fatty acid transporter CD36 that was further exacerbated by WD.Conclusions: Taken together, our data suggest that impaired FAO and increased expression of the lipid transporter CD36 are key mechanisms underlying lipid deposition in the BMPR2-mutant RV, which are exacerbated in the presence of dietary lipids. These findings suggest important features leading to RV lipotoxicity in pulmonary arterial hypertension and may point to novel areas of therapeutic intervention.
Identification of characteristic and prognostic values of chromosome 1p abnormality by multi-gene fluorescence in situ hybridization in multiple myeloma
Authors: F Li, L Hu, Y Xu, Z Li, S Yi, Z Gu, C Li, M Hao, K Ru, F Zhan, A Zetterberg, W Yuan, T Cheng, L Qiu
Journal: Leukemia (2015)
Case 16-2014
Authors: Doreen Ramogola-Masire, Anthony H. Russell, Scott Dryden-Peterson, Jason A. Efstathiou, Mukendi K.A. Kayembe, David C. Wilbur
Journal: New England Journal of Medicine (2014)

A 46-year-old woman with HIV and a high-grade squamous intraepithelial lesion was evaluated in Botswana because of postcoital bleeding. During examination of the cervix and vagina, a large fungating lesion was seen. Diagnostic procedures were performed.