tbuckley/cabot-search huggingface dataset:
P202 Assessment of bronchiectasis scoring systems: a long term cohort study
Authors: HC Ellis, S Cowman, M Fernandes, R Wilson, MR Loebinger
Journal: Thorax (2015)

<h3>Introduction</h3> Bronchiectasis is a chronic, disabling illness with an unpredictable clinical course. Two multidimensional scores have been developed to predict mortality in bronchiectasis: the bronchiectasis severity index (BSI) and the FACED score.<sup>1,2</sup> This study is a retrospective cohort study aiming to compare these scores and test their ability to predict long-term mortality in bronchiectasis. <h3>Methods</h3> Data was obtained for 74 subjects with bronchiectasis who had previously taken part in research at our centre. BSI and FACED scores were calculated and outcomes were ascertained after a median of 18.8 years follow-up. Receiver operator characteristic (ROC) curves for mortality were generated and survival between groups compared using univariate Cox proportional hazards analysis. <h3>Results</h3> Both scoring systems had similarly excellent predictive power for 5-year mortality, with area under the ROC curve (AUC) 0.79 for BSI and 0.8 for FACED. Both scores were also able to predict 15-year mortality (Figure 1), with the FACED score showing superior predictive power (AUC 0.82 vs 0.69 <i>P = 0</i>.0495). For both scores subjects with high scores had an increased risk of death compared to the low scoring group (hazard ratio (HR) for death 3.6 for BSI <i>P = 0</i>.02, 12.5 for FACED <i>P &lt; 0</i>.001). The intermediate scoring FACED group was also at an increased risk of death (HR 5.9 <i>P </i> &lt; 0.001), whereas the intermediate BSI group was not (HR 1.4 <i>P = 0</i>.58). The BSI tended to assign higher scores; accordingly the high BSI group was larger (33 vs 6 subjects) with a lower mortality (57% vs 83%) than the equivalent FACED group. <h3>Conclusion</h3> This study demonstrates the ability of the BSI and FACED score to predict mortality in bronchiectasis over a far longer period than previously described. Such tools will be valuable for stratification in clinical trials and for identifying individuals in a higher risk group for intensified treatment. <h3>References</h3> 1 Chalmers JD, Goeminne P, Aliberti S, <i>et al.</i> The bronchiectasis severity index. <i>An international derivation and validation study. Am J Respir Crit Care Med</i>. 2014;<b>189</b>:576–85 2 Martínez-García MÁ, de Gracia J, Vendrell Relat M, <i>et al</i>. Multidimensional approach to non-cystic fibrosis bronchiectasis. <i>The FACED score. Eur Respir J</i>. 2014;<b>43</b>:1357–1367
Long-Term Outcome Of Adolescents and Young Adults (AYA) After Autologous Transplantation For Lymphoma; Single Center Experience With Bu-CY-VP16 Conditioning Therapy
Authors: Rabi Hanna, Brian J. Bolwell, Ronald Sobecks, Brad Pohlman, Deepa Jagadeesh, Hien K. Duong, Brian T. Hill, Kelly Cherni, Christina Ferraro, Gina Green, Betty K. Hamilton, Lisa Rybicki, Matt Kalaycio
Journal: Blood (2013)
Specificity of lactate infusions in social phobia versus panic disorders
Authors: M R Liebowitz, A J Fyer, J M Gorman, D Dillon, S Davies, J M Stein, B S Cohen, D F Klein
Journal: American Journal of Psychiatry (1985)

Lactate infusions produced panic attacks in one of 15 patients with social phobia, four of nine with agoraphobia, and 10 of 20 with panic disorder in a blind study. The proportion of patients with social phobia who panicked in response to lactate was significantly lower than that of patients with agoraphobia or panic disorder. These findings lend validity to the DSM-III classification of anxiety states. They also suggest that the pathophysiology of social phobia differs from that of disorders characterized by spontaneous panic attacks.
Outbreak of Severe Hepatitis Due to Delta and Hepatitis B Viruses in Parenteral Drug Abusers and Their Contacts
Authors: L A Lettau, J G McCarthy, M H Smith, S C Hadler, L J Morse, T Ukena, R Bessette, A Gurwitz, W G Irvine, H A Fields
Journal: New England Journal of Medicine (1987)

We investigated an unusually large and severe outbreak of hepatitis B, primarily involving parenteral drug abusers and their sexual contacts, in Worcester, Massachusetts, over a 21-month period from 1983 to 1985. Of 135 patients with drug-related acute hepatitis B, 81 percent were parenteral drug abusers and 19 percent had sexual contact with drug abusers; 13 fulminant cases resulted in 11 deaths. Among the patients with hepatitis B, evidence of delta virus infection was found in 54 percent of drug abusers, 33 percent of their sexual contacts, and 9 percent of other patients with acute hepatitis B (P less than 0.001). Most of the delta infections (86 percent) were coinfections with hepatitis B virus; the balance were superinfections. Delta infection was strongly associated with fulminant hepatitis: 91 percent of patients with a fulminant outcome had delta infection, as compared with 45 percent of less severely ill drug abusers and their contacts (P = 0.0037). Alcohol, other drugs, and other hepatitis viruses could not be implicated as hepatotoxic cofactors for fulminant disease. This outbreak appeared to result from the concurrent spread of hepatitis B and delta viruses among new drug users. Control measures included the distribution to physicians of guidelines on prophylaxis in contacts of patients with hepatitis B, health education for drug abusers, and a hepatitis B vaccination program. Despite these efforts, the outbreak continued unabated until the number of new cases began to decline slowly in late 1986.
NIMG-07RADIOGRAPHIC PATTERNS OF PROGRESSION WITH ASSOCIATED OUTCOMES AFTER BEVACIZUMAB THERAPY IN GLIOBLASTOMA PATIENTS
Authors: David Cachia, Nabil A. Elshafeey, Carlos Kamiya-Matsuoka, Masumeh Hatami, Kristin D. Alfaro-Munoz, Jacob J. Mandel, Rivka R. Colen, John F. de Groot
Journal: Neuro-Oncology (2015)

INTRODUCTION: Patterns of progression following bevacizumab (bev) treatment and associated outcomes remain poorly characterized. In patients (pts) with glioblastoma (GB) treated with bev, we describe radiographic patterns of progression and their association with outcome. METHODS: 64 pts treated at MD Anderson matched the predetermined inclusion criteria. Tumor progression after bev treatment was assessed according to the RANO criteria and pts categorized into groups based on previously published data: Group1:exclusively T2-diffuse hyperintense tumor (T2-diffuse), Group2:initial decrease and subsequent flare-up of contrast enhancement (CE) at progression (cT1 Flare-up), Group3:no decrease in CE or development of new lesions at first follow-up imaging (non- responders), Group4:exclusively T2-circumscribed hyperintense tumor progression (T2-circumscribed). In addition, we screened for new diffusion-restricted lesions or pre-contrast T1-hyperintense lesions or both (double-positive). RESULTS: Pts were categorized into Group1:11%, Group2: 33%, Group3: 45%, Group4: 11%. 16 pts had T1-hyperintense lesions and 37 had restricted diffusion;10 pts had double-positive lesions. There was no significant difference in time-to-initiation of bev treatment in the 4 groups. After starting bev, median OS and PFS (months) was Group1:8.6, 4.2 Group2:12.3,3.9 Group3:5.6,1.4 and Group4:7.0,3.2 respectively. Comparing non-responders vs the rest of the groups (responders), OS from initiation of bev was 5.6 vs 10 months (p = <0.001). OS from diagnosis of GB was not significantly different between the 4 groups. Post-progression on bev, OS was: Group1:3.9,Group2:6.4, Group3: 3.8 and Group4:3.0. Pts with restricted diffusion had worse OS (23.4 vs17.4 months). There was no difference in survival based on presence/absence of T1-hyperintense or double-positive lesions. CONCLUSION: Compared to non-responders, cT1 Flare-up have better PFS/OS after bev initiation. Post-progression on bev, cT1 Flare pts lived significantly longer than T2-diffuse and non-responders. Though T2-diffuse and T2-circumscribed have a better PFS after bev initiation compared to non-responders, no OS benefit was seen. Restricted diffusion was a radiographic marker of worse outcomes.
A subgroup with improved overall survival from the phase 2 IMPACT study: Maintenance therapy of metastatic colorectal cancer patients with the TLR-9 agonist MGN1703.
Authors: Jorge Riera-Knorrenschild, Dirk Arnold, Hans-Georg Kopp, Frank Mayer, Hendrik Kroening, Dieter Nitsche, Jan Kuhlmann, Reinhard Ziebermayr, Johannes Andel, Alfredo Zurlo, Burghardt Wittig, Werner Scheithauer, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2015)

3049 Background: The double-blind placebo-controlled phase 2 IMPACT trial aimed to assess the clinical efficacy, safety, and immunological effects of the potent TLR9 agonist MGN1703, given at the dose of 60 mg subcutaneously twice weekly as switch maintenance after disease control due to first-line induction chemotherapy +/- bevacizumab in patients with metastatic colorectal cancer (mCRC). Methods: After randomization of 59 patients the trial was prematurely closed and final analysis showed a superior effect of MGN1703 compared to placebo with hazard ratios (HR) for the primary endpoint PFS on maintenance of 0.55 (p = 0.041) and 0.56 (p = 0.070) by local investigator assessment or independent radiological review, respectively. Exploratory PFS analyses of pretreatment characteristics identified patients with normalized CEA, objective response, and the presence of activated NKT cells at the end of induction chemotherapy to benefit the most from maintenance with MGN1703. The impact of these factors on the secondary endpoint overall survival (OS) is presented here. Results: OS data were not mature at time of final study analysis, since only 35% of MGN1703 patients and 50% of placebo patients had an event. The HR for OS of the whole study population was 0.63 (median 22.6 vs. 15.1 months). The subgroup of patients randomized into the study with confirmed RECIST response had a HR of 0.40 (median 24.5 vs. 15.1 months), suggesting this may be the population with greater benefit. HR for patients with normalized CEA or with activated NKT cells were 0.69 and 0.43, respectively. Based on this evidence, patients with mCRC and objective response after standard induction therapy are randomized in the phase 3 IMPALA study to standard treatment or switch maintenance with MGN1703. CEA and activated NKT cells are stratification factors for the study and will be prospectively assessed. Conclusions: The pretreatment characteristics predictive of a PFS benefit in the IMPACT study seem to retain their value also in exploratory analyses for OS. This information has been used to design the phase 3 IMPALA study, currently recruiting patients. Clinical trial information: NCT01208194.
The 1993 Epidemic of Pertussis in Cincinnati -- Resurgence of Disease in a Highly Immunized Population of Children
Authors: Celia Christie, Mary L. Marx, Colin D. Marchant, Shirley F. Reising
Journal: New England Journal of Medicine (1994)

In 1993 there was a resurgence of pertussis in the United States. Altogether, 6335 cases were reported, the most in 26 years.
Liver capsule: IRFs in hepatocytes: Pathophysiology
Authors: Pi‐Xiao Wang, Xiao‐Jing Zhang, Hongliang Li
Journal: Hepatology (2015)

1Department of CardiologyRenmin Hospital of Wuhan University 2Animal Experiment Center/Animal Biosafety Level‐III LaboratoryWuhan UniversityWuhanChina 3State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical Sciences, University of MacauMacau, China *Corresponding author: [email protected]
A Chronobiologic Abnormality in Luteinizing Hormone Secretion in Teenage Girls with the Polycystic-Ovary Syndrome
Authors: Barnett Zumoff, Ruth Freeman, Susan Coupey, Paul Saenger, Morri Markowitz, Jacob Kream
Journal: New England Journal of Medicine (1983)

We investigated possible abnormalities of central-nervous-system regulation of luteinizing hormone secretion in the polycystic-ovary syndrome by determining the plasma concentrations of luteinizing hormone over a 24-hour period in five teenage girls with the syndrome; profiles of prolactin and cortisol were also obtained. Four of the five patients had strikingly abnormal plasma luteinizing hormone profiles: whereas normal pubertal girls have a daily surge in secretion of luteinizing hormone that is coterminous with their nocturnal sleep period, our patients had surges that were grossly desynchronized from their sleep period, occurring seven to eight hours later in the daytime than normal. The chronobiologic disturbance involved only luteinizing hormone; the profiles of cortisol and prolactin were normal. This finding points to the central nervous system as the probable locus of the initiating pathophysiology of polycystic-ovary syndrome.
Case 70-1962
Authors: Robert H. Jones, Edgar B. Taft
Journal: New England Journal of Medicine (1962)

Presentation of Case First admission. A thirty-seven-year-old woman was referred to the hospital because of hepatosplenomegaly.Eight years previously the patient began to experience episodes of vague, transient pain in the joints of the knees, ankles and wrists, accompanied by abdominal discomfort, weakness and malaise. She was told that she was anemic and given "iron pills" for a few months. Two years before admission abdominal swelling and flatulence began, with no associated nausea, vomiting or diarrhea. There was no melena, jaundice or hematemesis, but she bruised easily and had several episodes of epistaxis for a few months before entry. . . .
HER2 (in the TACT and TEAM trials) differentially affects invasive potential in ER-ve and ER+ve breast cancers
Authors: J. Bartlett, E. A. Mallon, A. Forsyth, D. A. Cameron, E. Hall, S. Johnston, L. Johnson, P. Barrett-Lee, M. Grant, D. Rea
Journal: Journal of Clinical Oncology (2005)

9557 Background: HER2 status varies within different breast cancer populations and is inversely related to ER expression. Recent data, from the TACT trial, suggested that HER2 positivity in ER+ve disease was higher than previously reported (SABCS2003). Methods: We have analysed in a single department, HER2 expression in 1282 ER+ve & 330 ER-ve breast cancers from 2 recent UK adjuvant breast cancer trials (TEAM and TACT). Logistic regression was used to test for multivariate associations between HER2 and clinical parameters, including trial group. Results: For ER+ve cases HER2+ve rates were significantly lower in TEAM (16.2%) vs TACT (23.2%) patients (p = 0.0007). There were significant differences in the associations between conventional prognostic factors and HER2 according to ER status. In ER+ve tumours histological type (p =0.0064), grade (p <0.0001) and PgR status (0.0004) but not nodal status were significantly associated with HER2 status. Increasing grade was associated with increasing frequency of HER2 positivity in ER+ve cancers (G1 5.8%, G2 12.4%, G3 29%, OR vs G1; G2 = 2.114 G3 =4.616, p = 0.07 and 0.0002 respectively). Conversely in ER-ve cases a strong association between HER2 positivity and nodal status was observed and no significant association with grade was observed. ER+ve Infiltrating ductal carcinomas exhibited higher rates of HER2 positivity (21%) than ER+ve infiltrating lobular cancers (4%, p =0.0009, OR 0.236). PgR-ve cases were more frequently HER2 positive (OR 2.015, 95% CI 1.229–3.309, p = 0.006). Conclusion: No evidence of a selection bias, other than that predicted from the inclusion criteria of the TEAM and TACT trial, was observed with respect to HER2 status. Patient age, nodal status and tumour size were not independent predictors of HER2 status in this cohort. In ER+ve breast cancers, histological type, grade and PgR status are important risk factors for HER2 positivity. Conversely nodal status is an important risk factor for HER2 positivity in ER-ve disease. This provides evidence for a significant interaction between HER2 and ER in determining disease spread in breast cancer. We acknowledge the support of the TEAM & TACT management groups, patients and pathologists. No significant financial relationships to disclose.
Practical Considerations of Clinical Oxygen Lack
Authors: Charles S. Houston
Journal: New England Journal of Medicine (1949)

WHEN confronted with a patient whose problem may in part be due to oxygen lack, the physician often bases his opinion upon the presence or absence of dyspnea and cyanosis, forgetting that these important signs are but two of the many changes due to anoxia. He may not realize that either or both may be present even though oxygenation is adequate, and he may not appreciate that both may be absent even when oxygen lack is severe. In its classic form anoxia may be recognized at a glance, but in other circumstances, not infrequently encountered in practice, the most elaborate . . .
AB0197 Soluble Semaphorin 3E (SEMA3E): A Biomarker for Dysregulation of Vascular Tone Control in Systemic Sclerosis (SSC)
Authors: C. Mazzotta, E. Romano, S. Bellando-Randone, M. Manetti, A. Radicati, J. Blagojevic, M. Matucci-Cerinic, S. Guiducci
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> SSc is a vasculopathy characterised by dysregulation of angiogenesis and vascular tone control leading to severe ischemia and loss of capillaries. In the complex system of interconnection between blood vessels and nerves there is an emerging evidence suggesting that proteins involved in transmitting axonal guidance cues, such as class III semaphorins, play a role in the regulation of vascular development. Sema3E has been shown to repel endothelial cells, modulating the cytoskeleton and focal adhesion structures leading to cellular apoptosis. <h3>Objectives</h3> To investigate if soluble Sema3E could be involved in the dysregulation of vascular tone control in primary Raynaud9s phenomenon (pRP) and in secondary RP investigating (Very Early Diagnosis of Systemic Sclerosis) VEDOSS and SSc patients. <h3>Methods</h3> Sema3E serum levels were measured by quantitative colorimetric sandwich ELISA in 102 pRP serum samples without autoantibodies positivity and without nailfold videocapillaroscopy (NVC) alterations, 100 SSc, 48 VEDOSS patients and 104 age- and sex-matched healthy controls. SSc and VEDOSS patients were evaluated for internal organ damage. Sema3E levels were expressed as median and range and compared by Mann-Whitney U test. p≤0.05 were considered statistically significant. <h3>Results</h3> Sema3E levels were significantly increased in pRP (median 1.00 ng/mL, range 0.00-5.84 ng/mL), VEDOSS (median 0.79 ng/mL, range 0.00-1.45 ng/mL) and SSc patients (median 0.85 ng/mL; range 0.00-18.01 ng/mL) versus healthy controls (median 0.55 ng/mL; range 0.00-1.47 ng/mL) (p&lt;0.001). Sema3E was significantly higher in pRP than VEDOSS (p=0.025), while no significant differences were detected between pRP and SSc. In SSc with early NVC pattern, Sema3E levels were significantly increased (median 1.16 ng/mL range 0.63-9.53 ng/mL) in comparison to those detected in the late NVC pattern (median 0.75 ng/mL range 0.00-3.78 ng/mL, p=0.028). Moreover, Sema3E levels were significantly increased in SSc patients without ulcers (median 0.98 ng/mL; range 0.00-18.01 ng/mL) in comparison to those with digital ulcers (median 0.79 ng/mL; range 0.00-3.78 ng/mL, p=0.038). Sema3E was significantly higher in pRP compared to late SSc NVC pattern (p=0.04) and to SSc patients with digital ulcers (p=0.031). <h3>Conclusions</h3> Our data show that Sema3E sera levels are significantly increased in pRP, VEDOSS and SSc patients. Circulating Sema3E levels are higher in SSc patients without digital ulcers and with early NVC pattern. In particular, Sema3E may be involved in the early modifications of neuro-vascular mechanisms leading to dysregulation of vascular tone control. <h3>Disclosure of Interest</h3> None declared
The Pituitary-Testicular Axis in Men with Chronic Renal Failure
Authors: S. Holdsworth, R. C. Atkins, D. M. de Kretser
Journal: New England Journal of Medicine (1977)

We studied the effects of uremia on the pituitary-testicular axis in 35 men with creatinine clearances less than 4 ml per minute per 1.7m(2). We found significant elevation (p less than 0.001) of plasma luteinizing hormone and follicle-stimulating hormone (p less than 0.005) and subnormal levels of testosterone (p less than 0.005). Testicular histology revealed severe spermatogenic damage. Human chorionic gonadotropin produced a subnormal testosterone response. The initial response of plasma luteinizing hormone and follicle-stimulating hormone to luteinizing-hormone-releasing hormone was normal, but their subsequent decline was prolonged. The suppression of plasma luteinizing hormone levels by testosterone propionate was normal, but the nadir occurred late; the elevated plasma luteinizing hormone level was due to reduced metabolic clearnace and increased production. Chronic renal failure interferes with testicular steroid production and spermatogenesis.
PWE-169 Treatment of oesophageal cell lines with docosahexaenoic fatty acid (DHA) and oxaliplatin: effects on proliferation, expression of vascular endothelial growth factor and IL-6
Authors: AM Eltweri, LM Howells, AL Thomas, AR Dennison, DJ Bowrey
Journal: Gut (2015)

<h3>Introduction</h3> Oesophageal cancer is a very aggressive disease, and despite advances in cancer treatment, the prognosis is still poor. Growth factors such as vascular endothelial growth factor (VEGF) and pro-inflammatory markers have a major role in cancer progression, survival and metastasis. We examined anti-proliferative effects of DHA and oxaliplatin on two oesophageal cancer cell lines, in addition to assessing effects on VEGF and the inflammatory cytokine IL-6. <h3>Method</h3> Two Oesophageal cell lines (OE33 and OE19) were treated with either DHA or Oxaliplatin (0–50 µM) and incubated for up to 144 h. Cell counts were measured using a Z2 particle size analyser and expression of VEGF and IL-6 measured in cell culture supernatant using MSD ELISA kits. Three way ANOVA was used to analyse the data using StataIC 13 software. <h3>Results</h3> DHA reduced proliferation of OE33 and OE19 cell lines by 59% (p &lt; 0.001) and 26% (p = 0.019) respectively. Oxaliplatin reduced proliferation by 77% (p &lt; 0.001) and 76% (p &lt; 0.001) respectively, growth curve demonstrated in the Figure 1. Down regulation of VEGF expression in OE33 cells after 144 h DHA treatment (50 µM) was highly significant (p &lt; 0.0001, 95% CI -664.04 to -544.27) as was Oxaliplatin treatment (50 µM) (p &lt; 0.0001, 95% CI -803.97 to -581.70). OE19 cells exhibited sensitivity to both drugs at lower concentrations at this same time point; DHA (30 µM) (p = 0.005, 95% CI -63.88 to -19.57) and Oxaliplatin (20 µM) (p = 0.026 95% CI -73.1 to -6.54). The two drugs had no statistically significant inhibition of IL-6 expression in both cell lines despite inhibition of cell growth. <h3>Conclusion</h3> The data provide evidence that the DHA and Oxaliplatin have statistically significant down regulation effect of VEGF in the two oesophageal cell lines but didn't alter expression of pro-inflammatory markers such as IL-6. <h3>Disclosure of interest</h3> None Declared.