tbuckley/cabot-search huggingface dataset:
Infections with<i>Cryptococcus neoformans</i>in the Acquired Immunodeficiency Syndrome
Authors: S L Chuck, M A Sande
Journal: New England Journal of Medicine (1989)

We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital. We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis. In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS. Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40). Flucytosine had to be discontinued in over half the patients because of cytopenia. Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs. 141 days; P less than 0.004). The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source. The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively). From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.
Low Positioning of Umbilical-Artery Catheters Increases Associated Complications in Newborn Infants
Authors: Stefan T. Mokrohisky, Rodney L. Levine, Joel D. Blumhagen, Richard L. Wesenberg, Michael A. Simmons
Journal: New England Journal of Medicine (1978)

We performed a randomized prospective study of the effect of placement position of umbilical-artery catheters on complication rates in high-risk newborn infants. A higher complication rate (31 of 40 vs. 13 of 33) (P<0.005) occurred in the group with the catheter tip at the third to fourth lumbar segment, as compared to those with the tip at the seventh to eighth thoracic segment, owing to more episodes of blanching and cyanosis of the extremities. There was no difference between groups in the rate of complications requiring catheter removal. Aortography revealed thrombosis in 21 of 23 patients studied, but there was no clinical evidence of impaired circulation. In retrospect, we found that, independently of catheter position, administration of antibiotics through the catheter was associated with an increased rate of complications (63 vs. 20 per cent). Umbilical-artery catheterization entails potential risks regardless of the position of the catheter; placement of the catheter with its tip at the seventh to eighth thoracic segment may be associated with fewer complications than at lower positions. (N Engl J Med 299:561–564, 1978)
P1046 ENTECAVIR AND TENOFOVIR HAVE A COMPARABLE EFFICACY IN TREATMENT OF NUCLEOS(T)IDE ANALOGUE NAIVE PATIENTS WITH CHRONIC HEPATITIS B: A REAL LIFE EXPERIENCE
Authors: B. Baran, O.M. Soyer, A.C. Ormeci, S. Gokturk, S. Evirgen, F. Akyuz, C. Karaca, K. Demir, M. Gulluoglu, D. Onel, S. Badur, F. Besisik, S. Kaymakoglu
Journal: Journal of Hepatology (2014)
THU0507 The Effect of Mycophenolate Mofetil (MMF) on Plasmablasts/Plasma Cells (PB/PC) and Serum Free Light Chain (FLC) Levels in Patients with Systemic Lupus Erythematosus (SLE): Table 1
Authors: T. Fassbinder, U. Saunders, H. Becker, E. Jung, E. Mickholz, B. Schlüter, A.M. Jacobi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> B cell hyperactivity is a hallmark of SLE. Differential blood counts, lymphocyte subsets and serological parameters are affected by disease activity and therapy. <h3>Objectives</h3> To analyze the influence of MMF and other immunosuppressive drugs (ID) such as cyclophosphamide (CYC), azathioprine (AZA) or methotrexate (MTX) on B cell and PB/PC counts and FLC<sub>κ/λ</sub> levels. <h3>Methods</h3> We performed a retrospective cross-sectional analysis of cellular and serological parameters in patients with SLE. Lupus patients with comparably high disease activity and either on induction or on maintenance therapy were subdivided into different treatment groups and compared to activity-matched patients not on ID (Tab. 1). All parameters were also determined repeatedly after induction therapy with CYC (n=24) or MMF (n=23) and in another subset of patients with MMF-responsive quiescent disease during drug taper or withdrawel (n=27). <h3>Results</h3> Patients undergoing induction therapy with MMF had significantly lower PB/PC counts compared to patients treated with CYC or controls. In patients receiving maintenance therapy MMF was associated with a significantly lower PB/PC count compared to AZA and no ID. In addition PB/PC counts were also significantly lower in patients undergoing MTX treatment compared to controls. Consistent with these findings patients receiving MMF had significantly lower FLC<sub>κ</sub> serum levels compared to patients with CYC induction or controls. Patients receiving MMF to maintain remission had significantly lower FLC serum levels than controls, whereas AZA had no influence on FLC (Tab.1). A drastic decrease of FLC<sub>κ</sub> (p&lt;0.0007), FLC<sub>λ</sub> (p=0.0017), and PB/PC counts (p&lt;0.0001) was detected in patients who had been on MMF for 16 (10 to 65) weeks. In contrast, no significant change in FLC levels or PB/PC counts was noted 15 (10 to 39) weeks after starting CYC. Inversely, an increase of PB/PC counts was observed 92 (14 to 191) weeks after MMF had been tapered or discontinued (p&lt;0.0001). In the latter patients we also observed rising FLC levels, but this was not significant (FLC<sub>κ</sub> p=0.0807, FLC<sub>λ</sub> p=0.0501). <h3>Conclusions</h3> Compared to other ID used in patients with SLE, MMF leads to a fast and enduring reduction of PB/PC and FLC. Tapering MMF in clinically quiescent disease is associated with an increase in circulating PB/PC. We currently analyze if increased FLC levels or PB/PC counts predict clinical flares. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2241
Primary pure signet ring cell adenocarcinoma of non-Barrett’s esophagus
Authors: T. Terada
Journal: Endoscopy (2011)

Primary signet ring cell adenocarcinoma (SRCA) of the esophagus is very rare, with only two case reports [1] [2] and one case series [3] in the published literature. Most primary SRCAs arise in Barrett's esophagus [2] [3], with occurrence in non-Barrett's esophagus being extremely rare [1]. Moreover, primary pure SRCA (i. e., composed only of SRCA cells) has not been reported in the literature.
PWE-056 Delivery Of Bowelscope Screening – Experience From The Pilot Sites: Abstract PWE-056 Table 1
Authors: R Bevan, J Patnick, R Loke, B Saunders, J Stebbing, R Tighe, A Veitch, J Painter, CJ Rees
Journal: Gut (2014)

<h3>Introduction</h3> The NHS Bowel Cancer Screening Programme (BCSP) is being expanded to include a single flexible sigmoidoscopy (FSIG) called BowelScope, offered to all 55 year olds in addition to biannual faecal occult blood testing from age 60–75 years. 6 pilot sites began BowelScope screening in May 2013, with a view to full English coverage by the end of 2016. <h3>Methods</h3> We aim to describe practical issues involved in the delivery of BowelScope screening at the pilot centres, covering unit set-up, list format, and endoscopists delivering lists. A survey was sent to the 6 pilots for completion by screening staff. Data were also retrieved from the national BCSP database. <h3>Results</h3> The first BowelScope list was delivered in the South of Tyne Screening Centre on 7<sup>th</sup> May 2013. By December 2013, 4135 flexible sigmoidoscopy procedures had been performed in 6 centres. Centres have delivered 20–80 lists each, performing 2–7 lists per week. Sessions are run at varying times of day including evenings and Saturdays. 35 endoscopists undertake lists regularly, of whom 15 were already BCSP accredited. Other BCSP colonoscopists provide back up for lists when required. All non-BCSP were accredited through a combination of direct observation of procedural skills (DOPS) and an MQC exam. Specialist Screening Practitioners (SSPs) attend all lists, and are deployed in a variety of ways including: following patient journey, consenting or giving information, and supervision assistant SSPs. Table 1 shows details of screening lists by centre. <h3>Conclusion</h3> BowelScope screening is being successfully delivered at the six pilot centres. Each centre has developed a screening template and organisational pattern that works around patient needs and existing endoscopy and bowel screening services. New patterns of working have been required to deliver BowelScope and challenges remain regarding adequate numbers of endoscopists. <h3>Disclosure of Interest</h3> None Declared.
P2-11-01: Validation of Predictive DNA Damage Response (DDR) Assay in Luminal B and Basal-Like Breast Cancers.
Authors: AA Rodriguez, Y Mao, H Zhao, S Wong, JC Chang
Journal: Cancer Research (2011)

Abstract Background: We previously published a 69-gene DDR microarray signature that predicted for pathologic complete response (pCR) to anthracycline chemotherapy in women with basal-like breast cancer in two clinical studies1. Here, we sought to validate this predictive signature in independent data sets of breast cancers, selecting for basal-like and luminal B subtypes. We also customized a low density qRT-PCR array for use on formalin-fixed paraffin embedded tissue that will allow for prospective validation and clinical use. Methods: Six independent validation sets were selected with known response to DNA damaging agents, containing either anthracyclines or cisplatin2-7. One independent data set with known response to the microtubulin agent docetaxel (non-DNA damaging) was used. 8 Using PAM50 genes, the tumors were first classified according to the molecular subtype. The predictive value of the 69-gene DDR assay was then correlated with known pathologic response, and the receiver operating curve determined. We then performed qRT-PCR of these 69 genes with 5 controls, and correlated the expression of these genes with microarray RNA values in an additional 50 basal tumors. The data for individual genes was normalized, combined, and then hierarchically clustered. Results: In the 170 basal tumors treated with DNA damaging agents, a high score predicted response in basal-like tumors. A, p&amp;lt; 0.05. Conversely, for a non-DNA-damaging therapy, a high score significantly predicted for lack of response. B. In the 116 luminal B cancers, the DDR-assay also predicted for response to DNA damaging agent containing regimens with AUCs ranging from 0.67 to 0.80. C. Microarray of the 69 DDR gene expression values was compared with Ct values by q-RTPCR low density array for 50 paired samples. High concordance between these two platforms (48/50 samples) was observed. Conclusion: We have identified a robust predictive DDR assay that predicts for response to the DNA damaging agents, doxorubicin, epirubicin, and cisplatin in multiple studies, but not for docetaxel therapy. Future studies are underway to test for prediction of benefit of PARP1 inhibitor in basal-like and luminal B breast cancer. References: (1) Rodriguez AA et al: Breast Can Res Treat 123:189–96 (2) Tabchy A et al: Clin Cancer Res 16:5351–61 GSE 20271 (3) Farmer P et al: Nat Med 15:68–74, 2009 GSE 4779 (4) Popovici V et al: Breast Can Res 12:R5 GSE 20194 (5) Silver DP et al: J Clin Oncol 28:1145–53 GSE18864 (6) Desmedt C et al: J Clin Oncol 29:1578–86 GSE16446 (7) Iwamoto T et al: JNCI 264 GSE 23988 (8) Gluck S et al: Breast Can Res GSE 22358 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-01.
Antibodies to von Willebrand Factor–Cleaving Protease in Acute Thrombotic Thrombocytopenic Purpura
Authors: Han-Mou Tsai, Eric Chun-Yet Lian
Journal: New England Journal of Medicine (1998)

Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, von Willebrand factor is cleaved by a plasma protease. We explored the hypothesis that a deficiency of this protease predisposes patients with thrombotic thrombocytopenic purpura to platelet thrombosis.We studied the activity of von Willebrand factor-cleaving protease and sought inhibitors of this protease in plasma from patients with acute thrombotic thrombocytopenic purpura, patients with other diseases, and normal control subjects. We also investigated the effect of shear stress on the ristocetin cofactor activity of purified von Willebrand factor in the cryosupernatant fraction of the plasma samples.Thirty-nine samples of plasma from 37 patients with acute thrombotic thrombocytopenic purpura had severe deficiency of von Willebrand factor-cleaving protease. No deficiency was detected in 16 samples of plasma from patients with thrombotic thrombocytopenic purpura in remission or in 74 plasma samples from normal subjects, randomly selected hospitalized patients or outpatients, or patients with hemolysis, thrombocytopenia, or thrombosis from other causes. Inhibitory activity against the protease was detected in 26 of the 39 plasma samples (67 percent) obtained during the acute phase of the disease. The inhibitors were IgG antibodies. Shear stress increased the ristocetin cofactor activity of von Willebrand factor in the cryosupernatant of plasma samples obtained during the acute phase, but decreased the activity in cryosupernatant of plasma from normal subjects.Inhibitory antibodies against von Willebrand factor-cleaving protease occur in patients with acute thrombotic thrombocytopenic purpura. A deficiency of this protease is likely to have a critical role in the pathogenesis of platelet thrombosis in this disease.
Abstract 2241: Role of tissue markers in the prediction of bone metastases from breast cancer
Authors: Emanuele Sacanna, Toni Ibrahim, Michele Gaudio, Laura Mercatali, Rossana Ricci, Emanuela Scarpi, Marianna Ricci, Patrizia Serra, Luigi Serra, Chiara Arienti, Sara Bravaccini, Dino Amadori
Journal: Cancer Research (2010)

Abstract Introduction: Bone metastasis is a frequent event in patients with breast cancer. OPG (osteoprotegerin) protects bone from excessive resorption by binding to RANK-L (receptor activator of nuclear factor-kB-ligand) and by preventing it from binding to RANK. These molecules are closely involved in the process of metastasization to bone. CXCL12/SDF-1α, the ligand of CXCR4, is overexpressed in bone, and the local chemokine milieu is now emerging as a key determinant in organ selectivity by tumor cells. We carried out a retrospective analysis to evaluate the potential role of these biological markers in predicting bone metastasization in breast cancer patients. Materials and methods: OPG and CXCR4 expression was determined by avidin-biotin immunohistochemistry using a polyclonal (H-249, Santa Cruz) and monoclonal (Ab58176, Abcam) antibody, respectively. Immunohistochemical staining was carried out on sections from paraffin-embedded blocks of 40 primary breast cancers. Ten patients (median age of 64 years, range 48-78) were disease-free (DF) at a median of 9.8 (range 6.9-11.5) years, while 30 (median age 67 years, range 42-87) had relapsed. In the latter group, 10 (median age 66 years, range 42-87) had visceral metastases (VM) and 20 (median age 69 years, range 42-87) had bone metastases (BM). Results: Considering only strong cytoplasmic expression as positive, 22.5% of tumors were positive for OPG and 25% for CXCR4. In particular, OPG was expressed in 20% of tumors in DF patients and in 25% in BM patients. Conversely, CXCR4 was expressed in 10% of tumors in DF patients and in 45% in BM patients. OPG was expressed in only 20% of tumors in VM patients. There was no correlation between OPG and CXCR4 expression, and positivity to at least one of the two markers was observed in 30% of tumors in DF patients, 20% in VM patients and 55% in BM patients. In this last subgroup, there were no statistically significant associations between marker expression and tumor characteristics. Furthermore, no relation was observed between marker expression and disease-free or overall survival in BM patients. Conclusions: Our preliminary results suggest that cytoplasmic CXCR4 expression in primary breast cancers could play a role in predicting bone metastases. Enrolment of breast cancer patients in a larger study is ongoing to confirm these data and to evaluate the predictive role of RANK and RANK-L in bone metastasization. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2241.
PTH-164 What Issues need to be addressed Regarding Workforce Planning in Relation to the Changing Demographics of Doctors within the field of Gastroenterology?
Authors: R Preedy, M McStay
Journal: Gut (2013)

<h3>Introduction</h3> Many challenges lay ahead in the future development of the NHS including the changing workforce demographic, tighter funding and the prospect of increasing demands on services. Currently in the specialty of Gastroenterology 15% of consultants and 34% of trainees are female. To help realise the problems faced in workforce planning by this change of demographic we have tried to identify the current working patterns and perceptions of satisfaction and work-life balance amongst female Consultant Gastroenterologists. <h3>Methods</h3> A survey was developed using previously validated questions, these were then piloted amongst a group of female hospital doctors to ensure that they were fit for purpose. A total of 110 Female Gastroenterologists were then emailed with a web based link to the survey along with information explaining what the survey was for. The responses were managed by RAND Europe, an independent non-profit organisation who have experience of similar projects. <h3>Results</h3> There was a 63% response rate. The majority of respondents were between the ages of 41 to 50, and highly experienced of the NHS having worked for at least 15 years. 90% had achieved some form of higher degree, but only 2% worked in academic posts. 76% of respondents had had children, 73% of those felt that they provided the majority of childcare in comparison to their partner. 48% had delayed having children until they had become a consultant and 41% felt that they had had fewer children because of their career. A minority felt that their gender and parental status had negatively affected their career. The majority of respondents worked long hours with 30% working more than 49 hours per week. 11% of respondents worked part time, 19% were aware of a flexible working policy but not able to use it while 35% were not aware that one existed. Only 38% percent were satisfied with the recognition they got for their work. Almost 20% had experienced bullying from either mangers or other colleagues in the preceding 12 months and 27% had received harassment from patients or patient’s relatives. Almost 45% felt more stressed than usual and that their work life had a negative impact on their life. Although the majority of respondents felt happy with their current lifestyle, 10% were dissatisfied with their life, and 27% would change it if they could. <h3>Conclusion</h3> Current female Gastroenertologists are competently educated but underrepresented in academic posts. They are more likely to be the main care giver at home but face inflexible working arrangements. They reported high levels of bullying as well as a perceived lack of value from their NHS employer. To maintain a committed and motivated medical workforce the issues highlighted in this survey will need to be addressed in future workforce planning. <h3>Disclosure of Interest</h3> None Declared.
Unexplained Rabies in Three Immigrants in the United States
Authors: Jean S. Smith, Daniel B. Fishbein, Charles E. Rupprecht, Keith Clark
Journal: New England Journal of Medicine (1991)

Extensive investigation of three patients who died of rabies in the United States failed to reveal any source of exposure to the disease. The three patients had immigrated to the United States from areas in Laos, the Philippines, and Mexico where rabies is endemic.
PTH-017 Investigations, Cancer Diagnoses And Cost: A Prospective Study Of Two Week Rule Versus Non-two Week Rule Gastroenterology Referrals At A District General Hospital: Abstract PTH-017 Table 1
Authors: A Shalabi, C Alexakis, S Moodie
Journal: Gut (2014)

<h3>Introduction</h3> In 2000, the UK government introduced the two-week rule (TWR) referral initiative. This was to ensure all patients with symptoms potentially indicating a diagnosis of cancer were seen by a relevant specialist within two weeks of referral by their GP. Since its initiation, very little data has indicated improved survival outcomes for patients diagnosed with cancer via this pathway. <h3>Methods</h3> All patients referred to gastroenterology under Two Week Rule (TWR) and standard non-Two Week Rule (non-TWR) pathways were prospectively followed up for a 3 month period from date of referral. This was done covertly by the investigators to avoid influencing decision making by the clinic physicians. Data recorded included number of clinic visits, number and type of radiological/endoscopic investigations undertaken, end diagnosis and cancer diagnosis. Crude costs per patient were calculated using the hospital’s unit costing database. <h3>Results</h3> There were 52 TWR patients (mean age 72.5, male 48.1%) and 89 non-TWR patients (mean age 57.9 (p = 0.0001), male 36.0%). Reason for referral for TWR/non-TWR is shown in the table below: 76.9% of TWR patients had an endoscopic procedure compared to 62.9% of non TWR patients (p = 0.09). A similar percentage of patients in both groups underwent radiological investigation (TWR: 53.85%, non-TWR: 50.56%). More TWR patients underwent second imaging than non-TWR (9.6% vs. 6.7). 7.7% of TWR patients and 3.4% of non TWR patients had an end diagnosis of cancer, although this difference did not reach statistical significance. The mean age of the cancer patients in the TWR and non-TWR group was 70.3 years and 66.3 years respectively (although 2 of these in the non-TWR were below 65). 23.1 and 19.1% of patients had no clear diagnosis at 3 months in the TWR and non-TWR respectively. The mean cost of investigations and follow-up was significantly higher in the TWR cohort (£754.1 vs £613.1, p = 0.04). <h3>Conclusion</h3> In our sample of patients, those referred under the TWR pathway underwent a higher burden of invasive investigation with no significant increase in cancer pick up, despite being significantly more costly. The current system possibly delays cancer diagnoses in younger patients, who are more likely to be filtered through the non-TWR pathway. Perhaps alternative referral pathways need to be considered in a bid to improve cancer diagnosis in high risk patients. <h3>Disclosure of Interest</h3> None Declared.
Global Surveillance for Antituberculosis-Drug Resistance, 1994–1997
Authors: Ariel Pablos-Méndez, Mario C. Raviglione, Adalbert Laszlo, Nancy Binkin, Hans L. Rieder, Flavia Bustreo, David L. Cohn, Catherina S.B. Lambregts-van Weezenbeek, Sang Jae Kim, Pierre Chaulet, Paul Nunn
Journal: New England Journal of Medicine (1998)

Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organization–International Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997.