tbuckley/cabot-search huggingface dataset:
P1 Preliminary results for association of survival time in idiopathic pulmonary fibrosis cases with the 11p15.5 region
Authors: RJ Allen, MD Tobin, LV Wain, R Braybrooke, G Jenkins
Journal: Thorax (2015)

<h3>Introduction</h3> Idiopathic pulmonary fibrosis (IPF) is a restrictive lung disease of unknown cause. The median survival time after diagnosis is 3–5 years and there are limited treatments available. <i>MUC5AC</i>, <i>MUC5B</i> and <i>TOLLIP</i> in the 11p15.5 region have been shown to be associated with susceptibility to IPF. A variant in <i>TOLLIP</i> (rs5743890) has also been shown to be associated with both susceptibility and survival time however the effects were in opposite directions, i.e. the allele associated with increased susceptibility was also associated with increased survival time. <h3>Methods</h3> We performed survival analysis on 612 European IPF cases passing QC using a Cox proportional hazards model adjusting for age, sex, first 10 principal components and study centre. 134 variants were genotyped in a 200 kb region on chromosome 11 covering <i>MUC5AC</i>, <i>MUC5B</i> and <i>TOLLIP</i>. <h3>Results</h3> No SNPs in this region reached genome-wide significance (p &lt; 5 × 10<sup>–8</sup>). The most significant variant was rs56367042 (Hazard Ratio 3.38, 95% CI [1.91, 5.96]; p = 2.74 × 10<sup>–5</sup>) which is located downstream of <i>MUC5B</i>. The next significant SNP was rs5743894 (Hazard Ratio 0.67, 95% CI [0.54, 0.83]; p = 2.24 × 10<sup>–4</sup>) located in <i>TOLLIP</i>. For this SNP the allele we found associated with increased survival time has previously been reported as associated with increased susceptibility (showing a similar pattern to that reported for rs5743890) however this SNP has also been previously reported as not being associated with survival time. We found a proxy of rs5743890 (R<sup>2</sup> = 0.698) not to be associated with survival time (p = 0.881). <h3>Conclusions</h3> Our results did not replicate those previously reported; however they may support the hypothesis that variants in <i>TOLLIP</i> that increase susceptibility may also increase survival time. In future we will perform a GWAS for susceptibility and survival time and try and replicate the findings.
Expanding The TLX1-Regulome In T Cell Acute Lymphoblastic Leukemia Towards Long Non-Coding RNAs
Authors: Kaat Durinck, Joni Van der Meulen, Maté Ongenaert, Pieter-Jan Volders, Annelynn Wallaert, Nadine Van Roy, Yves Benoit, Bruce Poppe, Pieter Mestdagh, Jo Vandesompele, Pieter Rondou, Jean Soulier, Pieter Van Vlierberghe, Frank Speleman
Journal: Blood (2013)
PCSM-08EFFICACY AND TOLERABILITY OF LACOSAMIDE IN PATIENTS WITH GLIOMA AND SEIZURES: A PROSPECTIVE STUDY
Authors: Roberta Rudà, Alessia Pellerino, Michela Magistrello, Federica Franchino, Elisa Nicolotto, Riccardo Soffietti
Journal: Neuro-Oncology (2015)

BACKGROUND: Lacosamide (LCM) has been suggested to improve seizure control as add-on treatment in brain tumor patients. We present the results of a prospective study on the efficacy and tolerability of LCM in a cohort of patients with low (LGG) and high grade (HGG) gliomas with active epilepsy, either on chemotherapy or radiotherapy or during observation alone with MRI. METHODS: We enrolled 62 adult patients with persisting seizures (seizures > 1 per month) despite an adequate treatment with other antiepileptic drugs. The endpoints of the study were a significant reduction of seizure frequency (> 50% compared with baseline) and seizure freedom (SF) at 3 and 6 months, being concomitant AEDs and steroids unchanged or reduced. RESULTS: Among grade II gliomas a significant reduction of seizures was observed in 5/22 patients (22.7.%) and 7/22 (36.8%) at 3 and 6 months after start of LCM, respectively; a SF was obtained in 6/22 (23.3%) and 8/22 (42.1%) at 3 and 6 months after start of LCM, respectively. Among HGG a significant reduction of seizures was obtained in 10/41 patients (24.4%) and 7/33 patients (21.1%) at 3 and 6 months after start of LCM, respectively; a SF was obtained in 19/40 (47.5%) and 15/40 (45.5%) at 3 and 6 months after the start of LCM, respectively. Four out of 11 and 7/15 patients with LGG who responded to LCM did not receive any antineoplastic treatment, whereas 18/40 patients with HGG had the tumor stable or responding on MRI (RANO criteria) following antineoplastic treatment. A resolution of a status epilepticus was obtained in 7 patients. In 2 cases only LCM was withdrawn due to dizziness and fatigue or resistant seizures. CONCLUSIONS: This is the first prospective study showing a significant activity of LCM as add-on therapy in gliomas with different grades of malignancy.
NIMG-41MRI FINDINGS IN THE GLARIUS TRIAL: PROGNOSTIC AND PREDICTIVE IMPLICATIONS
Authors: Sied Kebir, Christina Schaub, Elke Hattingen, Nina Junold, Niklas Schäfer, Joachim P. Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Michael Niessen, Frederic Mack, Moritz Stuplich, Theophilos Tzaridis, Oliver Bähr, Martin Proescholdt, Martin Glas, Ulrich Herrlinger
Journal: Neuro-Oncology (2015)

BACKGROUND: The phase II GLARIUS trial assigned patients with newly diagnosed, O-6-methylguanine-DNA methyltransferase (MGMT) non-methylated glioblastoma to experimental bevacizumab/irinotecan (BEV/IRI) or standard temozolomide (TMZ). BEV/IRI prolonged progression-free survival but overall survival (OS) was similar in both arms. To identify subpopulations with a particularly favourable course, we assessed the prognostic potential of magnetic resonance imaging (MRI) markers at baseline and during the first 4 months of treatment. METHODS: MRIs at baseline, 8, and 16 weeks after therapy initiation were analyzed for T1-hyperintense and diffusion-restricted lesions, contrast-enhancing lesions qualifying for tumor progression (25% increase), and progression of Fluid-attenuated inversion recovery (FLAIR) hyperintense lesions. The MRI findings were correlated with survival. RESULTS: None of the baseline parameters was prognostic in the entire cohort or predictive in the BEV/IRI arm. The presence of diffusion-restricted lesions was neither prognostic nor predictive of BEV/IRI benefit at any timepoint. At 8 weeks of follow-up, 49 patients developing a new combined diffusion-restricted and T1-hyperintense lesion had significantly greater OS than 90 patients without such changes (median OS, 17.5 vs. 15.7 months, p = 0.003). This effect was significant in the BEV/IRI arm (median OS, 17.2 vs. 15.7 months, p = 0.026) whereas significance was narrowly missed in the TMZ arm (median, 18.0 vs. 14.8 months, p = 0.071). At 16 weeks, OS in BEV/IRI-treated patients experiencing exclusively progressive FLAIR hyperintensities (17 of 52 evaluable patients; median OS, 17.5 months) was no worse than in BEV/IRI-treated patients with no progression on FLAIR and T1-weighted contrast-enhancing images (median OS, 19.4 months). In contrast, patients with progressive contrast-enhancing lesions had significantly shorter OS (median, 14.3 months, p = 0.0003, logrank test). CONCLUSIONS: The development of combined T1-hyperintense and diffusion-restricted lesions in early follow-up MRIs is associated with improved OS, particularly in BEV/IRI-treated patients. FLAIR-only progression does not appear to be predictive of a worse outcome with BEV/IRI treatment.
Polyps and Pigment in the Peutz-Jeghers Syndrome
Authors: Joseph T. Freeman, Isidor S. Ravdin
Journal: New England Journal of Medicine (1955)

THE clinical condition described by Peutz,1 of Holland, in 1921 was characterized by him as a remarkable situation of familial polyposis of the mucosa of the small intestine with unusual skin and mucosal pigmentation.Generally, the pattern consists of areas of melanosis in the facial and digital skin as well as buccal and other mucosal sites associated with polyps of the small intestines. The majority of the patients are of dark complexion with a personal and family history of discrete blue, black or dark-brown pigmentation, or intestinal disturbances, or both.2 As a rule there is a fairly long story of . . .
Screening for genomic rearrangements in <i>BRCA1</i> and <i>BRCA2</i> genes in 16 Peruvian breast cancer families by Multiplex Ligation-dependent Probe Amplification (MLPA).
Authors: Jose Luis Buleje Sono, Francia Del Pilar Huaman, Maria Guevara-Fujita, Joseph A. Pinto, Jhajaira Araujo, Carlos Vigil, Jaime Ponce, Frank Lizaraso, Alfredo Aguilar, Ricardo Fujita, Henry Gomez
Journal: Journal of Clinical Oncology (2015)

e12553 Background: The large majority of alterations identified in the BRCA1 and BRCA2 genes are point mutations and small insertions/deletions. However, an increasing number of large genomic rearrangements are being identified, especially in BRCA1; whereas the frequency of genomic rearrangements in the BRCA2 gene is low in many populations. Numerous studies conducted primarily in Caucasian populations have shown that 4–28% of mutations in the BRCA genes may be due to large genomic rearrangements. The objective of our study was to characterize large genomic rearrangements of BRCA1 and BRCA2 genes in a cohort of breast cancer patients. Methods: Sixteen patients diagnosed with hereditary breast cancer in Oncosalud- AUNA (Lima-Peru) were evaluated. Genomic DNA was extracted from peripheral blood samples. MLPA was performed using the SALSA MLPA KIT P002-C2 BRCA1 probemix and SALSA MLPA KIT P045-B3 BRCA2/CHEK2 probemix (MRC-Holland, Amsterdam, Netherlands) for BRCA1 and BRCA2 genes following the manufacturer’s protocol. The data obtained were analyzed by using the Coffalyser.Net software. These kits could detect the deletion or duplication of an exon or the whole gene. Results: Analysis of BRCA1 and BRCA2 genes by MLPA revealed two different germline large genomic rearrangement alterations in two unrelated patients in the BRCA1 gene. An exon 7 duplication in one patient, and a second rearrangement consisting of a 3 times amplification of a fragment containing exon 7. MLPA analysis did not reveal any other genomic rearrangements in the BRCA1 or BRCA2 genes in any of the subjects studied. Conclusions: This is the first MLPA study in Peruvian hereditary breast cancer patients detecting large genomic rearrangements in BRCA genes. We report two new genomic rearrangements in BRCA1 gene in Peruvian breast cancer patients. In order to corroborate the amplifications detected by MLPA we are performing quantitative PCR or RT-PCR.
Case 35-1998
Authors: Paul T. Gross, Eugene J. Mark
Journal: New England Journal of Medicine (1998)

Presentation of CaseA 54-year-old, left-handed woman was admitted to the hospital because of pain and paresthesias in the legs and a gait disturbance.The patient had been well until eight weeks earlier, when she had pain in the soles of her feet and rectal paresthesias and numbness. During the next several weeks, painful paresthesias and dysesthesias slowly worsened as they extended to the legs and buttocks and perianal region; the gait became increasingly impaired. During the two weeks before admission, the patient had daily frontal and occipital headaches with nausea and photophobia. The results of a magnetic resonance imaging . . .
Bone Response to Phosphate Salts, Ergocalciferol, and Calcitriol in Hypophosphatemic Vitamin D-Resistant Rickets
Authors: Francis H. Glorieux, Pierre J. Marie, John M. Pettifor, Edgard E. Delvin
Journal: New England Journal of Medicine (1980)

We treated 11 children with vitamin D-resistant rickets with a phosphate mixture either alone (1.2 to 3.6 g per day) or combined with ergocalciferol (vitamin D2, to 50 x 103 IU per day) or with calcitriol (1,25-dihydroxyvitamin D3, 0.25 to 1 microgram per day). Serum calcitriol concentrations were normal in all patients. Calcitriol therapy circulating levels of the hormone to values above normal and increased intestinal phosphate absorption. In some patients this regimen decreased the need for phosphate supplements. None of the treatment regimens corrected the renal phosphate leak. Radiologic studies and bone histomorphometric analyses showed that phosphate (alone or with ergocalciferol) induced the mineralization of the growth plate but not of the endosteal bone surface. Combined calcitriol and phosphate therapy for a total of 2850 patient-days greatly improved the mineralization of trabecular bone. Short-term episodes of hypercalcemia were easily controlled by changes in calcitriol dosage. The data indicate that the combined calcitriol and phosphate regimen is useful in the treatment of vitamin D-resistent rickets.
Endoscopic Management of Complications Related to Esophageal Stenting by Repositioning the Stent without Extraction or Re-Stenting
Authors: I Tasci, U Korman
Journal: Endoscopy (2003)

Placement of self-expanding metallic stents is a widely accepted technique for palliative treatment of esophagorespiratory fistulas [1] [2]. Many reports have described technical aspects of extracting migrated stents [3] [4] [5]. We describe here a case of stent migration which was managed using a pull-up maneuver, with concomitant balloon dilation of the proximal tip.
The Applications of Spectrophotometry to Medicine
Authors: Joseph T. Walker
Journal: New England Journal of Medicine (1949)

THE APPLICATIONS OF SPECTROPHOTOMETRY TO MEDICINEThe development of simple, reliable ultraviolet and visible spectrophotometers within the last ten years has made available an analytical tool of great versatility and power. The role played by spectrophotometric methods in research on vitamins and hormones has been spectacular1: the application of these methods to analytical procedures promises to be equally impressive.Spectrophotometric methods possess certain advantages that are particularly desirable in toxicologic investigations: the results are subject to qualitative interpretations having fundamental structural chemical significance; they are quantitative; the procedure is direct and simple, and the results reproducible; and the sample . . .
Clinical Use of Coronary CTA–Derived FFR for Decision-Making in Stable CAD
Authors: Bjarne L. Nørgaard, Jakob Hjort, Sara Gaur, Nicolaj Hansson, Hans Erik Bøtker, Jonathon Leipsic, Ole N. Mathiassen, Erik L. Grove, Kamilla Pedersen, Evald H. Christiansen, Anne Kaltoft, Lars C. Gormsen, Michael Mæng, Christian J. Terkelsen, Steen D. Kristensen, Lars R. Krusell, Jesper M. Jensen
Journal: JACC. Cardiovascular imaging (2016)

The goal of this study was to assess the real-world clinical utility of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) for decision-making in patients with stable coronary artery disease (CAD). FFRCT has shown promising results in identifying lesion-specific ischemia. The real-world feasibility and influence on the diagnostic work-up of FFRCT testing in patients suspected of having CAD are unknown. We reviewed the complete diagnostic work-up of nonemergent patients referred for coronary computed tomography angiography over a 12-month period at Aarhus University Hospital, Denmark, including all patients with new-onset chest pain with no known CAD and with intermediate-range coronary lesions (lumen reduction, 30% to 70%) referred for FFRCT. The study evaluated the consequences on downstream diagnostic testing, the agreement between FFRCT and invasively measured FFR or instantaneous wave-free ratio (iFR), and the short-term clinical outcome after FFRCT testing. Among 1,248 patients referred for computed tomography angiography, 189 patients (mean age 59 years; 59% male) were referred for FFRCT, with a conclusive FFRCT result obtained in 185 (98%). FFRCT was ≤0.80 in 31% of patients and 10% of vessels. After FFRCT testing, invasive angiography was performed in 29%, with FFR measured in 19% and iFR in 1% of patients (with a tendency toward declining FFR-iFR guidance during the study period). FFRCT ≤0.80 correctly classified 73% (27 of 37) of patients and 70% (37 of 53) of vessels using FFR ≤0.80 or iFR ≤0.90 as the reference standard. In patients with FFRCT >0.80 being deferred from invasive coronary angiography, no adverse cardiac events occurred during a median follow-up period of 12 (range 6 to 18 months) months. FFRCT testing is feasible in real-world symptomatic patients with intermediate-range stenosis determined by coronary computed tomography angiography. Implementation of FFRCT for clinical decision-making may influence the downstream diagnostic workflow of patients. Patients with an FFRCT value >0.80 being deferred from invasive coronary angiography have a favorable short-term prognosis.
Rhabdomyosarcoma of the Tongue
Authors: Alex W. Ulin, William C. Shoemaker, Gregory F. Froio
Journal: New England Journal of Medicine (1954)

PRIMARY rhabdomyosarcoma of the tongue is a rare condition to which no reference is available for a complete pathological description or a sound therapeutic approach. The physician confronted with a malignant tumor of the tongue that is grossly and histologically unlike carcinoma must refer to a confused and sparse literature to cope with the question of exact diagnosis, treatment and prognosis. We attempted to solve this problem by applying concepts based on our experience and what we could learn in the literature about oral carcinomas, lingual sarcomas generally and rhabdomyosarcoma of the extremities. This paper is a compilation of the . . .
Prospective phase II trial of pazopanib plus CapeOX (capecitabine and oxaliplatin) in previously untreated patients with advanced gastric cancer.
Authors: Min-Young Lee, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Joon Oh Park
Journal: Journal of Clinical Oncology (2015)

4049 Background: We designed a single-arm, open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx (capecitabine and oxaliplatin) in metastatic and/or recurrent advanced gastric cancer (AGC) patients. Methods: Previously untreated AGC patients received capecitabine (850 mg/m2 bid, day 1–14) plus oxaliplatin (130 mg/m2, day 1) in combination with pazopanib (800 mg, day 1–21) every three weeks. Treatment was continued until progression of the disease or intolerable toxicity was observed. Results: In all, 66 patients were treated with pazopanib plus CapeOx. The median age of the patients was 51.5 years (range, 23.0–77.0 years), and the median ECOG performance status was 1 (0–1). Among all 66 patients, one complete response and 37 partial responses were observed (overall response rate, 57.6%; 95% confidence interval (CI), 46.7–67.9%). Stable disease was observed in 22 patients (33.3%), revealing a 90.9% disease control rate. The median progression free survival and overall survival were 6.5 months (95% CI, 5.6–7.4 months) and 10.5 months (95% CI, 8.1–12.9 months), respectively. Thirty-four patients (51.5%) experienced a treatment-related toxicity of grade 3 or more during the study. The most common toxicities of grade 3 or more were neutropenia (15.1% of all patients), anemia (10.6%), thrombocytopenia (10.6%), anorexia (7.6%), nausea (3.0%), and vomiting (3.0%). There were no treatment-related deaths. Conclusions: The combination of pazopanib and CapeOx showed moderate activity and an acceptible toxicity profile as a first-line treatment in metastatic and/or recurrent AGC patients (ClinicalTrials.gov NCT01130805). Clinical trial information: NCT01130805.
Primary Uterine Cervical Lymphoma Manifesting as Menolipsis Staged and Followed Up by FDG PET/CT
Authors: Weiyan Zhou, Fengchun Hua, Chuantao Zuo, Yihui Guan
Journal: Clinical Nuclear Medicine (2016)

Primary uterine non-Hodgkin's lymphoma of the cervix is rare. We report a 31-year-old woman presented with menolipsis for 8 weeks. Transvaginal ultrasonography and pelvic MRI detected a solid cervical mass invading the adjacent vaginal wall. The lesion showed obvious FDG uptake on PET/CT scan, and malignancy was considered. It proved to be primary diffuse large B-cell lymphoma of the cervix by biopsy. After 6-cycle R-CHOP chemotherapy, no abnormal FDG uptake was found on another FDG PET/CT scan.
PTH-305 A review of recurrent referrals to the lower gastro-intestinal (lgi) fast track service – is one referral enough?
Authors: J Stewart, N Appleton, D Vimalachandran, C McFaul
Journal: Gut (2015)

<h3>Introduction</h3> Average monthly referrals to our institution fast track LGI clinics have almost doubled between 2010 and 2014. Patients are being repeatedly referred, increasing the workload and cost of this service. We examined the outcomes of those re-referrals. <h3>Method</h3> A retrospective review of a prospectively maintained database and notes review was performed. <h3>Results</h3> Over the three-year study period, 3696 were referred to the fast track clinic. Eighty (2.2%) were referred twice or more. 19/80 (24%) were re-referred having missed their first appointment. 29/80 (36%) had repeated investigations that were normal with 24/80 (30%) confirming the presence of diverticular disease. Seven patients had colorectal cancer (CRC) diagnosed following the second referral and one after the third. Five of these newly diagnosed individuals had failed to attend or declined investigation initially. <h3>Conclusion</h3> <h3>Discussion</h3> Re-referral of patients to fast track LGI clinics has significant cost implications. The implication of patients attending such a clinic needs to be emphasised in the primary care setting to minimise non-attendance. 66% of those re-referred had diverticular disease or normal bowel diagnosed on repeat investigation, suggesting that second referral or repeat investigation was unnecessary. Further education/guidelines for both patient and health care professional would help minimise this repetition. CRC detection miss rates are a known phenomenon and need to be audited and highlighted to the LGI MDT to improve service provision and excellence. <h3>Disclosure of interest</h3> None Declared.