tbuckley/cabot-search huggingface dataset:
Methylene-tetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) in gemcitabine (gem)/cisplatin (cis)-treated non-small-cell lung cancer (NSCLC) patients (p)
Authors: V. Alberola, J. L. Ramirez, I. De Aguirre, R. Rosell, R. de las Penas, C. Camps, M. Cobo, M. Taron, M. Sanchez-Ronco, J. L. Marti
Journal: Journal of Clinical Oncology (2004)

7163 Background:: MTHFR 677 SNP results in an adenine to valine (C-T) substitution. Individuals homozygous for 677 TT have lower genomic DNA methylation than persons with wild-type (CC). Since MTHFR 677 SNP is involved in folate metabolism, DNA methylation and DNA repair, we have examined its potential influence on outcome and toxicity in gem/cis-treated NSCLC Methods: 208 stage IV NSCLC p were included from August 2001 to July 2002. TaqMan 5' nuclease assay was used to examine MTHFR 677 SNP from baseline peripheral blood lymphocytes Results: p characteristics: median age: 61; 91% male; PS 0: 23.4%, 1: 62.7%, 2: 13.9%; adenocarcinoma: 43.1%, pleural effusion: 16%. Overall: response rate (RR) 38.6%; time to progression (TTP) 6 months (m); median survival (MS) 10.56 m. MTHFR 677 genotypes: CC 30.3%; CT 57.4%; TT 12.3%. By genotype: RR: CC 35.9%, CT: 43.6%, TT 42.3%; TTP: CC 7.4 m, CT 5.4 m, TT 5.2 m; MS: CC 11.2 m, CT 10.3 m, TT 9.8 m. Toxicity analysis is ongoing. Conclusions: No differences in outcome were observed according to MTHFR 677 SNP, suggesting that MTHFR 677 SNP does not by itself play an important role in outcome with gem/cis. Complete data, including toxicity, will be presented. No significant financial relationships to disclose.
Occupational hypersensitivity pneumonitis: an EAACI position paper
Authors: S. Quirce, O. Vandenplas, P. Campo, M. J. Cruz, F. de Blay, D. Koschel, G. Moscato, G. Pala, M. Raulf, J. Sastre, A. Siracusa, S. M. Tarlo, J. Walusiak-Skorupa, Y. Cormier
Journal: Allergy (2016)

The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent.
Oxaliplatin plus paclitaxel for recurrent and metastatic cervical cancer (CC): New York Cancer Consortium Trial P5840
Authors: D. Y. Kuo, S. V. Blank, B. Kobrinsky, P. Christos, T. A. Caputo, C. D. Runowicz, B. Pothuri, P. Ivy, F. Muggia, S. Wadler
Journal: Journal of Clinical Oncology (2007)

5549 Background: Although cisplatin (cis) is an effective radiosensitizer, its activity in patients (pts) with advanced and recurrent CC is disappointing. Oxaliplatin (O) might exhibit greater activity and be suitable for combination with paclitaxel (P). Methods: Pts with advanced and recurrent CC who had not received prior chemotherapy except radiosensitizing cis were treated with P 175 mg/m 2 IV and O 130 mg/m 2 IV every 21 d. Response (R), as determined by RECIST criteria and confirmed at 9 weeks (wk), and toxicity were primary outcomes. If R in = 8 patients (pts) of 18, accrual to 46 could ensue. Results: Of 17 pts enrolled, 16 were treated. Histology: 7 adeno/10 squamous.The median age was 57 (range 33–78) and 13 had had prior radiation (10 with cis). Median cycles: 3 (0–8). One CR and 4 PRs were achieved for an overall response rate of 29% (95% confidence interval: 10.3%, 56.0%). Additionally, 4 had stable disease, but this was not confirmed at 15wk. Time to progression in those responding was 21 wk (range 11–51). 7 pts are alive. 6 pts experienced grade (gr) 3/4 hematologic toxicity. Neuropathy occurred following cycle 3 in 2 pts (gr3). Additonal gr 3/4 toxicities were gastrointestinal (GI)/metabolic in 6, thrombotic in 1 and hypersensitivity in 1. There were no treatment-related deaths. Conclusions: In the stage I of our Phase II trial, O and P demonstrate a 29% response rate when used to treat advanced and recurrent CC. Toxicities of this regimen are hematologic, gastrointestinal, and neurologic. Supported by N01-CM-62204. No significant financial relationships to disclose.
Pathogenesis of Mouse Scrapie: Patterns of Agent Replication in Different Parts of the CNS following Intraperitoneal Infection
Authors: R H Kimberlin, Carol A Walker
Journal: Journal of the Royal Society of Medicine (1982)

The dynamics of agent replication were studied at 8 levels of spinal cord and in 9 areas of brain of mice infected intraperitoneally with the 139A strain of scrapie agent. Replication in the CNS was first detectable at 2 levels of spinal cord between thoracic vertebrae 4 and 9. The onset of replication was progressively delayed by up to 4 weeks at increasingly lower levels of spinal cord. A similar trend was seen at higher levels of spinal cord and in brain. In brain, agent replication occurred first in medulla, then in the pons and midbrain, thalamus and hypothalamus and, finally, striatum, septum, hippocampus and cerebral cortex. These results are highly suggestive of spread of infection from peripheral sites of agent replication along autonomic fibres to midthoracic cord, followed by an ascending and descending spread of agent at an apparent rate of 0.5 to 1.0 mm/day until the whole CNS is infected. However, experiments involving sympathectomy gave inconclusive results and the evidence for neural spread of scrapie in the peripheral nervous system is circumstantial.
Problems with poor study adherence in a tuberculosis research project in children in Tanzania
Authors: Thomas Nørrelykke Nissen, Michala Vaaben Rose, Godfather Kimaro, Sayoki G. Mfinanga, Pernille Ravn
Journal: European Respiratory Journal (2011)

Background:  In clinical research poor follow-up has a significant effect on the validity of the data collected, affecting both the results and conclusions. For a diagnostic TB study, follow-up over time can be crucial to verify the presence or absence of active TB.   Objectives:  1) to identify factors influencing patient adherence to attend follow-up examination. 2) A qualitative evaluation of reasons for not attending follow-up examination.   Methods:  1) Baseline data such as health characteristics and demographic data from all the included patients were drawn from a TB study database. Risk factors for not attending follow-up were determined. 2) Semi-qualitative interviews of caretakers were used to investigate patients9 experiences and challenges in relation to attend follow-up examination.   Results:  Only 61% showed up for the follow-up examination. Being treated for active TB was a positive predictor for attending follow-up. OR: 0.24, CI: (0.12-0.50), p-value    Conclusion:  Patients lost to follow-up is a significant problem. We found, that receiving money for the transport to the hospital is crucial for patient adherence. Children with active TB had a significant higher frequency of attending follow-up. All TB patients attend the TB clinic at the hospital frequently, which could explain the better adherence to follow-up.
Safe percutaneous endoscopic colostomy for severe constipation with use of the introducer method
Authors: Yoshihiro Moriwaki, Jun Otani, Junzo Okuda, Toshiyuki Niwano, Ryo Maemoto
Journal: Endoscopy (2015)

Percutaneous endoscopic colostomy (PEC) has been established as an alternative method of intestinal decompression and irrigation for chronic intestinal pseudo-obstruction, relapsing sigmoid volvulus, neurogenic bowel, and constipation [1]. However, the thin, distended colonic wall can easily be torn during creation of the PEC with the pull method, and inadvertent traction of the PEC tube and colonic peristalsis can occur. By using an introducer method, we successfully prevented these complications.
A SARC multicenter phase III study of gemcitabine (G) vs. gemcitabine and docetaxel (G+D) in patients (pts) with metastatic soft tissue sarcomas (STS)
Authors: R. G. Maki, M. L. Hensley, J. K. Wathen, S. R. Patel, D. A. Priebat, S. Okuno, D. Reinke, P. F. Thall, R. S. Benjamin, L. H. Baker
Journal: Journal of Clinical Oncology (2006)

9514 Background: We sought to compare the response of metastatic STS to G vs. G+D in a phase III study using a novel Bayesian adaptive randomization strategy. Methods: Entry criteria included non-GIST STS diagnosis, age &gt; 10, measurable disease, ≤ 3 prior regimens, normal organ function, and Grade (Gr) ≤ 1 neuropathy. Pts were stratified by histology (leiomyosarcoma [LMS] vs. other), and history of prior pelvic radiation (PPR) or not, yielding 4 diagnostic subgroups. Therapy was G 1200 mg/m 2 (over 120 min, d1+d8) or G 900 mg/m 2 (over 90 min, d1+d8) and docetaxel (100 mg/m 2 d8) q21d; all pts received (peg)-filgrastim starting d9. 25% dose reductions were employed for PPR or toxicity. The primary endpoint was tumor response (CR, PR, or 24+ weeks stable), using a double-blind Bayesian adaptive randomization procedure to incrementally assign more pts to the superior treatment arm, while accounting for possible treatment-subgroup interactions. Although this study is not based on a 1:1 randomized phase III design, enrolling ∼120 pts would show a difference between a response rate (RR) of 10% for G and 30% with G+D with a power of 0.8 and two-sided alpha of 0.05. Results: 122 pts were randomized; 119 pts had evaluable outcomes. Median number of prior regimens was 1; median number of cycles was 4 (range 1–26). 49 pts were adaptively randomized to G and 73 to G+D, indicating superiority of G+D. Of 119 evaluable pts, 27% (G) and 32% (G+D) showed response as defined. The odds of pts with LMS receiving G+D instead of G increased from 1:1 at the start of the study to ∼6:1 at its completion. RR was 10% (G) vs. 16% (G+D) (p=0.15, Fisher exact test). Consistent with the RR outcomes, progression free survival (PFS) was 6.2 m (G+D, K-M 95%CI 3.6–8.8) vs. 2.6 m (G, 95%CI 2.0–3.2). Overall survival (OS) was 18.0 m (G+D, K-M 95%CI 11.7–24.1) vs. 11.2 m (G, 95%CI 6.8–15.5). Pts receiving G+D had a higher rate of discontinuation due to toxicity than those receiving G (p&lt;0.01, log rank). Conclusions: We observed substantial clinical activity in this pre-treated STS population. G+D yields superior PFS and OS to G, but at the price of increased toxicity. Adaptive randomization is an effective method that substantively reduces the number of pts receiving inferior therapy. [Table: see text]
Seven-year quality of life assessment in lung cancer
Authors: P. Yang, R. S. Marks, J. A. Wampfler, A. Jatoi, Y. I. Garces, A. L. Cheville, M. M. Clark, M. E. Johnson, S. D. Cassivi, D. E. Midthun, J. A. Sloan
Journal: Journal of Clinical Oncology (2008)

9531 Background: After decades of efforts on reducing lung cancer incidence and mortality, we are now challenged by the lack of understanding of the health conditions and quality of life (QOL) among the survivors. Methods: We evaluated 2,005 consecutive primary lung cancer patients diagnosed 1999- 2006. Two validated patient-reported assessments, the Lung Cancer Symptom Scale and Linear Analogue Self-Assessment, were used to measure overall QOL, pain, fatigue, appetite, symptoms, physical-, emotional-, mental-, and spiritual well-being, social activity/support, and financial/legal concerns. Cross-sectional and longitudinal analyses were performed. Assessments were translated onto a 0–100 (worst to best) scale, and a normative range was defined as 80.0±10.0 established in healthy individuals. Four QOL groups were defined: norm (70.0–90.0), above-norm (>90), below-norm (60.0–70.0), and poor (<60). Adjusted QOL was calculated by multiple regression models with variables at baseline (age, sex, ethnicity, marital status, years of education, employment status, smoking history, body weight, histology and stage, and comorbidities) and at each time a QOL questionnaire was answered (performance status, surgery, chemotherapy, and radiotherapy, weight change, and current tobacco use). Results: A total of 5,289 QOL questionnaires were answered by 2,005 patients from 6-month to 7-year post diagnosis. The mean (SD) overall QOL was 73.0 (23.2), ranging 70.8–76.0 across the 7 years, with and without covariates. Frequent pain and physical well-being were consistently below norm, fatigue scored as poor for all years, and shortness of breath was below norm between 6 months and year-4 and declined to poor thereafter. Longitudinally following patients in the four groups based on their initial overall QOL score, survivors stayed in the same QOL group throughout years, except those who started in the poor group (mean score 41.2) improved gradually to a mean score of 64.7 at year-5 although still below norm. Conclusions: This study describes health-related QOL by prospectively following a large lung cancer cohort. Modifiable contributors to poor QOL need to be identified and interventions should be designed to improve patients’ QOL in conjunction with prolonged survival. Supported by NIH grants CA77118, CA80127, and CA84354. No significant financial relationships to disclose.
Conserved sequence and functional domains in satellite 2 from three families of salamanders.
Authors: B Green, L M Pabón-Peña, T A Graham, S E Peach, S R Coats, L M Epstein
Journal: Molecular Biology and Evolution (1993)

Thirteen satellite 2 elements from Ambystoma talpoideum and 16 from Amphiuma tridactylum were cloned, sequenced, and compared with the satellite 2 consensus from Notophthalmus viridescens. These elements have maintained a high degree of similarity during the 65-200 Myr that the salamander families, represented by the three species, have been separated. The DNA sequences of the consensus elements from A. talpoideum and A. tridactylum are 81% similar, and both are approximately 65% similar to the N. viridescens consensus. In addition to its DNA sequence, the functional properties of satellite 2 have also been conserved. By selecting and analyzing clones that closely mimicked the consensus of each species, we were able to demonstrate that satellite 2 from each species was capable of promoting transcription after injection into Xenopus laevis oocytes and that synthetic transcripts of satellite 2 from each species were capable of catalyzing their own site-specific cleavage. These properties may be related to the process of retroposition, which was previously proposed to be responsible for the genomic proliferation of satellite 2. Each of these functional properties also has general biological interest.
Abstract 16934: Canadian Cardiovascular Society Angina Classification and Change in Quality of Life Following Percutaneous Coronary Intervention for Stable Coronary Disease
Authors: Edward McNulty, Paul Chan, Philip Jones, Megan Coylewright, John A Spertus
Journal: Circulation (2012)

Background:  Appropriate Use Criteria (AUC) have been developed to support the more rational use of percutaneous coronary intervention (PCI). To date, however, the AUC have not been empirically validated. A key component in AUC determination for patients with stable coronary artery disease (CAD) is their symptom burden, as measured by Canadian Cardiovascular Society (CCS) angina class. We compared the association of CCS class at the time of PCI with improvements in quality of life (QOL) after PCI.   Methods:  Within a 10-center PCI registry (PRISM [Personalized Risk Information Services Manager] Study), we examined the association between baseline CCS class and 1-year change in QOL, as assessed by the disease-specific and validated Seattle Angina Questionnaire (SAQ), in patients undergoing PCI for stable CAD.   Results:  Of 516 patients undergoing PCI for stable CAD, the mean age was 66 + 9.8 years and 73% were men. Most patients were treated with statins (75%) and beta blockers (66%) prior to PCI. Baseline CCS class of 0, I, II, III, and IV were present in 35%, 9%, 28%, 16% and 11% of patients, respectively. Compared to patients with CCS Class I or II angina, those with class III or IV angina had a lower baseline QOL (55 ± 23 v. 47 ± 24, p    Conclusions:  Among patients undergoing PCI for non-acute indications, improvements in QOL were similar for those with mild and more severe angina, as assessed by CCS class. CCS class appears to have limited discrimination in predicting the magnitude of QOL benefits in patients undergoing stable PCI.
<i>ERBB2</i> gene as a potential therapeutic target in small bowel adenocarcinoma.
Authors: Anais Laforest, Thomas Aparicio, Aziz Zaanan, Fabio pittella Silva, Audrey Didelot, Aurelien Desbeaux, Delphine Le Corre, Leonor Benhaim, Karine Pallier, Daniela Ellen Aust, Steffen Pistorius, Helene Blons, Magali Svrcek, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2014)

205 Background: Small bowel adenocarcinoma (SBA) is an aggressive tumor responsible for poor outcomes with an expected median OS at 5 years inferior to 30%. Because of its low incidence, few prospective studies have been performed leading to insufficient knowledge and absence of standard of care. Aiming to better understand the small bowel carcinogenesis process we screened for somatic mutations a large data set of patients in more than 740 mutational hotspots among 46 genes. Methods: In total, 83 SBA cases were selected from 2 European databases. The sequencing was performed using the Ion 316 Chip. We additionally looked into MSI status and ERBB2 expression (immunochemistry and FISH). Results: Tumors were mostly located in the duodenum (47%) and stage ≥ 3 (63%). Among the 46 genes investigated, 8 were mutated in more than 5% of the cases: KRAS, TP53, APC, SMAD4, PIK3CA, ERBB2, BRAF, and FBXW7. Compelling mutations (7 cases) and amplifications (3 cases) 12% of the patients had an ERBB2 alteration. In this group, ERBB2 alterations were positively associated with dMMR status (p=0.006) and APC mutations (p=0.02) but negatively associated with p53 mutations (p=0.038). Interestingly, ERBB2 mutations were mainly detected within tumors derived from the foregut while ERBB2 amplifications were limited those derived from the midgut. Conclusions: This study describes the first large screening of somatic mutations in SBA using next generation sequencing. ERBB2 mutation was revealed to be one of the most frequent alterations in SBA with a distribution dependent on tumor location. In most cases patients harbored the same p.L755S-ERBB2 mutation. In clinical practice, this study may suggest that more than 10% of the patients with SBA could be treated using anti-ERBB2-targeted agents.[Table: see text]
Cause-specific and all-cause mortality of HER2-positive, node-negative, T1a and T1b breast cancers.
Authors: H. K. Chew, M. Brown
Journal: Journal of Clinical Oncology (2010)

583 Background: The addition of trastuzumab significantly improved disease-free and overall survival, compared to chemotherapy alone, in prospective randomized trials of women with HER-positive early breast cancer. However, node-negative tumors ≤ 1cm were excluded. Retrospective analyses suggest that these tumors are more aggressive than their HER2-negative counterparts. We sought to confirm these findings in a large cancer registry and to compare outcomes in the eras before and after the use of adjuvant trastuzumab. Methods: All cases of T1a and T1b, pN0 breast cancer diagnosed from 2000 to 2007 were identified in the California Cancer Registry. Cases were omitted if tumor HER2 status, age, or race/ethnicity was unknown. Cases were stratified by era, 2000-2004 and 2005-2007. Data were analyzed using Kaplan-Meier all-cause and cause-specific 5-year overall survival using the log-rank test. Results: We identified 28,616 cases of T1a and T1b, N0 breast cancer; 20,188 cases (71%) reported HER2 testing results. Of the remaining cases, HER2 testing was not done (8%), HER2 testing was ordered, but no results were entered (1%), HER2 status was unknown (20%). Median age at diagnosis and race/ethnicity was the same by era and HER2 status. The frequency of HER2-positive breast cancers is shown. The breast-cancer specific 5-year overall survival was significantly shorter among HER2-positive breast cancers compared to HER2-negative (p value = 0.0001) in the 2000-2004 era. There was no significant difference in the 2005- 2007 era. There were no differences in all-cause mortality between the HER2-positve and negative groups in both eras. Conclusions: Our analysis agrees with prior retrospective reports suggesting that HER2-positive, node-negative tumors ≤ 1cm have a worse outcome compared to comparable HER2-negative breast cancer. A difference in breast-cancer specific mortality is seen in the era prior to the use of adjuvant trastuzumab. Total N = 20,188 2000-2004 N = 9,409 2005- 2007 N = 10,779 HER2-positive 3,196 (15.8%) 1,579 (16.8%) 1,617 (15%) HER2-negative 16,992 (84.2%) 7,830 (83.2%) 9,162 (85%) No significant financial relationships to disclose.
Administration of Zidovudine During Late Pregnancy and Delivery to Prevent Perinatal HIV Transmission—Thailand, 1996-1998
Journal: JAMA (1998)

The efficacy of a short-term regimen of zidovudine (ZDV) in preventing perinatal HIV transmission was investigated in a randomized case-placebo study conducted at two teaching hospitals in Bangkok Thailand in 1996-97.  The 198 women in the intervention group were given 300 mg of ZDV orally twice a day from 38 weeks of gestation until the onset of labor and 300 mg every 3 hours thereafter until delivery.  Another 199 women received a placebo.  Infants in both groups were fed formula rather than breast milk.  At 6 months of age 52 children (17 from the ZDV group and 35 in the placebo group) were HIV-positive; all HIV infections were evident at 2 months of age.  The HIV transmission risk was 9.2% (95% CI 5.0-13.5%) in the ZDV group and 18.6% in the placebo group (95% CI 13.0-24.0%) signifying a 51% decrease in risk.  The ZDV regimen used in this study is more feasible for implementation in developing country settings than the one currently used in the US (associated with a 66% reduction in HIV transmission): it costs US$50 starts later in pregnancy involves less frequent dosing and oral dosing during labor and does not involve infant treatment.  On the basis of these findings ministries of health and donor agencies are urged to develop strategies to increase access to prenatal HIV testing and ZDV treatment for HIV-infected pregnant women in resource-poor settings.  Further evaluation is needed of the effect of breast feeding on the efficacy of this regimen.