tbuckley/cabot-search huggingface dataset:
National Academies Hit the Brakes on Gene Drive–Modified Organisms
Authors: Jennifer Abbasi
Journal: JAMA (2016)

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Comparison of three molecular methods to detect mutations in KRAS, NRAS, BRAF and PIK3CA in metastatic colorectal cancer (mCRC).
Authors: Cristina Santos, Rocio Garcia-Carbonero, Pilar Garcia Alfonso, Daniel Azuara, Mar Varela, Valentín Navarro-Perez, Alfredo Carrato, Elena Elez, M.Auxiliadora Gomez-España, Ferran Losa, Clara Montagut, Bartomeu Massuti, Jose Luis Manzano, Jose M Vieitez, Manuel Valladares, Xavier Sanjuan, Gabriel Capella, Enrique Aranda, Josep Tabernero, Ramon Salazar
Journal: Journal of Clinical Oncology (2016)

3559 Background: Mutational analysis of RAS in mCRC has showed an improvement in patient (pts) selection for anti-EGFR drugs. The standard techniques (Techs) have an analytical sensitivity (Sns) of 1-5%. Digital PCR (dPCR) can detect mutated alleles at .05-.1% Sns, but it is unclear if this offers a clinical advantage. Objective:To compare the Sns and feasibility to detect point mutations in KRAS, NRAS, BRAF and PIK3CAby Cobas, Therascreen assays and quantitative dPCR (Fluidigm), and correlate them with progression-free survival (PFS) when treated with anti-EGFR- or bevacizumab (bev)-based therapies (Tx). Methods: 585 pts datasets treated with anti-EGFR- or bev-based Tx were pooled from several mCRC trials and retrospective series from the TTD/RTICC Spanish network. Concordance and predictability were evaluated using kappa and Harrel’s C index. Results: Out of the 585 pts, 385 were male (65.8%), median age 65, 192 pts (32.8%) included in trials (122 anti-EGFR (20.8%) and 70 bev (12%)), 393 pts (67.2%) treated as per label indication [143 anti-EGFR (24.4%) and 250 bev (42.7%)]. There were 4 invalid results for Therascreen and 6 for Cobas and dPCR, respectively (Table). No differences in PFS or OS in bev group were observed by molecular profiling with any platform. Globally, in pts who received anti-EGFR Tx, PFS was significantly better in RAS/BRAF wt groups (HR = 1.45, p = .016 for Cobas; HR = 1.78, p < .001 for Therascreen; and HR = 1.45, p = .005 for dPCR. Differences in OS in anti-EGFR group were detected for sensitive (HR = 2.041, p = .011) and chemorefractary (HR = 2.72, p = .001) pts by dPCR and considering all mutations. dPCR only outperformed the other Techs when predicting OS. Fine tunning of the optimal Sns threshold of quantitative Techs will be presented. Conclusions: Although the rate of mutations between Techs is different, the predictability of PFS to anti-EGFR Tx is similar in the first-line setting, but higher sensitivity methods tend to perform better in chemorefractory patients Mutations Cobas N % Kappa Therascreen N % Kappa dPCR N % Kappa dPCR/Cobas KRAS (exon2/3) 209 36 .87 208 36 .71 262 45 .77 RAS extended (exon2/3/4) 273 47 .73 276 47 .63 333 57 .64 Any mutation 333 57 .67 326 56 .58 361 62 .60
Triple-negative receptor status and prognosis in the NCIC CTG MA. 21 adjuvant breast cancer trial
Authors: M. J. Burnell, E. M. O'Connor, J. W. Chapman, M. N. Levine, K. I. Pritchard, P. S. O'Brien, K. J. Howarth, Z. Ding, T. J. Whelan, L. E. Shepherd
Journal: Journal of Clinical Oncology (2008)

550 Background: Triple-negative breast tumors which are negative for ER, PR, and HER2-neu receptors by immunohistochemistry are associated with a poor prognosis. The MA.21 trial compared 3 adjuvant chemotherapy regimens after surgery in pre- or early menopausal women 60 years or younger with breast cancer (Proceedings ASCO 2007, 25, 550). This analysis explored the outcome of the triple-negative subset of patients compared to nontriple negatives in the MA.21 trial with respect to relapse-free survival (RFS). Methods: Women with axillary node-positive or high-risk node-negative breast cancer were randomized to cyclophosphamide, epirubicin, 5FU (CEF), dose-dense epirubicin and cyclophosphamide plus filgrastim followed by paclitaxel (EC/T) or doxorubicin and cyclophosphamide followed by paclitaxel (AC/T), for six months. ER status was a known stratification factor for all patients. Median follow-up was 30.4 months with 261 recurrences. Characteristics of patients with and without knowledge of triple-negative status were compared with exact Fisher's tests. Step-wise multivariate Cox regressions were performed with forced inclusion of trial therapy and stratification factors. Additionally, RFS was determined from adjusted Cox survivor plots. Results: The trial enrolled 2,104 patients. ER, PR, and HER2 status based on local institutional results were known for 1,623; 551 patients had triple-negative tumors. After adjusting for treatment, stratification factors of lymph node status, surgery type, and age, highly significant differences in 3-year RFS were found when the triple-negative subgroup (RFS 80.5%) was compared to others where all PR and HER2-neu had known values (RFS 86.5%, p=0.0002), or not (RFS 87.7%, p< 0.0001). From multivariate analyses, triple-negative patients had significantly worse RFS (p< 0.0001). At this time, there are too few events to assess whether RFS differs by treatment arm for triple-negative patients. Conclusions: Pre- and postmenopausal women with triple-negative tumors had a reduced three-year relapse-free survival compared to women with nontriple-negative tumors. Supported by NCIC Canada and Canadian Cancer Society, Pfizer, Bristol-Myers Squibb, Amgen, Janssen Ortho, Ortho Biotech, and NCI US. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aventis, Biomira, Ortho Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca, Aventis, Pfizer, Pharmacia AstraZeneca, Aventis
Osteopontin (OPN) and interleukin-6 (IL-6) as predictive biomarkers in HCC receiving loco-regional treatment: preliminary results
Authors: A. Cubeddu, G. Astara, C. Madeddu, V. Ruggiero, C. Cabula, G. Serra, R. Ganga, L. Faloppi, S. Cascinu, M. Scartozzi
Journal: Annals of Oncology (2015)
PD-005 Response and resistance factor candidates to HER2 targeted therapy in gastric cancer (GC)
Authors: F. Lordick, I. Haffner, B. Luber, D. Maier, A. Kretzschmar, L. Fischer von Weikersthal, J. Riera-Knorrenschild, M. Ahlborn, K. Schierle, C. Wittekind
Journal: Annals of Oncology (2016)
18F-NaF PET/CT Findings in Fibrous Dysplasia
Authors: Hyunjong Lee, Kyu Sang Lee, Won Woo Lee
Journal: Clinical Nuclear Medicine (2015)

A 43-year-old woman with breast cancer underwent Tc-hydroxymethylene diphosphonate bone scintigraphy for preoperative workup. An abnormal lesion with increased uptake was found in the right humeral shaft, and F-NaF bone PET/CT was performed for clarification. There was high uptake of F-NaF without cortical bone disruption in the right humeral shaft, corresponding to the site on bone scintigraphy. Upper arm MRI was performed subsequently, and metastasis was suggested as a differential diagnosis. However, this lesion was pathologically diagnosed as fibrous dysplasia after curettage surgery.
Case 53-1965
Authors: Stephen M. Krane, Sanford I. Roth
Journal: New England Journal of Medicine (1965)

Presentation of Case First admission. A twenty-nine-year-old woman was admitted to the hospital because of menorrhagia. Eighteen months previously her menses became profuse, accompanied by severe dysmenorrhea. Uterine dilatation and curettage eleven months before admission revealed an incomplete miscarriage. Since the birth of her third child, five years earlier, she had experienced repeated episodes of headache, nausea and pain in the epigastrium and left upper quadrant of the abdomen. Physical examination revealed no abnormality except for an enlarged uterine fundus. The blood pressure was 130 systolic, 80 diastolic. The hemoglobin was 14 gm. per 100 ml., and the white-cell count . . .
Brain-Only Metastases Seen on FDG PET as First Relapse of Papillary Thyroid Carcinoma Two Years Post-Thyroidectomy
Authors: Sleiman Y. Naddaf, Ghulam Mustafa Shah Syed, Abdulrahman Hadb, Saif Al-Thaqfi
Journal: Clinical Nuclear Medicine (2016)

We report a case of a 60-year-old man diagnosed with papillary thyroid cancer who had a relapse seen only in the brain at FDG PET on standard images. Total thyroidectomy was performed in July 2013 after initial diagnosis. Patient received 131I ablation in December 2013, followed by external beam radiotherapy to the neck. In September 2015, the patient presented with neurological symptoms. Brain MRI showed multiple brain metastases later confirmed on histopathology. An FDG PET/CT scan was performed to evaluate the whole body in November 2015. Multiple hypermetabolic lesions were identified in the brain with no other lesion up to mid thighs.
A national training programme in field epidemiology launched in France
Authors: B Helynck
Journal: Eurosurveillance (2002)

Training in intervention epidemiology and assessment of health risks is a vital element in the network of the InVS partners (state departments, agencies and institutions). Those involved in health surveillance need to have a common culture and consistent intervention patterns in order to optimise the performance of surveillance and response mechanisms. For this reason, the InVS and the École Nationale de la Santé Publique (ENSP, national school of public health) have been involved in establishing a national training programme for several years now.
A transanal procedure using TST STARR Plus for the treatment of Obstructed Defecation Syndrome: ‘A mid-term study’
Authors: X.H. Ren, S.M. Yaseen, Y.L. Cao, W.C. Liu, S. Shrestha, Z. Ding, Y.H. Wu, K.Y. Zheng, Q. Qian, C.Q. Jiang
Journal: International Journal of Surgery (2016)
Case 26-1967
Authors: Maurice Victor, Edward P. Richardson, Benjamin Castleman
Journal: New England Journal of Medicine (1967)

Presentation of Case First admission. A fifty-six-year-old man was admitted to the hospital because of the radiologic demonstration of an abnormality in the lung field.Three months previously he entered the Massachusetts Eye and Ear Infirmary because of retinal detachment. At that time the white-cell count was 6000, with 61 per cent neutrophils, 33 per cent lymphocytes, 5 per cent monocytes and 1 per cent eosinophils. A week before admission he returned for repair of leakage at the site of the detachment. The white-cell count was 5100, with 65 per cent neutrophils, 26 per cent lymphocytes, 1 per cent . . .
Reply
Authors: Salvatore Petta, Giuseppe Cabibbo, Calogero Cammà
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. We thank Cortese et al. for their comments that give us the opportunity to further clarify and strengthen data from our analyses.1 Health‐related quality of life (HRQOL) in patients with chronic liver diseases is an area which has progressed considerably over recent years. There is now a growing body of literature, but this can be difficult to assimilate and the variety of HRQOL measures used in studies can be confusing. The National Institute for Health and Care Excellence (NICE) recommends the use of generic preference‐based measures (GPBMs) of health for its Health Technology Assessments (HTAs). Accordingly, among the three commonly used GPBMs (EQ‐5D, SF‐6D, and Health Utilities Index Mark 3), we used the HUI3. In the past, Salomon et al. suggested that in chronic hepatitis C (CHC), utilities vary widely across different patient populations.2 Recently, the assessment of the cost‐effectiveness of sofosbuvir‐based treatments for CHC by NICE underlined that the utility increment attributed by the manufacturer to the achievement of a sustained virological response (SVR) and propagated through the model exerts a significant effect on incremental cost‐effectiveness ratio (ICER).3 Thus, we consider life years gained (LYGs) the main outcome of all cost‐effectiveness analyses published by our group.4 Concerning the two sources of bias raised by Cortese et al. about our study, we provide the following answers. First, they question the utility indexes we used to calculate quality‐adjusted‐life‐years (QALYs). In response to Cortese et al., we clarify that in our analysis we used utilities reported in table 1 of our study1 and that were similar to those reported in a meta‐analysis by McLernon et al.6 using the EQ‐5D. Specifically, the utilities we used were those reported by Sullivan et al.,7 and not by Liu et al.,8 as wrongly reported due to a misprint. Cortese et al. suggest using the utilities recently reported by Scalone et al.9 using EQ‐5D. However, more primary research into the psychometric properties of the generic preference‐based measures is required and further research is needed for the development of a new reference standard.10 Second, Cortese et al. raised a question about the willingness‐to‐pay threshold of €25,000 per LYGs that we used to ascertain the cost‐effectiveness ratio. In response to the authors, although the threshold of cost‐effectiveness of medical interventions is thought to be £20,000‐30,000 in the UK, it is well known that these values are unjustified due to the lack of explicit scientific evidence.11 So the empirical threshold we used of €25,000 per LYG corresponds to the 2012 Italian Gross Domestic Product of about €25,000. In conclusion, we are confident that the analyses and assumptions used in our models are solid and acceptable, and allowed us to generate results potentially impacting the choices of National Health Care Systems.
A 1-day visit in a severe asthma centre: effect on asthma control, quality of life and healthcare use
Authors: Akke-Nynke van der Meer, Henk Pasma, Wilma Kempenaar-Okkema, Jo-Anneke Pelinck, Myrte Schutten, Huib Storm, Anneke ten Brinke
Journal: European Respiratory Journal (2016)

Patients with uncontrolled asthma report ongoing symptoms, poor quality-of-life and extensive healthcare use (HCU) and might benefit from management by a specialised severe asthma team. It is unknown whether a one-time evaluation by asthma experts, without long-term supervision by a specialised team, provides favourable outcomes. We evaluated asthma control (Asthma Control Questionnaire; ACQ), quality-of-life (Asthma-related Quality of Life Questionnaire; AQLQ) and HCU before and 1 year after a 1-day visit programme in a severe asthma centre, including a multidisciplinary assessment resulting in a personalised management plan to be implemented by patients own pulmonologists. 40 uncontrolled asthma patients completed questionnaires (ACQ, AQLQ, HCU) at baseline, and 6 and 12 months follow-up. ACQ improved from 2.6 (interquartile range 1.7–3.2) to 1.8 (1.2–3.2) (p=0.003) and AQLQ from 4.8 (4.0–5.2) to 5.3 (4.4–6.0) (p&lt;0.001). We found a reduction in patients with ≥2 exacerbations (95% versus 17%; p&lt;0.001), ≥1 emergency room visit (78% versus 37%; p&lt;0.001) and ≥1 hospitalisation (47% versus 10%; p=0.001). Evaluation of uncontrolled asthma patients in a 1-day visit programme in a severe asthma centre resulted in significant improvements in asthma control, quality-of-life and healthcare use after 1 year. This 1-day visit approach seems beneficial for uncontrolled asthma patients and might reduce their dependence on expensive treatment modalities and long-term management in specialised centres.
Transmission of Neurodegenerative Disorders Through Blood Transfusion
Authors: Gustaf Edgren, Henrik Hjalgrim, Klaus Rostgaard, Paul Lambert, Agneta Wikman, Rut Norda, Kjell-Einar Titlestad, Christian Erikstrup, Henrik Ullum, Mads Melbye, Michael P. Busch, Olof Nyrén
Journal: Annals of Internal Medicine (2016)

Background: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications. Objective: To investigate possible transfusion transmission of neurodegenerative disorders. Design: Retrospective cohort study. Setting: Nationwide registers of transfusions in Sweden and Denmark. Participants: 1 465 845 patients who received transfusions between 1968 and 2012. Measurements: Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed. Results: Among included patients, 2.9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors was 1.04 (95% CI, 0.99 to 1.09). Corresponding estimates for Alzheimer disease and Parkinson disease were 0.99 (CI, 0.85 to 1.15) and 0.94 (CI, 0.78 to 1.14), respectively. Hepatitis transmission was detected before but not after implementation of hepatitis C virus screening. Limitation: Observational study design, underascertainment of the outcome, and possible insufficient statistical power. Conclusion: The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare. Primary Funding Source: Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, and Danish Council for Independent Research.
NHS must rein in spending on specialised services, MPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The disproportionate growth in spending on specialised healthcare services in England is putting the financial sustainability of the wider NHS at risk, MPs have warned.

In a new report the House of Commons Public Accounts Committee said that NHS England would need to make “tough decisions” to stay within its budget for specialised commissioning in the future.1

Leaders must focus on ensuring that new drugs and medical equipment are affordable, that services are delivered cost effectively, and that levels of demand for specialised services are better managed, the report advised. Failure to do so would affect the …
TRH-induced TSH response in healthy volunteers: relationship to psychiatric history
Authors: P T Loosen, R Marciniak, K Thadani
Journal: American Journal of Psychiatry (1987)

The authors measured thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone in 32 healthy volunteers who had never sought or received psychiatric treatment. Nine (28%) had a family or personal history of depression or alcoholism. Five of these nine subjects and one of 22 subjects without such a history showed TSH blunting (TSH data were not available for one subject). This difference was statistically highly significant. Although there were sex differences in TSH response, TSH blunting occurred most frequently in men with a family or personal history of depression or alcoholism. The fault may have utility as a marker of past episodes or as a true marker of trait.
Developmental regulation of myeloerythroid progenitor function by the <i>Lin28b</i>–<i>let-7</i>–<i>Hmga2</i> axis
Authors: R. Grant Rowe, Leo D. Wang, Silvia Coma, Areum Han, Ronald Mathieu, Daniel S. Pearson, Samantha Ross, Patricia Sousa, Phi T. Nguyen, Antony Rodriguez, Amy J. Wagers, George Q. Daley
Journal: The Journal of Experimental Medicine (2016)

For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood. In this study, we find that expression of the heterochronic factor Lin28b decreases in common myeloid progenitors during hematopoietic maturation to adulthood in mice. This decrease in Lin28b coincides with accumulation of mature let-7 microRNAs, whose biogenesis is regulated by Lin28 proteins. We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. Conversely, deletion of Lin28b or ectopic activation of let-7 microRNAs in the fetal state induces a shift toward adult-like myeloid-dominant output. Furthermore, we identify Hmga2 as an effector of this genetic switch. These studies provide the first detailed analysis of the roles of endogenous Lin28b and let-7 in the timing of hematopoietic states during development.
Bendamustine Plus Melphalan As Conditioning Regimen for Second Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: Single Centre Experience
Authors: Massimo Martino, Giuseppe Messina, Tiziana Moscato, Roberta Fedele, Giuseppe Console, Giuseppe Console, Iolanda Donatella Vincelli, Francesca Ronco, Giuseppe Irrera
Journal: Blood (2014)