tbuckley/cabot-search huggingface dataset:
Novel Treatment Using Cimetidine for Erythropoietic Protoporphyria in Children
Authors: Joanna H. Tu, Sarah L. Sheu, Joyce M. Teng
Journal: JAMA Dermatology (2016)

Erythropoietic protoporphyria (EPP) is a rare hereditary disease of heme biosynthesis that manifests as severe photosensitivity and hepatotoxicity. There have been no effective treatments to date. Cimetidine has been shown to inhibit heme biosynthesis and results in symptomatic improvement in patients with acute intermittent porphyria (AIP) and porphyria cutanea tarda (PCT). There is only 1 report in the literature describing the use of cimetidine in the effective treatment of an adult patient with EPP.To describe the successful use of cimetidine in pediatric patients with EPP.Retrospective medical record review carried out in a pediatric dermatology practice at an academic institution of patients diagnosed with EPP who were younger than 18 years and treated with systemic cimetidine in the past 3 years.Systemic cimetidine.Resolution of skin photodamage was evaluated on clinical examination. Subjective measures including tolerability to sun exposure, ability to participate in outdoor activities, and objective evaluation including serum erythrocyte protoporphyrin levels and liver function tests following treatment were assessed.All 3 cases reported a rapid reduction in photosensitivity within weeks following initiation of systemic therapy. Their skin photodamage were also improved or resolved completely on subsequent examination. Laboratory study results also revealed reduction in serum erythrocyte protoporphyrin levels and improved liver function. None of the patients have reported any adverse effects of the systemic treatment after more than 2 years of treatment.Children with EPP currently have limited therapeutic options and experience substantial disease impact on their quality of life. This is the first case series demonstrating that cimetidine, a readily available oral medication, can be a promising treatment for children with EPP.
Randomized Noninferiority Trial of Telephone Delivery of <i>BRCA1/2</i> Genetic Counseling Compared With In-Person Counseling: 1-Year Follow-Up
Authors: Anita Y. Kinney, Laurie E. Steffen, Barbara H. Brumbach, Wendy Kohlmann, Ruofei Du, Ji-Hyun Lee, Amanda Gammon, Karin Butler, Saundra S. Buys, Antoinette M. Stroup, Rebecca A. Campo, Kristina G. Flores, Jeanne S. Mandelblatt, Marc D. Schwartz
Journal: Journal of Clinical Oncology (2016)

Purpose The ongoing integration of cancer genomic testing into routine clinical care has led to increased demand for cancer genetic services. To meet this demand, there is an urgent need to enhance the accessibility and reach of such services, while ensuring comparable care delivery outcomes. This randomized trial compared 1-year outcomes for telephone genetic counseling with in-person counseling among women at risk of hereditary breast and/or ovarian cancer living in geographically diverse areas. Patients and Methods Using population-based sampling, women at increased risk of hereditary breast and/or ovarian cancer were randomly assigned to in-person (n = 495) or telephone genetic counseling (n = 493). One-sided 97.5% CIs were used to estimate the noninferiority effects of telephone counseling on 1-year psychosocial, decision-making, and quality-of-life outcomes. Differences in test-uptake proportions for determining equivalency of a 10% prespecified margin were evaluated by 95% CIs. Results At the 1-year follow-up, telephone counseling was noninferior to in-person counseling for all psychosocial and informed decision-making outcomes: anxiety (difference [d], 0.08; upper bound 97.5% CI, 0.45), cancer-specific distress (d, 0.66; upper bound 97.5% CI, 2.28), perceived personal control (d, −0.01; lower bound 97.5% CI, −0.06), and decisional conflict (d, −0.12; upper bound 97.5% CI, 2.03). Test uptake was lower for telephone counseling (27.9%) than in-person counseling (37.3%), with the difference of 9.4% (95% CI, 2.2% to 16.8%). Uptake was appreciably higher for rural compared with urban dwellers in both counseling arms. Conclusion Although telephone counseling led to lower testing uptake, our findings suggest that telephone counseling can be effectively used to increase reach and access without long-term adverse psychosocial consequences. Further work is needed to determine long-term adherence to risk management guidelines and effective strategies to boost utilization of primary and secondary preventive strategies.
Strategies used for measuring long-term control in atopic dermatitis trials: A systematic review
Authors: Sebastien Barbarot, Natasha K. Rogers, Katrina Abuabara, Helene Aubert, Joanne Chalmers, Carsten Flohr, Jon Hanifin, Luigi Naldi, David J. Margolis, Carle Paul, Matthew J. Ridd, Marie-Louise Anna Schuttelaar, Eric Simpson, Marie Tauber, Annika Volke, Stephan Weidinger, Sally R. Wilkes, Andreas Wollenberg, Kim S. Thomas
Journal: Journal of the American Academy of Dermatology (2016)
Linguistic dimensions of affect and thought in somatization disorder
Authors: T E Oxman, S D Rosenberg, P P Schnurr, G J Tucker
Journal: American Journal of Psychiatry (1985)

DSM-III has established diagnostic criteria that separate somatization disorder from other overlapping symptom configurations. Nevertheless, information regarding the experience of somatization disorder is far from complete. Terms such as "masked depression" or "alexithymia" imply that a disturbance of affect is a central but guarded issue for at least some somatizing patients. Through content analysis of speech, the authors investigated the self-experience of somatization disorder in relation to affective disorder. Rather than defended depression, a distinctive characteristic found in the language of patients with somatization disorder reflects a confused, negative self-identity.
Efficacy of frontline antibiotics therapy in the treatment of Helicobacter pylori-negative gastric low-grade mucosa-associated lymphoid tissue lymphoma.
Authors: Sung Hsin Kuo, Kun-Huei Yeh, Ming-Shiang Wu, Chung-Wu Lin, Hui-Jen Tsai, Ming-Feng Wei, Hsiao-Wei Lee, Jyh-Ming Liou, Li-Tzong Chen, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2016)

e19024 Background: Previous series reports revealed that certain proportions of Helicobacter pylori (HP)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma may respond to antibiotics treatment. In this explorative study, we assess the response rate, the long-term disease-free, and potential biomarkers of localized HP-negative gastric MALT lymphoma patients receiving frontline antibiotics. Methods: Between 2007 and 2014, a total of 23 stage IE/IIE1 HP-negative gastric low-grade MALT lymphoma patients who received frontline HP eradication (HPE) regimen, consisting of amoxicillin, clarithromycin, and a proton-pump inhibitor, were included in this study. HP-negative status was defined by negative results for the biopsy urease test, histology, C13-Urea breath test and serology. The presence or absence of t(11;18)(q21;q21) was determined using multiplex RT-PCR to amplify the API2-MALT1 transcript. The expression of BCL10 and NF-κB was assessed using immunohistochemistry. Tumors that had resolved to complete remission (CR) score of GELA histological grading system after antibiotics were considered antibiotics-responsive. Results: Tumors were of stage I in twenty and IIE-1 in three. We observed CR in 7 (30.4%) of 23 patients, and the median time to CR was 6 months (95% CI, 3.43–8.57 mo). At a median follow-up of 26.9 months, all patients with CR after HPE therapy were alive and free of lymphomas. The API2-MALT1 fusion transcript was detected in 7 (43.7%) of 16 antibiotics-unresponsive cases (P = 0.057), but in none of 7 antibiotics-responsive cases. BCL10 nuclear expression was significantly higher in antibiotics-unresponsive than antibiotics-responsive tumors (12 of 16 [75.0%] vs 1 of 7 [14.3%]; P = 0.019). Nuclear expression of NF-κB was also significantly associated with antibiotics unresponsiveness of tumors (P = 0.027). Conclusions: A pertinent portion of HP-negative gastric MALT lymphoma patients are still responsive to frontline HPE. In addition to t(11;18)(q21;q21), nuclear expression of BCL10 or NF-κB is predictive of antibiotics-unresponsive status of HP-negative gastric MALT lymphoma.
Anti-Interleukin 6 Receptor Monoclonal Antibody Therapy Reduced Serum Interleukin 4 and IgE Production in Castleman’s Disease.
Authors: Hideko Nakahara, Naoko Hoshino-Yoshio, Yuzuru Kanakura, Yasuo Ikeda, Minoru Nakamura, Shuji Nakano, Toshio Tanaka, Takeshi Sasaki, Kiyoshi Nishioka, Masamichi Hara, Hirokuni Taguchi, Yukihiko Kimura, Yoshiro Kato, Hideki Asaoku, Fumio Kodama, Katsuyuki Aozasa, Takeshi Johkoh, Tadamitsu Kishimoto, Norihiro Nishimoto
Journal: Blood (2005)
Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis
Authors: M Jawhar, J Schwaab, D Hausmann, J Clemens, N Naumann, T Henzler, H-P Horny, K Sotlar, S O Schoenberg, N C P Cross, A Fabarius, W-K Hofmann, P Valent, G Metzgeroth, A Reiter
Journal: Leukemia (2016)
Recommendations for infection management in patients with sepsis and septic shock in resource-limited settings
Authors: C. Louise Thwaites, Ganbold Lundeg, Arjen M. Dondorp
Journal: Intensive Care Medicine (2016)

Introduction Studies indicate that sepsis and septic shock in resourcelimited settings are at least as common as in resourcerich settings. The surviving sepsis campaign (SSC) guidelines have been widely adopted throughout the world, but in resource-limited settings are often unfeasible [1]. The guidelines are based almost exclusively on evidence from resource-rich settings and are not necessarily applicable elsewhere due to differences in etiology and diagnostic or treatment capacity. An international team of physicians with extensive practical experience in resource-limited intensive care units (ICUs) identified key questions concerning the SSC’s infection management recommendations, and evidence from resourcelimited settings regarding these was evaluated using the grading of recommendations assessment, development and evaluation (GRADE) tools. This article focuses primarily on bacterial causes of sepsis and septic shock. Other infections common in resource-limited settings, such as malaria, are covered in a separate article in this series. Evidence quality was scored as high (grade A), moderate (B), low (C), or very low (D), and recommendations as strong (1) or weak (2). The major difference from the grading of recommendations in the SSC-guidelines was in taking account of contextual factors relevant to resource-limited settings, such as the availability, affordability and feasibility of interventions in resource-limited ICUs. Strong recommendations have been worded as ‘we recommend’ and weak recommendations as ‘we suggest’ (details in online supplement).
PD-039 Role of adjuvant radiotherapy following neo-adjuvant chemotherapy (NACT) and surgery in oesophageal cancer – a multi-centre retrospective cohort study
Authors: S. Teoh, P. Virdee, J. Mason, N. Warner, C. Blesing, K. Patel, R. Marshall, N. Maynard, B. Sgromo, R. Gillies, C. Streets, C. Barham, A. Hollowood, J. Blazeby, D. Titcomb, S. Falk, S. Mukherjee
Journal: Annals of Oncology (2016)
Comparative Effectiveness of Management Strategies for Renal Artery Stenosis
Authors: Gowri Raman, Gaelen P. Adam, Christopher W. Halladay, Valerie N. Langberg, Ijeoma A. Azodo, Ethan M. Balk
Journal: Annals of Internal Medicine (2016)

Background: Atherosclerotic renal artery stenosis (ARAS) is associated with high blood pressure (BP), decreased kidney function, renal replacement therapy (RRT), and death. Purpose: To compare benefits and harms of percutaneous transluminal renal angioplasty with stent placement (PTRAS) versus medical therapy alone in adults with ARAS. Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1993 to 16 March 2016; gray literature; and prior systematic reviews. Study Selection: Randomized, controlled trials (RCTs); nonrandomized, comparative studies (NRCSs); single-group studies; and selected case reports that reported all-cause and cardiovascular mortality, RRT, kidney function, BP, and adverse events. Data Extraction: Six researchers extracted data on design, interventions, outcomes, and study quality into a Web-based database. Data Synthesis: Eighty-three studies met eligibility criteria. In 5 of 7 RCTs, PTRAS and medical therapy led to similar BP control in patients with ARAS, and no RCTs showed statistically significant differences in kidney function, mortality, RRT, cardiovascular events, or pulmonary edema. Eight NRCSs had more variable results, finding mostly no significant differences in mortality, RRT, or cardiovascular events but heterogeneous effects on kidney function and BP. Procedure-related adverse events were rare, and medication-related adverse events were not reported. Two RCTs found no patient characteristics that were associated with outcomes with either PTRAS or medical therapy. Single-group studies found various but inconsistent factors that predict outcomes. Case reports provided examples of clinical improvement after PTRAS in patients with acute decompensation. Limitation: Limited clinical applicability and power in RCTs, and possible publication bias and lack of adjusted analyses in NRCSs. Conclusion: The strength of evidence regarding the relative benefits and harms of PTRAS versus medical therapy alone for patients with ARAS is low. Studies have generally focused on patients with less severe ARAS. Primary Funding Source: Agency for Healthcare Research and Quality.
Sam68 is a regulator of Toll-like receptor signaling
Authors: Jeffrey A Tomalka, Tristan J de Jesus, Parameswaran Ramakrishnan
Journal: Cellular and Molecular Immunology (2016)

Recognition of pathogens by Toll-like receptors (TLR) activate multiple signaling cascades and expression of genes tailored to mount a primary immune response, inflammation, cell survival and apoptosis. Although TLR-induced activation of pathways, such as nuclear factor kappaB (NF-κB) and mitogen-activated protein kinases (MAPK), has been well studied, molecular entities controlling quantitative regulation of these pathways during an immune response remain poorly defined. We identified Sam68 as a novel regulator of TLR-induced NF-κB and MAPK activation. We found that TLR2 and TLR3 are totally dependent, whereas TLR4 is only partially dependent on Sam68 to induce the activation of NF-κB c-Rel. Absence of Sam68 greatly decreased TLR2- and TLR3-induced NF-κB p65 activation, whereas TLR4-induced p65 activation in a Sam68-independent manner. In contrast, Sam68 appeared to be a negative regulator of MAPK pathways because absence of Sam68 enhanced TLR2-induced activation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK). Interestingly, TLR2- and TLR3-induced gene expression showed a differential requirement of Sam68. Absence of Sam68 impaired TLR2-induced gene expression, suggesting that Sam68 has a critical role in myeloid differentiation primary response gene 88-dependent TLR2 signaling. TLR3-induced gene expression that utilize Toll/Interleukin-1 receptor-domain-containing adapter-inducing beta interferon pathway, depend only partially on Sam68. Our findings suggest that Sam68 may function as an immune rheostat that balances the activation of NF-κB p65 and c-Rel, as well as MAPK, revealing a potential novel target to manipulate TLR signaling.
Lymph node image-guided core-needle biopsy for cutaneous T-cell lymphoma staging
Authors: M. Battistella, C. Sallé de Chou, C. de Bazelaire, J.M. Cayuela, E. de Kerviler, M. Bagot, A. Janin
Journal: British Journal of Dermatology (2016)

For lymph node (LN) pathological analyses, whole excision has long been recommended for detection of lymphoma, although complications such as infection, hypertrophic scar, lymphorrhoea and lymphoedema may occur1. For the patients, surgical LN excision requires general anesthesia during a surgery stay, with high cost for public health insurance, for private health insurance, and out of pocket. The development of percutaneous image-guided core-needle biopsy (CNB) to replace surgical LN excision has made short-time intervention using advanced medical technology a valuable opportunity. Image-guided CNB enables a precise selection of the biopsy site, based on the size and the depth of the abnormal LN, and imaging characteristics2.

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Ponatinib efficacy and safety in patients (pts) with advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitor (TKI) failure: Results from a phase 2 study.
Authors: Michael C. Heinrich, Margaret von Mehren, George D. Demetri, Jonathan A. Fletcher, Jichao G Sun, David Kerstein, Maureen G Conlan, Suzanne George
Journal: Journal of Clinical Oncology (2015)

10535 Background: The oral TKI ponatinib has potent pre-clinical activity against mutant KIT and PDGFRA, including clinically relevant mutants resistant to available TKIs. We hypothesized that ponatinib might be effective in GIST after prior TKI treatment failure. Methods: This phase 2, single-arm study (NCT01874665) evaluated efficacy and safety of ponatinib 45 mg qd in advanced GIST after TKI failure; N = 45. Cohorts were enrolled based on presence (A) or absence (B) of KIT exon 11 mutations. Primary endpoint is clinical benefit rate (CBR = CR + PR + SD) at 16 wk by modified RECIST 1.1 in Cohort A. Secondary endpoints include CBR (Cohort B and overall) and objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Due to arterial occlusive events in other ponatinib trials, enrollment criteria were revised in early 2014 to include only pts in whom all 3 TKIs approved for GIST had failed. Results: Enrollment is complete (Cohort A, 30 pts; B, 15 pts). Median age was 59 y. Most pts (76%) received ≥4 anticancer regimens; 36% received 2 and 58% received 3 approved TKIs. Median time since diagnosis was 6 y. At 10-mo median follow-up (data as of Dec 1, 2014), 9 pts were ongoing; 15 discontinued for progressive disease per RECIST, 9 for AEs, and 12 for other reasons. Cohort A CBR was 37% (10/27); ORR 7% (2/27). Best responses: PR 2; SD 16. Median PFS/OS: 4.3 mo/15.0 mo. Cohort B CBR was 14% (2/14); ORR 0%. Best response: SD 6. Median PFS/OS: 2.0 mo/13.5 mo. Treatment-emergent AEs (TEAEs) in ≥40% of pts: rash 58%; fatigue 51%; constipation 42%; headache 42%; myalgia 40%. Myocardial ischemia, cerebrovascular accident, peripheral artery stenosis, deep vein thrombosis, and pulmonary embolism occurred in 1 pt each; 4 pts had evidence of ventricular dysfunction. Serious TEAEs (other than disease progression) in ≥2 pts: abdominal pain 9%; pneumonia 7%; fatigue, nausea, small intestinal obstruction, vomiting, 4% each. Two deaths, from pneumonia and pulmonary embolism, were considered possibly ponatinib-related. Conclusions: Ponatinib has clinical activity in advanced GIST pts after TKI failure, particularly pts with KIT exon 11 mutations. Clinical trial information: NCT01874665.
Senators Urge Expedited Evaluation of Medical Use of Cannabidiol
Authors: Rita Rubin
Journal: JAMA (2016)

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CAR-T cell immunotherapies targeting type III variant epidermal growth factor receptor, a glioma-associated antigen.
Authors: Elodie Bole-Richard, Jean-Marie Certoux, Jean-Rene Pallandre, Idir Idirene, Christophe Borg, Christophe Ferrand, Marina Deschamps
Journal: Journal of Clinical Oncology (2015)

e14022 Background: Glioblastoma is the most common and lethal high grade brain tumors in adults. Epidermal Growth Factor Receptor Variant III (EGFRvIII) is an oncogenic variant expressed in 30% of glioma and is associated with resistance to chemotherapy and poor prognosis. Consequently, it can be an attractive target for cancer immunotherapy using CAR-T cells. Methods: We develop a third generation of CAR composed of a single chain of Ig (mus musculus EGRFvIII antibody MR1scFv, Genebank U76382.1) with signaling domains CD28, 4-1BB and CD3z. All these sequences have been cloned into a pSFG retroviral vector with a suicide gene sequence: inducible caspase-9 (iCasp9) and a selection marker (ΔCD19) in order to secure cell therapy. Results: A PG13 packaging cell line was generated to allow T-cell transduction. The CAR expression was assessed by anti-CD3z western blot and show expression in the membrane of PG13. To investigate the cell-surface expression of CAR, we performed a sub cellular separation and we demonstrated, by western blot analysis with HA-tag mAb, that CAR is expressed in membrane fraction. To confirm these experiments by flow cytometry, we used the EGFRvIII fusion peptide: biotin-conjugated Pep3 (LEEKKGNYVVTDHC). We confirmed the surface expression of the CAR on our transduced cells. The IFNγ release by CAR transduced PBMC against U87-EGFRvIII and U87MG target cell lines (Effector:Target ratio = 10:1) were assessed by intracellular flow cytometry staining. IFNγ staining was observed for transduced PBMC co-cultured with U87-EGFRvIII compared with PBMC co-cultured with U87MG cells in a specific manner. Conclusions: We developed genetically engineered T cells that express a chimeric receptor CAR for the treatment of tumors expressing variant EGFR. We confirmed its expression and specificity in T cells. Further experiments should be conducted to determine the efficacy of this approach in a murine mouse model. We have a secured third generation CAR allowing a quick immunomagnetic selection of transduced T-cells based on ΔCD19 expression, and a specific removing of this T-cells by apoptosis after exposure to AP1903 (Bellicum Pharmaceuticals).