tbuckley/cabot-search huggingface dataset:
Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and<i>TREX1</i>Mutation
Authors: Nick Zimmermann, Christine Wolf, Reiner Schwenke, Anne Lüth, Franziska Schmidt, Kerstin Engel, Min Ae Lee-Kirsch, Claudia Günther
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous lupus erythematosus that in most cases is caused by mutations in the 3 prime repair exonuclease 1 (<i>TREX1</i>). Familial chilblain lupus presents in early childhood with cold-induced painful erythematous infiltrates leading to mutilation and is associated with systemic involvement illustrated by an elevated type I interferon (IFN) signature in the skin and blood. Effective treatment is currently not available. <h3>Objectives</h3> To evaluate the clinical response to the Janus kinase inhibitor baricitinib in familial chilblain lupus and assess the effect of cold on patient fibroblasts. <h3>Design, Setting, and Participants</h3> In this case series, 3 patients with familial chilblain lupus due to<i>TREX1</i>mutation underwent treatment with baricitinib for 3 months. <h3>Interventions</h3> Doses of baricitinib, 4 mg, were administered daily for 3 months. <h3>Main Outcomes and Measures</h3> Reduction of cutaneous lupus lesions was measured by the revised cutaneous lupus area and severity index, pain due to skin and joint involvement was assessed by visual analog scale, type I IFN signature in blood was determined by polymerase chain reaction, and the in vitro response of fibroblasts to cold exposure was analyzed. <h3>Results</h3> All 3 patients (2 women and 1 man; mean [SD] age, 51 [24] years) showed a significant improvement of cutaneous lupus lesions with suppression of systemic type I IFN activation. One patient had a complete remission regarding pain and, in 2 patients, pain associated with joint inflammation was partially reduced. No severe adverse reactions were reported. Exposure of patient fibroblasts to cold induced a stress response and enhanced senescence along with induction of IFN-stimulated gene in vitro. <h3>Conclusions and Relevance</h3> These findings demonstrate the therapeutic efficacy of Janus kinase inhibition in a monogenic form of lupus among 3 patients and provide mechanistic insight into the process of disease exacerbation by cold in<i>TREX1</i>-deficient cells. This finding may be relevant to other type I IFN–mediated disorders and implicates Janus kinase inhibition as a potential therapeutic option also for multifactorial cutaneous lupus erythematosus.
Correction: Neratinib: Inching Up on the Cure Rate of HER2+ Breast Cancer?
Authors: Nisha Unni, Dhivya R. Sudhan, Carlos L. Arteaga
Journal: Clinical Cancer Research (2019)

In the original version of this article (1), the stated disclosure of the author Carlos L. Arteaga is incorrect. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Abstract 14096: Ischemic Postconditioning During Cardiopulmonary Resuscitation Normalizes Mitochondrial Function in a Porcine Model of Prolonged Cardiac Arrest
Authors: Timothy R Matsuura, Adamantios Tsangaris, Jason A Bartos, Kadambari Chandra Shekar, Matthew D Olson, Jennifer N Rees, Scott H McKnite, Michael C Lick, Qunli Cheng, Robert W Neumar, Martin Bienengraeber, Tom P Aufderheide, Matthias L Riess, Demetris Yannopoulos
Journal: Circulation (2015)

Introduction: Mitochondrial dysfunction is a hallmark of prolonged ischemia, however it’s onset during cardiac arrest (CA) and reperfusion with cardiopulmonary resuscitation (CPR) has yet to be elucidated. In a porcine model of CA, ischemic postconditioning (IPC) during CPR increased neurologically intact survival. We hypothesized that reperfusion injury, as evidenced by mitochondrial dysfunction, develops during CPR and is rescued with IPC. We investigated the effect of CA, CPR, and IPC on mitochondrial function and viability. Methods: After 15 min of ventricular fibrillation, 30 animals were randomized to no CPR (VF, n=10), active compression decompression + impedance threshold device (ACD-ITD) CPR (Control, n=9), or ACD-ITD CPR + IPC (IPC, n=11). Aortic blood pressure and ECG were continuously recorded. IPC consisted of 3 cycles of 20 sec compression / 20 sec pause for the first 2 min of CPR. Cardiac mitochondria were isolated via differential centrifugation 4 min after initiation of CPR. Additionally, mitochondria were isolated from 6 animals that did not suffer CA (non-ischemic controls). Respiration and calcium retention capacity (CRC) were measured for complex I (pyruvate+malate) and II (succinate+rotenone) substrates. Respiratory control index (RCI) was calculated as the ratio of states 3 to 4 respiration. Data were compared with ANOVA. A p value &lt; 0.05 was considered significant. Results: Coronary perfusion pressure was similar between groups during CPR. Compared to the non-ischemic group, VF resulted in decreased complex I and II RCI and decreased complex I CRC. Control CPR increased complex I and II RCI compared to VF but did not affect complex I CRC. IPC increased complex I and II RCI and complex I CRC compared to VF and Control to a level comparable with the non-ischemic group. Complex II CRC was unchanged between groups. Conclusion: Complex I and complex II RCI and complex I CRC are diminished during VF. Respiration is partially restored with standard CPR. IPC improved mitochondrial function to non-ischemic values as early as 4 min after initiation of CPR. These improvements were independent of changes in blood pressure, suggesting that initiation of CPR is a source of mitochondrial reperfusion injury and a critical time for intervention.
A phase II study of ADI-PEG 20 and FOLFOX6 in patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: James J. Harding, Shukui Qin, Tsai-Sheng Yang, Chia-Jui Yen, Yee Chao, Tsang-En Wang, Richard K. G. Do, Imane H. El Dika, Khrystyna Uhlitskykh, Brittanie M Millang, Xiaoxing Feng, Wint Swe, Amanda Johnston, John S. Bomalaski, Chien-Feng Li, Eileen Mary O'Reilly, Ching-Liang Ho, Yen-Yang Chen, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2019)

TPS477 Background: Arginine depletion interferes with pyrimidine metabolism as well as DNA damage repair pathways, and preclinical data indicate that pairing pegylated arginine deiminase (ADI-PEG 20) with fluoropyrimidines or platinum enhances cytotoxicity in vitro and in vivo in HCC models. A prior phase 1 study of FOLFOX6 and ADI-PEG 20 established the safety and recommended phase 2 dose of the combination in pts with advanced gastrointestinal tumors (Harding et al. CCP 2018). For 23 treatment-refractory HCC pts who were treated at the recommended phase 2 dose on an expansion cohort of the phase 1, the objective response rate (ORR) was 21% (95% CI 7.5-43.7) and median progression-free survival (PFS) was 7.3 months. These data were favorable when compared to historic data for FOLFOX alone where the ORR was ~8% and PFS was 2.93 months and suggest greater clinical activity of the combination (Qin et al. JCO 2013). Prospective confirmation of these results is required. Methods: This is an international, multicenter, single-arm, open-label phase 2 trial of ADI-PEG 20 and FOLFOX6 for advanced HCC pts with Child-Pugh A liver function who progressed on ≥ 2 prior lines of prior systemic therapy (NCT02102022). The primary objective is to define the ORR by RECIST 1.1 as assessed by blinded independent central review. Secondary objectives include determination of safety, disease control rate (DCR), duration of response (DOR), PFS, overall survival (OS), serum arginine, citrulline and anti-ADI-PEG 20 levels over 24 weeks, and alpha-fetoprotein response. Eligible pts receive intravenous FOLFOX6 biweekly at standard doses and ADI-PEG 20 intramuscularly weekly at 36 mg/m. 2 Cross-sectional imaging will be completed every 8 weeks until progression of disease. Based on a two-sided exact test of a one-sample proportion with an alpha of 0.05, under a presumed ORR of 22%, there is 80% power to yield 95% confidence interval of 15-26%, which will require 46 objective responses in 225 subjects. Futility will be assessed three times during the study based on having ORR data available for 56, 110, and 166 patients. This Phase 2 will be stopped for futility if the conditional power drops below 20% at any of these time points. Clinical trial information: NCT02102022.
Hyperprogressive disease (HPD) during nivolumab (Nivo) or irinotecan (IRI) as salvage line in patients with metastatic gastric cancer (MGC).
Authors: Naotoshi Sugimoto, Tomoyuki Otsuka, Akiko Hasegawa, Toshinari Yagi, Toshihiro Kudo, Koto Fujiishi, Minako Nishio, Sachiko Yamamoto, Fumie Fujisawa, Fumio Imamura
Journal: Journal of Clinical Oncology (2019)

126 Background: Nivo was approved in heavily treated MGC patients in September 2017 in Japan. HPD have been reported in patients with various tumor types treated with anti-PD-1/PD-L1 antibody therapy, but no data was existed in gastric cancer. Methods: We retrospectively compared tumor growth kinetics (TGK) on Nivo or IRI as salvage line and TGK on last treatment in patients with MGC in our hospital. The TGK ratio (TGK R , ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. HPD was defined as a TGK R ≥ 2. Results: 51 patients have been treated Nivo (n = 31) or IRI (n = 20) as salvage line before Aug 2018 in our hospital. The median age was 67 years (range 37-81) in Nivo and 68 years (range 46-80) in IRI.; 20 males and 11 females in Nivo and 16 males and 4 females in IRI; PS 0-1/2 score 19/12 in Nivo and 19/1 in IRI. Thirty-five patients (Nivo : IRI = 16:19) had target lesions according to RECIST 1.1 and performed CT pre, baseline and during treatment. HPD were observed in seven patients (44%) with Nivo. On the contrary, only one patient (5%) experienced HPD with IRI. Median PFS and OS (HPD vs. non-HPD) were 2.1 versus 3.5 months (HR: 0.29 (0.083-0.98), p = 0.046) and 5.3 versus 6.6 months (HR: 0.44 (0.078-2.5), p = 0.35) with Nivo. The rate of grade3-4 irAEs were colitis (6%), interstitial pneumonia (6%), and mytosis (3%) with Nivo. No treatment-related death and pseudo-progression were observed. Conclusions: HPD is more common with Nivo compared with IRI in patients with MGC as salvage line and associated with poor PFS in patients treated with Nivo. Further analysis will be warranted.
Comment on ‘Diagnostic accuracy of <i>ex vivo</i> fluorescence confocal microscopy for Mohs surgery of basal cell carcinomas: a prospective study on 753 margins’
Authors: E. Dika, A. Patrizi, M. Lambertini, F. Scarfì, P.A. Fanti
Journal: British Journal of Dermatology (2019)

Linked Article: Longo et al. Br J Dermatol 2019; 180:1473–1480.
Distribution of Pathogenic Variants in Von Willebrand Disease Type 2A in the American Population: Results from a National Clinical Reference Laboratory
Authors: Ruchika Sharma, Juliana Perez-Botero, Mia J Sullivan, Valerie Trapp-Stamborski, Mitchell Springer, Taquanda Gilbert, Jamie McCreery, Stefanie Dugan, Lijun Wang, Sandra L Haberichter, Kenneth Dale Friedman
Journal: Blood (2018)
A multicenter cohort study of sunitinib (SU) versus imatinib (IM) dose escalation as second-line therapy in patients with gastrointestinal stromal tumors (GISTs) after disease progression of 400 mg/d IM.
Authors: Xinhua Zhang, Xing Liu, Xiao Jun Wu, Zhizhong Pan, Hui-shan Lu, Yulong He
Journal: Journal of Clinical Oncology (2019)

356 Background: Lacking of robust evidence from prospective trials, whether to choose IM dose escalation or to directly change to SU in patients failure on standardized 400mg/d dosing of IM is still controversial. Methods: The aim of this study, is to compare the efficacy of sunitinib and imatinib dose escalation as second-line therapy in patients with GIST previously treated with 400mg/d IM. Data of patients with recurrent/metastatic GISTs who was treated by SU from 2008.1 to 2016.12, in three tertiary teaching hospitals in southern China were analyzed from prospectively registered databases, respectively. Time to SU failure (TTSF) was defined as from the time of disease progression of 400mg/d IM to failure of SU treatment in both groups. Results: A total of 240 patients received SU at least 8 weeks were collected. SU was given in 37.5mg continuous daily dose or 50mg 4 weeks on/2 weeks off. Data of 203 patients (male 136, female 67) with complete follow-up were analyzed. The median age was 52.6 years, ranged 20-79 years. KIT/PDGFRA mutational analysis was performed in 151 patients. KIT exon 11 and 9 mutations were found in 79 (52.3%) and 39 (25.8%) patients, respectively. PDGFRA D842V was in five patients (3.3%), and KIT/PDGFRA WT in 26 patients (17.2%). After failure on 400mg/d IM, 100 (49.3%) patients had a dose escalation to 600mg/800mg per day (IM group), and 103 directly changed to SU(SU group). The progression-free survival (PFS) of IM group and SU group was 5.8m and 16.9m, respectively ( P&lt;0.001). Either the TTSF or overall survival (OS) on both groups was not statistically different (18.3m VS 16.9m, P=0.219; 29.42m VS 29.45m, P=0.73). None of clinical factors that was correlated with survival using regress analysis, including primary site of lesion, metastatic sites, or mutational status, etc. Conclusions: This multi-center cohort study indicated better PFS in directly changed to SU than IM dose escalation when standardized dose IM failure. However, to those continued with SU therapy after failure of dose escalation, the outcome, both time to SU failure or OS, is similar.
A Woman in Her 40s With Non–ST-Elevation Myocardial Infarction
Authors: Michelle T. Lee, Clarence D. Gill, Enrique Garcia-Sayan
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Reduced Intensity Conditioned Bone Marrow Transplant with Post-Transplant Cyclophosphamide and Donor-Derived Mesenchymal Stromal Cell Infusions for Recessive Dystrophic Epidermolysis Bullosa
Authors: Christen L. Ebens, John A McGrath, Katsuto Tamai, Hovnanian Alain, John E. Wagner, Megan Riddle, Douglas R Keene, Todd E. DeFor, Rebecca Tryon, Mei Chen, David T Woodley, Kristin Hook, Jakub L Tolar
Journal: Blood (2018)
Correction: Is There a Future for AKT Inhibitors in the Treatment of Cancer?
Authors: Valerie M. Jansen, Ingrid A. Mayer, Carlos L. Arteaga
Journal: Clinical Cancer Research (2019)

In the original version of [this article][1] ([1][2]), the stated disclosure of the author Carlos L. Arteaga is incorrect. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.

1.  1.[↵][3]1.  Jansen VM,     2.  Mayer IA,     3.
Avadomide (CC-122) Alters T Cell Repertoire and Enhances Infiltration of Lymphocytes into Tumor Microenvironment in DLBCL Patients
Authors: Patrick R. Hagner, Fadi Towfic, Frank Schmitz, Xuehai Wang, Andrew P. Weng, Michael Pourdehnad, Anita K. Gandhi
Journal: Blood (2018)
Utility of the Pediatric Allergic Disease Quality of Life Questionnaire for childhood eczema
Authors: K.L. Hon, W.G.G. Ng, J.S.C. Kung, N.S. Cheng, D.K.K. Ng, T.F. Leung
Journal: British Journal of Dermatology (2019)

Childhood atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and sleep loss. It is important to evaluate quality-of-life (QoL) impairment objectively in atopic diseases in children.To investigate the utility of the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) in children with eczema.PADQLQ, Patient-Oriented Eczema Measure (POEM, a short-term subjective symptom score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptom score) and Children's Dermatology Life Quality Index (CDLQI, a short-term subjective symptom score) were compared and correlations evaluated.PADQLQ, POEM, NESS and CDLQI correlated well with each other (n = 132 sets; Spearman correlations: rho = 0·48-0·70, P < 0·001). A Bland-Altman plot showed a reasonably good agreement between CDLQI and PADQLQ. PADQLQ showed that symptoms of asthma, allergic conjunctivitis and allergic rhinitis were present in 20-30%, 45-71% and 58-67% of children with AD, respectively. Nevertheless, there was no association of eczema symptomatology by POEM or NESS with the severity of other allergic diseases.PADQLQ correlates well with AD-specific severity and QoL scores and reflects all allergic symptoms that holistically influence QoL in children with AD. PADQLQ is hence a composite severity score in terms of clinical symptomatology and QoL impairment for AD.
Longitudinal Changes of Impairments in Health-Related Quality of Life in Lower-Risk MDS Patients: A European Leukemianet Study
Authors: Reinhard Stauder, Ge Yu, Karin A Koinig, Dominic Culligan, Pierre Fenaux, Jaroslav Cermak, Argiris Symeonidis, Teresa Bernal, Eva Hellström-Lindberg, Moshe Mittelman, Saskia Langemeijer, Mette Skov Holm, Juliet Mills, Agnès Guerci-Bresler, Corine van Marrewijk, Hege Garelius, Fabio Efficace, Alexandra Smith, David Bowen, Theo M de Witte
Journal: Blood (2018)
Final Results of a CTEP Sponsored Phase I Study of Alistertib in Combination with Bortezomib and Rituximab in Relapsed and Refractory Mantle Cell and Low Grade Non-Hodgkin Lymphoma
Authors: Stefan Klaus Barta, Noah Kornblum, Bruce G. Raphael, Kenneth B. Hymes, Michael L. Grossbard, Tibor Moskovits, Elizabeth Handorf, Joseph Sparano, Richard Piekarz, Catherine Diefenbach
Journal: Blood (2018)
Thermal safety and effectiveness of tumor treating fields’ delivery to the abdomen as determined by computational simulations.
Authors: Uri Weinberg, Zeev Bomzon, Ariel Naveh, Ofir Yesharim, Ori Farber, Eilon Kirson
Journal: Journal of Clinical Oncology (2019)

272 Background: Tumor Treating Fields (TTFields), an antimitotic cancer treatment, utilizes low intensity (1-3 V/cm), intermediate frequency (100-300 kHz), alternating electric fields delivered non-invasively by transducer arrays placed on skin over tumor region. Safety of TTFields has been established in pancreatic cancer (Phase II study; PANOVA; NCT01971281). A Phase 3 study in locally-advanced pancreatic cancer (PANOVA-3) and a phase 2 study in hepatocellular cancer are ongoing. Preclinical studies suggest that TTFields’ intensity correlates with treatment efficacy. Simulations can determine the thermal safety of TTFields by evaluating tissue heating due to field absorption and resultant risk of thermal damage. We used computational simulations to study the effectiveness of field distribution and associated heating in realistic phantoms during TTFields delivery to the abdomen. Methods: Delivery of TTFields to computational phantoms of a male (DUKE 3.0), a female (ELLA 3.0) and an obese male (FATS 3.0) was simulated. For each phantom, 6-8 different transducer array layouts to the abdomen were tested. Specific Absorption Rate (SAR) levels were calculated to assess the risk of thermal damage to tissues, and compared to the SAR control level of 10 W/kg per International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines for occupational exposure (Health Physics 74 (4) 494; 1998). The field intensities were measured to determine the effectiveness of treatment delivery. Results: Altering the size and position of the arrays facilitates field intensities above the therapeutic threshold of 1 V/cm. Within the abdominal internal organs, the SAR values were generally below the ICNIRP recommended level of 10 W/kg. The maximum SAR levels did not exceed 20 W/kg. Conclusions: TTFields could be delivered at intensities above therapeutic threshold of 1 V/cm by strategizing the array size and placement. TTFields to the abdomen can be delivered to target gastrointestinal cancers without causing thermal damage to abdominal tissues. These results also indicate that TTFields delivery can be optimized in gastrointestinal cancers.
Safety and Tolerability of Shortened Updosing with 7 Injections of Subcutaneous Allergen Immunotherapy
Authors: Eike G. Wuestenberg, Andreas Horn, Hendrik Wolf, Santiago Martin Hurtado, Katerina Koutromanou, Nadia Ghaussy, Montserrat Fernandez-Rivas
Journal: Journal of Allergy and Clinical Immunology (2019)
Recent advances in circulating nucleic acids in oncology
Authors: A. Otandault, P. Anker, Z. Al Amir Dache, V. Guillaumon, R. Meddeb, B. Pastor, E. Pisareva, C. Sanchez, R. Tanos, G. Tousch, H. Schwarzenbach, A.R. Thierry
Journal: Annals of Oncology (2019)

Circulating cell-free DNA (cfDNA) is one of the fastest growing and most exciting areas in oncology in recent years. Its potential clinical uses cover now each phase of cancer patient management care (predictive information, detection of the minimal residual disease, early detection of resistance, treatment monitoring, recurrence surveillance, and cancer early detection/screening). This review relates the recent advances in the application of circulating DNA or RNA in oncology building on unpublished or initial findings/work presented at the 10th international symposium on circulating nucleic acids in plasma and serum held in Montpellier from the 20th to the 22nd of September 2017. This year, presenters revealed their latest data and crucial observations notably in relation to (i) the circulating cell-free (cfDNA) structure and implications regarding their optimal detection; (ii) their role in the metastatic or immunological processes; (iii) evaluation of miRNA panels for cancer patient follow up; (iv) the detection of the minimal residual disease; (v) the evaluation of a screening tests for cancer using cfDNA analysis; and (vi) elements of preanalytical guidelines. This work reviews the recent progresses in the field brought to light in the meeting, as well as in the most important reports from the literature, past and present. It proposes a broader picture of the basic research and its potential, and of the implementation and current challenges in the use of circulating nucleic acids in oncology.
68Ga-DOTATATE in Benign Prostate Hyperplasia
Authors: Jiaqiong Wang
Journal: Clinical Nuclear Medicine (2019)

A 79-year-old man had carcinoid syndrome and bilateral pulmonary nodules, which were biopsy confirmed as well-differentiated neuroendocrine tumor. PET/CT with Ga-[DOTA-Tyr]-octreotate (Ga-DOTATATE) showed multiple Ga-DOTATATE-avid bilateral pulmonary nodules, left hilar lymph node, as well as diffuse increased Ga-DOTATATE uptake in the prostate. A review of the history revealed that this patient had elevated prostate-specific antigen level. The prostate biopsy did not reveal evidence of prostate cancer but showed benign prostate hyperplasia.