tbuckley/cabot-search huggingface dataset:
Hydroxyurea Safe and Effective for Sickle Cell Anemia
Authors: M.J. Friedrich
Journal: JAMA (2019)

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Anthony Leslie Revell: surgeon general of the British Armed Forces who found himself at the forefront of investigations into “Gulf war syndrome”
Authors: Matt Limb
Journal: BMJ (2019)

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ECG Response: February 11, 2014
Authors: Philip Podrid
Journal: Circulation (2014)

ECG Challenge: A 59-year-old woman has a history of lupus with renal involvement for which she is taking glucocorticoids.She has no known heart disease.She presents to her rheumatologist with concerns of intermittent palpitations that first began ≈1 month ago.She was referred to a cardiologist and an ECG was obtained.
Response to: ‘Adipose stromal vascular fraction and regenerative therapy in SSc: response to the article by Magalon <i>et al</i>’ by De Benedetto <i>et al</i>
Authors: Jérémy Magalon, Mélanie Velier, Stéphanie Simoncini, Françoise Dignat-George, Brigitte Granel, Pascale Paul, Florence Sabatier
Journal: Annals of the Rheumatic Diseases (2019)

We would like to thank Di Benedetto et al 1 for their constructive comments on our recent publication in Annals of Rheumatic Disease entitled ‘Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis’.2 

Di Benedetto et al mentioned that the profibrotic signature of mesenchymal stem cells (MSCs) derived from patients with the diffuse cutaneous form of systemic sclerosis (dc-SSc) has been established from previous works. In line with this, they discussed the potential risk of increasing the fibrotic burden by using autologous adipose-derived stromal vascular fraction (ADVSF) in which MSCs are highly represented.

Although this is a fair question in the context of developing MSCs-based therapy for SSc, we would like to emphasise the fact that the biological findings …
Updated Results from an Open-Label, Multicenter, Expanded Treatment Protocol (ETP) Phase (Ph) 3b Study of Ruxolitinib (RUX) in Patients (Pts) with Polycythemia Vera (PV) Who Were Hydroxyurea (HU) Resistant or Intolerant and for Whom No Alternative Treatment (Tx) Was Available
Authors: Lynda Foltz, Gian-Matteo Pica, Hacene Zerazhi, Jan Van Droogenbroeck, Sorin Visanica, Enrique Báez de la Fuente, Brian Leber, Antonio Medina de Almeida, Dana Ranta, Mauricio Reyes Cartes, Jean-Jacques Kiladjian, Linda Chrit, Zhaoyu Yin, Juliane Morando, Timothy Devos
Journal: Blood (2018)
EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016
Authors: Marko Babjuk, Andreas Böhle, Maximilian Burger, Otakar Capoun, Daniel Cohen, Eva M. Compérat, Virginia Hernández, Eero Kaasinen, Joan Palou, Morgan Rouprêt, Bas W.G. van Rhijn, Shahrokh F. Shariat, Viktor Soukup, Richard J. Sylvester, Richard Zigeuner
Journal: European Urology (2016)
Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management
Authors: Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2014)

Disease overview : Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults. Diagnosis : CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR‐ABL fusion oncogene, which in turn translates into a Bcr‐Abl oncoprotein. Frontline therapy : Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first‐line treatment of patients with newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long‐term survival remains to be determined. Salvage therapy : For patients who fail frontline therapy, second‐line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR‐ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR‐ABL mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML‐CP who have failed at least 2 TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 89:547–556, 2014. © 2014 Wiley Periodicals, Inc.
Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis
Authors: Koji Hara, Atsuya Takeda, Yuichiro Tsurugai, Yusuke Saigusa, Naoko Sanuki, Takahisa Eriguchi, Shin Maeda, Katsuaki Tanaka, Kazushi Numata
Journal: Hepatology (2019)

Potentially curative treatments for early‐stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early‐stage HCC. Consecutive patients with ≤3 early‐stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3‐year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7‐9.2; versus 12.9%, 95% CI, 9.9‐16.2) ( P &lt; 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3‐year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2‐77.7; and 70.4%; 95% CI, 58.5‐79.4, respectively; P = 0.86). Conclusion : Radiotherapy has excellent local control and comparable overall survival in patients with well‐compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.
Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non–small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study
Authors: Nicholas Thatcher, Jerome H. Goldschmidt, Michael Thomas, Michael Schenker, Zhiying Pan, Luis Paz-Ares Rodriguez, Valery Breder, Gyula Ostoros, Vladimir Hanes
Journal: Clinical Cancer Research (2019)

Abstract Purpose: This phase III study compared clinical efficacy and safety of the biosimilar ABP 215 with bevacizumab reference product (RP) in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). Patients and Methods: Patients were randomized 1:1 to ABP 215 or bevacizumab 15 mg/kg every three weeks for 6 cycles. All patients received carboplatin and paclitaxel every three weeks for ≥4 and ≤6 cycles. The primary efficacy endpoint was risk ratio of objective response rate (ORR); clinical equivalence was confirmed if the 2-sided 90% confidence interval (CI) of the risk ratio was within the margin of 0.67 to 1.5. Secondary endpoints included risk difference of ORR, duration of response (DOR), progression-free survival (PFS), and overall survival (OS); pharmacokinetics, adverse events (AEs), and incidence of antidrug antibodies (ADAs) were monitored. Results: A total of 820 patients were screened; 642 were randomized to ABP 215 (n = 328) and bevacizumab (n = 314). Overall, 128 (39.0%) and 131 (41.7%) patients in the ABP 215 and bevacizumab groups, respectively, had objective responses [ORR risk ratio: 0.93 (90% CI, 0.80–1.09)]. In the ABP 215 and bevacizumab group, 308 (95.1%) and 289 (93.5%) patients, respectively, had at least 1 AE; 13 (4.0%) and 11 (3.6%) experienced a fatal AE. Anti-VEGF toxicity was low and comparable between treatment groups. At week 19, median trough serum drug concentration was 132 μg/mL (ABP 215 group) and 129 μg/mL (bevacizumab group). No patient tested positive for neutralizing antibodies. Conclusions: ABP 215 is similar to bevacizumab RP with respect to clinical efficacy, safety, immunogenicity, and pharmacokinetics. The totality of evidence supports clinical equivalence of ABP 215 and bevacizumab.
Body mass index and all cause mortality in HUNT and UK Biobank studies: linear and non-linear mendelian randomisation analyses
Authors: Yi-Qian Sun, Stephen Burgess, James R Staley, Angela M Wood, Steven Bell, Stephen K Kaptoge, Qi Guo, Thomas R Bolton, Amy M Mason, Adam S Butterworth, Emanuele Di Angelantonio, Gunnhild Å Vie, Johan H Bjørngaard, Jonas Minet Kinge, Yue Chen, Xiao-Mei Mai
Journal: BMJ (2019)

Abstract Editor’s Note on Methodological Criticism and an Updated Analysis Objective To investigate the shape of the causal relation between body mass index (BMI) and mortality. Design Linear and non-linear mendelian randomisation analyses. Setting Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom). Participants Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank. Main outcome measures All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality. Results 12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI &lt;18.5) and a 14% (−1% to 27%) lower risk in low normal weight participants (BMI 18.5-19.9). Non-linear mendelian randomisation indicated a J shaped relation between genetically predicted BMI and the risk of all cause mortality, with the lowest risk at a BMI of around 22-25 for the overall sample. Subgroup analyses by smoking status, however, suggested an always-increasing relation of BMI with mortality in never smokers and a J shaped relation in ever smokers. Conclusions The previously observed J shaped relation between BMI and risk of all cause mortality appears to have a causal basis, but subgroup analyses by smoking status revealed that the BMI-mortality relation is likely comprised of at least two distinct curves, rather than one J shaped relation. An increased risk of mortality for being underweight was only evident in ever smokers.
Pretreatment Health-Related Quality of Life Profile According to the EORTC QLQ-C30 in Patients with Myelodysplastic Syndromes (MDS): Analysis on 443 Lower-Risk MDS Patients
Authors: Fabio Efficace, Pasquale Niscola, Andrea Patriarca, Francesco Cottone, Giuseppe A. Palumbo, Giovanni Caocci, Marilena Fedele, Uwe Platzbecker, Reinhard Stauder, Duska Petranovic, Alessandra Ricco, Massimo Breccia, Chiara Frairia, Mario Luppi, Rosangela Invernizzi, Grazia Sanpaolo, Monica Crugnola, Luana Fianchi, Daniele Vallisa, Maria Teresa Voso, Claudio Fozza, Valeria Santini, Jo Caers, Isabella Capodanno, Chiara Sarlo, Maribel Pelaez Doro, Micaela Bergamaschi, Huiyong Zhang, Michael Lubbert, Manuela Canicattì, Charalampia Kyriakou, Nicola Di Renzo, Antonio Cuneo, Marina Karakantza, Marco Vignetti
Journal: Blood (2018)
HLA-a*0101 Expression Correlates with Increased Risk of Severe Cutaneous Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Maira Fonseca, Ann A. Jakubowski, Sean M Devlin, James W. Young, Samira A Fatmi, Molly Maloy, Sergio Giralt, Doris Ponce, Alina Markova
Journal: Blood (2018)
P154 Local low dose radiation induces systemic immune alterations in two experimental models of inflammatory arthritis
Authors: L Deloch, M Rückert, M Seeling, F Nimmerjahn, R Fietkau, B Frey, US Gaipl
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory autoimmune disease that mainly affects the joints with its hallmarks being synovial inflammation followed by cartilage and bone destruction. There are a plethora of treatment options available, however, not all patients respond properly. In these patients it is crucial to slow down bone loss and inflammation in a timely manner to prevent further damage. Here, a therapy with low-dose ionizing radiation, the so called low-dose radiotherapy (LD-RT), could be an additional option. Detailed knowledge on the underlying mechanisms of reduced bone destruction and immune-mediated pain levels in patients following LD-RT is still scarce. We already showed that LD-RT locally slows down disease progression in human <i>TNFα</i> transgenic (h<i>TNFα</i> tg) animals by mainly having an impact on bone metabolism. <h3>Objectives</h3> We now aim to take a closer look on systemic immune-mediated effects of LD-RT in both, h<i>TNFα</i> tg mice, as a cytokine mediated model, and in the KRN serum transfer model, as an example for arthritogenic antibody dependence. <h3>Methods</h3> h<i>TNFα</i> tg or serum-injected C57Bl/6 mice were locally irradiated with a single dose per fraction of 0.5Gy. After an observation period of 7 days (serum-injected mice) or 30 days (h<i>TNFα</i>-tg mice), blood, bone marrow as well as hind paws and synovial fluid was taken and analyzed using multicolor flow cytometry or histomorphometry. <h3>Results</h3> Treatment of hind paws of serum-injected C57Bl/6 mice with 1 × 0.5 Gy resulted in a systemic immune modulation. In the peripheral blood, an increase of eosinophils and a decrease of B cells and NK cells were observed. In the bone marrow, the prominent alteration was a shift from CD8+ to CD4+ T cells in both, the irradiated and non-irradiated leg. Furthermore, dendritic cells were decreased. In h<i>TNFα</i> tg animals, inflammation was modulated in a systemic manner after local LD-RT, while bone protection was a local effect. <h3>Conclusions</h3> We conclude that LD-RT is not only a valuable tool for locally reducing inflammation and bone loss in the affected joints, but also has beneficial systemic immune-mediated effects. The observed immune modulations in the peripheral blood were similar to those observed for patients treated with LD-RT within the observational IMMO-LDRT01 study (NCT02653079). In the future, placebo-controlled studies with high patient numbers are desirable to clinically prove LD-RT as therapy for RA. <h3>Acknowledgements</h3> Supported by the German Federal Ministry of Education and Research (GREWIS, 02NUK017G and GREWIS-alpha, 02NUK050E). <h3>Disclosure of Interest</h3> None declared.
Efficacy of L-carnitine on ribavirin-induced hemolytic anemia in patients with hepatitis C virus infection
Authors: Shinya Sato, Kei Moriya, Masanori Furukawa, Soichiro Saikawa, Tadashi Namisaki, Mitsuteru Kitade, Hideto Kawaratani, Kosuke Kaji, Hiroaki Takaya, Naotaka Shimozato, Yasuhiko Sawada, Kenichiro Seki, Koh Kitagawa, Takemi Akahane, Akira Mitoro, Yasushi Okura, Junichi Yamao, Hitoshi Yoshiji
Journal: Clinical and Molecular Hepatology (2019)

L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease.A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires.A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment.L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.
Nanoliposomes Co-Encapsulating CT Imaging Contrast Agent and Photosensitizer for Enhanced, Imaging Guided Photodynamic Therapy of Cancer
Authors: Hao Xu, Tymish Y. Ohulchanskyy, Artem Yakovliev, Roman Zinyuk, Jun Song, Liwei Liu, Junle Qu, Zhen Yuan
Journal: Theranostics (2019)

Fluorescence (FL) and X-ray computed tomography (CT) imaging-guided photodynamic therapy (PDT) can provide a powerful theranostic tool to visualize, monitor, and treat cancer and other diseases with enhanced accuracy and efficacy. Methods: In this study, clinically approved iodinated CT imaging contrast agent (CTIA) iodixanol and commercially available photosensitizer (PS) meso-tetrakis (4-sulphonatophenyl) porphine (TPPS4) were co-encapsulated in biocompatible PEGylated nanoliposomes (NL) for enhanced anticancer PDT guided by bimodal (FL and CT) imaging. Results: The NL co-encapsulation of iodixanol and TPPS4 (LIT) lead to an increase in singlet oxygen generation by PS via the intraparticle heavy-atom (iodine) effect on PS molecules, as it was confirmed by both direct and indirect measurements of singlet oxygen production. The confocal imaging and PDT of cancer cells were performed in vitro, exhibiting the cellular uptake of TPPS4 formulations and enhanced PDT efficacy of LIT. Meanwhile, bimodal (FL and CT) imaging was also conducted with tumor-bearing mice and the imaging results manifested high-efficient accumulation and retention of LIT in tumors. Moreover, PDT of tumor in vivo was shown to be drastically more efficient with LIT than with other formulations of TPPS4. Conclusion: This study demonstrated that LIT can serve as a highly efficient theranostic nanoplatform for enhanced anticancer PDT guided by bimodal (FL and CT) imaging.
HHV-6 Infection/Reactivation after Allogeneic Stem Cell Transplantation in Pediatric Patients: Epidemiology, Risk Factors and Outcome
Authors: Francesca Compagno, Stella Boghen, Sabrina Basso, Antonella Gurrado, Alessandra Maiello, Laura Catenacci, Tommaso Mina, Santina Recupero, Alessandra Tolva, Elena Bergami, Patrizia Comoli, Marco Zecca
Journal: Blood (2018)