tbuckley/cabot-search huggingface dataset:
Dramatic response of <i>STRN-NTRK</i>-fused malignant glioneuronal tumor to larotrectinib in adult
Authors: Julie Boyer, Cristina Birzu, Franck Bielle, Clara Goulas, Julien Savatovsky, Carine Karachi, Ahmed Idbaih
Journal: Neuro-Oncology (2021)

Dramatic response of STRN-NTRK-fused malignant glioneuronal tumor to larotrectinib in adultGlioneuronal tumors (GNT) are rare entities characterized by the proliferation of cells expressing a mixture of neuronal and glial markers.Most GNT are classified as low-grade, but some may present high-grade features.We report here a case on a left-handed 53-year-old Caucasian man with no medical history who presented in 2011 with partial seizures, revealing a right non-enhancing insular brain lesion compatible with a diffuse low-grade glioma (Figure 1A).The lesion was therefore monitored and remained stable for 8 years.In June 2019, the patient presented rapid clinical and radiological tumor progression.The tumor was surgically removed.Pathological examination identified a high-grade GNT exhibiting frequent mitosis, vascular proliferation, necrosis, and Ki-67 proliferative activity of 20%.Immunohistochemistry analysis revealed no IDH1R132H, FGFR3, BRAFV600E mutations, or EGFR expression.No microsatellite instability or 1p19q codeletion was detected.In contrast, pan-TRK (tropomyosin receptor kinase) staining was positive (Figure 1B), and transcriptomic analysis revealed STRN1-NTRK2 fusion.First-line treatment included concurrent radiochemotherapy delivering 59.4 Gy plus temozolomide, followed by 5 cycles of adjuvant temozolomide, which ended in February 2020.Follow-up MRI showed tumor progression in March 2020 and led to the initiation of a second-line treatment with larotrectinib (TRK inhibitor) starting March 30, 2020 with 75 mg twice a day, to 100 mg twice a day starting April 24, 2020.The patient then remained clinically stable with minor troubles with word finding.The patient has presented no seizures since September 2019 and is currently being treated with regular anticonvulsant monotherapy.Follow-up MRI performed in June 2020 showed complete response that was maintained in February 2021 (Figure 1C).Larotrectinib tolerance is good with no adverse events.NTRK genes are involved in neurodevelopment, three NTRK genes are described: NTRK1, NTRK2, and NTRK3, which respectively encode transmembrane tyrosine kinase receptors TrkA, TrkB, and TrkC proteins.When activated by their specific ligands (mainly neurotrophins and neuronal growth factors)
AB0884-HPR PERSONALISED TREATMENT GOALS IN PATIENTS WITH IMMUNE MEDIATED INFLAMMATORY DISEASE
Authors: S. Fadaei, H. Van Os-Medendorp, A. Sloeserwij, V. Sigurdsson, J. M. Van Laar, J. Spierings
Journal: Annals of the Rheumatic Diseases (2021)

Background: Immune mediated inflammatory diseases (IMIDs) often have a chronic character and large impact on daily life of patients. In order to provide patient-centred care, insight in personal goals is a key issue. Objectives: The aim of this study was to evaluate treatment goals of patients with IMIDs over time. Methods: Patients with IMIDs were invited to complete a self-designed questionnaire about lifestyle, personal treatment goals and perceived care at their first visit to our centre and one year after referral. Clinical information was collected through the electronic patient record system. Results: 41 (30%) patients of the 137 invited, completed both questionnaires. Participants had a mean age of 45.6 years (SD 13.4), N=35 (83%) was female, mean disease duration was 12.7 years (SD 12.7). Patients were diagnosed with connective tissue disease (CTD, n=19; 45%), antiphospholipid syndrome (APS, n=10; 24%), inflammatory arthritis (n=7; 17%) and psoriasis (n=7; 17%). We identified six categories of treatment goals: disease related, daily functioning, lifestyle, emotional wellbeing. Figure 1 shows the reported treatment goals at baseline and follow-up. Most frequently mentioned were goals related to disease, lifestyle and daily functioning. At follow-up we observed a vast increase in reported goals related to psychological wellbeing (from 5% to 16%). At baseline patients with APS chose lifestyle-related goals more often than other patients (RR=3.2; p=0.015). At follow-up patients with CTDs reported disease related-goals less often than other patients (RR=0.4; p=0.002). Patients did not report significant progress in reaching their goals on a Likert scale of 1-10. However, in 90% at first visit and in 83% of patients at follow-up, patients reported that the provided care was addressing issues they personally prioritized. Conclusion: IMID patients’ most frequent treatment goals relate to disease activity, lifestyle and daily functioning. Patients frequently change their treatment goals during the first year of treatment. Better understanding of personal goals can help physicians providing targeted and personalised medicine. Figure 1. themes of treatment goals at baseline and follow-up Acknowledgements: The researchers would like to thank all patients participating in this study and acknowledge the UMC Utrecht research program Infection and Immunity for supporting this initiative. Disclosure of Interests: None declared
AB0655 RHEUMATOID ARTHRITIS ACTIVITY BEFORE AND AFTER COVID-19 LOCKDOWN PERIOD
Authors: M. Jordhani, D. Ruci, F. Skana, E. Memlika
Journal: Annals of the Rheumatic Diseases (2021)

Background: The COVID-19 global pandemic has had a great impact on world population due to morbidity, mortality and restriction measures in order to stop the progression of COVID-19. Patients with rheumatic and musculoskeletic diseases, and especially rheumatoid arthritis (RA) patients, being one of the vulnerable classes of chronic patients, were recommended to follow the government’s rules 1 . Objectives: The aim of this study was to evaluate DAS-28-ESR in patients with rheumatoid arthritis before and after lockdown period. Methods: This is a multi-center observational study including 85 patients which were evaluated before and after lockdown for their disease activity score according to DAS-28-ESR score. They had been diagnosed with rheumatoid arthritis more than 5 years ago. A thorough physical examination was performed before and after the lockdown period. It included examination of tender and swollen joints and patient’s global health. They were completed with all required laboratory data, including erythrosedimentation rate. For a more accurate calculation, DAS-28-ESR was used in an electronic version. Patients with other inflammatory or infective diseases were excluded from the study. All data were statistically evaluated using statistical tests such as t-student test. Results: The first group (the one before lockdown) had an average DAS-28-ESR of 4.7 while after the lockdown period, the average DAS-28-ESR was 5.16. After statistically evaluating all data, it was found that there exists a significant difference between DAS-28-ESR score before and after COVID-19 lockdown (p=0.0011). Conclusion: Our study showed that lockdown period due to COVID-19 pandemic, has aggravated disease activity in patients with Rheumatoid Arthritis. This may be consequence of various causes such as physical inactivity and difficulty to follow-up or to take the medication properly. References: [1]Landewé RB, Machado PM, Kroon F , et al , EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2, Annals of the Rheumatic Diseases 2020; 79: 851-858. Disclosure of Interests: None declared.
Pharmaceutical applications of framework nucleic acids
Authors: Liang Chen, Jie Zhang, Zhun Lin, Ziyan Zhang, Miao Mao, Jiacheng Wu, Qian Li, Yuanqing Zhang, Chunhai Fan
Journal: Acta Pharmaceutica Sinica B (2021)

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.
Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry
Authors: Jeffrey A Sparks, Zachary S Wallace, Andrea M Seet, Milena A Gianfrancesco, Zara Izadi, Kimme L Hyrich, Anja Strangfeld, Laure Gossec, Loreto Carmona, Elsa F Mateus, Saskia Lawson-Tovey, Laura Trupin, Stephanie Rush, Patricia Katz, Gabriela Schmajuk, Lindsay Jacobsohn, Leanna Wise, Emily L Gilbert, Ali Duarte-García, Maria O Valenzuela-Almada, Guillermo J Pons-Estel, Carolina A Isnardi, Guillermo A Berbotto, Tiffany Y -T Hsu, Kristin M D’Silva, Naomi J Patel, Lianne Kearsley-Fleet, Martin Schäfer, Sandra Lúcia Euzébio Ribeiro, Samar Al Emadi, Liselotte Tidblad, Carlo Alberto Scirè, Bernd Raffeiner, Thierry Thomas, René-Marc Flipo, Jérôme Avouac, Raphaèle Seror, Miguel Bernardes, Maria Margarida Cunha, Rebecca Hasseli, Hendrik Schulze-Koops, Ulf Müller-Ladner, Christof Specker, Viviane Angelina de Souza, Licia Maria Henrique da Mota, Ana Paula Monteiro Gomides, Philippe Dieudé, Elena Nikiphorou, Vanessa L Kronzer, Namrata Singh, Manuel F Ugarte-Gil, Beth Wallace, Akpabio Akpabio, Ranjeny Thomas, Suleman Bhana, Wendy Costello, Rebecca Grainger, Jonathan S Hausmann, Jean W Liew, Emily Sirotich, Paul Sufka, Philip C Robinson, Pedro M Machado, Jinoos Yazdany
Journal: Annals of the Rheumatic Diseases (2021)

To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.
POS1317 PREDICTIVE FACTORS FOR RESPONSE TO TREATMENT IN A LONG-TERM COHORT OF PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS-ASSOCIATED UVEITIS
Authors: L. Marelli, F. Minoia, G. Beretta, C. Mapelli, G. Leone, G. Cincinelli, T. Giani, P. Nucci, R. Cimaz, E. Miserocchi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Uveitis is the main extraarticular complication of juvenile idiopathic arthritis (JIA) with still a significant impact on JIA morbidity, despite continuous improvement in systemic treatment. Although antinuclear antibody positivity and early onset of JIA have been associated with a high risk of uveitis onset, so far no clinical features have been widely recognized as predictive factors for JIA-associated uveitis (JIA-U) response to treatment. Objectives: To investigate clinical features associated with response to systemic treatment in a long-term cohort of patients with JIA-U Methods: Clinical records of patients with JIA-U were retrospectively reviewed with regard to clinical features, therapeutic choices and outcome. Clinical and laboratory variables were compared by means of Mann-Whitney U test or chi-square/Fisher exact test, as appropriate. Results: Data from 164 JIA-U patients were analysed (81.7% female), with a median follow up of 12.1 years (7.1-17.3). Median age at JIA and uveitis onset was 2.6 (1.6-4.8) and 4.8 (2.9 – 7.0) years, respectively. Monotherapy with a conventional disease-modifying antirheumatic drug (DMARD) was used in 25.0% of patients, while 111 patients (67.7%) received at least one biologic DMARD (bDMARDs). Compared to patients responsive to DMARDs, children requiring a bDMARDs for uveitis had a lower median age at both JIA (2.4 vs 4.3 years, p 0.0234) and uveitis onset (4.1 vs 6.2 years, p 0.0023). Despite no differences in ocular damage at onset and median disease duration, patients not responsive to conventional DMARDs showed a higher frequency of ocular damage at the last visit (66.2% vs 33.3%, p 0.011). Children requiring more than one bDMARD for uveitis presented a more frequent polyarticular course (87.0% vs 20.2%, p 0.0022), a longer disease duration (median follow-up: 14.2 vs 10.4 years, p 0.0397) and a higher frequency of visual loss (best corrected visual acuity &lt; 4/10: 23.3% vs 6.3%, p 0.0069). Conclusion: JIA-U patients with a lack of response to conventional DMARDs were significantly younger both at JIA and uveitis onset. Severe JIA-U requiring more than one bDMARDs was associated with polyarticular JIA course and longer disease duration. Children resistant to conventional treatment need prompt recognition and additional strategies to improve long-term outcome. References: [1]Heiligenhaus et al. Predictive factors and biomarkers for the 2-year outcome of uveitis in juvenile idiopathic arthritis. Rheumatology 2019. Disclosure of Interests: None declared
A Lancet Commission on 70 years of women's reproductive, maternal, newborn, child, and adolescent health in China
Authors: Jie Qiao, Yuanyuan Wang, Xiaohong Li, Fan Jiang, Yunting Zhang, Jun Ma, Yi Song, Jing Ma, Wei Fu, Ruyan Pang, Zhaofang Zhu, Jun Zhang, Xu Qian, Linhong Wang, Jiuling Wu, Hsun-Ming Chang, Peter C K Leung, Meng Mao, Duan Ma, Yan Guo, Jie Qiu, Li Liu, Haidong Wang, Robert J Norman, Joy Lawn, Robert E Black, Carine Ronsmans, George Patton, Jun Zhu, Li Song, Therese Hesketh
Journal: The Lancet (2021)
<i>Notes from the Field:</i> Impact of the COVID-19 Response on Scale-Up of HIV Viral Load Testing — PEPFAR-Supported Countries, January–June 2020
Authors: Shirley Lee Lecher, Mary Naluguza, Christina Mwangi, Jonathan N’tale, Dianna Edgil, George Alemnji, Heather Alexander
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
Reorganisation of UK public health agencies: meaningful change or smoke and mirrors?
Authors: Samuel P Trethewey
Journal: BMJ (2021)

Oliver’s commentary on the UK government’s reorganisation and rebranding of public health agencies is incisive.1 He raises several important issues including the potential negative effects on key health improvement functions previously performed by Public Health England.

As Oliver observes, the government does not seem to have made a clear pledge regarding investment in specific public health improvement and prevention services, including addiction services. Yet substantial investment is …
Prostate Cancer With Neuroendocrine Differentiation Recurring After Treatment With 177Lu-PSMA
Authors: Farnaz Nesari Javan, Kamran Aryana, Emran Askari
Journal: Clinical Nuclear Medicine (2021)

Abstract Prostate cancer with NED (neuroendocrine differentiation) may occur in various stages of the disease, which is associated with a poor prognosis and treatment resistance. We present a case of a patient with metastatic castration-resistant prostatic cancer, who was treated with 7 cycles of 177 Lu-PSMA and a very good response. Although only few foci with PSMA uptake were remained in the last posttreatment images, PSA levels dramatically began to rise. This raised suspicion for NED, and 68 Ga-DOTATATE was done showing sufficient uptake to consider a trial of 177 Lu-DOTATATE. The patient reported pain response, and PSA levels dropped after 1 cycle of the treatment.
AB0258 DMARD-TREATMENT OF UNDIFFERENTIATED ARTHRITIS INTENSIFIED DURING THE LAST DECENNIA, BUT DID NOT RESULT IN IMPROVED LONG TERM OUTCOMES
Authors: M. Verstappen, X. Matthijssen, A. Van der Helm - van Mil
Journal: Annals of the Rheumatic Diseases (2021)

Background: EULAR guidelines stress timely initiation of DMARD-treatment in early arthritis patients also when classification criteria are not yet fulfilled. Consequently, undifferentiated arthritis (UA) patients may be increasingly treated with disease modifying antirheumatic drugs (DMARDs), despite inadequate placebo-controlled evidence for its effectivity. Implementation of this guideline also hampers future placebo-controlled trials in UA. However, historical data, with inclusion period as instrumental variable, can provide insight whether long term outcome is improved with increased DMARD-use, and thus serve to investigate if DMARD-treatment is effective in UA. Objectives: With 25-years of observational data of newly referred UA-patients, we studied whether enhanced treatment strategies resulted in better long term outcomes for UA. Methods: Between 1993 and 2019, 1132 consecutive UA-patients, not fulfilling the 1987/2010 criteria for RA or any other distinct diagnosis, were included in the Leiden Early Arthritis Cohort; patients were divided in 5 inclusion periods (1993-1998, 1999-2005, 2006-2010, 2011-2014, 2015-2019). Frequency of DMARD-initiation after diagnosis was compared. We studied the following outcomes: the course of disease activity scores (DAS28-CRP) and Health assessment questionnaires (HAQ), progression to RA after 1-year (according to the 1987 and/or 2010 criteria) and the frequency of prolonged DMARD-free status within 10-years of follow-up (this was defined as either spontaneous remission or sustained remission after discontinuation of DMARD-treatment). Results: The current population of UA-patients, thus not fulfilling 1987 or 2010 criteria, had rather mild disease: the median SJC was 1, the median TJC 2, 95% was autoantibody-negative and the median HAQ was 0.6. These characteristics were similar in the different inclusion periods. Initiation of DMARD-treatment in UA increased over time: 18%, 35%, 38%, 43% up to 55% in respectively 1993-1998, 1999-2005, 2006-2010, 2011-2014 and 2015-2019, in which methotrexate became more common in the last decade. Frequency of progression to RA after 1-year did not decrease and was 14%, 21%, 26%, 19% and 28% in the respective inclusion periods. Long-term DAS28CRP-scores improved from 2011 onwards (range -0.18, -0.24; p&lt;0.05). However HAQ-score over time did not improve compared to the 1993-1998 period (range -0.00, -0.08; p&gt;0.05). Also the percentages of patients in DMARD-free status after 10-years of follow-up did not significantly improve over time: 57%, 58%, 59% (for 1993-1998, 1999-2005, 2006-2010 respectively, p=0.59). Conclusion: Intensified DMARD-treatment of patients with UA did not result in improved outcomes. These data may indicate overtreatment of UA-patients. Yet, methods to stratify which UA-patients should be treated remains warranted. Disclosure of Interests: None declared
The revolving door of HIV care: Revising the service delivery cascade to achieve the UNAIDS 95-95-95 goals
Authors: Peter Ehrenkranz, Sydney Rosen, Andrew Boulle, Jeffrey W. Eaton, Nathan Ford, Matthew P. Fox, Anna Grimsrud, Brian D. Rice, Izukanji Sikazwe, Charles B. Holmes
Journal: PLoS Medicine (2021)

Antiretroviral therapy (ART) for human immunodeficiency virus (HIV) prevents illness and death from HIV disease and transmission of HIV infection.To encourage global scale-up of ART, the Joint UN Program on HIV/AIDS (UNAIDS) issued the "95-95-95" targets for the HIV "cascade of care."These targets state that by 2030, 95% of individuals living with HIV will know their HIV status, 95% of people with diagnosed HIV infection will receive ART, and 95% of those taking ART will have achieved suppression of the virus.• While tremendous progress has been made toward achieving these targets, substantial gaps remain.The challenge of closing the final gaps requires reconsideration of the cascade itself.• The 95-95-95 HIV care cascade depicts a linear and unidirectional continuum of care with one starting point (HIV diagnosis) and one ending point (treatment discontination or death).This simplification of the cascade oversimplifies the complex cycle of engagement, disengagement, temporary disuptions, reengagement, and transitions in care experienced by many people living with HIV (PLHIV).• As the proportion of PLHIV who reinitiate ART after previously starting and stopping increases, we propose to update the HIV cascade of care to better reflect actual