tbuckley/cabot-search huggingface dataset:
Elevated aspartate transaminase (AST) and inflammatory markers are associated with acute kidney injury and increased mortality in hospitalized patients with COVID-19
Authors: K. Hasel, S. Verma, A. Salim, D. Arrup, C. D. Adamo, S. Dutta, R. Vinayek
Journal: Hepatology (2020)

Background: Recent studies from China have shown that liver biochemistries are abnormal in patients infected with SARS-CoV2 novel coronavirus, which may result from excessive inflammatory processes as a result of underlying cytokine storm However, there is a paucity of data on the association of elevated liver chemistries with the disease severity, acute kidney injury (AKI), coagulation markers, morbidity, and mortality in COVID-19 Methods: A retrospective analysis among hospitalized patients (n=149) with COVID-19 infection from March 17th to April 30th 2020 Data collection included patient demographics, co-morbidities (including diabetes mellitus, hypertension, chronic kidney disease, obesity (BMI>30)) and laboratory parameters, such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), international normalized ratio (INR), total bilirubin (TBIL), D-dimer, prothrombin time (PT), ferritin, C-reactive protein (CRP) and lactate dehydrogenase (LDH)  Pearson correlation coefficients and Chi-square tests were computed between liver chemistries and inflammatory markers  Chi-square tests were also used to evaluate the incidence of AKI and mortality Multivariate logistic regression models were constructed to estimate the independent effects of each potential prognostic factor Results: AST levels were elevated in 66% of patients while ALT was elevated in 24% and TBIL in 11% Elevated AST levels were associated with inflammatory markers including serum ferritin (r=0 4, p<0 001) and LDH (r=0 8, p<0 0001) Furthermore, the AST levels associated strongly with the coagulation parameters including D-dimer (r=0 5, p<0 0001) and PT (r=0 4, p<0 0001) Interestingly, ALT levels were also associated with serum ferritin (r=0 2, p<0 009), LDH (r=0 5, p<0 0001), D-dimer (r=0 2, p<0 01) and PT (r=0 2, p<0 02) Lastly, we also found correlation between high TBIL, D-Dimer (r=0 3, p<0 0007) and LDH (r=0 2, p<0 04) Increased levels of AST (p<0 03), TBIL (p=0 04) and ferritin (p=0 006) were associated with AKI in multivariate logistic regression analysis  While elevated liver chemistries and inflammatory markers were not associated with mortality in multivariate regression analysis, elevated AST levels neared statistical significance (p=0 08)  Conclusion: These results suggest that liver function abnormalities are associated with increased inflammatory markers and abnormal coagulation factors  Furthermore, elevated AST and ferritin was associated with AKI and increased mortality Abnormal liver function tests and inflammatory markers in COVID-19 patients were independent of associated co-morbidities
Feasibility Study of the Transcatheter Valve Repair System for Severe Tricuspid Regurgitation
Authors: Susheel Kodali, Rebecca T. Hahn, Mackram F. Eleid, Robert Kipperman, Robert Smith, D. Scott Lim, William A. Gray, Akhil Narang, Sorin V. Pislaru, Konstantinos Koulogiannis, Paul Grayburn, Dale Fowler, Katie Hawthorne, Abdellaziz Dahou, Shekhar H. Deo, Prashanthi Vandrangi, Florian Deuschl, Michael J. Mack, Martin B. Leon, Ted Feldman, Charles J. Davidson
Journal: Journal of the American College of Cardiology (2021)
Clearance of heparan sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice
Authors: Hideto Morimoto, Sachiho Kida, Eiji Yoden, Masafumi Kinoshita, Noboru Tanaka, Ryuji Yamamoto, Yuri Koshimura, Haruna Takagi, Kenichi Takahashi, Tohru Hirato, Kohtaro Minami, Hiroyuki Sonoda
Journal: Molecular Therapy (2021)

Mucopolysaccharidosis II (MPS II), a lysosomal storage disease caused by mutations in iduronate-2-sulfatase (IDS), is characterized by a wide variety of somatic and neurologic symptoms. The currently approved intravenous enzyme replacement therapy with recombinant IDS (idursulfase) is ineffective for CNS manifestations due to its inability to cross the blood-brain barrier (BBB). Here, we demonstrate that the clearance of heparan sulfate (HS) deposited in the brain by a BBB-penetrable antibody-enzyme fusion protein prevents neurodegeneration and neurocognitive dysfunctions in MPS II mice. The fusion protein pabinafusp alfa was chronically administered intravenously to MPS II mice. The drug reduced HS and attenuated histopathological changes in the brain, as well as in peripheral tissues. The loss of spatial learning abilities was completely suppressed by pabinafusp alfa, but not by idursulfase, indicating an association between HS deposition in the brain, neurodegeneration, and CNS manifestations in these mice. Furthermore, HS concentrations in the brain and reduction thereof by pabinafusp alpha correlated with those in the cerebrospinal fluid (CSF). Thus, repeated intravenous administration of pabinafusp alfa to MPS II mice decreased HS deposition in the brain, leading to prevention of neurodegeneration and maintenance of neurocognitive function, which may be predicted from HS concentrations in CSF.
A multicentre study of naevus‐associated melanoma vs. <i>de novo</i> melanoma, tumour thickness and body site differences*
Authors: C. Dessinioti, A.C. Geller, A. Stergiopoulou, N. Dimou, S. Lo, U. Keim, J.E. Gershenwald, L.E. Haydu, R. Dummer, J. Mangana, A. Hauschild, F. Egberts, R. Vieira, A. Brinca, I. Zalaudek, T. Deinlein, E. Evangelou, J.F. Thompson, R.A. Scolyer, K. Peris, C. Garbe, A.J. Stratigos
Journal: British Journal of Dermatology (2021)

Whether melanoma in histological contiguity with a naevus [naevus-associated melanoma (NAM)] is distinctly different from melanoma arising de novo remains unclear.
Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy
Authors: April A N Rose, Susan M Armstrong, David Hogg, Marcus O Butler, Samuel D Saibil, Diana P Arteaga, Thiago Pimentel Muniz, Deirdre Kelly, Danny Ghazarian, Ian King, Zaid Saeed Kamil, Kendra Ross, Anna Spreafico
Journal: Journal for ImmunoTherapy of Cancer (2021)

Purpose Anti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic subtype can function as predictive biomarkers for anti-PD1±anti-CTLA4 ICI in patients with advanced melanoma. Methods We performed a single-center retrospective cohort analysis of patients who received anti-PD1±anti-CTLA4 ICI for advanced melanoma between 2012 and 2019. Primary tumor type, BRAF and NRAS mutation status, and other covariates were abstracted from chart review. Log-rank tests and multivariable Cox regression models were used to assess differences in clinical progression-free (cPFS) and overall survival (OS). Results We identified 230 patients who received 249 lines of anti-PD1±anti-CTLA4 ICI for unresectable or metastatic disease. Of these patients, 74% were cutaneous, 11% mucosal, 8% unknown primary and 7% acral. BRAF and NRAS mutations were identified in 35% and 28% of patients, respectively. In multivariable analyses of the entire cohort, acral or mucosal primary tumor type, &gt;3 metastatic sites, elevated LDH were predictive of shorter cPFS and OS. Combination ICI therapy was associated with longer cPFS (HR 0.57, 95% CI 0.38 to 0.86, p=0.007) and OS (HR 0.42, 95% CI 0.28 to 0.65, p&lt;0.001). Combination ICI was significantly associated with longer OS in unknown primary and mucosal melanoma. There was a non-significant trend toward longer OS with anti-PD1+anti-CTLA4 in cutaneous melanoma, but not in acral melanoma. In multivariable analyses, combination ICI was associated with longer OS in NRAS (HR 0.24, 95% CI 0.10 to 0.62, p=0.003, n=69) and BRAF V600E/K (HR 0.47, 95% CI 0.24 to 0.90, p=0.024, n=86) mutant melanoma but not BRAF/NRAS wild-type (n=94) melanoma. Conclusions In our cohort, primary melanoma tumor type and genomic subtype were independent predictive markers of cPFS and OS for patients with metastatic melanoma receiving anti-PD1 ICI. Primary tumor type and genomic subtype—including NRAS—should be further evaluated in prospective clinical trials to determine their value as predictive markers. Biologic subtypes may facilitate clinical decision-making when recommending combination ICI treatment (anti-PD1±anti-CTLA4) versus anti-PD1 alone for patients with metastatic melanoma.
Clinical impact of COVID-19 on patients with cancer treated with immune checkpoint inhibition
Authors: Aljosja Rogiers, Ines Pires da Silva, Chiara Tentori, Carlo Alberto Tondini, Joseph M Grimes, Megan H Trager, Sharon Nahm, Leyre Zubiri, Michael Manos, Peter Bowling, Arielle Elkrief, Neha Papneja, Maria Grazia Vitale, April A N Rose, Jessica S W Borgers, Severine Roy, Joanna Mangana, Thiago Pimentel Muniz, Tim Cooksley, Jeremy Lupu, Alon Vaisman, Samuel D Saibil, Marcus O Butler, Alexander M Menzies, Matteo S Carlino, Michael Erdmann, Carola Berking, Lisa Zimmer, Dirk Schadendorf, Laura Pala, Paola Queirolo, Christian Posch, Axel Hauschild, Reinhard Dummer, John Haanen, Christian U Blank, Caroline Robert, Ryan J Sullivan, Paolo Antonio Ascierto, Wilson H Miller Jr, F Stephen Hodi, Karijn P M Suijkerbuijk, Kerry L Reynolds, Osama E Rahma, Paul C Lorigan, Richard D Carvajal, Serigne Lo, Mario Mandala, Georgina V Long
Journal: Journal for ImmunoTherapy of Cancer (2021)

Patients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer.
AB0016 Weak correlation of circulating immune complexes in sera of patients with conective tissues disease measured with polyethylen glicol and c1q binding assay
Authors: JM Nedovic, SK Stojanovic, BN Stamenkovic, AM Stankovic, AN Dimic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Circulating immune complex (CIC) are forming in a normal immune response, as a consequence of attachment of specifically reactive antibodies to antigens. As a result, most antigens are neutralised and/or eliminated. However, in some circumstances, CIC deposits in tissues with subsequent phlogogenic responces. Systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are organ nonspecific autoimmune diseases with a high prevalence of positive test for CIC. It seems that systemic character of these diseases is due to vascular entrapment of CIC in various tissues. Application of various methods on the same serum sample regularly gives a different level of CIC. <h3>Objectives</h3> Our objective was to correlate the levels of CIC measured with two different assays in sera of patients with SLE, SSc, and RA. <h3>Methods</h3> We used precipitation test with polyethylene glycol (PEG), molecular weight 6000 and C1q binding assay (C1q) with laser nephelometer in sera of 74 patients with SLE, 40 patients with SSc and 42 patients with RA. <h3>Results</h3> PEG revealed abnormally high levels of CIC in 62,16% SLE sera, 45% SSc sera and 47,61% RA sera. C1q was more sensitive in SLE (78,37%) and RA (76,1%) with exactly the same result in SSc (45%). The correlation of these two methods was weak, r – 0,089 for SLE, r – 0,22 for SSc, and r – 0,29 for RA. <h3>Conclusion</h3> These results are not only the consequence of the imperfection of these methods but also the consequence of the enormous heterogeneity of CIC. C1q binding assay is more sensitive, is WHO standardised, but partially gives false positive results in presence of DNA, CRP and RF, which are frequently present in sera of patients with connective tissues diseases. Besides, C1q das not detect CIC with isotypes of immunoglobulins that does not activate complement. Precipitation test with PEG detects immunoglobulins of all isotypes, does not depend from complement and RF, and is simple and inexpensive to perform. Besides, PEG is not standardised, is less sensitive and partially gives false positive results in state of hypergamaglobulinemia, also frequently present in patients with connective tissues diseases. This holds the allegations of WHO Working Group for the necessity of using more methods for detecting CIC from the single sample sera.
SAT0183 STATUS OF LYMPHOCYTE SUBSETS IN PERIPHERAL BLOOD OF PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME AND THEIR CHANGES AFTER RECEIVING OUR NEW IMMUNOREGULATORY COMBINATION THERAPY: A RETROSPECTIVE CROSS-SECTIONAL STUDY
Authors: J. Y. Yang, S. X. Zhang, L. Hao, Q. Y. Su, J. Bai, S. J. Guo, J. Luo, G. Y. Liu, C. Gao, X. Li
Journal: Annals of the Rheumatic Diseases (2020)

Background: Primary Sjögren’s syndrome (pSS) is a chronic inflammatory autoimmune disease mainly involving exocrine glands and involving multiple organs and systems 1 . Recent studies have reported that peripheral lymphocyte subsets such as Th1, Th2, Th17, and regulatory cells (Tregs), have been implicated in the pathogenesis of pSS 2 . However, the detailed statuses of lymphocyte subsets of pSS patients remain to be clearly evaluate and effects of immunomodulatory therapies on the lymphocyte subsets are unknown. Objectives: To explore the pathogenesis and evaluate the therapeutic effect of immunomodulatory drugs (IMiDs) by comparing the changes of lymphocyte subsets in peripheral blood (PB) before and after treatment. Methods: This study included 1,221 pSS patients and 206 healthy controls (HCs). Among these patient, 759 patients were received our new immunoregulatory therapies such as low-dose interleukin-2, rapamycin, metformin, retinoic acid etc. The absolute numbers of T, B, NK, CD4 + T, CD8 + T, Th1, Th2, Th17 and Tregs in PB of these subjects were detected by flow cytometry combined with standard absolute counting beads. Data were expressed as mean ± standard deviation to the distribution. Independent-samples T test and paired-samples T test were applied. P value &lt;0.05 were considered statistically significant. Results: The absolute numbers of circulating Tregs as well as T, NK cells in pSS patients were significantly lower than those of HCs ( P &lt;0.05). After immunoregulatory combination treatments, the number of Tregs was significantly increased ( P &lt;0.05). Though the absolute numbers of T, NK, CD4 + T, CD8 + T, Th1, and Th17 cells were also increased to some degree ( P &lt;0.05), the increased amount of Tregs was much more than other cells, resulting a new balance between pro- and anti- inflammatory lymphocyte homeostasis. Conclusion: The decrease of peripheral Tregs played an important role in the pathogenesis of primary Sjögren’s syndrome. Immunoregulatory combination therapies promoted the increase of Tregs and might help for the recovery of pSS. References: [1]Mariette X, Criswell LA. Primary Sjogren’s Syndrome. N Engl J Med 2018;378(10):931-39. doi: 10.1056/NEJMcp1702514 [published Online First: 2018/03/08] [2]Miao M, Hao Z, Guo Y, et al. Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjogren’s syndrome. Ann Rheum Dis 2018;77(12):1838-40. doi: 10.1136/annrheumdis-2018-213036 [published Online First: 2018/06/25] Acknowledgments : None. Disclosure of Interests: None declared
Prospective One Health genetic surveillance in Vietnam identifies distinct blaCTX-M-harbouring Escherichia coli in food-chain and human-derived samples
Authors: Minh Ngoc Nguyen, Ha Thi Thu Hoang, Basil Britto Xavier, Christine Lammens, Hai Thanh Le, Ngoc Thi Bich Hoang, Son Thai Nguyen, Ngoc Thi Pham, Herman Goossens, Anh Duc Dang, Surbhi Malhotra-Kumar
Journal: Clinical Microbiology and Infection (2021)
Investigating chemopotentiation by low-dose fractionated radiation therapy for disseminated intra-abdominal gastric cancer.
Authors: France Carrier, Palak Parekh, Eduardo Solano-Gonzalez, Xinrong Ma, Kayla Tighe, Andrea Casildo, Andrew Zodda, Christopher Johnstone, Yannick Poirier, Javed Mahmood, Kavita Bhalla, Sheri Li, Rena G. Lapidus
Journal: Journal of Clinical Oncology (2021)

242 Background: Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. There is currently no modality that has been shown to prolong survival of this patient sub-population. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, the Dual Oxidase 2 (DUOX2) enzyme. Methods: Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or lower levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; chemotherapy consisting of a modified regimen of docetaxel, cisplatin and 5’-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 15 cGy in three days), 4; mDCF and LD-WART. Blood was harvested at day 14 and 45 and cancer progression was evaluated by fluorescence imaging (Xenogen). Results: The combined regimen was well tolerated in all animals and led to DUOX2 upregulation, increased serum protein oxidation and reduced cancer progression in the DUOX2 positive tumors. Tumors expressing lower DUOX2 levels were more sensitive to chemotherapy but no additional benefit was obtained with LD-WART. The potential clinical significance of these findings is exemplified by a tumor microarray demonstrating that only about 46% of human gastric tumors expressed DUOX2. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-kB upregulation and VEGF down regulation. Moreover, the combined regimen of mDCF and LDFRT was also effective on a Cancer Stem Cell (CSC)-Like subpopulation of mouse gastric cancer cells. Conclusions: Taken together these data suggest that DUOX2 could be used as a potential biomarker for patient stratification for chemopotentiation by LD-WART for positive tumors while chemotherapy alone would be more effective for DUOX2 negative tumors. The absence of added toxicity suggests that these cycles could be repeated.
Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments
Authors: Judith Garcia-Aymerich, Milo A Puhan, Solange Corriol-Rohou, Corina de Jong, Heleen Demeyer, Fabienne Dobbels, Damijan Erzen, Anja Frei, Elena Gimeno-Santos, Nicholas S Hopkinson, Nathalie Ivanoff, Niklas Karlsson, Zafeiris Louvaris, Michael I Polkey, Roberto A Rabinovich, Mario Scuri, Maggie Tabberer, Ioannis Vogiatzis, Thierry Troosters
Journal: Thorax (2021)

The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation.To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries.We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID.We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score.The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables.
AB0089 Behcet’s disease in an arab community in israel
Authors: L Jaber, G Milo, GJ Halpern, I Krause, A Weinberger
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The prevalence of Behcet's disease (BD) varies in different parts of the world. <h3>Objectives</h3> To evaluate the prevalence of BD in an Israeli Arab town (Taibe). <h3>Methods</h3> Questionnaires about the occurrence and frequency of aphthous ulcers were distributed randomly to the parents of children attending a Paediatric Clinic in Taibe. The parents were asked whether they or any of their children aged over 10 years suffered from recurrent aphthous stomatitis (RAS), and if so, any who had had more than four episodes during the previous year where each episode had lasted for more than 7 days were invited to come for an extensive interview and examination by a rheumatologist or a paediatrician. <h3>Results</h3> Overall, six individuals (one male and five females) were diagnosed as suffering from BD. All of these, two of whom were siblings (a brother and a sister) had RAS, genital ulcers and joint manifestations. Five had skin and four had visual involvement, and one out of two had a positive pathergy test. Five of the six carried HLA-B5 antigens. This gave a prevalence in Taibe of 12/10,000. <h3>Conclusion</h3> The prevalence of BD found in our survey is high and concurs with that found in other Mediterranean and Asian countries where a high prevalence has also been noted.
SAT0024 Enthesitis and dactylitis as the beginnnig stage of psoriatic arthritis
Authors: C Montilla, CM González, FJ López-Longo, M Moreno-Zazo, R Castillo, N Caro, L Cebrián, C González-Montagut, S Gómez, I Monteagudo, L Carreño
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Enthesitis and dactylitis are characteristic features of psoriatic arthritis and the others spondyloarthropathies. Both may appear from the onset of the disease. <h3>Objectives</h3> To analize the clinical characteristic of a population of patients with psoriatic arthritis who presented enthesitis and dactylitis as their only clinical symptoms at the onset of the disease. <h3>Methods</h3> We have studied a group of 204 patients diagnosed with psoriatic arthritis following the Moll and Wright criteria, selecting only those who expressed either Enthesitis or dactylitis as initial symptoms of the disease. <h3>Results</h3> Twenty-eight patients (14%) proved to have Enthesitis or dactylitis 21 enthesitis, 7 dactylitis and 1 Enthesitis and dactylitis as disease onset, and seventeen were men (60.7%). The mean age of psoriatic arthritis onset was 38 years (range: 17–58). The mean time from Enthesitis and dactylitis onset and the Moll and Wright criteria was 6 months (range: 1–180). Enthesitis was most frequent in achilles tendon (81%) and the plantar fascia (72.7%). Twenty patients (71.4%) presented arthritis involving peripheral joints, 4 (14.3%) presented and axial skeleton distribution, and the remaining (14.3%) showed a mixed peripheral and axial distribution. <h3>Conclusion</h3> Enthesitis and dactylitis are initial clinical features of psoriatic arthritis, even though the majority of the patients with these symptoms at the beginning of the disease evolve towards a peripheral arthritis pattern.