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206


Auto-deconvolution and molecular networking of gas chromatography-mass spectrometry data

Aksenov, Alexander A; Laponogov, Ivan; Zhang, Zheng; Doran, Sophie L F; Belluomo, Ilaria; Veselkov, Dennis; Bittremieux, Wout; Nothias, Louis Felix; Nothias-Esposito, Mélissa; Maloney, Katherine N; Misra, Biswapriya B; Melnik, Alexey V; Smirnov, Aleksandr; Du, Xiuxia; Jones, Kenneth L; Dorrestein, Kathleen; Panitchpakdi, Morgan; Ernst, Madeleine; van der Hooft, Justin J J; Gonzalez, Mabel; Carazzone, Chiara; Amézquita, Adolfo; Callewaert, Chris; Morton, James T; Quinn, Robert A; Bouslimani, Amina; Orio, Andrea Albarracín; Petras, Daniel; Smania, Andrea M; Couvillion, Sneha P; Burnet, Meagan C; Nicora, Carrie D; Zink, Erika; Metz, Thomas O; Artaev, Viatcheslav; Humston-Fulmer, Elizabeth; Gregor, Rachel; Meijler, Michael M; Mizrahi, Itzhak; Eyal, Stav; Anderson, Brooke; Dutton, Rachel; Lugan, Raphaël; Boulch, Pauline Le; Guitton, Yann; Prevost, Stephanie; Poirier, Audrey; Dervilly, Gaud; Le Bizec, Bruno; Fait, Aaron; Persi, Noga Sikron; Song, Chao; Gashu, Kelem; Coras, Roxana; Guma, Monica; Manasson, Julia; Scher, Jose U; Barupal, Dinesh Kumar; Alseekh, Saleh; Fernie, Alisdair R; Mirnezami, Reza; Vasiliou, Vasilis; Schmid, Robin; Borisov, Roman S; Kulikova, Larisa N; Knight, Rob; Wang, Mingxun; Hanna, George B; Dorrestein, Pieter C; Veselkov, Kirill
We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC-MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.
PMID: 33169034
ISSN: 1546-1696
CID: 4664982

Key opinion leaders - a critical perspective

Scher, Jose U; Schett, Georg
Enormous progress has been made in the field of rheumatology in the past several decades, historically led by publicly funded academic innovators but in more recent times with much greater involvement of the pharmaceutical industry. This shift in resources has created a complex new model for reinvestment in the medical community in which the vast majority of private funds are redirected towards influencing the prescription behaviour of practitioners through 'key opinion leaders', with the main purpose of enhancing and perpetuating profit rather than innovation and critical thinking, and often at the expense of partnerships with scientists (that is, basic and translational researchers) and academic collaborations. This new episteme brings multiple opportunities to rethink approaches to sustaining long-term critical research in the field, ultimately maximizing the return on investment: scientific knowledge for the benefit of patients and society. Central to such strategies should be the rebalancing of academia-industry partnerships towards academic research and the involvement of 'innovation and knowledge leaders', rather than mostly key opinion leaders.
PMCID:7703499
PMID: 33257869
ISSN: 1759-4804
CID: 4735152

Another 'BEE'? - Brain-Eye-Ear (BEE) Disease Secondary to HbSC Disease Masquerading as Multiple Sclerosis [Case Report]

Wallach, Asya Izraelit; Borja, Maria J; Chen, Duan; Eisenberg, Rachel; Modi, Yasha S; Zhang, Cen; Shepherd, Timothy M; Nath, Avindra; Smith, Bryan; Scher, Jose U; Cho, Catherine; Kister, Ilya
Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.
PMID: 33482571
ISSN: 1532-8511
CID: 4761032

PROMIS and RAPID3 scores demonstrate significant differences between remission and low disease activity in psoriatic arthritis patients [Meeting Abstract]

Yedimenko, J; Jin, Y; Ogdie, A; Walsh, J A; Scher, J U; Reddy, S M; Husni, M E
Background/Purpose: Remission (REM), and at times low disease activity (LDA), are treatment targets in psoriatic arthritis (PsA) that can vary with different provider-assessed measures and patient perception of clinical response. This can lead to treatment dilemmas and patient dissatisfaction. In this study we examined the relationship between LDA and REM in PsA patients using commonly accepted disease activity measures and their relationship to PROs as measured by the Patient- Reported Outcomes Measurement Information System (PROMIS) Global Health questionnaire and Routine Assessment of Patient Index Data 3 (RAPID3).
Method(s): A cross-sectional study was performed within the Psoriatic Arthritis Research Consortium between 2016-2019 comparing MDA/VLDA, CDAI, and DAPSA scores with PROs. PROMIS Global Health (GH) physical and mental health subscores and PROMIS Fatigue (all expressed as Tscores) were compared between groups using t-tests. RAPID3 was compared using Chi-Squared test or Fisher's exact test, when appropriate. Correlations between MDA/VLDA, CDAI, and DAPSA scores and PROMIS domains were calculated using Spearman's rank correlation. Boxplots and scatterplots were used to present the results graphically. All tests are twosided, with an alpha level of 0.05 using SAS software (Version 9.4; Cary, NC).
Result(s): 227 patients (52.2% female, average age 52.7+/-14 years) were included. 72 patients were in MDA and 28 in VLDA; 84 in CDAI LDA and 23 in CDAI REM; 84 in DAPSA LDA and 50 in DAPSA REM. Patients meeting VLDA, CDAI REM and DAPSA REM had significantly higher PROMIS GH physical and mental T-scores (reflecting better outcomes) and better Fatigue T-scores compared to MDA, CDAI and DAPSA LDA (Figure 1, p<0.001). There was a correlation between MDA/VLDA, CDAI, and DAPSA scores and PROMIS GH physical and mental health and Fatigue domains; correlation was strongest for PROMIS GH physical health domain across all three disease activity measures (Figure 2, MDA r=0.69, CDAI r=-0.65, DAPSA r= -0.68). Majority of patients achieving VLDA, CDAI REM, or DAPSA REM had RAPID3 scores indicating low severity or remission, while >50% of patients in MDA/LDA reported moderate to severe impairment (Table 2, p<0.001).
Conclusion(s): PROMIS and RAPID3 measures successfully differentiated between low disease activity and remission as measured by disease activity measures MDA/VLDA, CDAI, and DAPSA. PROMIS measures correlated with all three disease activity measures, with strongest correlation for PROMIS GH physical health domain. These data contribute to the construct validity of using additional PRO measures such as PROMIS and RAPID3 for use in clinical practice
EMBASE:634218469
ISSN: 2475-5311
CID: 4810202

EVALUATION OF SARS-COV-2 IGG ANTIBODY REACTIVITY IN A MULTI-RACIAL/ETHNIC COHORT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS [Meeting Abstract]

Saxena, A; Guttmann, A; Masson, M; Kim, M Y; Haberman, R H; Castillo, R; Scher, J U; Deonaraine, K K; Engel, A J; Michael, Belmont H; Blazer, A D; Buyon, J P; Fernandez-Ruiz, R; Izmirly, P M
Background Patients with Systemic Lupus Erythematosus (SLE) represent a unique population at risk for COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. This study was initiated to evaluate for the presence of SARS-CoV-2 IgG antibodies in SLE patients with and without prior COVID-19-related symptoms or COVID-19 RT PCR testing. Methods A total of 329 patients with SLE from two cohorts, one serially monitored for COVID-19 in Spring 2020 (the Web-based Assesment of Autoimmune, Immune-Mediated and Rheumatic Patients (WARCOV) and one undergoing routine surveillance (NYU Lupus Cohort) were tested for SARS-CoV-2 IgG via commercially available immunoassays processed through hospital or outpatient laboratories between April 29, 2020 and February 9, 2021. Results Overall, 16% of 329 patients had a reactive SARSCoV- 2 IgG antibody test. Seropositive patients were more likely to be Hispanic. Other demographic variables, lupus-specific factors and immunosuppressant use were not associated with reactivity. Of the 29 patients with prior RT-PCR confirmed COVID-19, 83% developed an antibody response despite 62% being on immunosuppressants. Six percent of patients who had symptoms suspicious for COVID-19 but negative concurrent RT-PCR testing developed an antibody response. Twenty-three percent of patients who had COVID- 19-related symptoms but no RT-PCR testing and 5% of patients who had no symptoms of COVID-19 developed an antibody response. Among patients initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially. In COVID- 19-confirmed patients high percentages had antibody positivity beyond 30 weeks from disease onset, 88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks. Conclusions Most patients with SLE and confirmed COVID- 19 were able to produce a serologic response despite use of a variety of immunosuppressants. These findings provide reassurances regarding the efficacy of humoral immunity and possible reinfection protection in patients with SLE
EMBASE:638287648
ISSN: 2053-8790
CID: 5292912

Designing a Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Effect of Guselkumab (TREMFYA (R)/sup >) Dosing Interval in Psoriatic Arthritis Patients with Inadequate Response to Tumor Necrosis Factor Inhibition [Meeting Abstract]

Ogdie-Beatty, Alexis; Merola, Joseph; Mease, Philip; Ritchlin, Christopher; Scher, Jose; Chan, Daphne; Chakravarty, Soumya; Langholff, Wayne; Choi, Olivia; Krol, Yevgeniy; Rowland, Katelyn; Gottlieb, Alice
ISI:000744545207121
ISSN: 2326-5191
CID: 5183002

COVID-19 in Patients with Inflammatory Arthritis: A Prospective Study on the Effects of Comorbidities and DMARDs on Clinical Outcomes

Haberman, Rebecca H; Castillo, Rochelle; Chen, Alan; Yan, Di; Ramirez, Deborah; Sekar, Vaish; Lesser, Robert; Solomon, Gary; Niemann, Andrea L; Blank, Rebecca B; Izmirly, Peter; Webster, Dan E; Ogdie, Alexis; Troxel, Andrea B; Adhikari, Samrachana; Scher, Jose U
OBJECTIVE:To characterize the hospitalization and death rates among patients with inflammatory arthritis affected by COVID-19 and to analyze the associations between comorbidities and immunomodulatory medications and infection outcomes. METHODS:Clinical, demographic, maintenance treatment, and disease course data and outcomes of individuals with inflammatory arthritis (IA; rheumatoid arthritis and spondylarthritis) with symptomatic COVID-19 infection were prospectively assessed via web-based questionnaire followed by individual phone calls and electronic medical record review. Baseline characteristics and medication use were summarized for hospitalized and ambulatory patients, and outcomes were compared for each medication class using multivariable logistic regression. RESULTS:A total of 103 patients with IA were included in the study (n=80 confirmed and n=23 highly suspicious for COVID-19). Twenty-six percent of participants required hospitalization, and 4% died. Patients who warranted hospitalization were significantly more likely to be older (P<0.001) and have comorbid hypertension (P=0.001) and chronic obstructive pulmonary disease (P=0.022). IA patients taking oral glucocorticoids had a higher likelihood of being admitted for COVID-19 (P<0.001) while those on maintenance anti-cytokine biologic therapies did not. CONCLUSION/CONCLUSIONS:In patients with underlying IA, COVID-19 outcomes were worse in those receiving glucocorticoids but not in patients on maintenance anti-cytokine therapy. Further work is needed to understand whether immunomodulatory therapies affect COVID-19 incidence.
PMID: 32725762
ISSN: 2326-5205
CID: 4557002

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1

Gelfand, Joel M; Armstrong, April W; Bell, Stacie; Anesi, George L; Blauvelt, Andrew; Calabrese, Cassandra; Dommasch, Erica D; Feldman, Steve R; Gladman, Dafna; Kircik, Leon; Lebwohl, Mark; Lo Re, Vincent; Martin, George; Merola, Joseph F; Scher, Jose U; Schwartzman, Sergio; Treat, James R; Van Voorhees, Abby S; Ellebrecht, Christoph T; Fenner, Justine; Ocon, Anthony; Syed, Maha N; Weinstein, Erica J; Smith, Jessica; Gondo, George; Heydon, Sue; Koons, Samantha; Ritchlin, Christopher T
OBJECTIVE:To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN/METHODS:A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted. RESULTS:The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus. LIMITATIONS/CONCLUSIONS:The evidence behind many guidance statements is limited in quality. CONCLUSION/CONCLUSIONS:These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge.
PMCID:7471802
PMID: 32891785
ISSN: 1097-6787
CID: 4845052

Leveraging the United States Epicenter to Provide Insights on COVID-19 in Patients with Systemic Lupus Erythematosus

Fernandez-Ruiz, Ruth; Masson, Mala; Kim, Mimi Y; Myers, Benjamin; Haberman, Rebecca H; Castillo, Rochelle; Scher, Jose U; Guttmann, Allison; Carlucci, Philip M; Deonaraine, Kristina K; Golpanian, Michael; Robins, Kimberly; Chang, Miao; Belmont, H Michael; Buyon, Jill P; Blazer, Ashira D; Saxena, Amit; Izmirly, Peter M
OBJECTIVE:To characterize patients with Systemic Lupus Erythematosus (SLE) affected by COVID-19 and to analyze associations of comorbidities and medications on infection outcomes. METHODS:Patients with SLE and RT-PCR-confirmed COVID-19 were identified through an established New York University lupus cohort, query of two hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web-based questionnaire and review of medical records. Baseline characteristics were obtained for all patients with COVID-19 to analyze risk factors for hospitalization. Data were also collected from asymptomatic patients and those with COVID-19-like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID-19-positive patients. RESULTS:A total of 226 SLE patients were included: 41 patients with confirmed COVID-19; 19 patients who tested negative for COVID-19; 42 patients with COVID-19-like symptoms who did not get tested; and 124 patients who remained asymptomatic without testing. Of those SLE patients with COVID-19, 24 (59%) required hospitalization, four required intensive care unit-level of care, and four died. Hospitalized patients tended to be older, non-white, Hispanic, have higher BMI, history of nephritis, and at least one comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least one comorbidity, and BMI as independent predictors of hospitalization. CONCLUSION/CONCLUSIONS:In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID-19 outcomes in patients with SLE.
PMID: 32715660
ISSN: 2326-5205
CID: 4540102

Measuring outcomes in psoriatic arthritis: comparing Routine Assessment of Patient Index Data (RAPID3) and Psoriatic Arthritis Impact of Disease (PSAID)

Walsh, Jessica A; Wan, Marilyn T; Willinger, Christine; Husni, M Elaine; Scher, Jose U; Reddy, Soumya M; Ogdie, Alexis
OBJECTIVE:To examine the construct validity of Routine Assessment of Patient Index Data (RAPID3) and Psoriatic Arthritis Impact of Disease (PSAID) in patients with psoriatic arthritis (PsA). In examining construct validity, we also addressed scores among subgroups with severe psoriasis, polyarticular disease, enthesitis and dactylitis and evaluated influences of sociodemographic factors and comorbidities (contextual factors) on these patient-reported outcomes (PROs). METHODS:Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium (PARC) between 2014-2016. PARC is a longitudinal observational cohort study conducted at four United States institutions. In this cross-sectional study, construct validity was assessed by examining Spearman's correlation coefficients for RAPID3 and PSAID with physician-reported disease activity measures and other PROs (e.g., Short Form 12 (SF12-PCS/-MCS), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue). Contextual factors and disease subgroups were assessed in multivariable linear regression models with RAPID3 or PSAID12 as outcomes of interest and the hypothesized contextual factors as covariates. RESULTS:Among 401 patients enrolled in PARC, 347 completed RAPID3 or PSAID12. Of these, most were Caucasian females with a mean age of 51.74 (SD 14.02). RAPID3 and PSAID were highly correlated (r=0.90). These measures were also correlated with the SF12-PCS (r=-0.67) and FACIT-Fatigue (r=-0.77). Important contextual factors and disease subgroups included enthesitis, joint counts, education, insurance type, and depression. CONCLUSION/CONCLUSIONS:RAPID3 and PSAID12 have excellent construct validity in PsA and are strongly correlated despite differing items. Contextual factors (i.e., the presence of depression and obesity) should be considered when interpreting raw scores of the RAPID3 and PSAID12.
PMID: 31575704
ISSN: 0315-162x
CID: 4116232