tbuckley/cabot-search huggingface dataset:
Projected 30-day out-of-pocket and total spending on pancreatic enzyme replacement therapy under Medicare Part D.
Authors: Arjun Gupta, Naveen Premnath, Muhammad Shaalan Beg, Rohan Khera, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2021)

401 Background: Pancreatic enzyme replacement therapy (PERT) can reduce symptoms of indigestion and improve nutrition in patients with exocrine pancreatic insufficiency. PERT is under-prescribed, and this may be related to actual costs and prescriber sensitivity to these costs. Thus, we aimed to assess PERT costs. Methods: We used Medicare Part D formulary and pricing files for the first quarter of 2020 to conduct a patient-level modeling study to describe point-of-sale and out-of-pocket costs for each PERT formulation among Part D stand-alone and Medicare Advantage prescription drug plans. We calculated costs across nationwide plans under three scenarios: (1) standard benefit design ($435 deductible and 25% coinsurance after the deductible is met); (2) 25% coinsurance (for fills after the deductible and in the coverage gap until the patient spends $6,350 out-of-pocket); and (3) 5% coinsurance (once catastrophic coverage is reached). PERT doses are identified by the lipase content per capsule (in United States Pharmacopeia, USP, units). We calculated the number of units for each PERT formulation/ dose form that would provide optimally dosed PERT for the average US adult (250,000 USP units of lipase per day), based on guidelines and consensus. We first calculated costs for a single unit of PERT. Next, we calculated the number of units needed daily for each formulation/ dose form to provide optimally dosed PERT, and multiplied it by 30 to generate 30-day requirements and costs. Results: Across 3,974 plans nationwide, five PERT formulations in seventeen different doses were covered by Medicare plans in 2020. The range of lipase content in a single unit ranged from 3,000 to 40,000 USP units, and the per-unit list price ranged from $1.44 to $13.89. The point-of-sale price for a 30-day supply of optimally dosed PERT ranged from $2,109 to $4,840. For patients, the expected out-of-pocket costs for a 30-day supply of optimally dosed PERT averaged $999 across formulations (range, $853 to $1536) for those paying a deductible and coinsurance, $673 (range, $527 to $1210) for fills made after meeting the deductible until reaching catastrophic coverage, and $135 (range, $105 to $242) after reaching catastrophic coverage. Conclusions: In this analysis of 2020 Medicare Part D plans, the estimated out-of-pocket cost for just a 30-day supply of optimally dosed PERT was high— at least $100 in the catastrophic phase and approximately $1,000 in the initial phase. In the setting of pancreas cancer, already associated with heavy symptom burden and distress, the financial burden from a supportive care intervention (such as PERT) has been underappreciated. These costs may serve as a barrier to Medicare beneficiary drug access and contribute to financial toxicity.
Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018
Authors: Lore Merdrignac, Fatima Aït El Belghiti, Elisabetta Pandolfi, Mireia Jané, Jane Murphy, Kateřina Fabiánová, Manuel García Cenoz, Elmira Flem, Sophie Guillot, Alberto E Tozzi, Gloria Carmona, Adele Habington, Jana Zavadilová, Ana Navasués, Håkon Bøås, Daniel Lévy-Brühl, Beatrice Ferretti, Miguel Lanaspa, Niam O’Sullivan, Pavla Křížová, Leticia Fernandino, Terese Bekkevold, Thomas Hanslik, Carmen Muñoz-Almagro, Sabrina Bacci, Gianfranco Spiteri, Marta Valenciano, Alain Moren
Journal: Eurosurveillance (2021)

Introduction PERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites). Aim This observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity. Methods We developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites’ annual incidences by dividing case numbers by the catchment populations. Results From December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0–11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700–4,925; IQR: 720) and 39 weeks (range: 25–42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway. Conclusions Incidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.
ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism
Authors: Valentina Tassinari, Valeriana Cesarini, Sara Tomaselli, Zaira Ianniello, Domenico Alessandro Silvestris, Lavinia Ceci Ginistrelli, Maurizio Martini, Biagio De Angelis, Gabriele De Luca, Lucia Ricci Vitiani, Alessandro Fatica, Franco Locatelli, Angela Gallo
Journal: Genome biology (2021)

N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing are two of the most abundant RNA modification events affecting adenosines in mammals. Both these RNA modifications determine mRNA fate and play a pivotal role in tumor development and progression.Here, we show that METTL3, upregulated in glioblastoma, methylates ADAR1 mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1. We show that ADAR1 plays a cancer-promoting role independently of its deaminase activity by binding CDK2 mRNA, underlining the importance of ADARs as essential RNA-binding proteins for cell homeostasis as well as cancer progression. Additionally, we show that ADAR1 knockdown is sufficient to strongly inhibit glioblastoma growth in vivo.Hence, our findings underscore METTL3/ADAR1 axis as a novel crucial pathway in cancer progression that connects m6A and A-to-I editing post-transcriptional events.
New Therapeutics for Ulcerative Colitis
Authors: Robert P. Hirten, Bruce E. Sands
Journal: Annual Review of Medicine (2021)

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.
Computational modeling ofimmunologic response to immune checkpoint inhibitors inCOVID-19 patients with and without cancer
Authors: G. Russo, L. Falzone, B. Cacopardo, G. Nunnari, F. Torino, G. Scandurra, S. Stefani, F. Pappalardo, M. Libra
Journal: Clinical Cancer Research (2020)

Cancer patients have an increased risk of severe COVID-19 infection due to the suppression of the immune systemand the development of cytokine release syndrome (CRS) that favor respiratory syndromes and interstitialpneumonia  However, substantial differences exist between patients treated with chemotherapy and patients treated with immune checkpoint inhibitors (ICIs), for which the risk of COVID-19 infection and the immunologic and cytokineprofile in case of infection have not yet been well characterized  The administration of ICIs for the treatment ofsevere COVID-19 infection has been recently suggested  However, no conclusive data have been generated on thismatter  To recognize the therapeutic potential of ICIs administration in COVID-19 patients with or without cancer, theUniversal Immune System Simulator (UISS) prediction model was used to simulate the immunologic response ofCOVID-19 patients after ICIs administration  Briefly, UISS represents an appropriate computational modelinginfrastructure able to simulate the dynamics of every single entity of the immune system after a stimulus or atherapeutic intervention by using an agent-based methodology  Therefore, the UISS platform, already used for theprediction of the efficacy of specific SARS-CoV-2 candidate vaccines, was here adopted to characterize theimmunologic behavior in both COVID-19 and cancer patients and to predict the effects of ICIs in these patients  Thecomputational results allowed us to identify key inflammatory and immune-related factors responsible for severerespiratory syndromes in COVID-19 infected patients with and without cancer  UISS results suggest that theadministration of ICIs modulates the immune system and the inflammatory status in both groups of patients withCOVID-19 infection, reducing the risk of severe symptoms  Although the results of the present study are still undervalidation in peripheral blood samples obtained from COVID-19 patients and from cancer patients after two cycles oftreatment with ICIs, we can speculate that ICIs may be a good therapeutic approach for the treatment of COVID-19severe respiratory syndrome even with a concomitant cancer diagnosis  If this is the case, the lower expressionlevels of inflammatory biomarkers can result in the drop-down of the viral load, assessed by droplet digital PCR inCOVID-19 patients
Microglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1/6 pathway: Erratum
Authors: Chuan Qin, Qian Liu, Zi-Wei Hu, Luo-Qi Zhou, Ke Shang, Dale B Bosco, Long-Jun Wu, Dai-Shi Tian, Wei Wang
Journal: Theranostics (2020)

[This corrects the article DOI: 10.7150/thno.27882.].
FRI0241 INFLUENCE OF PATIENT REPORTED ‘’ARTHRITIS ACTIVITY’’ IN DETERMINING SHAQ, HAQ-DI AND COCHIN SCORES IN SYSTEMIC SCLEROSIS
Authors: K. Gjeloshi, F. Danzo, G. Abignano, A. M. Dean, F. Masini, G. Cuomo, F. Del Galdo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Arthritic involvement in systemic sclerosis (SSc) is a common manifestation impacting on the quality of life. A wide range of articular involvement is recognised including from arthralgia to inflammatory joint and tendon disease. Objectives: To assess the weight of patient reported ‘’arthritis activity’’ in determining Patient Reported Outcome Measures (PROMs) in an observational cohort of SSc patients. Methods: We conducted a retrospective study of 330 clinic episodes from 121 unselected patients diagnosed with SSc according to EULAR/ACR 2013 classification criteria, in annual follow-up (for a total of 165 patients/year) with Pulmonary Function Tests (PFTs), Health Assessment Questionnaire - Disability Index (HAQ-DI), Scleroderma Health Assessment Questionnaire (sHAQ) and Cochin Hand Function Score (CHFS). Hand disability index was assessed by CHFS and global disability index was assessed by HAQ and sHAQ. Patient reported arthritis activity was assessed by Visual Analogical Scale for Arthritis Activity (VAS3). Based on the median of VAS3, patients were classified in two groups and the evaluation of global and hand disability index was performed for each group. Furthermore, we assessed the correlation between the change of VAS3 and the modification of disability scores (ΔHAQ, ΔSHAQ, ΔCHFS) over 12 months of follow-up. Following analysis of distribution, Spearman or Pearson Test were used to determine correlation coefficients, as appropriate (Prism 7). Results: The median disease duration was 5 years (IQR 3-10). The median of VAS3 was 35 (IQR 2 - 66). In patients with VAS3 &lt;35 and VAS ≥35 the HAQ-DI medians were 0.625 (IQR 0.25 - 1.5) and 1.75 (IQR 1.125-2.25) respectively, (p&lt;0.0001); the sHAQ medians were 0.628 (IQR 0.255 - 1.114) and 1.701 (IQR 1.234-2.059), respectively, (p&lt;0.0001); and the CHFS medians were 4 (IQR 0 – 19) and 28 (IQR 10 – 46) respectively, (p&lt;0.0001). A significant correlation was observed between VAS3 and HAQ (r= 0.463, p&lt;0.0001), SHAQ (r=0.651, p&lt;0.0001), CHFS (r=0.497, p&lt;0.0001); between ΔVAS3 and ΔSHAQ (r=0.493, p&lt;0.0001). Conclusion: This analysis of a monocentric non-selected population supports the key role of joint involvement in determining global patient reported functional and hand disability in SSc. Severity of musculoskeletal involvement should be carefully considered when interpreting PROs in patients with SSc. References: [1]Sandler RD, Matucci-Cerinic M, Hughes M. Musculoskeletal hand involvement in systemic sclerosis. Seminars in Arthritis and Rheumatism (2019) Disclosure of Interests: None declared
AB0049 Rheumatoid arthritis and giant cell tumour of the tendon sheath: A case report
Authors: S Kiraz, D Altýnok, Ý Ertenli, MA Öztürk, S Apras, Y Karadeniz, M Calgüneri
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Here in this case report we present a patient complaining of soft-tissue swelling on his hand, who had excision of giant cell tumour of the tendon sheath 1 year ago which has recurrence rates range from 9%–44%. He also met American Rheumatism Association criteria for rheumatoid arthritis. We described plain radiography and magnetic resonance findings of this soft tissue mass, which firstly presumed to be recurrence of giant cell tumour of the tendon sheath and later on diagnosed to be pannus pathologically and have characteristic radiological findings of pannus. <h3>Objectives</h3> <h3>Methods</h3> Radiographs of the hands were undertaken, magnetic resonance imaging was performed on a 1.5 tesla imager using an extremity coil. Magnetic resonance imaging of the hand was performed using SE T1, T2, PD, FL2D 3O sequences and followed by T1 weighted postcontrast examination immediately after Gd-DTPA(0.1 mmol/kg body weight) was injected intravenously as a bolus. <h3>Results</h3> Plain films demonstrated cortex erosion on the second metacarpophalangeal joint. Magnetic resonance imaging demonstrated soft-tissue mass which is isointense with muscles on T1 weighted precontrast images and T2 weighted images showed relatively high signal intensity with heterogeneous enhancement of T1 weighted post-contrast images. Increased synovial fluid was interpreted as tenosynovitis was also demonstrated as well as the cortex erosions. <h3>Conclusion</h3> It is established that giant cell tumour of the tendon sheath can be evident in a joint or a tendon sheath of a patient with rheumatoid arthritis. Although this combination of diseases may represent no more than a coincidence, it is possible that rheumatoid arthritis predisposes a person to develop giant cell tumour of the tendon sheath. While evaluating a patient complaining soft tissue mass on his hand with a history of giant cell tumour of the tendon sheath excision, pannus due to rheumatoid arthritis should be considered as well as recurrence of giant cell tumour of the tendon sheath.
Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine
Authors: Tom Shimabukuro, Narayan Nair
Journal: JAMA (2021)

This JAMA Insights review provides clinical details of anaphylactic reactions reported to and verified by the CDC in the first week of use of the Pfizer-BioNTech COVID-19 vaccine in the US, December 14-23, 2020.
Canakinumab to Reduce Deterioration of Cardiac and Respiratory Function in Sars-cov2 Associated Myocardial Injury With Heightened Inflammation (canakinumab in Covid-19 Cardiac Injury): Results From the Randomized Three C Study
Authors: P. C. Cremer, C. Sheng, D. Sahoo, S. Dugar, R. Aguillon-Prada, J. Hernandez-Montfort, D. Wolinsky, T. Wang, O. Abou Hassan, D. Brennan, D. Culver, P. Rajendram, A. Duggal, A. M. Lincoff, S. E. Nissen, V. Menon
Journal: Circulation (2020)
THU0051 Proliferation and stability of cytokine expression of il-4 or il-10 secreting t helper cells
Authors: AH Radbruch, M Loehning, A Richter, T Stamm, O Soezeri, HD Chang, L Tykocinski, M Assenmacher
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The cytokines IL-4 and IL-10 have been implicated in the regulation of T cell proliferation and differentiation. IL-4 drives the development of Th2 cells from naive precursors and it is supposed to enhance T cell proliferation, whereas IL-10 has been suggested to support the differentiation of regulatory Th cells and to negatively affect T cell proliferation. <h3>Objectives</h3> To analyse the proliferation and stability of cytokine expression of individual cytokine-producing T cells. <h3>Methods</h3> We established the cellular affinity matrix technology for the immunofluorescent identification and isolation of IL-4- or IL-10-secreting cells. With this technology we purified IL-4- or IL-10-secreting and non-secreting Th cells, labelled them with the fluorescent dye CFSE to track their proliferation after antigen-specific or polyclonal restimulation, and analysed their cytokine expression upon later restimulation. <h3>Results</h3> Previously, we have shown that naive Th cells have to enter the initial S phase of the first cell cycle to respond to an IL-4 signal by production of IL-4 or IL-10 upon restimulation. By direct counterstaining of cytokines and DNA content we now tested whether in general cytokine production is restricted to certain cell cycle phases, which we found not to be the case. The isolated IL-4+ and IL-4- T cells showed the same proliferation behaviour over 6 days, and the sorted IL-10+ cells were not inhibited in their proliferation compared with the IL-10- T cells. Thus, neither IL-4 nor IL-10 production by an individual T cell directly influences the proliferation of the same cell. When we analysed the stability of cytokine memory of the sorted T cells in later restimulations, a substantial fraction of the purified cytokine-producing cells did not reexpress the cytokine that it had expressed in an earlier stimulation. <h3>Conclusion</h3> Thus, there is a certain degree of instability in the cytokine memory of Th cells, the molecular basis of which we are currently analysing.
AB0939 POLYMYALGIA RHEUMATICA FOLLOWING INFECTIVE TRIGGERS OR VACCINATIONS: A DIFFERENT SUBSET OF DISEASE?
Authors: E. Conticini, P. Falsetti, C. Acciai, C. Baldi, M. Bardelli, S. Gentileschi, L. Cantarini, B. Frediani
Journal: Annals of the Rheumatic Diseases (2020)

Background: Polymyalgia rheumatica (PMR) is the most common inflammatory disorder of elderly; an association with environmental triggers and deregulated immune response has been described. Objectives: The aim of this study was to investigate the presence of environmental triggers before the onset of PMR and its association to a particular subset of disease. Methods: The database of 58 consecutive PMR patients recruited from a single rheumatology secondary care setting was retrospectively analyzed to investigate the frequency of environmental triggers and correlations with clinical characteristics. Patients underwent multidistrict ultrasound examination of both proximal and distal sites. Laboratory tests were repeated after one month from first visit, when steroids were started, and about every three months during follow-up (for at least 24 months) Results: Fifteen PMR patients (26%) described a connection with environmental agents: six PMR patients reported a vaccination, 3 an upper respiratory tract infection and 1 pneumonia before the onset of disease. Five patients reported seasonal influenza as trigger of PMR. The model of multivariate linear regression which better predicted a shorter time to normalize inflammatory reactants (R squared 27,46%, p=0,0042) comprised the presence of an environmental trigger and a higher CRP. A linear regression analysis confirmed an inverse correlation between CRP at onset ant time to normalize inflammatory reactant (r= -0,3031, p=0,0208). A significant correlation was demonstrated between presence of environmental trigger and shorter time to normalize inflammation (r=-0,5215, p&lt;0,0001), lesser frequency of gleno-humeral synovitis on US (r=-0,3774, p=0,0038). Conclusion: Our work describes a correlation between environmental triggers in PMR and higher CRP at diagnosis and faster response to therapy. We may suppose that these patients belong to a more specific subtype of PMR, in whom external stimuli, such as vaccinations or infections, may lead to a deregulated response within the context of an impaired immune and endocrine system. We recommend a systematic research of previous infections or vaccination in recent onset PMR Disclosure of Interests: None declared
OP0037 Fibrinolytic system and ace i/d polymorphism in systemic sclerosis
Authors: C Angotti, F Gensini, C Fatini, B Battaglini, E Sticchi, S Fedi, A Righi, G Pepe, R Abbate, M Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In Systemic sclerosis (SSc), an imbalance of the fibrinolytic system was shown. <i>In vivo</i> and <i>in vitro</i> studies suggest a role for Renin Angiotensin System in the regulation of fibrinolytic balance: Angiotensin II (Ang II) increases the plasminogen activator inhibitor?1 (PAI-1) production and secretion, and ACE reduces t-PA production. A polymorphism in the ACE gene consisting of an insertion or deletion (I/D) of 287 bp fragment in intron 16 was described. The D allele of ID polymorphism is associated with an increased level of ACE and ACE gene polymorphism may influence the production of Ang II. <h3>Objectives</h3> To investigate possible alterations in the fibrinolytic system and to examine the role of ACE I/D polymorphism in SSc. <h3>Methods</h3> PAI-1 activity, t-PA and D-Dimer plasma levels were measured in 61 SSc patients (36 limited, 25 diffuse) and 108 healthy controls. ACE I/D polymorphism was genotyped by PCR. PAI-1 activity and t-PA levels were assayed by chromogenic method and D-Dimer levels by ELISA. <h3>Results</h3> A significant difference in ACE genotype distribution (chi2 = 9.79 p = 0.007) and allele frequency was observed between patients and controls (0.64 vs 0.50 p = 0.009). In limited SSc a higher frequency of ACE D allele was found (0.68 vs 0.56 in diffuse SSc p = 0.23). By univariate analysis an association between ACE D allele and limited, but not diffuse SSc, was found (OR DD+ID/II = 6.44 95% CI 1.45–28.54 p = 0.005 and OR DD+ID/II = 1.91 95% CI 0.60–6.08 p = 0.31 respectively). Median values of PAI-1, t-PA and D-Dimer were 6.2 U/ml (range 1–37.5),10.5 ng/mL (range 4.3–28.1) and 156 ng/mL (range 64–1064, respectively. Patients had higher t-PA and D-Dimer mean levels than controls (p = 0.000001 and p = 0.02, respectively). No difference was observed in PAI-1 plasma levels between patients and controls (p = 0.85). No association between high PAI-1, t-PA and D-Dimer plasma levels and ACE D allele was observed. <h3>Conclusion</h3> These data suggest that ACE D allele is highly associated with limited SSc. Thus, we could hypothesise that this allele may represent a risk factor for the development of limited SSc. Other mechanisms than the alterations of fibrinolytic system may have a role in determining the microvascular damage.