tbuckley/cabot-search huggingface dataset:
SAT0256 Economic impact of infliximab treatment in rheumatoid arthritis; correlation with disease activity score
Authors: A Kavanaugh, K Patel, M Bala, L Noe, C Antoni
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In the ATTRACT trial, rheumatoid arthritis (RA) patients treated with the anti-TNF monoclonal antibody infliximab showed significant improvement in the signs and symptoms of disease (e.g. as measured with using the Disease Activity Score [DAS]); treatment also achieved improvement in quality of life measures and inhibited the progression of structural damage at 54 weeks. The ultimate clinical utility of biologic agents may be impacted by their high acquisition costs. However, RA is itself associated with substantial direct and indirect costs that vary with the severity of disease. Therefore, highly effective therapies for RA may be cost effective. <h3>Objectives</h3> To assess the total costs of treating RA, exclusive of the costs of study medication, for patients enrolled in the ATTRACT trial, and to correlate total costs with disease activity and response to therapy using the DAS. <h3>Methods</h3> Economic evaluation was performed on patients in the ATTRACT trial over 54 weeks of study. The economic impact of improvement in disease activity was assessed by analysing costs according to clinical response using the DAS. DAS28 was calculated as follows: 0.56*SQRT(TJC) + 0.28*SQRT(SJC) +0.7ln (ESR) + 0.014*(pt global (VAS)). Clinical responses in the trial were characterised as 'None', 'Moderate' or 'Good' using DAS scores at endpoint and change in DAS during the study. Categorical variables were tested using Cochran-Mantel-Haenszel test. <h3>Results</h3> Clinical efficacy at 54 weeks was significantly greater among patients receiving infliximab compared to those receiving placebo (p = 0.001). Total cost among all patients with ?Good? DAS response was $3,836 compared to $5,613 and $13,125 among patients with ?Moderate? and ?None? response respectively. Thus, patients who had a ?Good? DAS response cost $9,289 less on average, compared to ?None? DAS response. DAS28 response rates and total cost by DAS response are presented below. <h3>Conclusion</h3> Improvement in DAS significantly reduced the cost of treating RA patients. In patients with severe RA, therapy with infliximab was effective, as assessed by DAS. Moreover, patients achieving moderate and good DAS responses incurred significantly less costs over 54 weeks of therapy than non-responders. This data shows that among patients with severe RA, highly effective therapy, such as infliximab, can reduce costs. Such therapy may be cost effective.
AB0140 The evaluation the factors that effect the clinical status of patients with primary knee osteoarthritis
Authors: H Tuna, A Hakgüder, G Ekuklu, S Kokino
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Primary knee osteoarthritis (PKO) leads functional degenaration of knee joints and cause disability in general population. There are a lot of faýctors that effect on the intensity and functional status of PKO in various degrees. <h3>Objectives</h3> To investigate the efficacies of age, body mass index (BMI), the Kellgren Lawrence Radiological Osteoarthiritis Index (KLOAI), medial tibiofemoral joint space (MTFJS) on the intensity and functional status of PKO. <h3>Methods</h3> Fifty subjects (ages 56 to 69), 40 female (%80) and 10 male (%20), diagnosed as PKO according to American College of Rheumotology were admitted to the study. AP knee radiography of the patients were taken while standing up and MTFJS were measured. Those films were evaluated according to the KLOAI. Lequesne index (LI), Sickness Impact Profile (SIP), painless walking duration (PWD1) and painless walking distance (PWD2) were used with purpose to determine the clinical status and intensity of the PKO. <h3>Results</h3> We found these formulas according to Backward Lineer Regression Model. SIP = 202.2 + (63.9 × KLOAI) PWD1 (minutes) = 14 + (0.37 × BMI) + (3.1 × Sex) ? (3.1 × KLOAI) PWD2 (metres) = 1417 + (217.7 × Sex) <h3>Conclusion</h3> KLOAI correlated with SIP and PWD1 moderately. However, we think that all of these factors should be evaluated in clinical status of PKO. <h3>References</h3> Mc Alindon TE, Cooper C, Kýrwan JR. Determinants of disability in osteoarthritis of the knee. Ann Rheum Dis. 1993;52:258–62 Hochberg MC, Cejku ML, Scott WW. The association of body weight, body fatness and body fat distribution with osteoarthritis of the knee: data from the Baltýmore longitudinal study of aging. J Rheumatol. l995;22(3):488–93 Mankin HJ. Clinical features of osteoarthritis. In: Kelly, Harris, Rudd, Sledge, eds. <i>Textbook of rheumatology</i>. Vol. 4. Philadelphia: WB Saunders Company, 1993: 1374–84 Lequesne MG, Samson M. Indicis of severity for OA. Eular Balot No:3, 85, 1992 Wade DT. Measurement in neurological rehabilitation. Oxford University Press, 1992: 208 Sowers M, Zobel D, Weis FF. Progression of osteoarthritis of the hand and metacarpal bone loss. Arthritis Rheum. 1991;34(1):36–42 Dequeker J, Dieppe P. Disorders of bone, cartilage and connective tissue. In: Klippel JH, Dieppe PA, eds. <i>Rheumatology</i>. Philadelphia: The Mosby Company, 1998: 8.1.1–8.12.16
Estrogen receptor beta signaling in CD8<sup>+</sup> T cells boosts T cell receptor activation and antitumor immunity through a phosphotyrosine switch
Authors: Bin Yuan, Curtis A Clark, Bogang Wu, Jing Yang, Justin M Drerup, Tianbao Li, Victor X Jin, Yanfen Hu, Tyler J Curiel, Rong Li
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The non-overlapping functions of the two estrogen receptor subtypes, ERα (Estrogen Receptor α)and ERβ (Estrogen Receptor β), in tumor cells have been studied extensively. However, their counterparts in host cells is vastly underinterrogated. Even less is known about how ERα and ERβ activities are regulated in a subtype-specific manner. We previously identified a phosphotyrosine residue (pY36) of human ERβ that is important for tumor ERβ to inhibit growth of breast cancer cells in vitro and in vivo. A role of this ERβ phosphotyrosine switch in regulating host ERβ remains unclear.Conventional gene editing was used to mutate the corresponding tyrosine residue of endogenous mouse ERβ (Y55F) in mouse embryonic stem cells. The derived homozygous mutant Esr2 Y55F/Y55F mouse strain and its wild-type (WT) counterpart were compared in various transplant tumor models for their ability to support tumor growth. In addition, flow cytometry-based immunophenotyping was carried out to assess antitumor immunity of WT and mutant hosts. Adoptive transfer of bone marrow and purified CD8 + T cells were performed to identify the host cell type that harbors ERβ-dependent antitumor function. Furthermore, cell signaling assays were conducted to compare T cell receptor (TCR)-initiated signaling cascade in CD8 + T cells of WT and mutant mice. Lastly, the ERβ-selective agonist S-equol was evaluated for its efficacy to boost immune checkpoint blockade (ICB)-based anticancer immunotherapy.Disabling the ERβ-specific phosphotyrosine switch in tumor-bearing hosts exacerbates tumor growth. Further, a cell-autonomous ERβ function was defined in CD8 + effector T cells. Mechanistically, TCR activation triggers ERβ phosphorylation, which in turn augments the downstream TCR signaling cascade via a non-genomic action of ERβ. S-equol facilitates TCR activation that stimulates the ERβ phosphotyrosine switch and boosts anti-PD-1 (Programmed cell death protein 1) ICB immunotherapy. Our mouse genetic study clearly demonstrates a role of the ERβ phosphotyrosine switch in regulating ERβ-dependent antitumor immunity in CD8 + T cells. Our findings support the development of ERβ agonists including S-equol in combination with ICB immunotherapy for cancer treatment.
AB0030 Biopsy findings in adult-onset still disease
Authors: CA Montilla, E Cuevas, J Abraham-Simón, CM González, FJ López-Longo, I Monteagudo, L Carreño, J Alcocer-Varela, D Alarcón-Segovia
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The differential diagnosis of adult-onset Still disease involves cancer, infections and other rheumatic diseases. Thus, differential diagnosis frequently requires the performance of biopsies. However, there are not many reports about histological findings in these patients. <h3>Objectives</h3> To describe biopsy findings in patients with adult-onset Still disease. <h3>Methods</h3> We have studied biopsies from 35 patients with adult-onset Still disease performed between April of 1979 and December of 1999 in Salvador Zubirán Nutrition Institute. <h3>Results</h3> 60% of all patients adult-onset Still disease underwent a biopsy. In lymphatic ganglions, which constitute the most frequent biopsy, the main finding is the loss of structure with lymphoid follicles of variable size and a sinusal part widened with arteries with hyalines and gross walls. In some samples, areas of necrosis and haemorrhage were found. In the liver appeared focal infiltrates of polymorphonuclear leukocytes in hepatic lobulille and lymphoplasmocitaries accumulates in porta spaces. In some patients an opening of sinusal and Disse spaces with focal necrosis area was described. In the spleen, polymorphonuclears were identified in red pulp, with a moderate amount of plasmatic cells and eosinophils, and an important widening of arterial walls. White pulp did not showed any disturbance. In the skin, it was demonstrated the presence of polymorphonuclears and lymphocytes infiltrates with a perivascular and perianexial predominance. Paraqueratosis areas were also described. Perivascular inflammatories infiltrates in the muscle with areas of necrosis were described. In the lung, a broadening of alveolar walls because of an inflammatory infiltrate composed by polymorphonuclears and lymphocytes was described. Areas of haemorrhage were also described. <h3>Conclusion</h3> We have not found any characteristic histological finding of Still disease in the adult. In most of the biopsies predominate non-specific inflammatories infiltrates.
Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AML
Authors: Mikkael A. Sekeres, Justin Watts, Atanas Radinoff, Montserrat Arnan Sangerman, Marco Cerrano, Patricia Font Lopez, Joshua F. Zeidner, Maria Diez Campelo, Carlos Graux, Jane Liesveld, Dominik Selleslag, Nikolay Tzvetkov, Robert J. Fram, Dan Zhao, Jill Bell, Sharon Friedlander, Douglas V. Faller, Lionel Adès
Journal: Leukemia (2021)
Racial ethnic disparities in clinical/pathological features, treatment, and survival among patients with early-onset colorectal cancer.
Authors: Michael Lyudmer, Riya Jayesh Patel, Adel Chergui, Seda Serra Tolu, Devika Rao, Andreas Kaubisch, Jennifer W. Chuy, Tarek N. Elrafei, Ana Acuna-Villaorduna, Sanjay Goel
Journal: Journal of Clinical Oncology (2021)

21 Background: Globally, the incidence of early-onset colorectal cancer has risen. Racial disparities in colorectal cancer (CRC) are well-described, however data in EO by race/ethnicity is lacking. We aim to compare the presenting features, treatment, and survival features of patients with metastatic early-onset CRC (EO). Methods: Patients with metastatic CRC diagnosed between 2010-2019 at two NYC hospitals were identified by tumor registry (n = 646). Clinical/pathological features, treatment and survival data was collected by chart review and compared between Non-Hispanic Whites (NHW), Non-Hispanic Blacks (NHB) and Hispanics (H) using Chi-square or Fisher’s exact test. Kaplan Meier curves were plotted to compare overall survival (OS) among groups. Stata v15 was used for statistical analysis. Results: Of 646 CRC patients, 126 (21.5%) were NHW, NHB or H diagnosed with EO with a frequency ranging from 16.6% in NHW to 26.1% in H. Non statistically significant lower frequencies of male gender, low/moderate grade, left-sided tumors,and higher frequency of KRAS mutations were seen in NHB (Table). Metastectomy was performed in 20 patients (13.9%) and did not differ between groups. There was no difference in the use of chemotherapy or biologics in general (Table), but NHW were more likely to get cetuximab than NHB (OR:4.5, p = 0.02) and H (OR:4.7, p = 0.02).There were no differences in median OS (1.8 vs. 2.2 vs. 2 years, p = 0.9)or 1-year OS (72% vs 72.3% vs 70.8%) in NHW, NHB and H, respectively. A lower 5-year OS was seen in NBH (14.5%) and Hispanics (24.4%) compared to NHW (44%). Conclusions: EO-CRC is more frequently seen in minority racial/ethnic groups. Despite no differences in the use of chemotherapy or biologic treatment in general, NHB have a lower 5-year survival rate compared to NHW and H. [Table: see text]
Covid-19: “We must learn the lessons of this dark death toll”
Authors: Alison Shepherd
Journal: BMJ (2021)

This week the number of people in the UK who have died with covid-19 passed 100 000.To mark the awful milestone the BMA projected a message of condolence and commemoration onto its building in Tavistock Square, London.As the message was displayed, Chaand Nagpaul, the BMA's chair of council, said, "We must not and will not forget this day.Among those who have died are many health and care workers who lost their lives in the course of doing their jobs.We know that some of those staff were not properly protected from the virus and yet felt under pressure to continue to work and do their duty by their patients."As the first nation in Europe to have reached this dark death toll, we must learn the lessons of this tragedy."Now is the time to express our immense sadness at these deaths, to remember the lives they led and the good they did, and to redouble our commitment to reducing the spread of infection, vaccinating the population, and protecting one another from this deadly disease.
The association between prenatal care and birth weight among women exposed to cocaine in New York City
Authors: A. Racine
Journal: JAMA (1993)

<h3>Objectives.</h3> —Although the association between antenatal cocaine use and adverse birth outcomes has been well documented, relatively little is known about interventions that may ameliorate these consequences. We therefore examined the relationship between prenatal care and birth weight among a population of prenatal cocaine users. <h3>Design.</h3> —Population-based retrospective analysis. <h3>Patients.</h3> —All single-gestation live births to white non-Hispanic, black non-Hispanic, and Hispanic residents of New York City who gave birth between 1988 and 1990 with a positive indication for cocaine recorded on birth certificates (N=7923). <h3>Main Outcome Measures.</h3> —We contrasted mean birth weight and rates of low birth weight (&lt;2500 g) among cocaine users with one to three prenatal care visits, four or more visits, and unknown numbers of visits with users who reported no prenatal care. We used ordinary least squares and logistic regression to control for age, parity, smoking, alcohol, other drugs, weight gain, prepregnancy weight, employment, marital status, participation in the Supplemental Food Program for Women, Infants and Children, and method of finance. <h3>Main Results.</h3> —Adjusted odds ratios of low birth weight for cocaine users with four prenatal care visits or more as compared with those who had none were 0.51 for blacks (95% confidence interval [CI], 0.44 to 0.59), 0.39 for whites (95% CI, 0.23 to 0.66), and 0.37 for Hispanics (95% CI, 0.28 to 0.48). Adjusted mean birth weight differences between users with four visits or more and those with none were 262 g for blacks (<i>P</i>&lt;.001), 247 g for whites (<i>P</i>&lt;.001), and 317 g for Hispanics (<i>P</i>&lt;.001). <h3>Conclusions.</h3> —The receipt of prenatal care among cocaine users is associated with significant improvements in birth weight. Enrollment of cocaine users in prenatal care may be an effective start to a more comprehensive approach to this problem. (<i>JAMA</i>. 1993;270:1581-1586)
FRI0043 Combination therapy with methotrexate and infliximab as treatment of refractory chronic polyarthritis: our experience
Authors: M Covelli, C Scioscia, M Compagno, F Iannone, V Grattagliano, G Lapadula
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A number of studies show that neutralisation of tumour necrosis factor alpha (TNF-alpha), by using chimeric monoclonal anti-TNF alpha antibody (infliximab) for at least three months, improves the clinical outcome of rheumatoid arthritis. A combination therapy with a standard weekly dose of Methotrexate have been recommended to prevent the activation of autoimmune processes stimulated by the administration of infliximab. <h3>Objectives</h3> To evaluate the efficacy and safety of infliximab, when combined with methotrexate, in patients affected by chronic polyarthritis, refractory to other DMARDs. <h3>Methods</h3> An open study, including 30 patients affected by different kinds of chronic polyarthritis, is running. Methotrexate (5–15 mg/week) and infliximab (3 mg/kg intravenously at weeks 0, 2, 6, and then every 8th week) are administered to all the patients. Clinical evaluation (VAS for pain, VAS as a global assessment by patient and physician, swollen and painful joint count, HAQ score, morning stiffness) and laboratory tests (ESR and CRP), are simultaneously assessed. <h3>Results</h3> A marked improvement in clinical symptoms and signs and a reduction of ESR and CRP were seen after the first administration of infliximab. Morning stiffness, swollen and tender joints counts were remarkably reduced and HAQ score significantly improved. One patient experienced allergic reaction at the third infliximab infusion. A cutaneous capillaritis was observed in one patient. Only one patient did not respond to the therapy. <h3>Conclusion</h3> Our data show that, after 30 weeks of treatment, combination therapy with methotrexate and infliximab is a safe and efficient treatment for patients affected by chronic polyarthritis, not responding to other DMARDs. In most patients a remarkable improvement of clinical activity (VAS for pain, VAS as a global assessment by patient and physician, swollen and painful joint count, HAQ score, morning stiffness) and laboratory tests (ESR, CRP) have been observed. The updated data will be presented. <h3>References</h3> Elliott MJ, Maini RN, <i>et al</i>. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994;344(8930):1105–10 Kavanaugh A, St Clair EW, <i>et al</i>. Chimeric anti-tumor necrosis factor-alpha monoclonal antibody treatment of patients with rheumatoid arthritis receiving methotrexate therapy. J Rheumatol. 2000;27(4):841–50 Lipsky PE, van der Heijde DM, <i>et al</i>. Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis. N Engl J Med. 2000;343(22):1594–602
Impaired prenatal motor axon development necessitates early therapeutic intervention in severe SMA
Authors: Lingling Kong, David O. Valdivia, Christian M. Simon, Cera W. Hassinan, Nicolas Delestrée, Daniel M. Ramos, Jae Hong Park, Celeste M. Pilato, Xixi Xu, Melissa Crowder, Chloe C. Grzyb, Zachary A. King, Marco Petrillo, Kathryn J. Swoboda, Crystal Davis, Cathleen M. Lutz, Alexander H. Stephan, Xin Zhao, Marla Weetall, Nikolai A. Naryshkin, Thomas O. Crawford, George Z. Mentis, Charlotte J. Sumner
Journal: Science Translational Medicine (2021)

Gene replacement and pre-mRNA splicing modifier therapies represent breakthrough gene targeting treatments for the neuromuscular disease spinal muscular atrophy (SMA), but mechanisms underlying variable efficacy of treatment are incompletely understood. Our examination of severe infantile onset human SMA tissues obtained at expedited autopsy revealed persistence of developmentally immature motor neuron axons, many of which are actively degenerating. We identified similar features in a mouse model of severe SMA, in which impaired radial growth and Schwann cell ensheathment of motor axons began during embryogenesis and resulted in reduced acquisition of myelinated axons that impeded motor axon function neonatally. Axons that failed to ensheath degenerated rapidly postnatally, specifically releasing neurofilament light chain protein into the blood. Genetic restoration of survival motor neuron protein (SMN) expression in mouse motor neurons, but not in Schwann cells or muscle, improved SMA motor axon development and maintenance. Treatment with small-molecule SMN2 splice modifiers beginning immediately after birth in mice increased radial growth of the already myelinated axons, but in utero treatment was required to restore axonal growth and associated maturation, prevent subsequent neonatal axon degeneration, and enhance motor axon function. Together, these data reveal a cellular basis for the fulminant neonatal worsening of patients with infantile onset SMA and identify a temporal window for more effective treatment. These findings suggest that minimizing treatment delay is critical to achieve optimal therapeutic efficacy.
Abstract 14544: Usefulness of Vascular Function Tests for Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD-J (Flow-Mediated Dilation Japan) Study A
Authors: Tatsuya Maruhashi, Yukihito Higashi, Masato Kajikawa, Shinji Kishimoto, Shogo Matsui, Haruki Hashimoto, Yuji Takaekou, Takayuki Hidaka, Farina M Yusoff, Kensuke Noma, Hirofumi Tomiyama, Akira Yamashina, Bonpei Takase, Toru Suzuki, Yasuki Kihara
Journal: Circulation (2018)

Introduction: The usefulness of vascular function tests for management of patients with a history of coronary artery disease (CAD) is not fully known. Methods: We measured flow-mediated vasodilatio...
Covid-19 vaccination for medical students: the grey area
Authors: Nikki Nabavi
Journal: BMJ (2021)

<h3>Background and objectives</h3> Outcomes reported in trials in adults with glomerular disease are often selected with minimal patient input, are heterogeneous, and may not be relevant for clinical decision making. The Standardized Outcomes in Nephrology–Glomerular Disease (SONG-GD) initiative aimed to establish a core outcome set to help ensure that outcomes of critical importance to patients, care partners, and clinicians are consistently reported. <h3>Design, setting, participants, and measurements</h3> We convened two 1.5-hour workshops in Melbourne, Australia, and Washington, DC, United States. Attendees were identified purposively with 50 patients/care partners and 88 health professionals from 19 countries; 51% were female. Patients and care partners were from the United States, Australia, and Canada, and had experience of a glomerular disease with systemic features (<i>n</i>=9), kidney-limited nephrotic disease (<i>n</i>=9), or other kidney-limited glomerular disease (<i>n</i>=8). Attendees reviewed the results of the SONG-GD Delphi survey and aims of the workshop and then discussed potential core outcomes and their implementation in trials among moderated breakout groups of eight to 12 people from diverse backgrounds. Transcripts of discussions were analyzed thematically. <h3>Results</h3> Three themes were identified that supported the proposed core outcomes: limiting disease progression, stability and control, and ensuring universal relevance (<i>i.e.</i>, applicable across diverse populations and settings). The fourth theme, preparedness for implementation, included engaging with funders and regulators, establishing reliable and validated measures, and leveraging existing endorsements for patient-reported outcomes. <h3>Conclusions</h3> Workshop themes demonstrated support for kidney function, disease activity, death, life participation, and cardiovascular disease, and these were established as the core outcomes for trials in adults with glomerular disease. Future work is needed to establish the core measures for each domain, with funders and regulators central to the uptake of the core outcome set in trials.