RESUMO
BACKGROUND: Shared decision-making (SDM) is a principle of humanistic, patient-centered health care within the field of rheumatology. However, clear communication between patients and their clinicians regarding the benefits and risks of immunomodulators may be challenging in a clinical setting. The design-thinking process is a human-centered approach to quality improvement that can help to identify insights to uphold high-quality communication. METHODS: The development process adhered to the Stanford design thinking process framework, encompassing 5 stages: (1) empathize, (2) define, (3) ideate, (4) prototype, and (5) test. During the empathy stage, quality improvement members spent 4 hours immersed in the clinical setting observing how patients and clinicians engage in SDM conversations. These observations were augmented by unstructured debriefing sessions to better understand the needs and drivers of high-quality SDM. Following this, a rapid ideation workshop was convened to generate creative solutions. These led to rapid prototyping and testing, yielding a final product. RESULTS: The iterative design process identified 4 critical needs: (1) ensuring comprehensibility of materials, (2) upholding accuracy of information, (3) balancing standardization with individualization, and (4) promoting retention of knowledge. During the rapid ideation workshop, the concept of a Worksheet for Immunomodulator Shared Decision-Making (WISDM) was introduced and selected for further elaboration. This led to the creation of 5 prototypes for methotrexate, which were subsequently tested. These were reconciled and modified to make a final product. CONCLUSION: The WISDM template contains 7 elements that support SDM. Forty-five WISDMs were created for 23 immunomodulators. Further investigation will focus on how WISDMs exactly impact SDM.
RESUMO
We have studied the effect of relative composition of γ-Oryzanol (γ-Or) on the liquid expanded-liquid condensed phase coexistence region in the mixed Langmuir monolayer of γ-Or and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecules at air-water interface. The surface manometry studies at a fixed temperature show that the mixture of γ-Or and DPPC forms a stable monolayer at air-water interface. As the relative composition of γ-Or increases the range of area per molecule over which the coexistence of liquid expanded (LE)-liquid condensed (LC) phases exists reduces. Although the LE-LC phase coexistence corresponds to the first-order phase transition, the slope of the surface pressure-area per molecule isotherm is non-zero. Earlier studies have attributed the non-zero slope in LE-LC phase coexistence region to the influence of the strain between the ordered LC phase and disordered LE phase. The effect of strain on the coexistence of LE-LC phases can be studied in terms of molecular density-strain coupling. Our analysis of the liquid condensed-liquid expanded coexistence region in the isotherms of mixed monolayers of DPPC and γ-Or shows that with the increase in the mole fraction of sterol in the mixed monolayer the molecular lateral density-strain coupling increases. However, at 0.6 mole fraction of γ-Or in the mixed monolayer the coupling decreases. This is corroborated by the observation of minimum Gibb's free energy of the mixed monolayer at this relative composition of γ-Or indicating better packing of molecules.
Assuntos
Fenilpropionatos , Glicerilfosforilcolina , Esteróis , Água , 1,2-Dipalmitoilfosfatidilcolina , Propriedades de SuperfícieRESUMO
We have studied the kinetics of pore formation in giant unilamellar vesicles (GUV) with the antimicrobial peptide nisin. The role of charged lipid composition in the rate of pore formation by nisin in the vesicle membrane is investigated using fluorescence microscopy. We propose a model and obtain an analytical expression for the variation in the fluorescence intensity of a GUV as a function of time. We find that the analytical equation fits well to the experimental data, and the membrane surface potential can be estimated from the fit parameters. We further show that the formation of multiple pores on the vesicle membrane is affected by the charged lipid composition of the membrane.
Assuntos
Nisina , Lipossomas Unilamelares , Lipossomas Unilamelares/química , Nisina/farmacologia , Cinética , Membrana Celular/metabolismo , LipídeosRESUMO
OBJECTIVE: Annual program evaluations are important activities of all graduate medical education programs. Although the Accreditation Council for Graduate Medical Education provides general guidelines, there is substantial scope for educational innovation. Strengths, opportunities, aspirations, and results (SOAR) is a strengths-based framework for strategic planning. Because SOAR emphasizes positivity and engagement, it is an appealing framework for evaluating graduate medical education programs. Our objective was to demonstrate the feasibility and acceptability of SOAR in a program evaluation committee of a fellowship program to generate strategic initiatives. METHODS: The authors used the four steps of SOAR within the program evaluation committee in 2022. Interviewers collected positive stories to understand program strengths. Then, rapid ideation was used to translate strengths into opportunities. These opportunities were condensed and refined for fellows to assess how well they align with aspirations. The ones that aligned best with aspirations were prioritized for implementation. Results were monitored through a scorecard based on specific, measurable, achievable, relevant, and time-bound (SMART) goals every month. RESULTS: Of 15 divisional members, 11 participated (73.3%). Five major strengths were identified: supportive environment, variety of cases, scheduling flexibility, integration with larger networks, and multidisciplinary collaboration. These 5 yielded 15 opportunities, which were refined and condensed to 9. Four were selected for implementation: scholarly works accountability group, hybrid-flex curriculum, fellowship weekly huddles, and structured electives. Scorecards have shown successful implementation during a 4-month period. CONCLUSIONS: SOAR is an innovative and feasible approach to program evaluation that uses trainee engagement to translate and synergize existing program strengths into actionable program improvement.
Assuntos
Currículo , Educação de Pós-Graduação em Medicina , Humanos , Avaliação de Programas e Projetos de Saúde , Bolsas de Estudo , AcreditaçãoRESUMO
BACKGROUND: After-visit summaries (AVS) are patient-specific documents curated by providers to summarize the content of medical encounters. Despite widespread use, little is known about rheumatology patient preferences for AVS content and style. The aims of this quality improvement project are to identify patient preferences and to design a rheumatology-specific AVS, using the Kano method. METHODS: This quality improvement project consists of 4 parts. First, investigators interviewed veterans and clinic staff to derive a list of potential features. Second, a Kano questionnaire assessing satisfaction with the presence or absence of each feature was distributed to veterans. Third, qualitative and quantitative Kano analyses were performed to categorize features as mandatory, performance, attractive, or indifferent. Fourthly, based on these findings, an AVS was drafted and distributed to Veterans with an associated survey to assess satisfaction with content, visual appeal, and readability. RESULTS: Nine physicians, 5 veterans, 5 schedulers, 3 nurses, and 3 medical assistants identified 15 features for inclusion in a Kano-style questionnaire. The questionnaire was distributed to 50 Veterans using consecutive sampling. Quantitative Kano analysis demonstrated 4 mandatory, 2 performance, and 3 attractive features that were ultimately included in the AVS; 6 indifferent features were excluded. A postintervention survey of 50 Veterans showed high satisfaction scores in AVS content (4.3/5), visual appeal (4.6/5), and readability (4.4/5). CONCLUSIONS: We developed an AVS that included 9 mandatory, attractive, and performance features, as identified by the Kano method. Veterans were highly satisfied by the content, visual appeal, and readability of the AVS.
Assuntos
Preferência do Paciente , Reumatologia , Humanos , Registros Eletrônicos de Saúde , Nigéria , Melhoria de Qualidade , Satisfação do PacienteRESUMO
Objective: To determine the current trends in complete denture education in undergraduate dental colleges. METHODS: The survey-based study was conducted in April and May 2020 at undergraduate dental colleges of Pakistan, and comprised heads of the Prosthodontics Department at all dental colleges across Pakistan having at least one batch of final year dental students. Data was collected using an online predesigned questionnaire that explored theoretical and practical teaching patterns of complete denture prosthodontics in the undergraduate years, and the materials and practices of students when constructing complete dentures in the clinics. The participants were given the option of choosing more than one option where needed. Data was analysed using SPSS 23. RESULTS: Of the 49 subjects approached, 40(81.6%) returned the forms duly filled; 11(27.5%) from public-sector institutions and 29(72.5%) from the private sector. There were 26(65%) institutions which required that their undergraduate students fabricate 2-4 conventional complete dentures. In all 40(100%) colleges, faculty gave live clinical demonstrations before students fabricated conventional complete dentures in the outpatient departments. Teaching strategy included small group discussions in 25(62.5%) institutions. Green stick 40(100%), zinc oxide eugenol 40(100%) and impression compound 39(97.2%) were the materials of choice for various steps of impression making. In all the 40(100%) institutions, students fabricated conventional complete dentures during their prosthodontics rotation. Immediate, copy and overdentures were constructed by students in 8(20%), 3(7.5%) and 8(20%) institutions, respectively. Conclusion: Majority of the dental schools used similar impression materials and techniques for fabricating conventional complete dentures. Didactic teaching of conventional and unconventional complete dentures was being carried out at a huge majority of the dental institutions studied.
Assuntos
Currículo , Educação em Odontologia , Humanos , Paquistão , Educação em Odontologia/métodos , Faculdades de Odontologia , Prótese Total , EstudantesRESUMO
OBJECTIVES: Legislation dictating federal healthcare policy is drafted largely by members of the US Senate and House of Representatives. As such, their personal and professional backgrounds play important roles in setting the national healthcare agenda. We examine the professional and legislative records of the 28 federal physician legislators with voting privileges between 2011 and 2020. METHODS: Two researchers compiled the names of every federal legislator in both the US Senate and the US House of Representatives who served at any time between 2011 and 2020. The researchers used publicly available records to abstract information regarding their professional and legislative records. Data were then analyzed using descriptive statistics. RESULTS: The majority of the 28 federal physician legislators are Doctor of Medicine graduates (96%), Republican (86%), represent southern states (71%), were in private practice before serving as legislators (78.5%), and have not previously held elected positions as legislators (57%). Approximately 15% of the bills that they sponsor are related to health policy. Obstetrics/Gynecology, Surgery, and Family Medicine are the most common specialties. On average, it takes 25 years from medical school graduation to election to their federal legislative position. Approximately half represent states, or districts within states, in which they attended medical school or completed residency. CONCLUSIONS: To engage in meaningful healthcare policy advocacy, professional organizations must support and encourage leadership training for physicians, increase the geographic and professional diversity of physician legislators, prioritize the election of physicians from both political parties, and inculcate deep and lasting professional relationships to physicians in Congress.
Assuntos
Internato e Residência , Médicos , Feminino , Política de Saúde , Humanos , Política , GravidezRESUMO
BACKGROUND: The advent of multiple safe and effective vaccines to prevent SARS-CoV-2 infection represents a major step in resolving the COVID-19 global pandemic. Vaccination of individuals with rheumatologic diseases on immunomodulators represents an additional challenge because data suggest that certain immunomodulators may impact vaccine efficacy. METHODS: At a large, predominantly rural Midwestern Veterans Affairs rheumatology clinic, an interprofessional group of investigators conducted a quality improvement project to develop a COVID-19 vaccine readiness kit, consisting of patient education materials and a readiness questionnaire to help guide veteran decision-making. Using a Lean Six Sigma approach and the DMAIC (Define-Measure-Analyze-Improve-Control) framework, the investigators identified customer values, needs, and barriers to participation. Return rates and responses from the questionnaire were tracked over 28 days. RESULTS: One hundred seventy-nine veterans were identified and mailed kits; 129 (73%) returned the questionnaire within 28 days. Ninety-seven percent of those opted to hold immunomodulators after at least 1 administration of the vaccine; 3.1% were not interested in vaccination. Veterans voiced satisfaction at the simplicity of the process, comprehensibility of materials, and the clarity of communication. CONCLUSIONS: The Lean Six Sigma approach, systematically focusing on identifying the values, needs, and barriers of veterans on immunomodulators, was critical to high participation rates from veterans. This approach is cost-effective for resource-poor settings, audiences without access or familiarity to digital content, and rural settings separated by large geographic distances.
Assuntos
Artrite Reumatoide , COVID-19 , Veteranos , Vacinas contra COVID-19 , Humanos , Fatores Imunológicos , Melhoria de Qualidade , SARS-CoV-2RESUMO
BACKGROUND/OBJECTIVE: Physician well-being is being increasingly recognized for its important role in high-quality patient care, integrity of the healthcare system, and vitality of the workforce. However, little is known about well-being, resiliency, and burnout among rheumatologists, particularly early-career rheumatologists. In this qualitative study, the investigators explore these concepts among early-career rheumatologists. METHODS: We performed a qualitative study using semistructured phone interviews of rheumatologists who completed fellowship in 2017. Participants were recruited through purposive sampling. Twenty questions were devised by the investigators, covering sample demographics, exploring definitions of well-being, resiliency, and burnout, and probing potential solutions.Interviews were recorded and transcribed independently and verified for consistency. The investigators used grounded theory to code the transcripts and iteratively derive categories, subthemes, and themes until reaching theoretical sufficiency. RESULTS: Sixty-four rheumatologists were interviewed, accounting for 30.6 hours of material. Seven major themes were identified: (1) well-being as a holistic state where an individual is able to translate one's potential to maximal performance, (2) work-family balance as a dynamic equilibrium changing over time, (3) inadequacy of training in addressing self-doubt over autonomy, (4) uncertainty over career development and progression, (5) excessive administrative burdens, (6) protective nature of longitudinal relationships, and (7) addressing burnout requires a multifaceted approach at multiple levels. CONCLUSIONS: New rheumatologists face a series of challenges as they enter the workforce. Investments into well-being can help reduce the risk of burnout and enlarge our community. Our results highlight drivers and potential solutions, as identified by recent fellowship graduates.
Assuntos
Esgotamento Profissional , Médicos , Esgotamento Profissional/epidemiologia , Humanos , Pesquisa Qualitativa , Reumatologistas , Recursos HumanosRESUMO
BACKGROUND: Kidney disease accounts for more than 49 billion dollars in healthcare expenditures annually. Early detection and intervention may reduce the burden of disease. We describe a quality improvement project to develop a telenephrology dashboard that proactively monitors kidney disease. METHODS: One hundred eighty-four thousands Veterans within the Iowa City Veterans Affairs Health Care System were eligible for telenephrology consultation. The dashboard accessed the charts of 53,085 Veterans at risk for kidney disease. We utilized Lean-Six Sigma tools and principles and the Define-Measure-Analyze-Improve-Control Framework to develop and deploy a telenephrology dashboard in 4 community-based outpatient clinics (CBOCs). The primary measure was the number of days to complete consultation. Secondary measures included number of electronic consultations per month, distance and cost of Veteran travel saved, and number of steps for completion of consult. RESULTS: The data of 1384 Veterans at the 4 CBOCs were analyzed by the telenephrology dashboard, of which 459 generated telenephrology consults. The number of days to complete any type of consultation was unchanged (48.9 days in 2019, compared to 41.6 days in 2017). The average Veteran saved between $21.60 to $63.90 per trip to Iowa City. Between March 2019 and August 2019, there were 27.3 telenephrology consults per month. The number of steps needed to complete the consult request was decreased from 13 to 9. CONCLUSIONS: Utilization of the telenephrology dashboard system contributed to an increase in consultations completed through electronic means without decreasing face-to-face consults. Electronic consults now outnumber traditional face-to-face consultations at our institution. Telenephrology consultation improved early detection and identification of kidney disease and saved time and costs for Veterans in travel, but did not decrease the average number of days to complete consultation requests.
Assuntos
Apresentação de Dados , Nefropatias , Melhoria de Qualidade , Telemedicina , Interface Usuário-Computador , Veteranos , Atitude Frente aos Computadores , Atenção à Saúde , Humanos , Nefrologia , Serviços de Saúde Rural , Gestão da Qualidade Total , Estados Unidos , United States Department of Veterans AffairsRESUMO
BACKGROUND: With the increasing recognition that leadership skills can be acquired, there is a heightened focus on incorporating leadership training as a part of graduate medical education. However, there is considerable lack of agreement regarding how to facilitate acquisition of these skills to resident, chief resident, and fellow physicians. METHODS: Articles were identified through a search of Ovid MEDLINE, EMBASE, CINAHL, ERIC, PsycNet, Cochrane Systemic Reviews, and Cochrane Central Register of Controlled Trials from 1948 to 2019. Additional sources were identified through contacting authors and scanning references. We included articles that described and evaluated leadership training programs in the United States and Canada. Methodological quality was assessed via the MERSQI (Medical Education Research Study Quality Instrument). RESULTS: Fifteen studies, which collectively included 639 residents, chief residents, and fellows, met the eligibility criteria. The format, content, and duration of these programs varied considerably. The majority focused on conflict management, interpersonal skills, and stress management. Twelve were prospective case series and three were retrospective. Seven used pre- and post-test surveys, while seven used course evaluations. Only three had follow-up evaluations after 6 months to 1 year. MERSQI scores ranged from 6 to 9. CONCLUSIONS: Despite interest in incorporating structured leadership training into graduate medical education curricula, there is a lack of methodologically rigorous studies evaluating its effectiveness. High-quality well-designed studies, focusing particularly on the validity of content, internal structure, and relationship to other variables, are required in order to determine if these programs have a lasting effect on the acquisition of leadership skills.
Assuntos
Currículo , Educação de Pós-Graduação em Medicina , Educação , Liderança , Canadá , Humanos , Avaliação de Programas e Projetos de Saúde , Estados UnidosRESUMO
Metal alloys exhibit functionalities unlike those of single metals. Such alloying has drawn considerable research interest, particularly for nanoscale particles (metal clusters/nanoparticles), from the viewpoint of creating new functional nanomaterials. In gas phase cluster research, generated alloy clusters can be spatially separated with atomic precision in vacuum. Thus, the influences of increases or decreases in each element on the overall electronic structure of the cluster can be elucidated. However, to further understand the related mixing and synergistic effects, alloy clusters need to be produced on a large scale and characterized by various techniques. Because alloy clusters protected by thiolate (SR) can be synthesized by chemical methods and are stable in both solution and the solid state, these clusters are ideal study materials to better understand the mixing and synergistic effects. Moreover, the alloy clusters thus created have potential applications as functional materials. Therefore, since 2008, we have been working on establishing a precise synthesis method for SR-protected alloy clusters and elucidating their mixing and synergistic effects. Early research focused on the precise synthesis of alloy clusters wherein some of the Au in the stable SR-protected gold clusters ([Au25(SR)18]- and [Au38(SR)24]0) is replaced by Pd, Ag, or Cu. These studies have shown that Pd, Ag, or Cu substitute at different metal sites. We also have examined the as-synthesized alloy clusters to clarify the effect of substitution by each element on the physical and chemical properties of the clusters. However, in early studies, the number of substitutions could not be controlled with atomic accuracy for [Au25- xM x(SR)18]- (M = Ag or Cu). Then, in following research, methods have been established to obtain alloy clusters with control over the composition. We have succeeded in developing a method for controlling the number of Ag substitutions with atomic precision and thereby elucidating the effect of Ag substitution on the electronic structure of clusters with atomic precision. Concurrently, we also studied alloy clusters containing multiple heteroelements with different preferential substitution sites. These results revealed that the effects of substitution of each element can be superimposed on the cluster by combining multiple elemental substitutions at different sites. In addition, we successfully developed methods to synthesize alloy clusters with heterometal core. These findings are expected to lead to clear design guidelines for developing new functional nanomaterials.
RESUMO
BACKGROUND: Program directors are often perceived as strong and independent leaders within the academic medical environment. However, they are not as omnipotent as they initially appear. Indeed, PDs are beholden to a variety of different agents, including trainees (current residents, residency applicants, residency alumni), internal influencers (departmental faculty, hospital administration, institutional graduate medical education), and external influencers (the Accreditation Council for Graduate Medical Education (ACGME), medical education community, and society-at-large). Altogether, these agents form a complex ecosystem whose dynamics and relationships shape the effectiveness of program directors. MAIN BODY: This perspective uses management theory to examine the characteristics of effective PD leadership. We underline the importance of authority, accessibility, adaptability, authenticity, accountability, and autonomy as core features of successful program directors. Additionally, we review how program directors can use the six power bases (legitimacy, referent, informational, expert, reward, and coercive) to achieve positive and constructive change within the complexity of the academic medical ecosystem. Lastly, we describe how local and national institutions can better structure power relationships within the ecosystem so that PD leadership can be most effective. CONCLUSION: Keen leadership skills are required by program directors to face a variety of challenges within their educational environments. Understanding power structures and relationships may aid program directors to exercise leadership judiciously towards fulfilling the educational missions of their departments.
Assuntos
Pessoal Administrativo , Educação Médica , Relações Interprofissionais , Liderança , Humanos , Autonomia Profissional , Avaliação de Programas e Projetos de Saúde , Responsabilidade SocialRESUMO
The addition of phenyllithium to a polycyclic quinone, 9,11,12,21,22,24-hexaphenyltetrabenzo[a,c,n,p]hexacene-10,23-dione (10), followed by SnCl2 -mediated reduction of the diol intermediate, yielded 9,10,11,12,21,22,23,24-octaphenyltetrabenzo-[a,c,n,p]hexacene (4). Crystallographic analysis of hexacene 4 showed it to possess a longitudinal twist of 184°, which was in good agreement with AM1 calculations. In addition to being the most twisted acene synthesized to this point, compound 4 contains within its substructure the most twisted naphthalene, anthracene, tetracene, and pentacene moieties described.
RESUMO
Seven longitudinally twisted acenes (an anthracene, two tetracenes, three pentacenes, and a hexacene) have been synthesized by the addition of aryllithium reagents to the appropriate quinone precursors, followed by SnCl2 -mediated reduction of their diol intermediates, and several of these acenes have been crystallographically characterized. The new syntheses of the three previously reported twisted acenes, decaphenylanthracene (1), 9,10,11,20,21,22-hexaphenyltetrabenzo[a,c,l,n]pentacene (2), and 9,10,11,12,13,14,15,16-octaphenyldibenzo[a,c]tetracene (14), resulted in a reduction of the number of synthetic steps. As a consequence their overall yields were increased by factors of 50-, 24-, and 66-fold, respectively. All of the twisted acene syntheses reported here are suitable for the synthesis of at least gram quantities of these remarkable hydrocarbon materials.
RESUMO
OBJECTIVE: We assessed the clinical features and outcomes based on therapeutic options adopted during hospital stay for adult patients with macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis (MAS/sHLH). METHODS: We conducted a retrospective chart review of all adult patients (age ≥ 18 years) diagnosed with MAS/sHLH at our center between 2010 and 2015. Inclusion criteria for patients were diagnosis of MAS/sHLH during admission and patients meeting at least 5 out of 8 of Henter's criteria or at least 4 out of 6 of the criteria that were tested. RESULTS: Nineteen adult patients with MAS/sHLH met the inclusion criteria from January 2010 to October 2015 (median age 48 years; female 68.4%). Treatment had been personalized, depending on the clinical presentation and course of disease. Majority of the patients received anakinra, cyclosporine, intravenous immunoglobulins (IVIG), and steroids. Fourteen (74%) patients survived, with clinical improvement by the time of discharge. After excluding the three patients with underlying leukemia/lymphoma who opted for palliative care and subsequently died, the survival rate was 88%. CONCLUSION: A modified diagnostic and treatment protocol for adult patients with MAS/sHLH that incorporated graded introduction of medications based on clinical presentation and cytokine profile resulted in the best adult survival rate reported in literature.
Assuntos
Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Ciclosporina/uso terapêutico , Citocinas/imunologia , Feminino , Humanos , Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Linfo-Histiocitose Hemofagocítica/imunologia , Síndrome de Ativação Macrofágica/imunologia , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Esteroides/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
It is now possible to accurately synthesize thiolate (SR)-protected gold clusters (Aun (SR)m ) with various chemical compositions with atomic precision. The geometric structure, electronic structure, physical properties, and functions of these clusters are well known. In contrast, the ligand or metal atom exchange reactions between these clusters and other substances have not been studied extensively until recently, even though these phenomena were observed during early studies. Understanding the mechanisms of these reactions could allow desired functional metal clusters to be produced via exchange reactions. Therefore, we have studied the exchange reactions between Aun (SR)m and analogous clusters and other substances for the past four years. The results have enabled us to gain deep understanding of ligand exchange with respect to preferential exchange sites, acceleration means, effect on electronic structure, and intercluster exchange. We have also synthesized several new metal clusters using ligand and metal exchange reactions. In this account, we summarize our research on ligand and metal exchange reactions.
RESUMO
B cells play an important role in systemic lupus erythematosus by acting not only as precursors of autoantibody-producing cells but also as antigen-presenting, cytokine-secreting, and regulatory cells. Unopposed activation of B cells through their B-cell receptor for antigen, as seen in B cells lacking Lyn kinase, results in systemic autoimmunity. The B-cell activating factor of the TNF family (BAFF), nucleic acid-sensing Toll-like receptors (TLRs), and type I interferon can affect B-cell survival and decrease their threshold for activation. Herein we discuss both direct and indirect strategies aimed at targeting B cells in patients with lupus by blocking BAFF, type I interferon, or TLR7 to TLR9. Although BAFF-depleting therapy with belimumab achieved approval for lupus, other BAFF inhibitors were much less beneficial in clinical trials. Inhibitors of the B-cell receptor for antigen signaling and antibodies against type I interferon are in the pipeline. The TLR7 to TLR9 blocker hydroxychloroquine has been in use in patients with lupus for more than 50 years, but oligonucleotide-based inhibitors of TLR7 to TLR9, despite showing promise in animal models of lupus, have not reached the primary end point in a recent phase 1 trial. These data point toward possible redundancies in B-cell signaling/survival pathways, which must be better understood before future clinical trials are executed.