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1.
AEM Educ Train ; 8(4): e11018, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39220774

RESUMEN

Background: Use of ultrasound (US) for procedural needle guidance can improve success rates, safety, and accuracy. Often, training is performed on task trainers, which can be prohibitively expensive. Determining undesired needle placement is difficult when the needle is poorly visualized with US. Currently available simulation phantoms cannot provide real-time feedback on the location of needle placement. Objectives: The primary objective was to develop and determine feasibility of a low-cost simulation phantom with an internal circuit and LED light system to determine when a needle contacts internal structures. We also aimed to determine whether its use was associated with increased comfort level. Methods: Emergency medicine (EM) residents (PGY-1 to PGY-3) performed in-plane and out-of-plane US needle guidance using homemade phantoms. Comfort levels were assessed by pre- and post intervention survey. Outcomes were measured on Likert scale (minimum = 1, maximum = 5). The primary outcome was change in confidence markers before and after the simulation task. Secondary outcomes were survey results of comparisons of these models to prior training experiences on simulators and humans. Results: All EM residents (30) in our program were invited to participate. Twenty participants enrolled and completed the study. In the primary outcome, median comfort with out-of-plane and in-plane guidance increased after using the model but was more pronounced for out-of-plane guidance. On a posttest survey, residents rated the models overall very similar to prior experience on simulators (median 5/5 [IQR 4.0-5.0]) and moderately similar to humans (median 3/5 [IQR 3.0-4.0]). Conclusions: We created a low-cost ballistic gelatin phantom with an internal electric needle guidance system. Use of the phantom for training was associated with increased learner comfort with the procedure. Learners rated the characteristics of the phantom as similar to higher-cost commercial equipment and humans.

2.
J Rheumatol ; 51(Suppl 2): 70-73, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39089826

RESUMEN

Two presentations at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting focused on unintended consequences of immunomodulatory therapy for psoriasis (PsO). Dr. Elizabeth Wallace presented on unintended consequences of tumor necrosis factor inhibitors for treating PsO and other inflammatory disorders. These consequences include paradoxical PsO, which is defined as unexpected new PsO cases or worsening PsO symptoms seemingly induced by treatment. Dr. Bruce Kirkham focused on unintended consequences of dupilumab treatment, which can include a musculoskeletal syndrome similar to psoriatic arthritis.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Enfermedades Musculoesqueléticas , Psoriasis , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Enfermedades Musculoesqueléticas/inducido químicamente , Enfermedades Musculoesqueléticas/inmunología , Artritis Psoriásica/tratamiento farmacológico , Inmunoterapia/efectos adversos , Inmunoterapia/métodos
3.
J Rheumatol ; 51(Suppl 2): 43-50, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39009389

RESUMEN

Psoriasis and psoriatic arthritis are associated with an increased risk of mental health conditions such as depression and anxiety. People with psoriatic disease (PsD) are also more likely to die by suicide than those without. Mood disorders affect people with PsD in a multitude of ways, such as in effectiveness of care, response to treatment, remission rates, and quality of life. Although the links between PsD and mental health conditions have not been fully elucidated, this review will highlight recent studies investigating shared biologic mechanisms between depression and PsD. Since mental health disorders can be assessed and treated effectively, dermatologists and rheumatologists should be aware of the mental health burden in individuals with PsD to accomplish the following: (1) educate their patients with PsD about this association, (2) screen for mental health conditions on an ongoing basis in their clinical practice, (3) refer their patients with PsD to a mental health professional when needed, and (4) ensure selection of a safe PsD treatment in the setting of comorbid mental health disease. Finally, important treatment considerations for individuals with PsD and depression are reviewed. This topic was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting.


Asunto(s)
Artritis Psoriásica , Depresión , Psoriasis , Calidad de Vida , Humanos , Artritis Psoriásica/psicología , Artritis Psoriásica/complicaciones , Psoriasis/psicología , Psoriasis/complicaciones , Depresión/psicología , Comorbilidad
4.
medRxiv ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38946973

RESUMEN

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.

5.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38928454

RESUMEN

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Matriz Extracelular , Proteómica , Microambiente Tumoral , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Proteómica/métodos , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Proteoma/metabolismo , Proteoma/análisis , Invasividad Neoplásica , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Persona de Mediana Edad
6.
J Am Acad Dermatol ; 91(2): 251.e1-251.e11, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38499181

RESUMEN

BACKGROUND: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication. OBJECTIVE: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery. METHODS: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery. RESULTS: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. CONCLUSION: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib.


Asunto(s)
Artritis Psoriásica , Metotrexato , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Metotrexato/uso terapéutico , Atención Perioperativa/métodos , Talidomida/uso terapéutico , Talidomida/análogos & derivados , Talidomida/efectos adversos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/epidemiología , Piperidinas/uso terapéutico , Ciclosporina/uso terapéutico , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Inhibidores de Fosfodiesterasa 4/efectos adversos , Ustekinumab/uso terapéutico , Ustekinumab/efectos adversos , Agentes Inmunomoduladores/uso terapéutico , Abatacept/uso terapéutico , Abatacept/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos
7.
Pediatr Neurol ; 153: 103-112, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38367484

RESUMEN

BACKGROUND: Although millions of children sustain concussions each year, a rapid and objective test for concussion has remained elusive. The aim of this study was to investigate quantitative pupillometry in pediatric patients in the acute, postinjury setting. METHODS: This was a prospective case-control study of concussed patients presenting to the emergency department within 72 hours of injury. Pupillary measurements were gathered using NeurOptics' PLR 3000; evaluation included a symptom checklist and neurocognitive assessment. Data were analyzed using descriptive statistics and regression models. RESULTS: A total of 126 participants were enrolled. One significant difference in pupillometry between concussed and control participants was found: left minimum pupil diameter in 12- to 18 year-olds (P = 0.02). Models demonstrating odds of a concussion revealed significant associations for time to 75% recovery (T75) of the left pupil in five- to 11-year-olds and average dilation velocity of the left pupil in 12- to 18-year-olds (P = 0.03 and 0.02 respectively). Models predicting symptom improvement showed one significant association: percent change of the right pupil in five-to-11-year-olds (P = 0.02). Models predicting neurocognitive improvement in 12- to 18-year-olds demonstrated significant association in T75 in the left pupil for visual memory, visual motor processing speed, and reaction time (P = 0.002, P = 0.04, P = 0.04). CONCLUSIONS: The limited statistically significant associations found in this study suggest that pupillometry may not be useful in pediatrics in the acute postinjury setting for either the diagnosis of concussion or to stratify risk for prolonged recovery.


Asunto(s)
Traumatismos en Atletas , Conmoción Encefálica , Humanos , Niño , Estudios de Casos y Controles , Pruebas Neuropsicológicas , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico , Traumatismos en Atletas/diagnóstico , Percepción Visual
8.
J Am Acad Dermatol ; 90(6): 1170-1181, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38331098

RESUMEN

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.


Asunto(s)
Artritis Psoriásica , Productos Biológicos , Consenso , Técnica Delphi , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Productos Biológicos/administración & dosificación , Administración Oral , Vacunación/normas , Adulto , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2 , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico
9.
Nat Commun ; 15(1): 816, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280878

RESUMEN

Despite increased Atlantic hurricane risk, projected trends in hurricane frequency in the warming climate are still highly uncertain, mainly due to short instrumental record that limits our understanding of hurricane activity and its relationship to climate. Here we extend the record to the last millennium using two independent estimates: a reconstruction from sedimentary paleohurricane records and a statistical model of hurricane activity using sea surface temperatures (SSTs). We find statistically significant agreement between the two estimates and the late 20th century hurricane frequency is within the range seen over the past millennium. Numerical simulations using a hurricane-permitting climate model suggest that hurricane activity was likely driven by endogenous climate variability and linked to anomalous SSTs of warm Atlantic and cold Pacific. Volcanic eruptions can induce peaks in hurricane activity, but such peaks would likely be too weak to be detected in the proxy record due to large endogenous variability.

10.
Sci Rep ; 14(1): 489, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38177192

RESUMEN

N-glycosylation is an abundant post-translational modification of most cell-surface proteins. N-glycans play a crucial role in cellular functions like protein folding, protein localization, cell-cell signaling, and immune detection. As different tissue types display different N-glycan profiles, changes in N-glycan compositions occur in tissue-specific ways with development of disease, like cancer. However, no comparative atlas resource exists for documenting N-glycome alterations across various human tissue types, particularly comparing normal and cancerous tissues. In order to study a broad range of human tissue N-glycomes, N-glycan targeted MALDI imaging mass spectrometry was applied to custom formalin-fixed paraffin-embedded tissue microarrays. These encompassed fifteen human tissue types including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, and uterus. Each array contained both normal and tumor cores from the same pathology block, selected by a pathologist, allowing more in-depth comparisons of the N-glycome differences between tumor and normal and across tissue types. Using established MALDI-IMS workflows and existing N-glycan databases, the N-glycans present in each tissue core were spatially profiled and peak intensity data compiled for comparative analyses. Further structural information was determined for core fucosylation using endoglycosidase F3, and differentiation of sialic acid linkages through stabilization chemistry. Glycan structural differences across the tissue types were compared for oligomannose levels, branching complexity, presence of bisecting N-acetylglucosamine, fucosylation, and sialylation. Collectively, our research identified the N-glycans that were significantly increased and/or decreased in relative abundance in cancer for each tissue type. This study offers valuable information on a wide scale for both normal and cancerous tissues, serving as a reference for future studies and potential diagnostic applications of MALDI-IMS.


Asunto(s)
Procesamiento Proteico-Postraduccional , Sarcoma , Masculino , Femenino , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Glicosilación , Polisacáridos/metabolismo
11.
J Am Acad Dermatol ; 89(5): 974-983, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37495173

RESUMEN

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

12.
Surg Open Sci ; 14: 46-51, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37519328

RESUMEN

Purpose: Electric bicycles (e-bikes) achieve higher speeds than pedal bicycles, but few studies have investigated the impact on injury rates specific to the pediatric population. Utilizing the National Electronic Injury Surveillance System (NEISS), we compared rates of pediatric injury for e-bikes, bicycles, and gas-engine bicycles (mopeds) from 2011 to 2020. Methods: Descriptive and bivariate inferential analyses were performed upon NEISS estimates of e-bike, bicycle, and moped injuries in children aged 2-18 years. Analyses were stratified by patient age and helmet usage. The Mann-Kendall test of trends was used. Results: We identified 3945 e-bike, 23,389 moped, and 2.05 million bicycle injuries. Over time, the incidence of injury increased for e-bikes (Kendall's τ=0.73, p = 0.004), decreased for pedal bicycles (Kendall's τ= - 0.91, p = 0.0003), and did not change for mopeds (Kendall's τ = 0.06, p = 0.85). Males accounted for 82.5 % of e-bike injuries. The age group most commonly affected by e-bike injury (44.3 %) was 10-13 years old. The proportion of injuries requiring hospitalization was significantly higher for e-bikes (11.5 %), compared to moped and bicycle (7.0 and 4.8 %, respectively, p < 0.0001). In cases where helmet use or absence was reported, 97.3 % of e-bike riders were without a helmet at the time of injury, compared to 82.1 % of pedal bicycle riders and 87.2 % of moped riders. Conclusions: The rate of pediatric e-bike injuries increased over the study period. Compared to riders on pedal bicycles or mopeds, children on e-bikes had infrequent helmet use and increased rate of hospitalization. These findings suggest that attention to e-bike safety and increasing helmet usage are important to public health among the pediatric population. Level of evidence: IV.

13.
JAAD Int ; 12: 32-36, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37274387

RESUMEN

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit.

14.
Healthc (Amst) ; 11(2): 100690, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36996736

RESUMEN

This article describes the implementation of an equity-focused strategy to increase the uptake of COVID-19 vaccination among communities of color and in traditionally underserved geographic areas using mobile health clinics (MHCs). The MHC Vaccination Program was implemented through a large integrated healthcare system in North Carolina using a grassroots development and engagement strategy along with a robust model for data-informed decision support to prioritize vulnerable communities. Several valuable lessons from this work can replicated for future outreach initiatives and community-based programming: •Health systems can no longer operate under the assumption that community members will come to them, particularly those experiencing compounding social and economic challenges. The MHC model had to be a proactive outreach to community members, rather than a responsive delivery mechanism. •Barriers to access included financial, legal, and logistical challenges, in addition to mistrust among historically underserved and marginalized communities. •A MHC model can be adaptable and responsive to data-informed decision-making approaches for targeted service delivery. •A MHC model is not a one-dimensional solution to access, but part of a broader strategy to create diverse points of entry into the healthcare system that fall within the rhythm of life of community members.


Asunto(s)
COVID-19 , Telemedicina , Humanos , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Atención a la Salud , Telemedicina/métodos , Vacunación
16.
J Psoriasis Psoriatic Arthritis ; 8(1): 11-18, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39296952

RESUMEN

Background: Despite their impressive efficacy in phase 3 trials, biologic agents for psoriasis (PsO) may lose efficacy over time. The factors associated with loss of efficacy have yet to be fully elucidated. Objective: We aimed to identify factors associated with PsO patients using multiple biologics in comparison to patients who used 1 biologic. We also reviewed the literature comparing the survival of different biologic agents for PsO. Methods: We examined clinical data from 222 psoriasis patients at the University of California San Francisco, of whom 51 reported use of 3 or more biologics and of whom 171 reported use of only a single biologic agent at the time of enrollment into a research database from 2006-2020. This study was IRB-approved at UCSF (#10-02830) and all subjects provided written informed consent. We performed univariate and multivariate regression analysis to identify significant demographic features, clinical features, and co-morbidities associated with multi-biologic use. We performed a literature review of studies comparing psoriasis biologic survival at 1, 2, and 5 years and factors associated with single biologic failure. Results: In univariate analysis, duration of PsO, initial presentation of PsO on the gluteal cleft, erythrodermic psoriasis, and acne were associated with using 3 or more biologics. In multivariate analysis, duration of PsO, erythrodermic psoriasis, and acne remained significant. Our review of biologic survival revealed differences according to biologic class. Conclusion: We identified novel factors associated with multi-biologic use in PsO. Further studies in this area are needed to achieve a precision medicine approach.

17.
JMIR Dermatol ; 5(3): e35379, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36187494

RESUMEN

Background: Clinical trials have led to the development of new and effective therapies for many dermatologic conditions. To our knowledge, there is no published study that has quantified and described the degree of involvement in clinical trials among academic dermatologists and their university affiliates. Objective: The purpose of this study was to characterize the involvement of academic dermatology departments in clinical trials research. Methods: An online survey was sent to 211 Veterans Affairs (VA)-employed dermatologists. It comprised 20 questions related to the number of clinical trials, support staff dedicated to clinical research, skin diseases studied, and the effect of the COVID-19 pandemic on conducting clinical research. Three rounds of survey invitations were sent over a 3-month period (March to May 2021). Data from all survey responses were reviewed for quantitative and descriptive analyses of the key outcome measures. Results: A total of 48 dermatologists completed the survey and provided their university affiliations and details of involvement in clinical trials research. Over half of participants (n=25, 58.1%) with a university affiliate reported that their affiliated dermatology department had a dedicated clinical trials unit. Basal cell carcinoma was the most frequently studied skin condition (n=9, 18.8%), followed by atopic dermatitis and psoriasis (n=4, 8.3% each); 66.7% of participants reported no current clinical trials participation. Of those conducting clinical trials, 87% (n=18) noted that COVID-19 was a barrier to conducting trials, with 52.2% (n=11) citing disrupted or decreased trials due to the pandemic. Conclusions: Although many dermatologists with university affiliations reported having a dedicated clinical trials unit at their institution, a majority of those surveyed reported not taking part in any active trials. Overall, the diseases investigated in academic clinical trials appear to follow national trends, though some of the top dermatological diseases are underrepresented in clinical trials research. A key limitation of our study was the low response rate (~23%) and that the survey responses from the sample of VA-based dermatologists may not be generalizable to all academic dermatology departments in the United States. The effect of the COVID-19 pandemic appeared to play a significant role in disrupting active trials.

18.
Curr Opin Pharmacol ; 67: 102292, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36228472

RESUMEN

Psoriasis and psoriatic arthritis are chronic inflammatory diseases affecting the skin and joints, respectively. Psoriasis and psoriatic arthritis are associated with a high comorbidity burden as well as negative impact on quality of life. Impact on health-related quality of life is optimized when both skin and joint manifestations are effectively treated. The identification of key cytokines involved in disease pathogenesis has led to the development of several therapeutic options for psoriatic disease. When selecting a therapy, it is important to consider disease severity, psoriasis disease subtypes or domains of psoriatic arthritis, comorbidities, patient preference for treatment, among other factors. This review summarizes current biologic and small molecule treatment options as well as emerging therapies for moderate-to-severe adult plaque psoriasis and psoriatic arthritis.


Asunto(s)
Artritis Psoriásica , Productos Biológicos , Psoriasis , Adulto , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Calidad de Vida , Psoriasis/tratamiento farmacológico , Comorbilidad , Productos Biológicos/uso terapéutico
19.
Nat Commun ; 13(1): 3016, 2022 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-35641523

RESUMEN

Double-strand breaks (DSBs) are one of the most toxic forms of DNA damage and represent a major source of genomic instability. Members of the bromodomain and extra-terminal (BET) protein family are characterized as epigenetic readers that regulate gene expression. However, evidence suggests that BET proteins also play a more direct role in DNA repair. Here, we establish a cell-free system using Xenopus egg extracts to elucidate the gene expression-independent functions of BET proteins in DSB repair. We identify the BET protein BRD4 as a critical regulator of homologous recombination and describe its role in stimulating DNA processing through interactions with the SWI/SNF chromatin remodeling complex and resection machinery. These results establish BRD4 as a multifunctional regulator of chromatin binding that links transcriptional activity and homology-directed repair.


Asunto(s)
Roturas del ADN de Doble Cadena , Proteínas Nucleares , ADN , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Reparación del ADN por Recombinación , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
20.
J Pediatr Surg ; 57(5): 908-914, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35101261

RESUMEN

PURPOSE: To describe the distribution of injuries attributed to inflatable bounce house devices in children 2-18 years old in the United States from 2000 to 2019. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to identify patients <18 years of age with injuries from activities classified as amusements (NEISS Code 1293 and 3219) during the period from 2000 to 2019. RESULTS: A weighted estimate of 159,569 injuries was obtained using NEISS statistical weights. Injury estimates and rate of estimated injury per year showed a continued linear increase from 2000-2019 (p<0.0001). Bounce house-related injuries were more common in males (53.9%) than in females (46.1%). The injuries reported most commonly were fracture (25.8%), muscle strain (25.7%), and contusion (14.5%). The factors associated with bounce house-related injury were compared between "younger" patients ≤6 years of age and "older" patients >6 years of age. In both age groups, the patient's residence was the most prevalent location of injury (≤6 yr, 95.6%; >6 yr, 97.2%), and the lower extremity was the most prevalent anatomic site of injury (≤6 yr, 34.6%, >6 yr 35.3%). Concussion was rare in both groups (≤6 yr, 1.6%; >6 yr, 2.9%); however, concussion was 86% more prevalent in those >6 years of age (p<0.0001). CONCLUSIONS: The frequency and rate of pediatric bounce house injuries has increased steadily since 2000. The most severe injuries occur disproportionately in children > 6 years old.


Asunto(s)
Conmoción Encefálica , Fracturas Óseas , Adolescente , Distribución por Edad , Niño , Preescolar , Servicio de Urgencia en Hospital , Femenino , Humanos , Extremidad Inferior , Masculino , Estados Unidos/epidemiología
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