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When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort. Consequently, little is known about how each component of reproductive allocation affects a male's future performance. Here, we ran an experiment using a novel technique to distinguish the life history costs of mating effort and ejaculation for mosquitofish (Gambusia holbrooki). We compared manipulated males (mate without ejaculation), control males (mate and ejaculate), and naïve males (neither mate nor ejaculate) continuously housed with a female and 2 rival males. We assessed their growth, somatic maintenance, mating and fighting behavior, and sperm traits after 8 and 16 weeks. Past mating effort significantly lowered a male's future mating effort and growth, but not his sperm production, while past sperm release significantly lowered a male's future ejaculate quantity, but not his mating effort. Immune response was the only trait impacted by both past mating effort and past ejaculation. These findings challenge the assumption that male reproductive allocation draws from a common pool of resources to generate similar life history costs later in life. Instead, we provide clear evidence that allocation into traits under pre- and postcopulatory sexual selection have different trait-specific effects on subsequent male reproductive performance.
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Ejaculação , Reprodução , Comportamento Sexual Animal , Masculino , Animais , Ejaculação/fisiologia , Feminino , Comportamento Sexual Animal/fisiologia , Reprodução/fisiologia , Preferência de Acasalamento Animal/fisiologia , Espermatozoides/fisiologia , Seleção SexualRESUMO
Histone acetylation is a key component in the consolidation of long-term fear memories. Histone acetylation is fueled by acetyl-coenzyme A (acetyl-CoA), and recently, nuclear-localized metabolic enzymes that produce this metabolite have emerged as direct and local regulators of chromatin. In particular, acetyl-CoA synthetase 2 (ACSS2) mediates histone acetylation in the mouse hippocampus. However, whether ACSS2 regulates long-term fear memory remains to be determined. Here, we show that Acss2 knockout is well tolerated in mice, yet the Acss2-null mouse exhibits reduced acquisition of long-term fear memory. Loss of Acss2 leads to reductions in both histone acetylation and expression of critical learning and memory-related genes in the dorsal hippocampus, specifically following fear conditioning. Furthermore, systemic administration of blood-brain barrier-permeable Acss2 inhibitors during the consolidation window reduces fear-memory formation in mice and rats and reduces anxiety in a predator-scent stress paradigm. Our findings suggest that nuclear acetyl-CoA metabolism via ACSS2 plays a critical, previously unappreciated, role in the formation of fear memories.
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Acetato-CoA Ligase , Acetilcoenzima A , Condicionamento Clássico , Medo , Histonas , Consolidação da Memória , Acetato-CoA Ligase/genética , Acetato-CoA Ligase/metabolismo , Acetilcoenzima A/metabolismo , Acetilação , Animais , Condicionamento Clássico/fisiologia , Medo/fisiologia , Hipocampo/enzimologia , Histonas/metabolismo , Camundongos , Camundongos Knockout , RatosRESUMO
BACKGROUND: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple chronic rhinosinusitis with nasal polyps (CRSwNP) outcomes with dupilumab. OBJECTIVE: To gain a better understanding of dupilumab response dynamics over 52 weeks. METHODS: Post hoc analysis using data from the SINUS-52 (NCT02898454) intention-to-treat population, of patients with severe CRSwNP who received dupilumab 300 mg once every 2 weeks (q2w) or placebo. Response, defined as an improvement from baseline of ≥ 1 point for Nasal Polyp Score (NPS), nasal congestion (NC), and loss of smell (LoS), and ≥ 8.9 points for 22-item Sino-Nasal Outcome Test (SNOT-22), was assessed for rapidity, maintenance, and durability. RESULTS: 303 patients (dupilumab, n = 150; placebo, n = 153) were included. For each outcome measure, a greater proportion of patients achieved first response by Week 16 (rapidity) with dupilumab vs placebo: NPS, 75.3% vs 39.2%; NC, 60.0% vs 24.2%; LoS, 60.7% vs 15.7%; and SNOT-22, 83.3% vs 66.0%. Among dupilumab patients with a response by Week 16, more than 80% maintained response at Week 52 (maintenance). Over 52 weeks, greater proportions of dupilumab patients were responders at ≥ 80% of time points: NPS, 46.7% vs 2.6%; NC, 46.7% vs 9.2%; LoS, 47.3% vs 3.9%; and SNOT-22, 62.0% vs 21.6% (durability). CONCLUSION: Most CRSwNP patients achieve clinically meaningful responses to dupilumab by Week 16, and most of these patients had maintenance and durability of response with continued treatment over time.
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BACKGROUND: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined. OBJECTIVE: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls. METHODS: Flow cytometry was used to measure B-cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate-to-severe AD and age-matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11-color flow cytometry panel were used to determine frequencies of circulating B-cell subsets. Serum total and allergen-specific IgE (sIgEs) levels were measured using ImmunoCAP®. RESULTS: Adolescents with AD had lower frequencies of major B-cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL-17-producing T-cells and B-cell subsets, most significantly non-switched memory (NSM) B-cells (r = .41, p = .0005). AD severity positively correlated with a list of B-cell subsets (p < .05). IL-9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls. CONCLUSIONS: Multiple correlations between B-cells and T-cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B-cell signature during adolescence, with concurrent allergen sensitization and IL-9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march.
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Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.
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Pólipos Nasais , Rinossinusite , Humanos , Doença Crônica , Gerenciamento Clínico , Pólipos Nasais/terapia , Pólipos Nasais/diagnóstico , Rinossinusite/diagnóstico , Rinossinusite/terapiaRESUMO
AIMS: Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial. METHODS: Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators. RESULTS: Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL-1); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm-2 at baseline to 0 cells mm-2 at week 56 (P < .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil-derived neurotoxin was significantly reduced at weeks 24 and 56 (P < .001) and interleukin-17 at week 56 (P < .05) with benralizumab. CONCLUSION: Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP.
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Anticorpos Monoclonais Humanizados , Eosinófilos , Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Sinusite/tratamento farmacológico , Sinusite/complicações , Masculino , Doença Crônica , Feminino , Rinite/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Eosinófilos/efeitos dos fármacos , Método Duplo-Cego , Basófilos/efeitos dos fármacos , Idoso , Contagem de Leucócitos , Injeções Subcutâneas , Resultado do Tratamento , RinossinusiteRESUMO
BACKGROUND/OBJECTIVES: Second primary cancers (SPCs) are a leading cause of morbidity and mortality among cancer survivors. In this study, we aimed to characterize the incidence of SPCs among pediatric and young adult survivors of CM. METHODS: Using the Surveillance, Epidemiology, and End Results Program data spanning 2000-2018, we calculated standardized incidence ratios (SIR) to assess SPC risk in all pediatric (0-18 years) and young adult (19-29 years) patients with a first primary cancer diagnosis of CM. RESULTS: Of 7,169 total CM survivors, 632 (8.82%) developed a SPC, corresponding to a 5-fold increased risk (standardized incidence ratio [SIR] 4.98; 95% confidence interval [CI] 4.60-5.38) compared to the general population. There was a highly elevated risk for second primary melanoma across all age groups (SIR 32.5; 95% CI 29.7-35.6), constituting the majority of SPC diagnoses (N = 485). Infants diagnosed with CM before 1 year of age had the highest risk for any SPC (SIR 164; 95% CI 19.8-592) and young adults diagnosed at 25-29 years had the lowest risk (SIR 4.64; 95% CI 4.19-5.13). SPC incidence was highest within the first year of CM diagnosis (SIR 27.5; 95% CI 23.7-31.6) and progressively decreased with time. CONCLUSIONS: Variation exists in the incidence and type of SPC according to age among pediatric and young adult survivors of CM.
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Sobreviventes de Câncer , Melanoma , Segunda Neoplasia Primária , Lactente , Humanos , Adulto Jovem , Criança , Melanoma/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Sobreviventes , Risco , Incidência , Fatores de RiscoRESUMO
Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.
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Rinite Alérgica Perene , Rinite Alérgica , Rinite , Sinusite , Humanos , Alérgenos/uso terapêutico , Rinite/diagnóstico , Rinite/terapia , Rinite Alérgica/terapia , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica Perene/diagnóstico , Dessensibilização Imunológica , Testes de Provocação Nasal/métodosRESUMO
OBJECTIVE: To analyze published reports on the efficacy and safety of CSI in CRS and evaluate the clinical implications of current gaps in evidence. Corticosteroid irrigation (CSI) is commonly used for management of chronic rhinosinusitis (CRS) with nasal polyps; however, such use is not approved by the US Food and Drug Administration (FDA). DATA SOURCES: Publications were obtained through PubMed searches through January 2022. STUDY SELECTION: Searches were conducted using 2 terms: "chronic rhinosinusitis" or "nasal polyps" as the first term and "corticosteroid irrigation," "steroid nasal lavage," or "sinus rinse" as the second term. We reviewed relevant, peer-reviewed literature (19 original research [9 controlled, 10 uncontrolled trials], 7 reviews, and 1 meta-analysis) reporting safety and efficacy of CSI in patients with CRS. RESULTS: Studies were difficult to compare because they used a variety of solution volumes (60 mL to 125 mL per nostril), corticosteroid agents (budesonide, betamethasone, mometasone, or fluticasone), corticosteroid doses, preparation protocols (by compounding pharmacy or by patient), and administration (frequency, time of day, body positioning). It is difficult to determine which parameters might substantially influence clinical effects because studies were generally small, showed marginal benefits, and rarely assessed safety. To date, no studies evaluating CSI have shown statistically significant differences in a type-I error-controlled primary end point over any comparator, possibly owing to small sample sizes. CONCLUSION: Designing more robust clinical trials may help determine whether CSI is a valid treatment option. Until more evidence supporting CSI use exists, health care professionals should strongly consider choosing FDA-approved therapies for the treatment of CRS.
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Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/tratamento farmacológico , Corticosteroides/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Esteroides/uso terapêutico , Lavagem Nasal , Sinusite/tratamento farmacológico , Doença CrônicaRESUMO
BACKGROUND: Acne keloidalis nuchae (AKN) is an inflammatory disorder primarily seen in individuals of color, characterized by acneiform and keloidal lesions on the occipital scalp/nuchal region. More than 50% of patients with keloids are known to search their condition on the internet. We sought to determine the level of readability of patient education materials (PEM) available to patients. The term 'acne keloidalis nuchae' was searched and screened for the top 100 search results on the Google® search engine. For evaluation, 6 readability metrics (Flesch-Kincaid grade level, Gunning Fog index, Coleman-Liau index, SMOG index, automated readability, and Linsear Write Formula) were collected by entering text from each reference site into an automatic readability calculator for computation. Median readability scores of AKN PEMs ranged from 10.3th to 13.5th grade levels. Overall, readability median above the 8th-grade level were consistently seen across all 6 readability measures, with some median scores reaching university undergraduate levels. More readable educational tools are needed for acne keloidalis nuchae online. J Drugs Dermatol. 2023;21(2):195-196. doi:10.36849/JDD.7110.
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Acne Queloide , Letramento em Saúde , Humanos , Compreensão , Acne Queloide/terapia , Benchmarking , InternetRESUMO
PURPOSE: Assess if a rigid, image-guided balloon could be used effectively and safely in revision sinus surgery. MATERIALS AND METHODS: A prospective, non-randomized, single-arm, multicenter study to assess the safety and device performance of the NuVent™ EM Balloon Sinus Dilation System. Adults with CRS in need of revision sinus surgery were enrolled for balloon sinus dilation of a frontal, sphenoid, or maxillary sinus. The primary device performance endpoint was the ability of the device to (1) navigate to; and (2) dilate tissue in subjects with scarred, granulated, or previously surgically-altered tissue (revision). Safety outcomes included the assessment of any operative adverse events (AEs) directly attributable to the device or for which direct cause could not be determined. A follow-up endoscopy was conducted at 14 days post-treatment for assessment of any AEs. Performance outcomes included the surgeon's ability to reach the target sinus (es) and dilate the ostia. Endoscopic photos were captured for each treated sinus pre- and post-dilation. RESULTS: At 6 US clinical sites, 51 subjects were enrolled; 1 subject withdrew before treatment due to a cardiac complication from anesthesia. 121 sinuses were treated in 50 subjects. The device performed as expected in 100 % of the 121 treated sinuses, with investigators able to navigate to the treatment area and dilate the sinus ostium without difficulty. Ten AEs were seen in 9 subjects, with 0 related to the device. CONCLUSION: The targeted frontal, maxillary or sphenoid sinus ostium were safely dilated in every revision subject treated, with no AEs directly attributed to the device.
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Rinite , Adulto , Humanos , Dilatação , Estudos Prospectivos , Rinite/cirurgia , Seio Maxilar/cirurgia , Cateterismo , Endoscopia , Doença Crônica , Resultado do TratamentoRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) frequently remains uncontrolled despite maximal medical therapy and sinonasal surgery, presenting several unmet needs and challenges. Omalizumab previously demonstrated efficacy in CRSwNP in duplicate phase 3, randomized, placebo-controlled trials (POLYP 1, POLYP 2). OBJECTIVE: This open-label extension evaluated the continued efficacy, safety, and durability of response of omalizumab in adults with CRSwNP who completed POLYP 1 or 2. METHODS: After 24 weeks of omalizumab or placebo in POLYP 1 and 2, patients (n = 249) received open-label omalizumab plus background nasal mometasone therapy for 28 weeks and were subsequently followed for 24 weeks after omalizumab discontinuation. Efficacy end points assessed change from baseline for the coprimary end points, Nasal Polyp Score and Nasal Congestion Score, and the secondary end points of Sino-Nasal Outcome Test 22, Total Nasal Symptom Score and its components, and University of Pennsylvania Smell Identification Test scores. Safety objectives included incidence of adverse events and adverse events leading to omalizumab discontinuation. RESULTS: Patients who continued omalizumab experienced further improvements across coprimary end points and secondary end points through 52 weeks. Patients who switched from placebo to omalizumab experienced favorable responses across end points through week 52 that were similar to POLYP 1 and 2 at week 24. After omalizumab discontinuation, scores gradually worsened over the 24-week follow-up, but remained improved from pretreatment levels for both groups. The safety profile was similar to previous reports. CONCLUSIONS: The efficacy and safety profile from this study supports extended omalizumab treatment up to 1 year for CRSwNP with inadequate response to nasal corticosteroids.
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Pólipos Nasais , Omalizumab , Adulto , Doença Crônica , Humanos , Pólipos Nasais/tratamento farmacológico , Omalizumab/efeitos adversos , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: In the phase III SYNAPSE study, mepolizumab reduced nasal polyp (NP) size and nasal obstruction in chronic rhinosinusitis with NP. OBJECTIVE: We sought to assess the efficacy of mepolizumab in patients from SYNAPSE grouped by comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and baseline blood eosinophil count (BEC). METHODS: SYNAPSE, a randomized, double-blind, 52-week study (NCT03085797), included patients with severe bilateral chronic rhinosinusitis with NP eligible for surgery despite intranasal corticosteroid treatment. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care for 52 weeks. Coprimary end points were change in total endoscopic NP score (week 52) and nasal obstruction visual analog scale score (weeks 49-52). Subgroup analyses by comorbid asthma and AERD status, and post hoc by BEC, were exploratory. RESULTS: Analyses included 407 patients (289 with asthma; 108 with AERD; 371 and 278 with BEC counts ≥150 or ≥300 cells/µL, respectively). The proportion of patients with greater than or equal to 1-point improvement from baseline in NP score was higher with mepolizumab versus placebo across comorbid diseases (asthma: 52.9% vs 29.5%; AERD: 51.1% vs 20.6%) and baseline BEC subgroups (<150 cells/µL: 55.0% vs 31.3%; ≥150 cells/µL: 49.5% vs 28.1%; <300 cells/µL: 50.7% vs 29.0%; ≥300 cells/µL: 50.4% vs 28.1%). A similar trend was observed in patients without comorbid asthma or AERD. More patients had more than 3-point improvement in nasal obstruction VAS score with mepolizumab versus placebo across comorbid subgroups. CONCLUSIONS: Mepolizumab reduced polyp size and nasal obstruction in chronic rhinosinusitis with NP regardless of the presence of comorbid asthma or AERD.
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Asma Induzida por Aspirina , Asma , Obstrução Nasal , Pólipos Nasais , Sinusite , Anticorpos Monoclonais Humanizados , Asma/tratamento farmacológico , Doença Crônica , Comorbidade , Eosinófilos , Humanos , Obstrução Nasal/tratamento farmacológico , Pólipos Nasais/tratamento farmacológico , Sinusite/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Eosinophilic inflammation has been implicated in the pathogenesis, severity, and treatment responsiveness of chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We sought to assess the efficacy and safety of benralizumab-mediated eosinophil depletion for treating CRSwNP. METHODS: The phase 3 OSTRO study enrolled patients with severe CRSwNP who were symptomatic despite treatment with intranasal corticosteroids and who had a history of systemic corticosteroid (SCS) use and/or surgery for nasal polyps (NP). Patients were randomized 1:1 to treatment with benralizumab 30 mg or placebo every 4 weeks for the first 3 doses and every 8 weeks thereafter. Coprimary end points were change from baseline to week 40 in NP score (NPS) and patient-reported mean nasal blockage score reported once every 2 weeks. RESULTS: The study population comprised 413 randomized patients (207 in the benralizumab group and 206 in the placebo group). Benralizumab significantly improved NPS and nasal blockage score compared to placebo at week 40 (P ≤ .005). Improvements in Sinonasal Outcome Test 22 score at week 40, time to first NP surgery and/or SCS use for NP, and time to first NP surgery were not statistically significant between treatment groups. Nominal significance was obtained for improvement in difficulty in sense of smell score at week 40 (P = .003). Subgroup analyses suggested influences of comorbid asthma, number of NP surgeries, sex, body mass index, and baseline blood eosinophil count on treatment effects. Benralizumab was safe and well tolerated. CONCLUSION: Benralizumab, when added to standard-of-care therapy, reduced NPS, decreased nasal blockage, and reduced difficulty with sense of smell compared to placebo in patients with CRSwNP. TRIAL REGISTRATION: ClinicalTrials.gov NCT03401229.
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Obstrução Nasal , Pólipos Nasais , Rinite , Sinusite , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença Crônica , Humanos , Obstrução Nasal/induzido quimicamente , Obstrução Nasal/tratamento farmacológico , Pólipos Nasais/induzido quimicamente , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Rinite/induzido quimicamente , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/induzido quimicamente , Sinusite/complicações , Sinusite/tratamento farmacológicoRESUMO
Background: The COVID-19 pandemic required a rapid expansion of teledermatology services. Objective: Analyze demographic shifts in a pediatric dermatology practice session with children of color. Methods: A retrospective chart review of pediatric dermatology patients seen in the 4 practice weeks preceding the New York COVID-19 lockdown and comparable teledermatology visits during the COVID-19 pandemic lockdown. Demographic differences (e.g., race, age, gender, and household income) were analyzed. Results: A greater proportion of patients seen were White during lockdown (59.7%), compared with pre-lockdown (43.6%), with a reduction in Asian patients seen in lockdown (6.0%) compared with pre-lockdown (24.5%). A lower proportion of no-show patients (4.3%, 3/70 scheduled) were noted in lockdown compared with pre-lockdown (16%, 18/112). Preferred provider organizations (PPO) and higher-income zip codes were more common for children seen during lockdown. Limitations: The sample addresses a limited New York pediatric dermatology practice during a short time period. Conclusions: White patients and patients with PPO were more likely to access telehealth, supporting disparity in teledermatology services. These results demonstrate reduced health care access for lower-income and Asian children during the COVID-19 pandemic lockdown.
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COVID-19 , Dermatologia , Telemedicina , Criança , Humanos , Dermatologia/métodos , COVID-19/epidemiologia , Estudos Retrospectivos , Pandemias , Controle de Doenças Transmissíveis , Telemedicina/métodosRESUMO
ABSTRACT: Radiotherapy (RT) is a modality for cancer management that frequently causes critical injury to tissues adjacent to the targeted cancer site. Acute radiation dermatitis (RD) is one of the most common adverse effects of RT and may lead to secondary infection, disfigurement, and discontinuation of therapy. The authors report the efficacy of a multidisciplinary collaboration between radiation oncology, dermatology, and wound care teams in the management of severe, acute RD. This case report describes the use of noncontact, low-frequency ultrasound (NCLFU)-assisted saline wash therapy leading to accelerated healing of severe RD in an older man treated with RT for scalp squamous cell carcinoma. Although NCLFU-assisted saline wash therapy provides gentle debridement of wound surfaces and has demonstrated efficacy in the management of chronic wounds, the potential role for NCLFU therapy in RD management has not yet been explored.
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Radiodermite , Terapia por Ultrassom , Masculino , Humanos , Cicatrização , Radiodermite/etiologia , Radiodermite/terapia , DesbridamentoRESUMO
Research in dermatology education highlights the lack of skin of color (SOC) instruction for medical students, leading to concerning healthcare outcomes. Because of the already limited opportunity for students to have dedicated teaching in pathophysiology, management, and treatment of dermatologic diseases in medical school, we developed an educational module that addresses these gaps. We created a one-hour virtual lecture for medical students focused on common skin diseases tested on the United States Medical Licensing Examination with visual images across all skin types. A questionnaire was administered before and after the educational module to assess outcomes comparing disease identification in lighter (Fitzpatrick scale I-III) versus darker (Fitzpatrick scale IV-VI) skin tones and to determine medical school student attitudes. An analysis of 43 examination scores before, and after attending the educational module determined rosacea, psoriasis, and basal cell carcinoma to be conditions in SOC patients that demonstrated the most significant improvement (47.3%, 54.9%, and 30.8%, respectively). Our results also highlighted worse performance outcomes for diseases in SOC in the pre-examination questionnaire. Thus, our study indicates that a concise education module focused on disease presentations inclusive of all skin types may efficiently increase students' ability to identify diseases commonly misdiagnosed in the clinical setting.
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Dermatologia , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Estados Unidos , Dermatologia/educação , Pigmentação da Pele , Educação de Graduação em Medicina/métodos , EscolaridadeRESUMO
Psoriasis increases the risk of cardiovascular disease (CVD). Biomarkers for cardiovascular (CV) risk stratification in psoriasis are lacking, and the effects of psoriasis biologics on CV risk reduction remain unclear. The goal of this study was to identify biomarkers of CV risk in psoriasis blood that are reduced by ustekinumab. We quantified 276 inflammatory and CV-related serum proteins with Olink's multiplex assay in 10 psoriasis patients (vs. 18 healthy controls) and after 12 weeks of ustekinumab treatment. For each protein down-regulated after treatment, the literature was reviewed for studies assessing the protein's association with CVD. Data were collected from each study to calculate CV risk thresholds for each protein, which were compared with protein levels in psoriasis patients before and after treatment. Our results showed that 43 out of 276 proteins were down-regulated after treatment, 25 of which were initially up-regulated at baseline (vs. controls, all p-values ≤0.1). 8 down-regulated proteins were initially elevated above thresholds associated with enhanced CV risk in the literature (myeloperoxidase, C-X-C motif chemokine 10, E-selectin, interleukin-6, cystatin B, von Willebrand factor, tumor necrosis factor receptor 1 and N-terminal prohormone brain natriuretic peptide). Treatment lowered these proteins to below their risk thresholds, except for IL-6, which was lowered but remained at its risk threshold despite successful psoriasis skin treatment. In summary, 12 weeks of ustekinumab treatment reduced serum proteins present at levels associated with CV risk in psoriasis patients. Further studies can evaluate these proteins as potential ustekinumab-modulated biomarkers of CV risk in psoriasis and the impact of ustekinumab on CV risk reduction.
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Doenças Cardiovasculares , Psoríase , Biomarcadores , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Interleucina-6 , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/patologia , Fatores de Risco , Índice de Gravidade de Doença , Ustekinumab/uso terapêuticoRESUMO
Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil-reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin-5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add-on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real-world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI-A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.
Assuntos
Antiasmáticos , Asma , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Eosinofilia Pulmonar , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados , Síndrome de Churg-Strauss/tratamento farmacológico , Eosinófilos , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Eosinofilia Pulmonar/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: About one-tenth of patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, is an approved add-on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID-ERD. METHODS: Data were pooled from the phase 3 SINUS-24 and SINUS-52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment-subgroup interactions were assessed for patients with and without NSAID-ERD. RESULTS: Of 724 patients, 204 (28.2%) had a diagnosis of NSAID-ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund-Mackay computed tomography, 22-item Sinonasal Outcome Test (SNOT-22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six-item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID-ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID-ERD for NC (p = .0044), SNOT-22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123). CONCLUSIONS: In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient-reported symptoms to a greater extent in the presence of comorbid NSAID-ERD than without. Dupilumab was well tolerated in patients with/without NSAID-ERD.