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Biomedicines Feb 2021Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing... (Review)
Review
Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.
PubMed: 33572373
DOI: 10.3390/biomedicines9020171 -
The AAPS Journal Dec 2021Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant...
Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. Following debate at the American Association of Pharmaceutical Sciences National Biotechnology Conference, a group was formed to address these gaps. Over the last 3 years, 44 members from 29 organizations (including 5 members from Europe and 10 members from FDA) discussed gaps in understanding immunogenicity assay requirements and have developed harmonization tools for use by industry scientists to facilitate filings to health authorities. Herein, this team provides testing and reporting strategies and tools for the following assessments: (1) pre-study validation cut point; (2) in-study cut points, including procedures for applying cut points to mixed populations; (3) system suitability control criteria for in-study plate acceptance; (4) assay sensitivity, including the selection of an appropriate low positive control; (5) specificity, including drug and target tolerance; (6) sample stability that reflects sample storage and handling conditions; (7) assay selectivity to matrix components, including hemolytic, lipemic, and disease state matrices; (8) domain specificity for multi-domain therapeutics; (9) and minimum required dilution and extraction-based sample processing for titer reporting.
Topics: Antibodies; Biological Assay; Europe; United States
PubMed: 34853961
DOI: 10.1208/s12248-021-00649-y -
The New England Journal of Medicine Jul 2020Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019...
BACKGROUND
Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.
METHODS
We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms.
RESULTS
We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).
CONCLUSIONS
Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).
Topics: Adolescent; Betacoronavirus; COVID-19; Centers for Disease Control and Prevention, U.S.; Child; Coronavirus Infections; Critical Care; Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunomodulation; Inflammation; Length of Stay; Male; Mucocutaneous Lymph Node Syndrome; Pandemics; Pneumonia, Viral; Prospective Studies; Respiration, Artificial; Retrospective Studies; SARS-CoV-2; Systemic Inflammatory Response Syndrome; United States
PubMed: 32598831
DOI: 10.1056/NEJMoa2021680 -
Genetics in Medicine : Official Journal... Aug 2022Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all... (Review)
Review
Recent reviews have emphasized the need for a health equity agenda in genomics research. To ensure that genomic discoveries can lead to improved health outcomes for all segments of the population, a health equity agenda needs to go beyond research studies. Advances in genomics and precision medicine have led to an increasing number of evidence-based applications that can reduce morbidity and mortality for millions of people (tier 1). Studies have shown lower implementation rates for selected diseases with tier 1 applications (familial hypercholesterolemia, Lynch syndrome, hereditary breast and ovarian cancer) among racial and ethnic minority groups, rural communities, uninsured or underinsured people, and those with lower education and income. We make the case that a public health agenda is needed to address disparities in implementation of genomics and precision medicine. Public health actions can be centered on population-specific needs and outcomes assessment, policy and evidence development, and assurance of delivery of effective and ethical interventions. Crucial public health activities also include engaging communities, building coalitions, improving genetic health literacy, and building a diverse workforce. Without concerted public health action, further advances in genomics with potentially broad applications could lead to further widening of health disparities in the next decade.
Topics: Ethnicity; Genomics; Health Equity; Humans; Minority Groups; Precision Medicine; Public Health
PubMed: 35482015
DOI: 10.1016/j.gim.2022.04.009 -
The New England Journal of Medicine Feb 2022NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America.
METHODS
We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed.
RESULTS
Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose.
CONCLUSIONS
NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).
Topics: Adolescent; Adult; Aged; COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Vaccines; Humans; Incidence; Male; Mexico; Middle Aged; SARS-CoV-2; Single-Blind Method; United States; Vaccine Efficacy
PubMed: 34910859
DOI: 10.1056/NEJMoa2116185 -
JAMA Mar 2021Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. (Comparative Study)
Comparative Study
IMPORTANCE
Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes.
OBJECTIVE
To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19).
SETTING, DESIGN, AND PARTICIPANTS
Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement.
EXPOSURE
SARS-CoV-2.
MAIN OUTCOMES AND MEASURES
Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19.
RESULTS
Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days.
CONCLUSIONS AND RELEVANCE
This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
Topics: Adolescent; Age Factors; Biomarkers; COVID-19; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Intensive Care Units, Pediatric; Male; Patient Acuity; Regression Analysis; Stroke Volume; Systemic Inflammatory Response Syndrome; United States; Young Adult
PubMed: 33625505
DOI: 10.1001/jama.2021.2091 -
The Journal of Clinical and Aesthetic... Feb 2018Within the field of dermatology, advances in the use of light emitting diodes (LEDs) have led to their clinical application for a variety of medical and cosmetic uses.... (Review)
Review
Within the field of dermatology, advances in the use of light emitting diodes (LEDs) have led to their clinical application for a variety of medical and cosmetic uses. Of note, one phototherapy device has demonstrated beneficial effects over a range of clinical applications (Omnilux™; GlobalMed Technologies, Glen Ellen, California). The study included a literature review of published studies. Using LEDs with frequencies of 415nm (blue), 633nm (red), and 830nm (infrared), this device has demonstrated significant results for the treatment of medical conditions, including mild-to-moderate acne vulgaris, wound healing, psoriasis, squamous cell carcinoma in situ (Bowen's disease), basal cell carcinoma, actinic keratosis, and cosmetic applications. Although photodynamic therapy with the photosensitizer 5-aminolevulinic acid might cause stinging and burning, phototherapy is free of adverse events. We determined that phototherapy using LEDs is beneficial for a range of medical and aesthetic conditions encountered in the dermatology practice. This treatment displays an excellent safety profile.
PubMed: 29552272
DOI: No ID Found -
Indian Dermatology Online Journal 2022Bowen's disease (BD) is an in-situ squamous cell carcinoma of epidermis. The etiology of BD is multifactorial with high incidence among Caucasians. BD is common in... (Review)
Review
Bowen's disease (BD) is an in-situ squamous cell carcinoma of epidermis. The etiology of BD is multifactorial with high incidence among Caucasians. BD is common in photo-exposed areas of skin, but other sites can also be involved. Lesions are usually solitary. The morphology of BD differs based on age of the lesion, site of origin, and the degree of keratinization. BD is considered as the "lull before the storm," which precedes an overt squamous cell carcinoma. Histopathology is the gold standard diagnostic modality to confirm the diagnosis. Immunohistochemistry, dermoscopy, and reflectance confocal microscopy are the adjuvant modalities used in the diagnosis of BD. The treatment depends on various factors like site, size, immune status, patient's age, esthetic outcome, etc. The available therapeutic modalities include topical chemotherapy, surgical modalities, light-based modalities, and destructive therapies. It requires a combined effort of dermatologist, oncosurgeon, and plastic surgeon to plan and execute the management in various presentations of BD.
PubMed: 35287414
DOI: 10.4103/idoj.idoj_257_21