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International Journal of... 2024TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of...
INTRODUCTION
TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of JAK/STAT pathway, but it is currently unclear whether their combination will enhance the effect on psoriasis. In this study, we used imiquimod (IMQ)-induced psoriasis mouse model to investigate the therapeutic effects of the combined administration of deucravacitinib (TYK2 inhibitor) and shikonin.
METHODS
Aldara cream containing 5% IMQ was used to topically treat the dorsal skin of each mouse for a total of six consecutive days to induce psoriasis. The psoriasis area and severity index (PASI) scores were recorded every day. On the 7 day, skin tissues were taken for histopathological examination and the content of cytokines in skin were evaluated. The frequency of immune cells in peripheral blood, spleen and skin were detected through flow cytometry.
RESULTS
Compared to the vehicle control group, the psoriasis symptoms and immune disorder improved significantly in the combination therapy group and deucravacitinib treatment group on the 7th day, and the expressions of p-STAT3 and Ki67 in skin were reduced as well. Moreover, the combined treatment of deucravacitinib and shikonin for psoriasis was superior to the monotherapy group, especially in inhibiting abnormal capillaries proliferation, reducing immune cells infiltration and decreasing the concentration of IL-12p70 in skin.
CONCLUSION
The combination of deucravacitinib and shikonin is a promising clinical application.
Topics: Animals; Psoriasis; Imiquimod; Naphthoquinones; Drug Therapy, Combination; Mice; Skin; Disease Models, Animal; Cytokines; Mice, Inbred BALB C; Male; Female; Benzimidazoles; Quinolones
PubMed: 38876119
DOI: 10.1177/03946320241260262 -
Frontiers in Medicine 2024The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy.
MATERIALS AND METHODS
This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis.
RESULTS
The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254-0.973, = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (T) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803], = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0-0.531], = 0.011).
CONCLUSION
Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.
PubMed: 38873214
DOI: 10.3389/fmed.2024.1417358 -
JAAD International Sep 2024Nail psoriasis remains a challenging condition with limited satisfaction from current treatments. An increasing number of neuropeptides were reported in psoriatic tissue.
BACKGROUND
Nail psoriasis remains a challenging condition with limited satisfaction from current treatments. An increasing number of neuropeptides were reported in psoriatic tissue.
OBJECTIVE
To compare the efficacy of botulinum toxin A (BoNT-A) injection, triamcinolone acetonide (TA) injection, topical combination of vitamin D/steroid (VitD/steroid) and placebo in improving nail psoriasis.
METHODS
A 24-week randomized intraindividual comparative-controlled study involved participants with at least 4 psoriatic fingernails, each with a total target nail psoriasis severity index (NAPSI) score of at least 3 points. Nails were randomly received different treatments; intralesional BoNT-A injection at baseline, intralesional TA at baseline and eighth week, daily topical VitD/steroid application for 16 weeks and placebo.
RESULTS
Evaluation of 64 psoriatic fingernails showed a 40% reduction in the total target NAPSI score at 24 weeks following BoNT-A injection ( = .001). BoNT-A significantly improved nail bed lesions more than TA and topical VitD/steroid ( = .038), with no reported serious adverse effects.
LIMITATIONS
Relatively small sample size; hand hygiene during the COVID-19 pandemic may interfere NAPSI score evaluation.
CONCLUSIONS
BoNT-A injection emerges as a promising and effective therapy for nail psoriasis, providing sustained efficacy lasting up to 6 months with a single injection.
PubMed: 38873171
DOI: 10.1016/j.jdin.2024.03.021 -
Cureus May 2024Background Acquired palmoplantar keratodermas (PPKs) pose diagnostic and therapeutic challenges due to their varied clinical presentations and overlapping features. This...
Background Acquired palmoplantar keratodermas (PPKs) pose diagnostic and therapeutic challenges due to their varied clinical presentations and overlapping features. This study aims to elucidate diagnostic criteria; assess correlations between clinical, dermoscopic, and histopathological features; and evaluate treatment outcomes for acquired PPKs, particularly palmoplantar psoriasis. Methods A prospective, cross-sectional study will be conducted at the Department of Dermatology, Venereology, and Leprosy, Acharya Vinoba Bhave Rural Hospital (AVBRH), Wardha, Maharashtra. Patients with acquired PPKs will undergo comprehensive clinical, dermoscopic, and histopathological evaluations. Treatment outcomes for palmoplantar psoriasis will be assessed following standard therapy. Statistical analysis will include descriptive statistics, diagnostic accuracy assessments, correlation analyses, and treatment outcome evaluations. Results The study is anticipated to establish reliable diagnostic criteria for acquired PPKs, identify correlations between features, and demonstrate the effectiveness of standard therapies for palmoplantar psoriasis. The findings are expected to inform evidence-based guidelines and protocols for diagnosing and managing acquired PPKs. Conclusion This study aims to advance the understanding and management of acquired PPKs by providing insights into diagnostic accuracy, correlations between features, and treatment outcomes. The study seeks to enhance patient care and outcomes for individuals affected by acquired PPKs by improving diagnostic precision and guiding therapeutic interventions.
PubMed: 38872653
DOI: 10.7759/cureus.60262 -
International Journal of Surgery Case... May 2024Psoriasis, a chronic inflammatory skin condition, affects 4 % of the population and is associated with various comorbidities, making it a public health concern.
INTRODUCTION
Psoriasis, a chronic inflammatory skin condition, affects 4 % of the population and is associated with various comorbidities, making it a public health concern.
CASE REPORT
We discuss the case of a 50-year-old man with severe erythrodermic psoriasis who presented with a ruptured saccular abdominal aortic aneurysm (AAA), requiring emergency surgery with good postoperative follow-up. shedding light on the link between psoriasis and cardiovascular complications.
DISCUSSION
Psoriasis severity correlates with cardiovascular risk and shares common development pathways with aortic aneurysms such as systemic and aortic inflammation, and arterial stiffness, emphasizing the importance of managing both skin symptoms and systemic inflammation to reduce vascular comorbidities. Psoriasis patients have a higher risk of AAA, warranting consideration for AAA screening. Controversies exist regarding corticosteroid therapy and choice of surgical intervention for AAA in psoriatic patients.
CONCLUSION
Psoriasis patients face an increased risk of AAA, highlighting the need for vigilant screening and comprehensive management. Further research is essential to understanding the pathophysiological connections between psoriasis and arterial diseases, guiding preventive strategies and optimal medical treatments for these high-risk patients.
PubMed: 38870660
DOI: 10.1016/j.ijscr.2024.109829 -
Research (Washington, D.C.) 2024The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic... (Review)
Review
The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places aerobic glycolysis in a dominant position, the TCA cycle remains indispensable for tumor cells as a hub for the metabolic linkage and interconversion of glucose, lipids, and certain amino acids. TCA intermediates such as citrate, α-ketoglutarate, succinate, and fumarate are altered in tumors, and they regulate the tumor metabolism, signal transduction, and immune environment to affect tumorigenesis and tumor progression. This article provides a comprehensive review of the modifications occurring in tumor cells in relation to the intermediates of the TCA cycle, which affects tumor pathogenesis and current therapeutic strategy for therapy through targeting TCA cycle in cancer cells.
PubMed: 38867720
DOI: 10.34133/research.0351 -
Journal of Atherosclerosis and... Jun 2024Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory.
AIM
Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory.
METHODS
A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) database. Cardiovascular AEs associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) were evaluated using a disproportionality analysis. To reduce potential confounders, adjusted ROR and subgroup analyses were performed.
RESULTS
After excluding duplicates, 9,817 cardiovascular reports were associated with the five TNF-α inhibitors. Only adalimumab had positive signals for myocardial infarction (ROR=1.58, 95%CI=1.51-1.64) and arterial thrombosis (ROR=1.54, 95%CI=1.49-1.58). The remaining four TNF-α inhibitors did not show a risk association with any type of cardiovascular event. Further analyses of specific indication subgroups and after adjusting for any confounding factors demonstrated that adalimumab was still significantly associated with cardiovascular events, especially in patients with psoriasis (adjusted ROR=2.16, 95%CI=1.95-2.39).
CONCLUSIONS
This study revealed that adalimumab was the only TNF-α inhibitor associated with an elevated risk of thrombotic cardiovascular AEs, whereas the other four TNF-α inhibitors did not show any risk effect. However, given the limitations of such pharmacovigilance studies, it is necessary to validate these findings in prospective studies in the future.
PubMed: 38866553
DOI: 10.5551/jat.64767 -
Einstein (Sao Paulo, Brazil) 2024Palhano et al. demonstrate the feasibility of incorporating secukinumab and ustekinumab into the Clinical Protocol and Therapeutic Guidelines for moderate to severe...
UNLABELLED
Palhano et al. demonstrate the feasibility of incorporating secukinumab and ustekinumab into the Clinical Protocol and Therapeutic Guidelines for moderate to severe psoriasis in pediatric patients.
OBJECTIVE
Therefore, this study aimed to evaluate the impact of secukinumab and ustekinumab against moderate-to-severe plaque psoriasis in a Brazilian pediatric population with access to public healthcare.
METHODS
A survey of immunobiological treatments registered for use against pediatric psoriasis at the National Health Surveillance Agency was conducted. These treatments were compared to the list available in the same treatment category in the public health system through the Clinical Protocol and Therapeutic Guidelines for psoriasis. A quantitative analysis of the data of patients treated with immunobiological drugs the previous year in accordance with the Clinical Protocol and Therapeutic Guidelines was performed using data available in the DATASUS portal.
RESULTS
The public budget impact scenarios analyzed were comparable to the investment already planned for acquiring the only available drug option.
CONCLUSION
The incorporation of two therapeutic options in the Clinical Protocol and Therapeutic Guidelines list for moderate-to-severe pediatric psoriasis was feasible in a horizon of 5 years compared to the investment into the single option available to pediatric patients. These findings can facilitate the local analysis of budgetary impact and discussions on the feasibility of this therapeutic incorporation at the state level. Incorporation of secukinumab and ustekinumab was economically feasible. These drugs are options for those who do not respond to or have contraindications to etanercept.
Topics: Humans; Psoriasis; Child; Ustekinumab; Brazil; Antibodies, Monoclonal, Humanized; Severity of Illness Index; Dermatologic Agents; Adolescent; Practice Guidelines as Topic; Male; Female
PubMed: 38865570
DOI: 10.31744/einstein_journal/2024GS0413 -
JAMA Dermatology Jun 2024Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst...
IMPORTANCE
Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN.
OBJECTIVE
To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN.
DESIGN, SETTING, AND PARTICIPANTS
In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2.
EXPOSURES
Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks.
MAIN OUTCOMES AND MEASURES
WI-NRS score at specified time points up to 24 weeks after randomization.
RESULTS
A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods.
CONCLUSION AND RELEVANCE
This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN.
TRIAL REGISTRATION
NCT04183335 (PRIME) and NCT04202679 (PRIME2).
PubMed: 38865146
DOI: 10.1001/jamadermatol.2024.1634 -
Cureus May 2024Metaplastic thymoma is a rare biphasic thymic tumor with indolent behavior and recurrent gene rearrangement. Although the diagnosis of this tumor is usually...
Metaplastic thymoma is a rare biphasic thymic tumor with indolent behavior and recurrent gene rearrangement. Although the diagnosis of this tumor is usually straightforward based on hematoxylin and eosin (H&E) findings alone, cases with scant spindle-cell ("pseudosarcomatous stroma") components can be easily confused with more commonly occurring type A thymoma. We present a case of metaplastic thymoma with a sparse stroma-like spindle-cell component, discussing its histological and immunohistochemical hints and drawing attention to the visual similarity to type A thymoma. This is also the first published case of metaplastic thymoma with associated psoriasis.
PubMed: 38864046
DOI: 10.7759/cureus.60136