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Pediatric Dermatology 2023
PubMed: 37767651
DOI: 10.1111/pde.15190 -
Pharmaceutics Sep 2023Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective...
Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective treatment available or clear pathological mechanisms known for this syndrome. In this study, a Connectivity Map (CMap) bioinformatics model of POCD was established by using differently expressed landmark genes in the serum samples of POCD and non-POCD patients from the only human transcriptome study. The predictability and reliability of this model were further supported by the positive CMap scores of known POCD inducers and the negative CMap scores of anti-POCD drug candidates. Most retinoic acid receptor (RAR) agonists were negatively associated with POCD in this CMap model, suggesting that RAR might be a novel target for POCD. Most importantly, acitretin, a clinically used RAR agonist, significantly inhibited surgery-induced cognitive impairments and prevented the reduction in RARα and RARα-target genes in the hippocampal regions of aged mice. The study denotes a reliable CMap bioinformatics model of POCD for future use and establishes that RAR is a novel therapeutic target for treating this clinical syndrome.
PubMed: 37765280
DOI: 10.3390/pharmaceutics15092311 -
Pathogens (Basel, Switzerland) Sep 2023A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and...
A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease was attended in the Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to the failure of other treatments (phototherapy, oral acitretin) for psoriasis and a Psoriasis Area Severity Index >10. We evaluated the impact of treatment with ustekinumab on severe infectious diseases in a patient with uncontrolled psoriasis and LOCID followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, cultures of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation; pathogenic variants in genetic sequencing, and clinically significant variants in the whole exome for primary immunodeficiencies were not detected. The main infections before and after treatment with ustekinumab were chronic sinusitis and gastroenteritis. The patient was infected with COVID-19, dengue (twice) and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence the susceptibility of the patient with LOCID to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease.
PubMed: 37764964
DOI: 10.3390/pathogens12091156 -
Case Reports in Women's Health Sep 2023Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial...
Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial folds, ears, and, less frequently, the oral mucosa. A typical eruption consists of keratotic and crusted skin-colored papules and plaques. Pruritus occurs in 80% of patients, and pain is rare. Lesions can be triggered by exposure to ultraviolet light, heat, or stress. Secondary infections of the lesions are a common complication. A definitive diagnosis is obtained by a biopsy showing histological features such as acantholysis, suprabasal clefts, and "corps rond and grains". Here we present a 37-year-old woman admitted to the gynecology department with pruritic lesions she had noticed on her vulva and perineum for three months. A vulvar biopsy led to the diagnosis of Darier disease. She was referred to the dermatology department and treated with oral acitretin since systemic retinoids are offered as the first-line treatment of the disease.
PubMed: 37753222
DOI: 10.1016/j.crwh.2023.e00545 -
Dermatology (Basel, Switzerland) 2023Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics.
BACKGROUND
Mycosis fungoides (MF) in solid-organ transplant recipients (SOTRs) is rare, with limited data on disease characteristics.
OBJECTIVE
The aim was to study the characteristics of MF in SOTRs with an emphasis on the immunosuppressive therapy.
METHODS
A retrospective cohort of patients diagnosed with MF, who were also SOTRs, were followed at 3 cutaneous lymphoma outpatient clinics, between January 2010 and February 2022.
RESULTS
Ten patients were included (7 male; median ages at transplantation and at diagnosis of MF were 33 and 48 years, respectively; 40% were diagnosed before the age of 18 years). Median time from transplantation to diagnosis of MF was 8 years (range 0.5-22). Transplanted organs and immunosuppressive treatments included: liver (n = 5; 4 treated with tacrolimus, 1 with tacrolimus and prednisone), kidney (n = 3), liver and kidney (n = 1), and heart (n = 1), all treated with mycophenolic acid, tacrolimus, and prednisone. Nine had early-stage MF (IA - 4, IB - 5; 40% with early folliculotropic MF), treated with skin-directed therapies, in 2 combined with acitretin, achieving partial/complete response. One patient had advanced-stage MF (IIIA) with folliculotropic erythroderma, treated with ultraviolet A and narrow-band ultraviolet B with acitretin, achieving partial response. Immunosuppression was modified in 3. At last follow-up (median 4 years, range 1-8), no stage progression was observed; 5 had no evidence of disease, 5 had active disease (IA/IB - 4, III - 1).
CONCLUSIONS
MF in SOTRs is usually diagnosed at an early stage, with overrepresentation of folliculotropic MF, and of children. Immunosuppressive therapy alterations, not conducted in most patients, should be balanced against the risk of organ compromise/rejection. Disease course was similar to MF in immunocompetent patients, during the limited time of follow-up.
Topics: Child; Humans; Male; Adolescent; Retrospective Studies; Acitretin; Prednisone; Tacrolimus; Mycosis Fungoides; Skin Neoplasms; Organ Transplantation
PubMed: 37751718
DOI: 10.1159/000534224 -
Acta Dermatovenerologica Alpina,... Sep 2023Patients receiving immune checkpoint inhibitors (ICIs) commonly experience cutaneous immune-related adverse events (irAEs). We present two cases, a 51-year-old female...
Patients receiving immune checkpoint inhibitors (ICIs) commonly experience cutaneous immune-related adverse events (irAEs). We present two cases, a 51-year-old female and a 70-year-old male, that were undergoing treatment with pembrolizumab for metastatic melanoma and developed scaly, erythematous papules on their skin. Following skin biopsies, histological analysis confirmed the diagnosis of lichen planus. In the first patient, acitretin at a dosage of 25 mg/day was administered for 6 months, resulting in complete resolution of lichen lesions. Imaging scans showed no signs of melanoma. The second patient was treated with topical betamethasone dipropionate ointment for several weeks, which led to a favorable therapeutic response. During follow-up, a thoracic CT scan showed several micronodular lesions in the right lung, whereas brain and abdomen CT scans showed no signs of the disease. Lichen planus is not a commonly reported irAE in patients treated with ICIs. This report underscores the importance of conducting skin biopsies in patients receiving ICI therapy and highlights the potential prognostic importance of skin irAEs in patients with melanoma receiving such treatment.
Topics: Female; Male; Humans; Middle Aged; Aged; Prognosis; Skin; Lichen Planus; Melanoma
PubMed: 37749972
DOI: No ID Found -
Oncology Research 2023The low survival rate of Kidney renal clear cell carcinoma (KIRC) patients is largely attributed to cisplatin resistance. Rather than focusing solely on individual...
The low survival rate of Kidney renal clear cell carcinoma (KIRC) patients is largely attributed to cisplatin resistance. Rather than focusing solely on individual proteins, exploring protein-protein interactions could offer greater insight into drug resistance. To this end, a series of and experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy. The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information (NCBI) database using search terms as "Kidney renal clear cell carcinoma" and "Cisplatin resistance". The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool. Expression and promoter methylation profiling of the hub genes was done using UALCAN, GEPIA, OncoDB, and HPA databases. Mutational, survival, functional enrichment, immune cell infiltration, and drug prediction analyses of the hub genes were performed using the cBioPortal, GEPIA, GSEA, TIMER, and DrugBank databases. Lastly, expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines (786-O and A-498) and a normal renal tubular epithelial cell line (HK-2) using two high throughput techniques, including targeted bisulfite sequencing (bisulfite-seq) and RT-qPCR. A total of 124 genes were identified as being associated with cisplatin resistance in KIRC. Out of these genes, MCL1, IGF1R, CCND1, and PTEN were identified as hub genes and were found to have significant ( < 0.05) variations in their mRNA and protein expressions and effects on the overall survival (OS) of the KIRC patients. Moreover, an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes. In addition to this, hub genes were also linked with different cisplatin resistance-causing pathways. Thus, hub genes can be targeted with Alvocidib, Estradiol, Tretinoin, Capsaicin, Dronabinol, Metribolone, Calcitriol, Acetaminophen, Acitretin, Cyclosporine, Azacitidine, Genistein, and Resveratrol drugs. As the pathogenesis of KIRC is complex, targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance, which might uplift overall survival among KIRC patients.
Topics: Humans; Cisplatin; Carcinoma, Renal Cell; Kidney Neoplasms; Kidney
PubMed: 37744271
DOI: 10.32604/or.2023.030760 -
Pediatric Investigation Sep 2023Generalized pustular psoriasis (GPP) is a severe subtype of psoriasis, commonly combined with systemic inflammation. Gene mutations have been found to be associated with... (Review)
Review
Generalized pustular psoriasis (GPP) is a severe subtype of psoriasis, commonly combined with systemic inflammation. Gene mutations have been found to be associated with GPP and vary by ethnicity. Systemic treatments are usually required for the severity and potential complications of GPP. However, there is no common consensus in China, especially among pediatric patients, whose data are scarce. Acitretin, methotrexate, and cyclosporine are widely used in pediatrics with GPP, while the adverse effects should be highlighted. The emergence of different biological agents brings us into a new era. This article discusses the genetic background of Chinese patients and demonstrates the evidence of treatment in pediatrics with GPP.
PubMed: 37736368
DOI: 10.1002/ped4.12395 -
Pediatric Investigation Sep 2023Keratinopathic ichthyosis (KPI) represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the , , or genes. In KPI, the...
IMPORTANCE
Keratinopathic ichthyosis (KPI) represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the , , or genes. In KPI, the relationship between genotype and phenotype is complex.
OBJECTIVE
To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.
METHODS
Clinical data were collected from 13 children diagnosed with KPI, and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel, and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.
RESULTS
Genetic analysis identified missense mutations in either or in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis. A missense hotspot mutation in was identified in one patient with superficial epidermolytic ichthyosis. Additionally, two truncation mutations in were detected, leading to the development of generalized ichthyosiform erythroderma. Ear malformation and ectropion at birth, scalp involvement, and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.
INTERPRETATION
We analyzed the genotype-phenotype correlations in KPI, revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics. Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.
PubMed: 37736367
DOI: 10.1002/ped4.12391 -
Actas Dermo-sifiliograficas Apr 2024
Topics: Humans; Acitretin; Hair Diseases; Hair
PubMed: 37709132
DOI: 10.1016/j.ad.2023.01.022