Biologics in Psoriasis: Updated Perspectives on Long-Term Safety and Risk Management.

Biologics targeting Th1/Th17 cytokines have revolutionised psoriasis treatment. In addition to treatment effectiveness, it is important to define and understand the long-term risks of biologic therapy in order to guide therapy selection and minimise these risks for patients where possible. This review article summarises available evidence from trial data, observational studies and pharmacovigilance registries to explore key long-term risks of biologic treatment, and how these risks might be managed in clinical practice.

Global Guidelines in Dermatology Mapping Project (GUIDEMAP): a scoping review of dermatology clinical practice guidelines.

BACKGROUND: Clinical practice guidelines (CPGs) play a critical role in standardizing and improving treatment outcomes based on the available evidence. It is unclear how many CPGs are available globally to assist clinicians in the management of patients with skin disease. OBJECTIVES: To search for and identify CPGs for dermatological conditions with the highest burden globally. METHODS: We adapted a list of 12 dermatological conditions with the highest burden from the Global Burden of Disease (GBD) study 2019. A systematic literature search was done to identify CPGs published between October 2014 to October 2019. The scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. RESULTS: A total of 226 CPGs were included. Melanoma had the greatest representation in the CPGs, followed by dermatitis and psoriasis. Skin cancers had a relatively high CPG representation but with lower GBD disease burden ranking. There was an uneven distribution by geographical region, with resource-poor settings being under-represented. The skin disease categories of the CPGs correlated weakly with the GBD disability-adjusted life-years metrics. Eighty-nine CPGs did not have funding disclosures and 34 CPGs were behind a paywall. CONCLUSIONS: The global production of dermatology CPGs showed wide variation in geographical representation, article accessibility and reporting of funding. The number of skin disease CPGs were not commensurate with its disease burden. Future work will critically appraise the methodology and quality of dermatology CPGs and lead to the production of an accessible online resource summarizing these findings.

Sequence Analysis of Transcription Factor 7-like 2 Protein (TCF7L2) in Iraqi Patients with Diabetic Mellitus Type 2 Using Bioinformatics Methods.

Several previously published reports have suggested a relationship between type 2 diabetes mellitus (T2DM) and chromosome 10q. The results of genotyping of 228 microsatellite markers in Icelandic people with T2DMrevealed that a microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with T2DM. The present study was aimed to analyze the sequence of TCF7L2 in Iraqi patients with T2DM. This study was performed on the blood samples of 10 patients within the age range of 18-70 years old with T2DM. The DNA was extracted from the whole blood samples and the TCF7L2 gene was purified and amplified using the polymerase chain reaction (PCR) technique. Afterward, the PCR products were run in gel electrophoresis to detect the gene. Moreover, the BLAST software was used to analyze the gene TCF7L2 sequence which was compared with the reference sequence of the template gene from NCBI. The results of TCF7L2 gene sequences obtained from the samples collected from the Iraqi patients with T2DMwere received from Macogen Company, Korea, and analyzed using the BLAST software. The findings showed mutations in the gene sequence of all patients, compared to the gene sequences in NCBI. Hence, the mutation in the TCF7L2 gene was present in Iraqi patients with T2DM, and it could be one of the factors causing and increasing the risk of T2DM disease.

Analytical Computation of Interleukin17A Activity in Breast Cancer Patients Using Bioinformatics Methods.

Interleukin-17A (IL-17A) is a member of the Interleukin-17 family, which belongs to the pro-inflammatory cystine-knot cytokines. Recent studies on the etiology of breast cancer have focused on the role of immunity and inflammation. The pro-inflammatory cytokines IL-17A can medicate cancer-related inflammation. The present study aimed to analyze the mutation in physicochemical properties and structure of the Interleukin-17 A gene in developing breast cancer using bioinformatics methods. A total of 60 blood samples were obtained from Iraqi women aged 25 to 75 with breast cancer. Twenty blood samples were obtained from healthy women in the same age range as a control group. Deletion and missense mutations detected by BLAST in samples with breast cancer. The present study determined the physicochemical properties of IL-17A such as hydrophilic nature, alpha-helical and 3D structure. The results of this study indicated that IL-17A is considered a marker for a patient with breast cancer. Also, mutations in the IL-17A gene affect the structure and physicochemical properties of the IL-17A protein complex.

Investigation of Interferon Gamma Activity Using Bioinformatics Methods.

Breast cancer grows from the breast tissue and is a severe health problem worldwide. Genetics is believed to be the primary cause of all cases of breast cancer via gene mutation. Bioinformatics methodology has been used to determine the sequences and structures of bioactive substances. This study aimed to analyze the function and structure of the Interferon Gamma (IFNγ) in healthy controls and patients with breast cancer using bioinformatics methods. Blood samples were collected from 75 patients with breast cancer and 25 healthy subjects as control samples. The results showed transition mutation (30%) and transversion mutation (70%) in patients with breast cancer. Moreover, missense mutations (84%) and silent mutations (16%) were detected by BLAST. In addition, the amino acid of the IFNγ protein consisting of alpha-helical, ß-sheet, and coil of secondary structure was determined in this study using BioEdit. The results of the physicochemical properties of the IFNγ protein reflect the function, stability, molecular weight, isoelectric point, and instability index of the IFNγ protein using ProtParam. Moreover, the results of mutation affected the percentage of alpha-helix, ß-turns, and coil in breast cancer patients compared to healthy groups with reference of NCBI using PSIpred program. Additionally, the PHYRE2 server and RasMol program showed a tertiary structure of the IFNγ protein in breast cancer patients. Furthermore, the STRING program revealed the poly IFNγ protein interacted with other proteins to perform its functions normally. From the recorded data in the current study, it was concluded that IFNγ is considered a marker for patients with breast cancer.

Update on risankizumab for the treatment of moderate to severe psoriasis.

INTRODUCTION: The therapeutic landscape for psoriasis is ever-changing. Risankizumab is the newest approved biologic and one of three currently licensed that targets the p19 subunit of interleukin-23 (IL-23). It is increasingly clear that different biologics vary in their efficacy, effectiveness, and safety profiles, highlighting that there is a need to understand for which patients and in which circumstances to use each drug. AREAS COVERED: This article summarizes original clinical trial data, and reviews in more detail recent post-marketing studies and meta-analyses that differentiate risankizumab from other biologics. It also briefly explores the evidence for risankizumab in the treatment of other immune-mediated inflammatory diseases. EXPERT OPINION: Risankizumab is a highly effective biologic for the treatment of moderate-to-severe plaque psoriasis. Recent open-label extension data for risankizumab shows sustained treatment responses to week 136. Indirect comparisons suggest IL-17 inhibitors have a faster onset, though head-to-head comparison with secukinumab shows non-inferiority at week 16 and superiority of risankizumab at week 52. Risankizumab is very well tolerated and data from the IMMhance trial suggests that risankizumab can be used in patients with latent tuberculosis without risk of reactivation.

Phenotypic switch to eczema in patients receiving biologics for plaque psoriasis: a systematic review.

The use of biologic therapies for the treatment of chronic plaque psoriasis has been linked to the development of atopic eczema, amongst other cutaneous adverse events. This can cause diagnostic confusion and create difficulty in the management of patients with plaque psoriasis. The main objective of this systematic review was to review all cases of eczema, including atopic eczema, reported in patients treated with biologics for chronic plaque psoriasis. PubMed, Medline and Embase databases were used to identify studies reporting eczema in patients treated with biologic therapy for chronic plaque psoriasis. A total of 92 patients were identified from 24 studies, with patients treated with either: adalimumab; etanercept; infliximab; ixekizumab; secukinumab; or ustekinumab. Factors common to some reported cases include: a prior history of atopy; eosinophilia; raised serum immunoglobulin E. Twenty-three had documented treatment outcomes; 14 had biologic therapy discontinued or switched. Management strategies included topical or oral corticosteroids, and treatment with alternative systemic agents such as ciclosporin or apremilast. This adverse event occurred in 1.0-12.1% of patients within trial data and observational studies. This review demonstrates that there are consistent reports of a switch to an atopic eczema phenotype from psoriasis in patients taking biologics inhibiting tumour necrosis factor alpha and the interleukin (IL)-17/IL-23 axis. The majority stopped the implicated biologic, but conservative management was successful in some cases. Those with an atopic diathesis may be more at risk. Elucidation of mechanisms and risk factors would contribute to optimal therapy selection for individual patients.

Q-switching near-infrared multiwavelength generation by intracavity tungsten-oxide-induced four-wave mixing in an erbium-doped fiber laser.

We report on the generation of a stable multiwavelength Q-switched erbium-doped fiber laser based on tungsten oxide nanoparticles (WO3 NPs) combined with an intracavity comb filter for the first time, to the best of our knowledge. The prepared WO3-PVA thin film has a modulation depth and saturable intensity of 20% and 100 MW/cm2, respectively. A spectrum of up to 15 peaks with a channel spacing of 0.48 nm has been obtained. In the Q-switching regime, a minimum pulse width of 4.24 µs and a maximum repetition rate of 52.49 kHz were achieved at a maximum pump power of 300 mW. The dual effect of WO3 NPs in saturable absorption and high optical nonlinearity has induced pulsed and four-wave mixing effects. Therefore, the intrinsic advantages of WO3 nanomaterial provide a promising source for the realization of a stable multiwavelength fiber laser.

Risankizumab vs. ustekinumab for plaque psoriasis: a critical appraisal.

AIM: Gordon et al. investigated the efficacy and safety of risankizumab [an anti-interleukin (IL)-23p19 biologic] compared with ustekinumab (anti-IL-12/23p40) and placebo in patients with moderate-to-severe chronic plaque psoriasis. This was a parallel-group controlled study up to 16 weeks with a planned switch of the placebo group to risankizumab at 16 weeks. SETTING AND DESIGN: This study consisted of two replicate phase III, double-blinded randomized controlled trials (UltIMMa-1 and UltIMMa-2) conducted across 139 centres in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain and the U.S.A. STUDY EXPOSURE: Patients with a minimum 6-month history of chronic plaque psoriasis were randomly assigned to receive either 150 mg risankizumab, 45 mg or 90 mg ustekinumab or placebo. Prior to this, each group was also stratified by weight (either more than or less than 100 kg) and previous exposure to tumour necrosis factor inhibitors. Those assigned to receive placebo were transitioned onto risankizumab at week 16. The study drugs were given at weeks 0, 4, 16, 28 and 40. OUTCOMES: The severity of psoriasis was measured using the Psoriasis Area and Severity Index (PASI) and a static Physician's Global Assessment (sPGA). The authors additionally recorded the number of adverse events in each treatment arm, and a measure of quality of life. PRIMARY OUTCOME MEASURES: The coprimary outcomes were the proportions of patients achieving ≥ 90% reduction in their baseline PASI (PASI 90) and an sPGA score of 0 or 1 (clear or almost clear) at week 16. RESULTS: In total 506 patients were included in UltIMMa-1 and 491 patients in UltIMMa-2. In UltIMMa-1, PASI 90 by week 16 was achieved by 75·3% of patients receiving risankizumab, compared with 42·0% receiving ustekinumab and 4·9% receiving placebo (P < 0·001 vs. placebo and ustekinumab). sPGA of 0 or 1 by week 16 was achieved by 87·6% of patients receiving risankizumab, compared with 63·0% receiving ustekinumab and 7·8% receiving placebo (P < 0·001 vs. placebo and ustekinumab). The results for UltIMMa-2 are similar. The frequencies of adverse events in the risankizumab, ustekinumab and placebo groups were similar in both studies. CONCLUSIONS: Gordon et al. conclude that risankizumab has a higher efficacy than placebo and ustekinumab in the treatment of moderate-to-severe chronic plaque psoriasis, and that the adverse-event profiles were similar across all treatment groups.

Characterization of biofilm formed on intrauterine devices.

PURPOSE: Intrauterine device (IUD) is one of the most convenient contraceptive procedures used by women of Asian and African countries. Previous surveys have revealed that 75% of the IUDs recovered from patients suffering from reproductive tract infections (RTIs) were covered with a consortium of microbes. This study was designed to characterize these microbes and recommend remedial measures. METHODS: Quantitative measurement of biofilm formation was assessed by a microtitre plate assay on 86 samples of microorganisms dislodged from IUDs of patients with RTIs. Susceptibility of biofilm to various antimicrobial agents was also quantified. Scanning electron microscopy (SEM) was used to scrutinize the microorganisms adherent to IUDs. RESULTS: The organisms associated with IUDs were predominantly composed of Staphylococcus aureus (16%), Staphylococcus epidermidis (18%), Pseudomonas aeruginosa (5%), Escherichia coli (27%), Neisseria gonorrhoeae (2%), Candida albicans (20%) and Candida dubliniesis (12%). SEM studies indicated that these organisms were organized into biofilms. Studies on the in vitro adherence pattern by crystal violet staining on 96 well microtitre plates revealed that the biofilms were stably established after 60 hours. These biofilms are resistant to an array of antibiotics tested. CONCLUSION: Biofilm formation may be one of the major causes for persistent infection and antibiotic resistance in IUD users.

Effect of vitamin C administration on serum and egg-yolk cholesterol level of the chicken.

Ascorbic acid (vitamin C) was given to 144-days-old layer chickens mixed with their ration at three concentrations: 30, 60 and 90 p.p.m. for 6 months. Cholesterol levels in blood serum (CS) and egg yolk (CE) were measured every 6 weeks (four periods); there was a marked decrease in CS in most treated birds, especially those receiving the highest concentration of vitamin C. There was also a slight decrease in CE in most treated birds. Thyroidal weight showed a significant increase in most treated groups, especially those receiving the highest concentration of vitamin C.

Changes in ovarian function associated with oxytocin injection to immature rats.

The effects of oxytocin on ovarian function have been studied in immature rats of 25 days of age. The hormone was injected subcutaneously daily for 5 days in two doses: 50 and 250 millimicrons per animal, to intact females, hysterectomized or injected simultaneously with indomethacin (2 mg/kg). Ovarian and uterine weights increased in all treated animals. Plasma estradiol 17 beta levels increased, while plasma progesterone level did not change. The relevance of this study was to precise the trophic role of oxytocin on ovary and uterus. The changes observed did not seem to be associated with prostaglandin E secretion.