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Background. Methotrexate is a highly effective systemic treatment for moderate to severe psoriasis, but drug toxicity may limit its use. Recent evidence suggests that it is necessary to take into account the individual characteristics of methotrexate pharmacokinetics, which are determined by the presence of polymorphisms of genes encoding methotrexate carrier proteins, to predict the risk of methotrexate-induced toxicity. Aims. The research aim is the assessment of associations of ABCB1 rs1045642 (3435CT) polymorphism with methotrexate safety for the patients with moderate and severe forms of psoriasis. Materials and methods. The study included 75 patients diagnosed with psoriasis treated with methotrexate during 21 day. Data on adverse drug reactions were collected using a clinically structured questionnaire, complete and biochemical blood tests, and urinalysis. The severity of adverse drug reactions was assessed using visual analog scales and the CTCAE toxicity scale. The severity of gastrointestinal ADR was assessed using the GSRS questionnaire. Genotyping was carried out by real-time PCR. Results. The gastrointestinal toxicity was detected in 38 patients (50.67%). The mean GSRS score was 7.97 9.18. Analysis of differences in the incidence of adverse drug reactions showed the presence of statistically significant differences in the frequency of adverse drug reactions in the gastrointestinal tract: the toxic effect of methotrexate was more often observed in carriers of the T allele of the ABCB1 rs1045642 polymorphism (3435CT), (CC 2 (14.3%), TC 18 (52.9%), TT 18 (66.7%), p = 0.006). Binomial regression demonstrated the presence of a statistically significant effect of the rs1045642 SNP polymorphism of the ABCB1 gene on the incidence of ADR from the gastrointestinal tract (OR = 8.64, p = 0.008). Conclusions. An association of ABCB1 rs1045642 SNP with the safety of gastrointestinal methotrexate therapy in patients with moderate and severe forms of psoriasis was revealed. The data obtained can be used to personalize the prescription of methotrexate to patients with psoriasis.

Background. Early detection of psoriatic arthritis in patients with psoriasis remains an unmet medical need. Early diagnosis and treatment initiation in patients with psoriatic arthritis decreases the risk of adverse patient outcomes and improves patients quality of life. Aims. To describe a period between psoriasis and psoriatic arthritis onset and a period between psoriatic arthritis onset and diagnosis in Russian patients with moderate to severe psoriasis. Materials and methods. Analysis of data from the psoriasis patient registry. Patients aged 18 years and older with an established diagnosis of psoriasis and psoriatic arthritis were included in the analysis. Noninclusion criteria: no data on psoriasis and/or psoriatic arthritis onset (for the period between psoriasis and psoriatic arthritis onset description); no data on psoriatic arthritis onset and/or diagnosis (for the period between psoriatic arthritis onset and diagnosis description). Results. Sample size for the descriptive characteristic of period between psoriasis and psoriatic arthritis onset was 891 patients; sample size for the descriptive characteristic of period between psoriatic arthritis onset and diagnosis was 849 patients. Psoriatic arthritis onset preceeded cutaneous manifestation of psoriasis in 2.5% of patients. Concurrent onset of cutaneous psoriasis and psoriatic arthritis (within one year) had 10.7% of patients. In 86.8% of patients, cutaneous manifestation of psoriasis preceded manifestation of psoriatic arthritis. Exclusively of patients with psoriatic arthritis developed before or concurrently with cutaneous manifestation of psoriasis, the mean duration of period between psoriasis and psoriatic arthritis onset was 13.7 10.3 years, the median [IQR] 12 [619] years. In 24% of patients psoriatic arthritis was diagnosed 1 year and more after its onset. The mean (SD) period from signs and|or symptoms onset till psoriatic arthritis diagnosis was 3.9 5.0 years; median [IQR] was 2 [14.5] years. Conclusions. A diagnostic delay in 24% Russian patients with psoriatic arthritis is one year or more. In this subgroup of patients the mean delay in diagnosis of psoriatic arthritis is about 4 years.

Rationale and aim of the study. The incidence of diseases of the skin and subcutaneous tissue is in the forth place in the Russian Federation. The aim of the study is to investigate the prevalence and incidence of diseases of the skin and subcutaneous tissue, the structure and dynamics of medical care provided to the population of three age groups in 2010– 2020.Materials and methods. Analysis of national statistical monitoring data and rates calculated for 2010–2020. The calculations and analysis were carried out for the entire population of the Russian Federation, and for the population of three age groups: children 0–17 years old, adults of working age and adults of over working age using the approach approved by Federal State Statistics Service.Results. In 2010–2019 there was a decrease in the number and incidence of diseases of the skin and subcutaneous tissue among children and adults of working age. In the structure of diseases of the skin and subcutaneous tissue, the proportion of diseases among population over working age is increasing. The number of 24-hour hospital admissions for diseases of the skin is decreasing among children and adults of working age. In contrast, there was an increase in the number of skin diseases and hospital admissions of patients over the working age.Conclusion. In the Russian Federation, the highest prevalence and incidence rates of diseases of the skin and subcutaneous tissue are registered in the group of children 0–17 years old. At the same time, there is a steady decline of both rates among population of this age group. There is an increase in the number of diseases and as a consequence in the need and volume of specialized medical care in 24-hour hospitals provided to the population of over the working age. The COVID-19 pandemic has led to decrease in prevalence and incidence rates, and number of hospital admissions for skin diseases similar in three age groups.

The article presents the results of analysis of resources and performance rates of medical organizations providing medical care in the field of dermatovenereology over 20192021 in the Russian Federation. The changes in the rates of provision of the population of the Russian Federation with dermatovenereologists are reflected. The rates of provision of the population of the Russian Federation with round-the-clock and daytime dermatovenereological beds are presented. The rates of dermatovenereologic medical care provided to the population of the Russian Federation in 2021 in outpatient, inpatient and day hospital conditions were compared with those before the pandemic. The dynamics of incidence of sexually transmitted infections as well as dynamics of prevalence and incidence of skin and subcutaneous tissue disorders among the population of the Russian Federation, and specifically in different age groups, during the period under review is presented.

Сlinical, immunological and genetic differences between patients with early and late onset psoriasis are reported. Comparative studies of clinical characteristics of psoriatic arthritis according to age of psoriasis onset (skin manifestation) are lacking.Aim – to compare the prevalence and clinical characteristics of psoriatic arthritis depending on age of psoriasis onset (skin manifestation) in patients included to the psoriasis patient registry of Russian Society of Dermatovenereologists and Cosmetologists.Materials and methods. Prevalence of psoriatic arthritis in 3,227 patients with psoriasis aged 18 years and older was calculated. Comparison of the clinical characteristics of psoriatic arthritis according to the age of onset of psoriasis was performed on 916 patients with psoriasis and psoriatic arthritis.The U-test was used to compare quantitative variables. To identify the association between qualitative variables, the χ2 test was used; odds ratio and 95% confidence interval were calculated, unadjusted and adjusted for other independent variables.Results. In the majority of patients (73%), psoriasis manifested before the age of 40. Psoriatic arthritis at the time of inclusion to the registry was diagnosed in 31.7% of patients with early onset psoriasis and in 19.5% of patients with late onset psoriasis (p=0.0005).The odds of having psoriatic arthritis were almost two times lower in patients with late onset psoriasis (p=0.0005). When adjusted for sex and age, the odds of having psoriatic arthritis among patients with late onset psoriasis became 4 times lower than in patients with early onset psoriasis (p=0.0005). However, when adjusted for sex and duration of psoriasis, the odds ratio lost its statistical significance.The axial involvement (32.1% vs 20.5%; p=0.003) and the involvement of foot joints (59.7% vs 51.5%; p=0.048) was more likely in patients with early onset psoriasis. The odds ratio for axial involvement was still statistically significant when adjusted for other independent variables.Conclusions. Age of onset of psoriasis before 40 years of age is associated with more frequent axial involvement in psoriatic arthritis.

Background. Psoriasis is a chronic skin disorder that impairs patients health-related quality of life. It is associated with patients need in specialized medical care and with essential medical costs. Psoriasis may be the reason for temporary or permanent disability. Patient registries are important sources of epidemiological and clinical data on patients with psoriasis and medical care provided. Aims. To describe demographic characteristics, characteristics of the disease, prevalence of concomitant and past diseases in adult (18 years and older) patients with moderate and severe psoriasis included in the patient registry of the Russian Society of Dermatovenereologists and Cosmetologists. Materials and methods. The data of 3,268 patients with psoriasis aged 18 years and older were analyzed as of inclusion in the registry. Data lock point was June 3, 2021. Descriptive statistics methods were applied in data analysis. Results. The mean ( SD) age of adult patients at inclusion in the registry was 46.1 14.4 years. Male patients accounted for 60.5%. The mean age of onset of psoriasis is 31.1 16.1 years. Most of the patients (89.5%) have psoriasis vulgaris. The mean body surface area at inclusion was 43.3% 24.7%. 28.9% of patients had psoriatic arthritis at inclusion in the registry. A high prevalence of cardiovascular diseases was revealed: arterial hypertension 28.5%, coronary heart disease 5.4%, myocardial infarction and acute cerebrovascular accident 0.9% each. More than half of patients are pre-obese or obese according to the WHO body mass index classification. 2.2% of patients have impaired glucose tolerance, 6.7% of patients have type 2 diabetes mellitus. 3.8% of patients have diseases or dysfunction of the thyroid gland. The prevalence of diseases of the digestive system is high: any disease of the esophagus, stomach and duodenum was noted in 10.2% of patients, any disease of the liver, gallbladder, biliary tract and pancreas in 11.8% of patients. The prevalence of viral hepatitis C among patients with psoriasis was 2.6%. Conclusions. The prevalence of comorbidities is high among Russian patients with moderate and severe psoriasis.

The aim of this work was to study the resistance to macrolides (azithromycin) in the modern Russian population of N. gonorrhoeae with the analysis of genetic resistance determinants. Azithromycin is not used to treat gonococcal infection in Russia. However, among 162 isolates collected in 2020–2021, 22 isolates (13.6%) were phenotypically resistant to azithromycin. Mutations in 23S rRNA genes were found only in two isolates; erm and mefA genes were absent. Azithromycin resistance was shown to be predominantly associated with mutations in the mtrR and mtrD genes of the MtrCDE efflux pump and their mosaic alleles which may have formed due to a horizontal transfer from N. meningitidis. A total of 30 types of mtrR alleles and 10 types of mtrD alleles were identified including mosaic variants. Matching between the mtrR and mtrD alleles was revealed to indicate the cooperative molecular evolution of these genes. A link between the mtrR and mtrD alleles and NG-MAST types was found only for NG-MAST 228 and 807, typical of N. gonorrhoeae in Russia. The high level of resistance to azithromycin in Russia may be related to the spread of multiple transferable resistance to antimicrobials regardless of their use in the treatment of gonococcal infection.

Many current gonococcal clinical isolates in Russia show atypical taxonomically significant biochemical activity, which leads to species misidentification. Molecular typing of such cultures according Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) protocols assigned them to the G807 NG-MAST GENOGROUP/ST1594 MLST that has been predominant in Russia in recent years. The goal of the study was to analyze the molecular mechanisms of biochemical atypia in N. gonorrhoeae clinical isolates characterized as the members of G807 NG-MAST GENOGROUP/ST1594 MLST. Sixteen isolates of this genogroup were included in the study, eight showed defective amino acid metabolism or loss of D-glucose fermentation. Comparative bioinformatic analysis based on WGS data divided these isolates into two clusters strictly associated with typical or atypical biochemical activity. Cultures with defective amino acid metabolism had a 5-nucleotide insertion in the pip-gene that caused a stop codon and led to synthesis of the non-functional enzyme. Comparison of the sequenced genomes with publicly available N. gonorrhoeae genomes showed the rarity of this insertion. In the global N. gonorrhoeae phylogenetic tree the G807 NG-MAST GENOGROUP/ST1594 MLST forms a distinct branch characterized by 170 SNPs, most of which are non-synonymous. We hypothesized a unique strategy for G807 NG-MAST GENOGROUP/ST1594 MLST clone persistence in the global N. gonorrhoeae population via escape of antimicrobial therapy due to diagnostic misidentification.

Many current gonococcal clinical isolates in Russia show atypical taxonomically significant biochemical activity, which leads to species misidentification. Molecular typing of such cultures according

The goal of this work was to determine the factors affecting the emergence of azithromycin-resistant Neisseria gonorrhoeae isolates in Russia, where azithromycin was never recommended for the treatment of gonococcal infections. Clinical N. gonorrhoeae isolates collected in 2018–2021 (428 isolates) were analyzed. No azithromycin-resistant isolates were found in 2018–2019, but in 2020–2021, a significant increase in the ratio of azithromycin-resistant isolates was observed: 16.8% and 9.3%, respectively. A hydrogel DNA microarray was developed for the analysis of resistance determinants: mutations in the genes encoding the mtrCDE efflux system and in all four copies of the 23S rRNA gene (position 2611). A majority of the azithromycin-resistant Russian isolates belonged to the NG-MAST G12302 genogroup, and the resistance was associated with the presence of a mosaic structure of the mtrR gene promoter region with the −35 delA deletion, an Ala86Thr mutation in the mtrR gene, and a mosaic structure of the mtrD gene. A comparative phylogenetic study of modern Russian and European N. gonorrhoeae populations allowed us to conclude that the emergence of azithromycin resistance in Russia in 2020 was the result of the appearance and spread of European N. gonorrhoeae strains belonging to the G12302 genogroup due to possible cross-border transfer.

N. gonorrhoeae strains producing plasmid-mediated broad- and extended-spectrum β-lactamases (ESBLs) have been obtained in vitro and studied for their viability and susceptibility to β-lactam antibiotics. The artificial pblaTEM-1 and pblaTEM-20 plasmids were constructed by site-directed mutagenesis from a pblaTEM-135 plasmid of the Toronto/Rio type, which was extracted from the clinical isolate. MIC values were determined for a series of β-lactam antibiotics, including benzylpenicillin, ampicillin, cefuroxime, ceftriaxone, cefixime, cefotaxime, cefepime, meropenem, imipenem, and doripenem. The N. gonorrhoeae strain carrying the pblaTEM-20 plasmid exhibited a high level of resistance to penicillins and II-IV generation cephalosporins (MIC ≥ 2 mg/L) but not to carbapenems (MIC ≤ 0.008 mg/L). However, this strain stopped growing after 6 hours of cultivation. The reduced viability was not associated with the plasmid loss but can be explained by the following factors: the presence of the plasmid itself, which requires additional costs for its reproduction, and the expression of ESBL, which can affect the structure of the peptidoglycan layer in the cell membrane. The cell growth was mathematically modeled using the generalized Verhulst equation. The parameter, characterizing the maximum possible number of cells grown under given conditions, decreased within the wild type (without plasmids) - pblaTEM-135 - pblaTEM-1 - pblaTEM-20 series, i.e., the plasmid-bearing strains had reduced viability compared to that of the wild-type strain. The kinetics for the cell death of N. gonorrhoeae strains without the pblaTEM-20 plasmid in the presence of ceftriaxone can be described by a modified Chick-Watson law. For the N. gonorrhoeae strain that harbors the pblaTEM-20 plasmid, the kinetics for cell number changes with time reflected several processes: the hydrolysis of ceftriaxone by TEM-20 β-lactamase, growth and gradual death of cells. The demonstrated reduced viability of N. gonorrhoeae strains with the pblaTEM-20 plasmid probably explains the absence of clinical isolates of N. gonorrhoeae that produce ESBL.

Comparative whole-genome analysis was performed for Neisseria gonorrhoeae isolates belonging to the Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) types predominant worldwide — 225, 1407, 2400, 2992, and 4186 — and to genogroup 807, the most common genogroup in the Russian Federation. Here, for the first time, the complete genomes of 25 N. gonorrhoeae isolates from genogroup 807 were obtained. For NG-MAST types 225, 1407, 2400, 2992, and 4186, genomes from the Pathogenwatch database were used. The phylogenetic network constructed for 150 genomes showed that the clustering according to NG-MAST type corresponded to the clustering according to genome. Comparisons of genomes of the six sequence types revealed 8-20 genes specific to each sequence type, including the loci for phase variations and genetic components of the gonococcal genetic island (GGI). NG-MAST type 2992 and 4186 isolates either lacked the GGI or carried critical mutations in genes essential for DNA secretion. In all analyzed genogroup 807 isolates, substitution of the essential atlA gene with the eppA gene was found, accompanied by a change in the traG allele, replacement of the ych gene with ych1, and the absence of the exp1 gene, which is likely to result in loss of GGI functionality. For the NG-MAST type 225, 1407 and 2400 isolates, no premature stop codons or reading frameshifts were found in the genes essential for GGI function. A relationship between isolate susceptibility to ciprofloxacin, penicillin, tetracycline and the presence of lesions in GGI genes necessary for DNA secretion was established. The N. gonorrhoeae evolutionary pathways, which allow a particular sequence type to maintain long-term predominance in the population, may include changes in genes responsible for adhesion and virulence, changes in the GGI structure, preservation of genes carrying drug resistance determinants, and changes in genes associated with host adaptation or encoding enzymes of biochemical pathways.

Comparative whole-genome analysis was performed for

This work aimed to study penA gene polymorphisms in clinical isolates of Neisseria gonorrhoeae collected in Russia in 2018–2019 and the contribution of the penA allele type to susceptibility to β-lactam antibiotics. A total of 182 isolates were analyzed. penA allele types were determined by sequencing, and the minimum inhibitory concentrations (MICs) of benzylpenicillin and ceftriaxone were measured. The influence of genetic factors on MICs was evaluated by regression analysis. All isolates were susceptible to ceftriaxone, and 40.1% of isolates were susceptible to penicillin. Eleven penA allele types were identified. The mosaic type XXXIV penA allele and the Gly120Lys substitution in PorB made the greatest contributions to increasing the ceftriaxone MIC; the presence of the blaTEM plasmid, Gly120Asp, Ala121Gly/Asn substitutions in PorB, and the adenine deletion in the promoter region of the mtrR gene caused an increase in the penicillin MIC. Among 61 NG-MAST types identified, the most frequent were types 228, 807, 9486, 1993, and 6226. A link between penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST) types was established. Resistance to two groups of β-lactam antibiotics was associated with non-identical changes in penA alleles. To prevent the emergence of ceftriaxone resistance in Russia, NG-MAST genotyping must be supplemented with penA allele analysis.

The article analyzes the clinical picture and course of rosacea in patients with Demodex mites. It presents the advantages of using the method of confocal laser scanning microscopy over the method of light microscopy of facial skin scrapes. The aimes were to study the influence of Demodex mites on the clinical picture and course of rosacea; to compare laboratory and instrumental diagnostic methods for detecting Demodex mites; to evaluate the effectiveness of external therapy aimed at eliminating Demodex mites. 212 people were examined. The study included healthy patients, patients with a diagnosis of rosacea with the presence and absence of Demodex. The presence of Demodex mites was confirmed by two methods of study (light microscopy of skin scrapes and confocal laser scanning in vivo microscopy). Demodex mites promote the development of acute-inflammatory morphological elements, increase the duration of the condition (more than 5 years, P

The article analyzes the clinical picture and course of rosacea in patients with Demodex mites. It presents the advantages of using the method of confocal laser scanning microscopy over the method of light microscopy of facial skin scrapes. The aimes were to study the influence of Demodex mites on the clinical picture and course of rosacea; to compare laboratory and instrumental diagnostic methods for detecting Demodex mites; to evaluate the effectiveness of external therapy aimed at eliminating Demodex mites. 212 people were examined. The study included healthy patients, patients with a diagnosis of rosacea with the presence and absence of Demodex. The presence of Demodex mites was confirmed by two methods of study (light microscopy of skin scrapes and confocal laser scanning in vivo microscopy). Demodex mites promote the development of acute-inflammatory morphological elements, increase the duration of the condition (more than 5 years, P

The article presented our reviews on methodological advances in the diagnosis of demodicosis via our own research on demodicosis diagnosis efficiency with the aid of fluorescence lifetime measurement using confocal laser scanning microscopy. Under our supervision, there were 60 patients with acne and rosacea complicated with demodicosis, 60 patients with acne and rosacea without demodicosis, and 30 healthy volunteers. All patients underwent skin scraping and epilation of eyebrows and/or eyelashes, and the examination of skin morphology was conducted using confocal laser scanning microscopy. The research has shown the advantages of in vivo confocal laser scanning microscopy over the conventional microscope.

BackgroundPlaque psoriasis affecting palms and soles is disabling and often resistant to treatment.ObjectiveEvaluate the efficacy and safety of secukinumab, an anti-interleukin 17A antibody, in subjects with palmoplantar psoriasis.MethodsIn this double-blinded, randomized controlled trial, 205 subjects were randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo. The primary endpoint was Palmoplantar Investigator's Global Assessment (ppIGA) 0 (clear) or 1 (almost clear/minimal) response at week 16.ResultsAt week 16, the percentage of subjects who achieved clear or almost clear palms and soles (or ppIGA 0/1) with secukinumab 300 mg (33.3%) and 150 mg (22.1%) was superior to the percentage achieved with placebo (1.5%, P

Item does not contain fulltext BACKGROUND: New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population. METHODS: In this phase 3, randomised, multicentre, double-dummy, placebo-controlled, 12-week, non-inferiority trial, adult patients with chronic stable plaque psoriasis (for >/=12 months) who were candidates for systemic or phototherapy and had a Psoriasis Area and Severity Index (PASI) score of 12 or higher and a Physician's Global Assessment (PGA) of moderate or severe, and had failed to respond to, had a contraindication to, or were intolerant to at least one conventional systemic therapy, were enrolled from 122 investigational dermatology centres worldwide. Eligible patients were randomly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals, etanercept 50 mg subcutaneously twice weekly at about 3-4 day intervals, or placebo. Randomisation was done by a computer-generated randomisation schedule, and all patients and study personnel were masked to treatment assignment. The co-primary endpoints were the proportion of patients at week 12 with at least a 75% reduction in the PASI score from baseline (PASI75 response) and the proportion of patients achieving a PGA score of "clear" or "almost clear" (PGA response), analysed in the full analysis set (all patients who were randomised and received at least one dose of study drug). This study is registered with ClinicalTrials.gov, number NCT01241591. FINDINGS: Between Nov 29, 2010, and Sept 13, 2012, we enrolled 1106 eligible adult patients with chronic plaque psoriasis and randomly assigned them to the four treatment groups (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg twice daily, 336 to etanercept 50 mg twice weekly, and 108 to placebo). Of these patients, 1101 actually received their assigned study medication (329 in the tofactinib 5 mg group, 330 in the tofacitinib 10 mg group, 335 in the etanercept group, and 107 in the placebo group). At week 12, PASI75 responses were recorded in 130 (39.5%) of 329 patients in the tofacitinib 5 mg group, 210 (63.6%) of 330 in the tofacitinib 10 mg group, 197 (58.8%) of 335 in the etanercept group, and six (5.6%) of 107 in the placebo group. A PGA response was achieved by 155 (47.1%) of 329 patients in the tofacitinib 5 mg group, 225 (68.2%) of 330 in the tofacitinib 10 mg group, 222 (66.3%) of 335 in the etanercept group, and 16 (15.0%) of 107 in the placebo group. The rate of adverse events was similar across the four groups, with serious adverse events occurring in seven (2%) of 329 patients in the tofacitinib 5 mg group, five (2%) of 330 in the tofacitinib 10 mg group, seven (2%) of 335 in the etanercept group, and two (2%) of 107 in the placebo group. Three (1%) of 329 patients in the tofacitinib 5 mg group, ten (3%) of 330 in the tofacitinib 10 mg group, 11 (3%) of 335 in the etanercept group, and four (4%) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events. INTERPRETATION: In patients with moderate-to-severe plaque psoriasis, the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice weekly and was superior to placebo, but the 5 mg twice daily dose did not show non-inferiority to etanercept 50 mg twice weekly. The adverse event rates over 12 weeks were similar for tofacitinib and etanercept. This study indicates that in the future tofacitinib could provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis. FUNDING: Pfizer Inc.

The goal of the study was to identify amino acid replacements in the structure of penicillin-binding protein PBP2, which may influence on the development of resistance N. gonorhoeae to the III cephalosporins generation. The gene penA of 50 strains of N. gonorrhoeae was sequenced: 20 strains with high sensitivity to ceftriaxone (MIC, Minimum Inhibitory Concentration, = 0.002 mg/L) and 30 strains with decreased sensitivity to ceftriaxone (MIC = 0.03-0.25 mg/L). The difference of MIC sensitivity between these strains was 30-250 times. Then nucleotide sequence was transformed into the amino acid sequence of PBP2 protein. Mutations in the gene penA and amino acid replacements in the protein PBP2 were found in 16 of 20 strains (80%) with high sensitivity to ceftriaxone and in all strains with decreased sensitivity to ceftriaxone. Amino acid replacements in the PBP2 protein were compared with amino acid replacements in groups, which characterize the PBP2 structure in accordance with the international classification Ito M. The amino acid replacement of PBP2 at positions 346, 505, 511, 517, 543, 567, 575, 576 are associated with V group by Ito M and have features of resistance of N. gonorrhoeae to ceftriaxone authentically (OR = 3.9 ± 2.5; χ2 = 4.9; p0.05). It was shown that the replacement of glycine to serine at position 543 of PBP2 in the analyzed strains induced the multiple increase of resistance to ceftriaxone. These data may be significant as showing strong influence of amino acid replacements at positions 346, 505, 511, 517, 567, 575 and, in particular, 543 for development of resistance N. gonorrhoeae strains to ceftriaxone.

Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis.In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14).Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]).Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments.Janssen ResearchDevelopment.