The Influence of Acid-Base Balance on Anesthetic Muscle Relaxants: A Comprehensive Review on Clinical Applications and Mechanisms.

Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.

Does the effectiveness of biological medications in the treatment for psoriasis depend on the moment of starting therapy? A preliminary study.

Introduction: It is well known that biological medications acting on selected elements of the immune response are highly effective in psoriasis treatment. It is a common perception that psoriasis is a seasonal disorder with improvement in warmer months, however it has not been unequivocally confirmed. It is not known whether the time of year of starting systematic therapy for psoriasis influences treatment outcomes. Material and methods: Changes in psoriasis severity scores during treatment with biologics were investigated. The scores were recorded for 62 patients with moderate to severe psoriasis at the beginning, after 1, 4 and 7 months of the therapy. Patients were divided into two groups: those beginning the treatment in the cold period of the year (November-March) and in the warm period (May-September). The seasonal groups were also divided into subgroups according to the type of biologics used: interleukin inhibitors and tumor necrosis factor α (TNF-α) inhibitors. Results of the treatment were analysed using standard statistical tests of differences between samples. Results: After 1 and 4 months of the therapy, better efficacy of interleukin inhibitors was found in patients starting treatment in summer. The course of psoriasis improvement in patients taking TNF-α inhibitors resulted in consistent improvement regardless of the season. The outcome of the treatment after 7 months was similar for both seasonal groups and types of biologics used. Conclusions: Our understanding of the effectiveness of the treatments depending on the time of the year combined with the type of biologics used, may further improve results of the therapy.

The effectiveness of omalizumab therapy in patients with chronic spontaneous urticaria: the experience of a single-centre study in Poland.

Introduction: Omalizumab, which is a recombinant, humanised anti-immunoglobulin-E antibody, is the only approved drug for antihistamine refractory chronic spontaneous urticaria (CSU). It has been reported that it is an effective and safe drug, but the data about long-term effectiveness are still lacking. Aim: To perform a retrospective analysis of the patients with CSU treated with omalizumab at the dermatology department to assess effectiveness of omalizumab therapy in the single centre in Poland. Material and methods: A two-and-a-half-year retrospective analysis of patients with CSU undergoing the therapy with omalizumab was conducted. Patients' data were analysed for many factors such as age, gender, severity indexes (UAS7, DLQI), duration and effects of the treatment used. Results: Sixty-one patients with CSU have been treated with omalizumab in the drug program. The number of female patients - 42 (68.9%) significantly dominated over the number of male patients - 19 (31.1%). The mean UAS7 during the first course of treatment declined from 33.2 to 2.8, during the second from 30.9 to 1.7 and during the third 32.7 to 2.5. In case of DLQI the mean scores decrease from 18 to 2.1 in the first cycle, from 16.9 to 1.9 in the second and from 18.6 to 1.1 in the third. Conclusions: Our study confirmed that omalizumab is an effective medicine in a long-term treatment which improves a physical as well as psychological condition of the patients with antihistamine-resistant CSU. To our knowledge, it is the first study in Poland that presents omalizumab effectiveness during three courses of treatment.

The Structure of Ordered Mesoporous Materials Synthesized from Aluminum Phyllosilicate Clay (Bentonite).

This paper reports the synthesis and structural analysis of mesoporous silica materials with the use of aluminum phyllosilicate clay (bentonite) as an alternative silica source. In the proposed synthesis, bentonite, as natural aluminosilicate, was used instead of commercially available and quite expensive tetraethyl orthosilicate (TEOS) silica source. The objective of the research study was to determine the effect of aluminum loading in the mesoporous silica body for ordering structure, porosity, and potential sorption capacity to thorium ions. The unique direction developed in this procedure is focused on preparing advanced materials from natural sources with their own desired functionality and general availability. The applied procedure based on the classic, one-step synthesis of SBA-15 silicates was modified by gradually increasing the bentonite amount with simultaneous reduction of the TEOS content. The structural and morphological characterization, as well as evaluation of the porous structure of the obtained materials, was performed using powder wide-angle X-ray diffraction (XRD), small-angle scattering (SAXS), transmission and scanning electron microscopy (TEM, SEM), low-temperature nitrogen adsorption-desorption methods and potentiometric titration. The new, cost-effective composites for the removal of Th(IV) ions are proposed. The synergistic effect of expanding the porous surface using bentonite as a silica precursor and the presence of thorium-binding groups (such as Al2O3) is indicated.

Off-label medications in the treatment of hospitalized children with atopic dermatitis.

Introduction: Off-label prescribing is defined as using medications outside conditions of the marketing authorisation including their licensed indications, dosage, age and route. Atopic dermatitis (AD) is the most common chronic skin condition in children which can be related to a high level of off-label prescribing. Aim: To investigate the frequency of off-label prescribing and the medications involved in relation to indications and age in paediatric patients hospitalized for atopic dermatitis in a paediatric dermatology ward in 2019. Material and methods: One hundred and seventy-five consecutive discharge letters of patients were analysed regarding gender, age and medications used during hospital stay and prescribed on discharge. Each medication was checked against the licensed age and indications. Results: Altogether 564 medications were prescribed, including 289 topical and 275 systemic ones with 278 prescribed off-label (49.1%). Out of 289 topical medications, 113 (39.1%) were prescribed off-label regarding indications and 34 (11.76%) regarding the age of the patients. In the systemic medications group, 96 (34.53%) were prescribed off-label as AD was not a registered indication and 35 (12.73%) as the age of the patients was outside the marketing authorization. The most frequent medications prescribed off-label were antihistamines, antibiotics and corticosteroids. Conclusions: Prescribing off-label in paediatric population is a common practice. Both topical and systemic medications are frequently used in AD patients off-label, therefore doctors should be familiar with the pitfalls of prescribing beyond the licensed indications and age.

Pros and cons of using systemic acitretin in the paediatric population.

Acitretin, a synthetic analogue of vitamin A is widely used in dermatology. It has an important role in the treatment of psoriasis and keratinization disorders. In adults its safety and efficacy has been proven in many studies, but there are some concerns regarding the use of acitretin in paediatric population, especially in high doses and as a long-term therapy. In this article we present the main indications of acitretin in children as well as the positive and negative aspects of acitretin treatment in this age population.

The role of inflammasomes in cutaneous pathology.

Inflammasomes are large intracellular multiprotein complexes, which constitute a novel part of the innate immune system. In response to danger signals from pathogens or other harmful agents, inflammasomes assemble resulting in production of the inflammatory cytokines. We discuss recent knowledge of the role of deregulated inflammasome activity in skin pathologies such as autoinflammatory diseases as well as common skin diseases such as psoriasis and atopic dermatitis. We also present an insight into the activation and effector mechanisms of inflammasomes in skin carcinogenesis. The complex influence of inflammasome on cutaneous disorders raises new challenges and opportunities for the treatment of skin diseases.

Gut microbiota in alopecia areata.

Introduction: In the past few years, the advancement of 16S rRNA metagenomic analysis sequencing has enabled assessing the impact of gut microbiota on the development of skin disease. Alopecia areata (AA) is a nonscarring hair loss disorder with an unknown etiopathogenesis, however, it is hypothesised that a combination of genetic and environmental factors might be involved. Although numerous studies have shown that the microbiome plays a key role at the beginning of skin diseases, the link between AA and gut dysbiosis remains unclear. Aim: To analyse the intestinal microbiome in patients suffering from AA. Material and methods: The study describes the conceivable involvement of gut microbiota in the unclear pathogenesis of AA. We enrolled 25 patients, over 18 years of age with an active state of AA who donated their stool samples. The samples were examined at the human gut microbial community at the species level by metataxonomic analysis of the full-length 16S V3-V4 sequencing. Results: The four major genera that constitute the microbiome's core are Lachnoclostridium, Bifidobacterium, Streptococcus, and Eubacterium, as well as three major phyla: Firmicutes, Proteobacteria, and Actinobacteria. Firmicutes and Proteobacteria are overrepresented in the microflora, which might suggest a disturbed microflora. Furthermore, the composition of bacterial communities suggests a loss of overall richness and a decrease in taxonomic diversity across all samples. Conclusions: This study describes, for the first time, the characteristics of the gut microbiome in AA patients and may provide new insight into the gut microbiome that may play a role in the development of AA.

Alterations of the Skin and Gut Microbiome in Psoriasis and Psoriatic Arthritis.

Numerous scientific studies in recent years have shown significant skin and gut dysbiosis among patients with psoriasis. A significant decrease in microbiome alpha-diversity (abundance of different bacterial taxa measured in one sample) as well as beta-diversity (microbial diversity in different samples) was noted in psoriasis skin. It has been proven that the representation of Cutibacterium, Burkholderia spp., and Lactobacilli is decreased and Corynebacterium kroppenstedii, Corynebacterium simulans, Neisseria spp., and Finegoldia spp. increased in the psoriasis skin in comparison to healthy skin. Alterations in the gut microbiome in psoriasis are similar to those observed in patients with inflammatory bowel disease. In those two diseases, the F. prausnitzii, Bifidobacterium spp., Lactobacillus spp., Parabacteroides and Coprobacillus were underrepresented, while the abundance of Salmonella sp., Campylobacter sp., Helicobacter sp., Escherichia coli, Alcaligenes sp., and Mycobacterium sp. was increased. Several research studies provided evidence for the significant influence of psoriasis treatments on the skin and gut microbiome and a positive influence of orally administered probiotics on the course of this dermatosis. Further research is needed to determine the influence of the microbiome on the development of inflammatory skin diseases. The changes in microbiome under psoriasis treatment can serve as a potential biomarker of positive response to the administered therapy.

The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review.

Inflammasomes are high-molecular-weight protein complexes that may cleave the two main proinflammatory cytokines, pro-interleukin-1ß and pro-interleukin-18, into active forms, and contribute to psoriasis. Despite recent advances made in the pathogenesis of psoriasis, mainly studied as an autoimmune condition, activation of immune response triggers of psoriasis is still not completely understood. Recently, focus was placed on the role of inflammasomes in the pathogenesis of psoriasis. Multiple types of inhibitors and activators of various inflammasomes, inflammasome-related genes, and genetic susceptibility loci were recognized in psoriasis. In this systemic review, we collect recent and comprehensive evidence from the inflammasomes, NLRP1, NLRP3, and AIM2, in pathogenesis of psoriasis.

Psoriasis and Atherosclerosis-Skin, Joints, and Cardiovascular Story of Two Plaques in Relation to the Treatment with Biologics.

It is known that both psoriasis (PSO) limited to the skin and psoriatic arthritis (PSA) increase the risk of cardiovascular complications and atherosclerosis progression by inducing systemic inflammatory response. In recent decades, the introduction of biological medications directed initially against TNF-α and, later, different targets in the inflammatory cascade brought a significant breakthrough in the efficacy of PSO/PSA treatment. In this review, we present and discuss the most recent findings related to the interplay between the genetics and immunology mechanisms involved in PSO and PSA, atherosclerosis and the development of cardiac dysfunction, as well as the current PSO/PSA treatment in view of cardiovascular safety and prognosis.

Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations.

INTRODUCTION: Chronic venous disease (CVD) is a disabling condition affecting about 1% to 3% of the general population. Besides varicose veins, CVD can result also in the formation of severe skin lesions, especially venous ulcerations (VU). The exact mechanism of VU is still unknown. AIM: To evaluate immunoexpression of vascular endothelial growth factor (VEGF) and cathepsin K in healthy individuals and patients with VU. MATERIAL AND METHODS: The study included 12 patients with venous ulcers and 10 healthy individuals who served as controls; both groups were sex- and age-matched. Biopsy samples were obtained from lower leg areas and submitted to histochemical analysis. RESULTS: There was a significant difference between the study group and the control group in cathepsin K expression (1.007 ±0.3 vs. 0.22 ±0.2, respectively, p < 0.001) and VEGF expression (1.17 ±0.59 vs. 0.27 ±0.19, respectively, p < 0.001). Additionally, the microvessel density (per mm2) differed significantly between the study group and the control group (97.6 ±28.81 vs. 59.32 ±12.71, respectively, p < 0.001). We found no correlation between cathepsin K and microvessel density, and cathepsin K and VEGF in both groups, but there was a significant correlation between microvessel density and VEGF immunoexpression in the study group (r = 0.82, p = 0.002). CONCLUSIONS: Increased immunoexpression of VEGF and cathepsin K suggests that both of these proteins may play a role in VU development.

Prospective Clinical Study: Full-Body Blue Irradiation in the Treatment of Atopic Dermatitis.

INTRODUCTION: Ultraviolet-free (UV-free) blue light phototherapy has emerged as a promising option due to its reported efficacy and minimal adverse effects. This study aims to evaluate the effectiveness of full-body blue light irradiation in both adult and pediatric patients with atopic dermatitis (AD), assessing its impact on skin condition and mood regulation by investigating serum concentrations of serotonin and kynurenine pathway metabolites. METHODS: 20 patients (age 9-45) with moderate and severe AD were included in the study. Treatment consisted of 10 irradiations with Full Body Blue device (453 nm). Serum concentrations of serotonin, quinolinic acid, kynurenic acid, tryptophan, and kynurenine were measured before and after irradiations. RESULTS: After 10 sessions of full blue light therapy (453 nm) statistically significant improvements were observed in Eczema Area Severity Index (EASI 13.16 vs. 8.65; p = 0.00016), SCORing Atopic Dermatitis (SCORAD 44.99 vs. 23.73; p < 0.00001), Visual Analogue Scale (VAS 6.53 vs. 3.95; p = 0.00251), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001). Moreover, statistically significant decrease in Dermatology Life Quality Index (DLQI) was noted (14.37 vs. 7.42; p = 0.00351). Additionally, increase in the serum concentration of serotonin was observed after completing 10 irradiation sessions (median 139.77 mg/ml vs. 274.92 mg/ml; p < 0.00001). CONCLUSION: Blue light may be a promising and safe treatment in patients with AD. It might also positively influence mood. Further investigations are needed to confirm those findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06516783.

Case report: Successful treatment with biologics in a pediatric patient with a severe inflammatory skin disease and novel CARD14 mutation.

CARD14 (caspase activation and recruitment domain) mutations have been associated with psoriasis vulgaris, psoriatic arthritis, generalized and palmoplantar pustular psoriasis, pityriasis rubra pilaris, and atopic dermatitis. We present a pediatric patient with a novel CARD14: c.394A > T/- (Ile123Phe) mutation, diagnosed with CARD14-associated papulosquamous eruption (CAPE), who was successfully treated with biological treatment.