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.

Antibiotic-Drug Interactions in the Intensive Care Unit: A Literature Review.

Interactions between drugs are a common problem in Intensive Care Unit patients, as they mainly have a critical condition that often demands the administration of multiple drugs simultaneously. Antibiotics are among the most frequently used medications, as infectious diseases are often observed in ICU patients. In this review, the most important antibiotic-drug interactions, based on the pharmacokinetic and pharmacodynamic mechanisms, were gathered together and described. In particular, some of the most important interactions with main groups of antibacterial drugs were observed in patients simultaneously prescribed oral anticoagulants, NSAIDs, loop diuretics, and valproic acid. As a result, the activity of drugs can be increased or decreased, as dosage modification might be necessary. It should be noted that these crucial interactions can help predict and avoid negative consequences, leading to better patient recovery. Moreover, since there are other factors, such as fluid therapy or albumins, which may also modify the effectiveness of antibacterial therapy, it is important for anaesthesiologists to be aware of them.

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.

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.

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.

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.

Secukinumab for the Treatment of Psoriasis in Pediatrics: Patient Selection and Acceptability.

Psoriasis (PsO) is a chronic, systemic, immune-mediated inflammatory skin disease affecting 1% to 5% population worldwide. In one-third of patients, the first symptoms of PsO manifest in childhood, with a mean age of nine years. Psoriasis in children under 16 years of age constitutes 4% of dermatological problems in this age group. Chronic inflammation of the skin observed in PsO is associated with a development of potentially serious comorbidities, including psoriatic arthritis, hypertension, metabolic syndrome, cardiovascular diseases, inflammatory bowel disease, depression and anxiety. It is reported that among children with psoriasis between 5 and 16 years of age health-related quality of life is reduced by 30.5%. Early diagnosis and effective treatment are crucial in pediatric psoriatic patients to avoid future complications and stigmatization. Treatment for psoriasis consists of a range of topical medications, phototherapy and non-biologic and biologic systemic therapies. Approved biologics for PsO in pediatric patients include etanercept, adalimumab, ustekinumab, ixekizumab and secukinumab. Secukinumab, a recombinant, fully human monoclonal antibody targeting IL-17A, was approved by the EMA (2020) and FDA (2021) in pediatric patients above 6 years of age for the treatment of moderate to severe plaque psoriasis who are candidates for systemic therapy. This review discusses the selection and acceptability of secukinumab in children with psoriasis.

Promising Immune Treatment of Advanced Cutaneous Squamous Cell Carcinoma with Cemiplimab-Real-World Experience in the Global SARS-CoV-2 Pandemic.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. The standard curative treatment is surgical resection, but the treatment of locally advanced and metastatic disease apart from radiotherapy is currently based on cemiplimab. Cemiplimab has demonstrated efficacy in the treatment of advanced and metastatic cSCC in clinical trials, although real-world data are still limited. We present four cases of cSCC, which showed a tremendous response to cemiplimab-one patient achieved complete response and three of them achieved partial response. Immunotherapy with cemiplimab, a recently approved PD1 inhibitor, is an important addition to the cutaneous oncology therapeutic options that may be considered in patients with advanced disease not amenable to surgery or radiotherapy. In all four cases, the patients postponed visits to the doctor because of the fear of SARS-CoV-2 infection or for administrative and organizational reasons declared difficult access to doctors caused by the pandemic.

Risk Factors and Clinicopathological Features for Developing a Subsequent Primary Cutaneous Squamous and Basal Cell Carcinomas.

BACKGROUND: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. METHODS: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. RESULTS: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. CONCLUSIONS: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.

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.

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.

Tumor of the Nose - A Rare Manifestation of a Metastatic Lung Cancer.

Lung cancer most often metastasizes to the central nervous system, bone and liver. Although metastases to the skin are quite rare, it is estimated that they may be the first clinical manifestation of this disease in 0.7%-12% of cases. Metastases to the skin are caused by adenocarcinoma (about 30%), squamous cell carcinoma (30%) and undifferentiated carcinoma (40%). Nasal tip metastases are extremely rare. They can be confused with more common skin problems, including non-melanoma skin cancers, rhinophyma, inflammatory tumors or infectious diseases. We report two patients with a tumor on the nose, which proved to be the first sign of the metastatic lung cancer.

COVID-19 in Patients with Atopic Dermatitis Treated with Dupilumab: Three Cases and a Literature Review.

There are limited clinical data on the impact of the SARS-CoV2 infection on patients with dermatological conditions treated with biologics. Dupilumab is a recombinant human IgG4 human monoclonal antibody that inhibits IL4 and IL13 signaling, and is used for moderate-severe atopic dermatitis treatment. We present three patients with atopic dermatitis (AD) treated with dupilumab who contracted COVID-19. In all patients, the infection had a mild course, and only in one, as documented by SCORAD, EASI, and DLQI scores, the condition of the skin deteriorated, and a prolonged positive PCR COVID-19 test was observed. The mechanism of dupilumab action and more evidence for IL13 importance in lung damage caused by SARS-CoV2 suggest a possible explanation for a mild-moderate course of the infection in treated AD patients. Based on current knowledge, there is evidence to continue dupilumab treatment in AD patients with mild-moderate COVID-19; however, careful assessment is needed for each patient.