IL-17 inhibitors (IL-17i) are medicines used to treat dermatological and rheumatic diseases They belong to a class of medicines called biological disease-modifying anti-rheumatic drugs (bDMARDs). This class of drugs has had a major impact on the therapy of autoimmune diseases, being much safer and more effective than treatment with small molecules. At the same time, they have highly beneficial effects on skin and joint changes, and their efficacy has been extensively monitored and demonstrated in numerous clinical trials. More and more such drugs are still being discovered today to ensure the best possible treatment of these patients, but more frequently and relatively constantly three agents are used. Two of them (Secukinumab and Ixekizumab) inhibit IL-17A directly, and the third, Brodamulab, inhibits the IL-17A receptor. Although they are extremely effective in the treatment of these diseases, sometimes their administration has been associated with paradoxical effects, i.e., there is an exacerbation of the inflammatory process. Tough, clinical trials of IL-17i have described cases of exacerbation or even onset of inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, after administration of these drugs in patients previously diagnosed with psoriasis (PS), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). The pathophysiological mechanism of action is not well understood at present. One explanation would be that this hyperreactive inflammatory process would be triggered by Interferon 1 derived from dendritic plasma cells. Even though there are many reports in the recent literature about the role of IL17i in the onset of IBD, conclusions of studies do not converge. Some of them show an increased incidence of IBD in patients treated with IL17i, while some others affirm their safety of them. In the near future we will surely have more data emerging from ongoing meta-analyses regarding safety of use IL17i in patients who are at risk of developing IBD. Clinical and paraclinical evaluation (inflammatory intestinal markers) are carefully advised before recommending treatment with IL-17i and after initiation of treatment, and prospective surveillance by clinical and biomarkers of patients treated with IL-17i is absolutely essential to capture the onset of IBD.

Aminopeptidases are a group of enzymatic proteins crucial for protein digestion, catalyzing the cleavage of amino acids at the N-terminus of peptides. Among them are ERAP1 (coding for endoplasmic reticulum aminopeptidase 1), ERAP2 (coding for endoplasmic reticulum aminopeptidase 2), and LNPEP (coding for leucyl and cystinyl aminopeptidase). These genes encoding these enzymes are contiguous and located on the same chromosome (5q21); they share structural homology and functions and are associated with immune-mediated diseases. These aminopeptidases play a key role in immune pathology by cleaving peptides to optimal sizes for binding to the major histocompatibility complex (MHC) and contribute to cellular homeostasis. By their ability to remove the extracellular region of interleukin 2 and 6 receptors (IL2, IL6) and the tumor necrosis factor receptor (TNF), ERAP1 and ERAP2 are involved in regulating the innate immune response and, finally, in blood pressure control and angiogenesis. The combination of specific genetic variations in these genes has been linked to various conditions, including autoimmune and autoinflammatory diseases and cancer, as well as hematological and dermatological disorders. This literature review aims to primarily explore the impact of ERAP1 polymorphisms on its enzymatic activity and function. Through a systematic examination of the available literature, this review seeks to provide valuable insights into the role of ERAP1 in the pathogenesis of various diseases and its potential implications for targeted therapeutic interventions. Through an exploration of the complex interplay between ERAP1 and various disease states, this review contributes to the synthesis of current biomedical research findings and their implications for personalized medicine.

Infective spondylodiscitis (ISD), the infection of vertebral bodies and surrounding tissues, is a rare complication with major impact on the long-term survival of hemodialysis (HD) patients. Although the most frequent etiology is staphylococcal, identifying these pathogens in blood cultures and biopsy cultures is often difficult. This paper aims to present suitable antibiotic combinations for the treatment of these patients, which is usually challenging in the case of an unidentified pathogen. We presented the therapies applied for 13 HD patients and 19 patients without chronic kidney disease (CKD), diagnosed with ISD between 2013 and 2023 in Bihor County. The percentage of positive blood cultures was low in both groups (30.78% HD vs. 15.78% non-HD). The average length of antibiotic therapy was 5.15 weeks in HD patients and 6.29 weeks in non-HD patients. The use of Carbapenem alone (e.g., Meropenem) for an average of 19.6 days for patients in HD when the pathogen was not identified has proven to be efficient in most cases, similarly to using Vancomycin and Fluoroquinolone/Cephalosporines in combination. Regarding the non-CKD patients, the use of Clindamycin in various combinations for an average of 30.3 days has proven to be efficient in more than 90% of cases of ISD with a nonidentified pathogen. Within 2 years after ISD was diagnosed, 12 of the 13 HD patients passed away, mainly due to cardiovascular causes. Unfortunately, there are no guidelines in the literature concerning the empiric treatment of ISD in the particular case of HD patients. Upon checking the literature on PubMed and Google Scholar, only 10 studies provided relevant data regarding ISD treatment for HD patients. More data about the treatment and evolution of these patients is needed in order to elaborate a truly relevant metanalysis.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with musculoskeletal and extra-articular manifestations and associated cardiometabolic comorbidity. Brain-derived neurotrophic factor (BDNF) is involved in pain processing, neuroplasticity, inflammatory signaling, and metabolic regulation. The functional BDNF Val66Met polymorphism (rs6265) affects intracellular trafficking and activity-dependent BDNF secretion, but its clinical relevance in AS remains poorly characterized. This study evaluated the distribution of BDNF Val66Met and explored its associations with disease activity, inflammation, pain, depressive symptoms, and metabolic parameters in patients with AS. Methods: This single-center, cross-sectional study included 81 patients with AS and no healthy control group. Genotyping was performed using a tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) assay. Clinical assessment included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP), pain Numerical Rating Scale (NRS), and depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), together with CRP and metabolic measurements. ASDAS-CRP was designated as the primary clinical outcome. Statistical analyses included the Mann–Whitney U test, Fisher’s exact test, Spearman correlation with Benjamini–Hochberg false discovery rate correction, Hardy–Weinberg equilibrium testing, and exploratory multivariable linear and logistic regression. Results: The cohort comprised 81 patients (61 men and 20 women; mean age 53.2 ± 12.5 years). T-ARMS-PCR yielded 57 GG (70.4%) and 24 GA (29.6%) genotype calls, with no AA banding pattern observed; the Met allele frequency was 14.8%. The genotype calls were not independently confirmed by sequencing or restriction fragment length polymorphism analysis. No significant associations were identified between genotype and the clinical, inflammatory, or metabolic variables. Genotype was not associated with ASDAS-CRP after adjustment for age, sex, disease duration, current biologic-therapy status, and current smoking status (B = 0.045, 95% CI −0.238 to 0.328, p = 0.754; n = 80). After Benjamini–Hochberg correction, pain NRS remained correlated with BASDAI and CRP, while HADS-D remained correlated with BASDAI. Metabolic syndrome was present in 24 of 81 participants (29.6%) according to the harmonized Joint Interim Statement definition; medication use for individual metabolic components was not systematically available. Conclusions: No evidence of an association between BDNF Val66Met and disease activity, inflammatory markers, depressive symptoms, or metabolic parameters was found in this AS cohort. This study had 80% power to only detect an effect of Cohen’s d ≥ 0.69, and smaller genotype-associated differences cannot be excluded. The findings also describe the cardiometabolic profile of the cohort and the relationships among pain, inflammation, and depressive symptoms.