Background/Objectives: This study assessed the impact of variations in autophagy-related genes (ATG) on baseline characteristics of cutaneous melanoma, laboratory parameters (including inflammatory biomarkers), response to therapy, and survival in patients treated with immune checkpoint inhibitors (ICIs) as first-line therapy. Methods: DNA was extracted from blood samples of 144 melanoma patients. Genotyping of ATG5 (rs2245214 and rs510432), ATG10 (rs1864183 and rs1864182), and ATG16L1 (rs2241880) was performed using an allelic discrimination method on the StepOnePlus^TM Real-Time PCR System. Correlations with laboratory parameters, response to therapy, and survival were assessed only in the subgroup of patients who received ICIs in first-line treatment (n = 74). Statistical significance was calculated, and p values were adjusted for multiple testing using the Benjamini–Hochberg False Discovery Rate (FDR). Results: Considering baseline characteristics of 144 patients, ATG5 rs2245214 showed a trend with regression (p = 0.042) and lymphovascular invasion (p = 0.05), while ATG16L1 rs2241880 was associated with lymphovascular invasion (p = 0.056), with corrected FDR q value for all histopathological characteristics of 0.076. In patients who received ICIs in first-line, ATG5 rs2245214 genotypes were associated with LDH (p = 0.001, q = 0.004) and the number of metastatic sites (p < 0.001, q = 0.004). Also, ATG5 rs2245214 was associated with neutrophil-to-lymphocyte ratio (NLR) (p = 0.036, q = 0.045) systemic immune-inflammation (SII) index (p = 0.038, q = 0.048) and pan-immune-inflammation value (PIV) (p = 0.031,q = 0.041), while ATG10 rs1864183 was associated with PIV (p = 0.047, q = 0.047). The association of ATG genotypes with disease control rate (DCR) was demonstrated for ATG5 rs2245214 (p = 0.013, q = 0.029) and ATG16L1 rs2241880 (p = 0.032,q = 0.032). Progression-free survival (PFS) was significantly associated with ATG10 rs1864183 (p = 0.023, q = 0.046). The significance of the ATG10 rs1864183 C/T genotype as a prognostic marker for progression was confirmed in both univariate and multivariate Cox proportional hazards regression analyses (p = 0.025, q = 0.028 and p = 0.022, respectively). Conclusions: This study shows that ATG5 rs2245214, ATG10 rs1864183, and ATG16L1 rs2241880 correlate with systemic inflammation, response to ICIs, and had a trend toward melanoma characteristics. However, these findings should be confirmed in larger patient cohorts.

Background/Objectives: Immunotherapy and targeted therapy improve melanoma survival but raise costs. Real-world cost and outcome data are scarce, especially in Central and Eastern Europe. We estimated per-patient costs and outcomes in Serbia’s public healthcare system. Methods: This retrospective, single-centre study assessed costs in 183 patients with cutaneous melanoma who received systemic therapy at a Serbian tertiary centre (2019–2026). Direct medical costs were reconstructed from invoices and discharge letters from the healthcare-sector perspective. Censoring-adjusted mean 24-month costs were estimated from diagnosis (n = 165) and treatment start (n = 179). Outcomes included overall survival (OS), real-world progression-free survival (rwPFS), and time to next treatment or death (TNT-D). Results: Mean 24-month costs per patient were EUR 66,466 (95% CI 58,465–75,334) from diagnosis (EUR 75,388 with the partitioned estimator), 94.7% for systemic therapy, and EUR 107,229 (95% CI 97,405–118,201) from treatment start. At diagnosis, costs were about twice as high in stages III–IV as in stages I–II. By stage at treatment start, costs were similar in stages III and IV (EUR 102,122 vs. 104,535) despite shorter stage IV survival (p < 0.001). Two-year OS was 91.5% for adjuvant and 51.9% for metastatic first-line intent. Conclusions: Systemic therapy drove costs, which were similar in stages III and IV despite poorer stage IV survival. The cost measurement starting point substantially affected estimates and should be reported.

Objectives: To analyze the structure of direct treatment costs for FUO and identify key cost-driving factors. Methods: A retrospective pharmacoeconomic analysis using a bottom-up approach was conducted on 71 patients treated for FUO at the Clinic for Infectious Diseases, University Clinical Centre Kragujevac, between 2016 and 2022. Treatment cost data were extracted from the electronic medical records. Results: The total direct cost was €81,655.20, with a mean of €1,150.07 ± 3,434.60 per patient with a median of €549.55 (IQR=€512.62). Major cost components included pharmacotherapy (49.40 %; €40,337.26), diagnostic procedures (30.52 %; €24,923.44), and hospitalisation (10.32 %; €8,324.00). Significant cost determinants were the following: gender, the Charlson comorbidity index, hospital stay duration, number of medications administered per patient, and number of specialist consultations. Conclusions: Pharmacotherapy, especially broad-spectrum antibiotics and antifungals, along with diagnostics and hospitalisation, are the main contributors to FUO treatment costs. Patient-specific factors, particularly comorbidities and service utilisation, play a significant role in determining overall healthcare expenditure.

Isotretinoin is an oral medicine prescribed for the management of severe acne that is insensitive to conventional therapy, including systemic antibiotics. Acute psychosis refers to a severe mental illness characterized by a loss of touch with realism, visions, delusions, confused thinking, and abnormal behaviors. The study aims to analyze and document these cases to better understand the potential relationship between isotretinoin use and the development of acute psychosis, as well as to find out which therapy is best for treating this problem. We searched the following electronic databases independently with no linguistic or date limit: PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and Serbian Citation Index (SCIndeks). Our results included 14 studies (13 case reports and 1 cohort study) with 18 individual cases. The oldest patient was 27 years old, and the youngest was 13 years old. Both genders were represented with 9 individuals each. We can conclude that, in addition to discontinuation of isotretinoin, therapy with olanzapine and eventually risperidone could improve the symptoms of psychosis caused by isotretinoin.

Background: Immune checkpoint inhibitors (ICIs) are effective against melanoma, but are often limited by adverse events (AEs). We aimed to characterise the incidence, characteristics and predictors of AEs. Methods: This ambispective study included 141 patients with melanoma (165 ICI treatment episodes) treated between March 2017 and April 2026. Predictors of AE occurrence, seriousness and severity were analysed per treatment episode and per AE using generalised estimating equations. Results: We recorded 206 AEs in 95 patients (67.4%). At least one AE occurred in 59.8% of pembrolizumab, 59.5% of nivolumab and 81.0% of nivolumab/ipilimumab episodes. Most AEs were Grade 1–2 (88.3%); skin disorders were the most frequent (29.1%) and endocrine AEs had the lowest resolution rate (3.2%). Time to first AE was shortest with nivolumab/ipilimumab (p < 0.001). Per episode, nivolumab/ipilimumab was associated with more serious AEs than nivolumab (p = 0.042) and, borderline, than pembrolizumab (p = 0.051), and with Grade 3–4 AEs (p = 0.001); the lower odds of AE with monotherapy were not significant (p = 0.063, 0.242). Systemic treatment for unresectable disease was associated with AE occurrence (p = 0.029), serious (p = 0.009) and Grade 3–4 AEs (p = 0.016), and BRAF mutation with AE occurrence (p = 0.029). Conclusions: Patients receiving combination immunotherapy and those treated for unresectable disease may warrant closer monitoring.