Pain remains one of the most burdensome symptoms in rheumatoid arthritis (RA), often persisting despite inflammatory remission and profoundly impairing quality of life. This review aimed to evaluate the clinical efficacy and mechanistic pathways by which Janus kinase (JAK) inhibitors alleviate RA-related pain. Evidence from randomized clinical trials demonstrates that JAK inhibitors have demonstrated rapid and significant pain relief, often exceeding that of methotrexate or biologic DMARDs. Improvements in patient-reported pain scores seem to typically emerge within 1–2 weeks and are sustained over time. Beyond anti-inflammatory effects, JAK inhibitors modulate central sensitization and nociceptive signaling by attenuating IL-6 and GM-CSF activity, reducing astrocyte and microglial activation, and downregulating nociceptor excitability in dorsal root ganglia and spinal pathways. Preclinical models further suggest that JAK inhibition interrupts neuroimmune feedback loops critical to chronic pain maintenance. Comparative and network meta-analyses consistently position JAK inhibitors among the most effective agents for pain control in RA. However, individual variability in response, partly due to differential JAK-STAT activation and cytokine receptor uncoupling, underscores the need for biomarker-guided treatment approaches. JAK inhibitors represent a mechanistically distinct and clinically impactful class of therapies that target both inflammatory and non-inflammatory pain in RA. Their integration into personalized pain management strategies offers a promising path to address one of RA’s most persistent unmet needs.

Introduction: It is suggested that bladder cancer (BC) development is linked to glutathione S-transferase (GST) enzymes. This study aimed to determine the correlation between glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase Theta 1 (GSTT1), and N-acetyltransferase 2 (NAT2) variants with BC progression and recurrence rating. Materials and methods: This study included 105 Bosnian and Herzegovinian subjects: 60 patients with histopathologically confirmed BC and 45 controls without urological diseases. GSTM1, GSTT1 (rs36631 and rs17856199, respectively), and NAT2 (rs1799929, rs1799930, and rs1799931) were investigated. Results: Both one- and five-year probabilities of progression were not significantly different in GSTM1 and NAT2 polymorphisms. One-year probability of progression was significantly higher in the GSTT1 T-- (null) than the T++ (wildtype) genotype (14.7% (±6.9) vs. 8.9% (±6.7), respectively; p=0.048). Five-year probability of progression was significantly higher in the GSTT1 T-- than the T++ genotype (39.4% (±14.7) vs. 25.5% (±16.6), respectively; p=0.045). THE GSTT1 T-- genotype was an independent predictor in the one-year probability of recurrence and progression (p=0.03 and p=0.01, respectively). GSTT1 T-- genotype and age were independent predictors for the five-year probability of recurrence (p=0.032 and p=0.04, respectively) as well as independent predictors of the five-year probability of progression (p=0.012 and p=0.03, respectively). Conclusions: The GSTT1 T-- genotype was an independent predictor in the one- and five-year probabilities of both recurrence and progression of BC. GSTT1 rs17856199 may be a significant factor in the development of tumors and the course of disease in Bosnian and Herzegovinian BC patients.

Introduction: The risk of cognitive impairment, including dementia and moderate cognitive impairment (MCI), is higher in patients with diabetes and prediabetes. The need for early diagnosis biomarkers has increased due to the rise in the prevalence of type 2 diabetes mellitus (T2DM) and its related cognitive problems worldwide, as well as the lack of clear biochemical indicators and efficient treatments for dementia or cognitive decline. Chronic low-grade inflammation, reflected by elevated complete blood count-derived inflammatory indices (CBCIIs), has been implicated in both metabolic dysregulation and neurodegeneration. However, their relationship with cognitive impairment in T2DM remains insufficiently explored. The objective of this study was to investigate the association between CBCIIs and cognitive function in patients with T2DM. Methods and materials: This cross-sectional observational study included 116 patients with T2DM recruited from diabetes counseling centers in the Public Institution Health Center of Sarajevo Canton, Bosnia and Herzegovina. Based on the assessed cognitive status, patients with T2DM were divided into two groups: with cognitive impairment (n= 76) and without cognitive impairment (n=40). A validated assessment tool, the Montreal Cognitive Assessment (MoCA), a quick test designed to screen for milder forms of cognitive impairment, was used for cognitive screening. Venous blood samples were analyzed for standard complete blood count parameters, from which 11 CBCIIs were calculated: neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-platelet ratio (NPR), neutrophil-to-lymphocyte-to-platelet ratio (NLPR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), lymphocyte-to-monocyte ratio (LMR), and monocyte-to-neutrophil ratio (MNR).. Results: The results of our study showed that NLR, dNLR, NPR, NLPR, PLR, MLR, SII, AISI, and SIRI were significantly higher in the group of T2DM patients with cognitive impairment compared to the group without cognitive impairment. On the other hand, LMR and MNR were significantly lower in the group of T2DM patients with cognitive impairment compared to the group without cognitive impairment (p<0.05). The MoCA score was significantly negatively correlated with NLR, dNLR, NPR, NLPR, and SII, and positively with MNR (p<0.05) Conclusion: Elevated CBCIIs are significantly associated with cognitive impairment in patients with T2DM. These inexpensive and widely available indices may serve as adjunctive markers for early cognitive screening in this population.

Background/Objectives: Children remain underserved in pharmaceutical development, with off-label prescribing still prevalent in part due to a lack of age-appropriate formulations. This study aimed to evaluate the national uptake of Pediatric Use Marketing Authorisation (PUMA)-labelled medicines in Croatia from 2017 to 2024. Methods: We conducted a retrospective, descriptive pharmacoepidemiological study using the IMS (Intercontinental Medical Statistics) and IQVIA (Information, Quintiles, VIA; formerly IMS Health and Quintiles) datasets to track utilization and the expenditure of all PUMA products. Utilization was assessed using defined daily doses per 1000 inhabitants per day (DDDs/1000/day) and annual product dispensation counts. Results: Over the study period, five PUMA medicines entered the Croatian market, with usage rising from 853 packages in 2018 to 9232 in 2024. The DDDs/1000/day increased 33.8-fold, while the expenditure escalated nearly 5.8-fold, from EUR 145,898 to EUR 844,145. Midazolam and melatonin were the most frequently prescribed, yet the overall utilization remained marginal relative to pediatric needs. Conclusions: In conclusion, while regulatory availability of PUMA products has improved, their clinical adoption in Croatia remains limited. Addressing economic, educational, and policy barriers is essential to close the gap between authorization and utilization.

Simple Summary The alarming rise in early-onset cancers among adolescents and young adults parallels the global surge in ultra-processed food (UPF) consumption. Beyond poor nutrition, UPFs act as “Trojan horses,” introducing biologically active compounds, particularly endocrine-disrupting chemicals (EDCs), that interfere with hormonal regulation, immune responses, and microbial balance. These exposures, often occurring during vulnerable developmental stages, disrupt endocrine signalling; promote chronic, low-grade inflammation; alter the gut microbiota; and induce epigenetic changes, thereby creating a permissive environment for carcinogenesis. Key EDCs migrate from packaging into foods, while additives and high-temperature processing further compound the risk. This review integrates emerging evidence across disciplines to highlight UPFs as silent but systemic disruptors of metabolic and genetic homeostasis. The “Trojan horse” model reframes UPFs as long-term, multifactorial risk factors, underscoring the need for multi-omics research and personalised dietary strategies to assess and mitigate cancer risks in younger populations.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that extends beyond musculoskeletal and dermatologic involvement to elevate cardiometabolic risk. Emerging evidence highlights the critical role of systemic inflammation in metabolic dysregulation, accelerating insulin resistance, dyslipidemia, and oxidative stress, all of which contribute to the increased burden of cardiovascular disease in PsA. This review explores the intricate interplay between inflammatory mediators—such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17),—adipokine imbalances, and lipid metabolism abnormalities, all of which foster endothelial dysfunction and atherosclerosis. The dysregulation of adipokines, including leptin, adiponectin, and resistin, further perpetuates inflammatory cascades, exacerbating cardiovascular risk. Additionally, the metabolic alterations seen in PsA, particularly insulin resistance and lipid dysfunction, not only contribute to cardiovascular comorbidities but also impact disease severity and therapeutic response. Understanding these mechanistic links is imperative for refining risk stratification strategies and tailoring interventions. By integrating targeted immunomodulatory therapies with metabolic and cardiovascular risk management, a more comprehensive approach to PsA treatment can be achieved. Future research must focus on elucidating shared inflammatory and metabolic pathways, enabling the development of innovative therapeutic strategies to mitigate both systemic inflammation and cardiometabolic complications in PsA.