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.

Importance Rapid digitalization of health care and a dearth of digital health education for medical students and junior physicians worldwide means there is an imperative for more training in this dynamic and evolving field. Objective To develop an evidence-informed, consensus-guided, adaptable digital health competencies framework for the design and development of digital health curricula in medical institutions globally. Evidence Review A core group was assembled to oversee the development of the Digital Health Competencies in Medical Education (DECODE) framework. First, an initial list was created based on findings from a scoping review and expert consultations. A multidisciplinary and geographically diverse panel of 211 experts from 79 countries and territories was convened for a 2-round, modified Delphi survey conducted between December 2022 and July 2023, with an a priori consensus level of 70%. The framework structure, wordings, and learning outcomes with marginal percentage of agreement were discussed and determined in a consensus meeting organized on September 8, 2023, and subsequent postmeeting qualitative feedback. In total, 211 experts participated in round 1, 149 participated in round 2, 12 participated in the consensus meeting, and 58 participated in postmeeting feedback. Findings The DECODE framework uses 3 main terminologies: domain, competency, and learning outcome. Competencies were grouped into 4 domains: professionalism in digital health, patient and population digital health, health information systems, and health data science. Each competency is accompanied by a set of learning outcomes that are either mandatory or discretionary. The final framework comprises 4 domains, 19 competencies, and 33 mandatory and 145 discretionary learning outcomes, with descriptions for each domain and competency. Six highlighted areas of considerations for medical educators are the variations in nomenclature, the distinctiveness of digital health, the concept of digital health literacy, curriculum space and implementation, the inclusion of discretionary learning outcomes, and socioeconomic inequities in digital health education. Conclusions and Relevance This evidence-informed and consensus-guided framework will play an important role in enabling medical institutions to better prepare future physicians for the ongoing digital transformation in health care. Medical schools are encouraged to adopt and adapt this framework to align with their needs, resources, and circumstances.

Background In addition to age, body mass index (BMI), abdominal circumference, and parity, measuring the mother's pelvic diameters is a non-invasive, cost-effective method that can assist gynecologists in determining the optimal management of labor. Our study aimed to examine the associations between maternal age, pelvic diameters, BMI, abdominal circumference, and parity with delivery outcomes and investigate differences in pelvic diameters in relation to maternal age, BMI, delivery outcomes, parity, and episiotomy. Materials and methods The observational, cross-sectional study included 108 pregnant women in the active phase of labor who were admitted to the Gynecological Clinic at the Clinical Center University of Sarajevo. During admission, maternal data were registered: age, body height, body weight, abdominal circumference, and BMI. Using a pelvinometer, pelvic diameters were recorded: interspinous diameter (DS), intertrochanteric diameter (DT), intercristal diameter (DC), and external conjugate (CE). The Anterior Pelvic Index (API) was calculated by dividing the DS by the participants' height and multiplying the result by 100. Data were analyzed using SPSS Statistics for Windows, Version 17 (Released 2008; SPSS Inc., Chicago, United States). Results Women who underwent cesarean section were significantly older compared to those with spontaneous vaginal delivery. A significant correlation was observed between maternal age, BMI, and delivery outcomes. Obese women had significantly higher DT compared to women with normal or overweight BMI. Primiparous and multiparous women differed significantly in CE, while other pelvic diameters did not differ. Women with episiotomy had significantly lower DS and CE diameters compared to those without episiotomy during vaginal delivery. Conclusion Maternal age, BMI, and pelvic diameters are significant delivery outcome determinants; our findings suggest that these parameters deserve to be included in delivery outcome assessment as they provide substantial information in the journey of achieving personalized delivery care and decision-making.

Background and Objectives: This study aimed to investigate the novel adiponectin–resistin (AR) index as a predictor of the development of metabolic syndrome (MetS) in individuals with type 2 diabetes mellitus (T2DM). MetS is common in T2DM and increases cardiovascular risk. Adiponectin and resistin, adipokines with opposing effects on insulin sensitivity and inflammation, make the AR index a potential marker for metabolic risk. Materials and Methods: This prospective observational study included 80 T2DM participants (ages 30–60) from Sarajevo, Bosnia and Herzegovina, over 24 months. The participants were divided into two groups: T2DM with MetS (n = 48) and T2DM without MetS (n = 32). Anthropometric data, biochemical analyses, and serum levels of adiponectin and resistin were measured at baseline and every six months. The AR index was calculated using the formula AR = 1 + log10(R) − 1 + log10(A), where R and A represent resistin and adiponectin concentrations. Logistic regression identified predictors of MetS. Results: T2DM patients who developed MetS showed a significant decline in adiponectin levels (40.19 to 32.49 ng/mL, p = 0.02) and a rise in resistin levels (284.50 to 315.21 pg/mL, p = 0.001). The AR index increased from 2.85 to 2.98 (p = 0.001). The AR index and resistin were independent predictors of MetS after 18 months, with the AR index showing a stronger predictive value (p = 0.007; EXP(B) = 1.265). Conclusions: The AR index is a practical marker for predicting MetS development in T2DM participants, improving metabolic risk stratification. Incorporating it into clinical assessments may enhance early detection and treatment strategies.

ABSTRACT Background: The triglyceride/high-density lipoprotein (TG/HDL) ratio emerges as a promising marker for cardiovascular risk. However, the relationship between overall serum lipid levels and hemorrhagic stroke (HS) remains uncertain. Therefore, our study aims to explore the association between this novel index and mortality in HS patients. Methods: Utilizing a retrospective-prospective framework from January 2020 to August 2023, we scrutinized data from 104 hospitalized patients diagnosed with HS, with particular attention to their medical backgrounds and lipid profiles. Results: Age (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.032–1.125; P = 0.001), atrial fibrillation (OR, 0.237; 95% CI, 0.074–0.760; P = 0.015), glucose level (OR, 1.121; 95% CI, 1.007–1.247; P = 0.037), and TG/HDL index (OR, 0.368; 95% CI, 0.173–0.863; P = 0.020) emerged as independent predictors for in-hospital mortality, as determined by both univariable and multivariable logistic regression analyses. Conclusion: Our results add weight to the growing evidence backing the utility of the TG/HDL index in assessing cardiovascular risk among HS patients. They emphasize the necessity of adopting a comprehensive risk assessment and management strategy that incorporates both traditional markers and novel indicators.