Small intestinal bacterial overgrowth (SIBO) is a major yet underrecognized driver of gastrointestinal morbidity in systemic sclerosis (SSc). Disordered motility, fibrosis, and dysbiosis promote microbial stasis, malabsorption, and malnutrition, contributing substantially to impaired quality of life and survival. Diagnostic accuracy remains limited: jejunal aspirate culture is invasive, whereas breath testing offers only moderate sensitivity and specificity. Empirical antibiotic therapy yields transient symptom relief, but recurrence is common, and evidence guiding optimal eradication strategies is sparse. Adjunctive measures, including probiotics, prokinetics, and dietary interventions, remain variably applied, with heterogeneous outcomes across studies. Novel microbiome-targeted, neuromodulatory, and antifibrotic therapies are emerging as promising mechanism-based options. Bearing this in mind, this narrative review aims to consolidate current knowledge on SIBO eradication in SSc. We first outline the pathophysiological rationale and clinical relevance of bacterial overgrowth. We then synthesize available evidence for treatment strategies, appraise barriers to durable remission, and discuss implications for multidisciplinary management. Finally, we highlight emerging approaches, including microbiome-directed therapies, novel prokinetics, and antifibrotic interventions, and define priorities for future clinical research.

Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine.

This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance—receptor-level, post-receptor, and secretory—highlighting their distinct pathways and therapeutic implications. This model promotes personalized care by moving beyond the oversimplified ‘non-responder’ classification.

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.

Objectives: This study aimed to analyze the clinical presentation, diagnostic process, therapeutic approaches, pathological features, and treatment outcomes of children diagnosed with Wilms tumor (WT) and evaluate the time intervals from symptom onset to seeking medical attention and subsequent diagnosis. Patients and methods: This retrospective study reviewed the records of 18 children (11 males, 7 females; median age: 3.72 years; range, 0.13 to 8.33 years) diagnosed with WT who underwent surgery between January 1, 2010, and December 31, 2023. Data on demographics, clinical presentation, treatment, and outcomes were collected and analyzed. All patients underwent radical nephrectomy and received preoperative and postoperative chemotherapy as per the UMBRELLA protocol of the International Society of Pediatric Oncology Renal Tumor Study Group. Results: The median age at diagnosis was 37 months. The most common presenting sign was a palpable abdominal mass (100%), followed by abdominal swelling (61%) and distension (67%). The mixed histopathological type was most prevalent (50%). The median time from symptom onset to seeking medical attention was 13.9 days, and the median from initial medical consultation to diagnosis was 9.9 days. Complications occurred in three (17%) patients, and one (6%) patient experienced relapse. The survival rate was 94%. Conclusion: This study's survival and relapse rates are comparable to global data, reflecting advances in the diagnosis and management of WT at our institution. However, further research is needed to address the study’s limitations and enhance outcomes, particularly in resource-limited settings.

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.

Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.

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.