Tomislav Bulum

Diabetes and its chronic complications are still the leading global causes of mortality and disability

Background/Objectives: We aim to determine whether prior cataract surgery affects the intraocular pressure (IOP)-lowering effect of selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG). Methods: This prospective interventional cohort study initially included 92 patients with POAG who were inadequately controlled or intolerant to topical therapy and were treated with SLT. Of these, 84 patients completed all scheduled visits and constituted the final analyzed dataset. Patients were divided into phakic and pseudophakic groups, with cataract surgery performed at least one year before SLT in all pseudophakic eyes. All patients underwent standardized 360-degree SLT by a single specialist. The primary outcome was IOP reduction at one year. Secondary outcomes included percentage IOP reduction and treatment success, defined as ≥20% IOP reduction. Data were analyzed using Statistica^TM 14.0.1.25 (TIBCO Software Inc., Palo Alto, CA, USA, USA). Results: Before SLT, the median IOP was 20.5 mmHg in phakic eyes and 21 mmHg in pseudophakic eyes. One year after SLT, median IOP decreased insignificantly in phakic eyes (4.0 mmHg; p = 0.262), whereas it decreased significantly in pseudophakic eyes (5.5 mmHg; p = 0.004). At one year post-SLT, an IOP reduction of ≥20% was observed in 53.6% of phakic and 72.7% of pseudophakic eyes. Pseudophakic patients were significantly older than phakic patients, as expected, because age-related senile cataract is more common in older individuals, and the groups also differed by gender distribution. This gender imbalance was coincidental and reflected the non-randomized inclusion of POAG patients according to clinical need for SLT rather than predefined matching. In unadjusted analyses, one-year IOP reduction was positively associated with age (p = 0.048), pretreatment IOP (p < 0.001), and prior cataract surgery (p = 0.047). However, after adjusting for age, gender, and baseline IOP in a multivariate sensitivity analysis, prior cataract surgery was not an independent predictor of success; only pretreatment IOP predicted a significant reduction (p = 0.031) in the analysis of 84 eyes. Conclusion: Although pseudophakic eyes showed greater unadjusted IOP reduction after SLT over one year, lens status was not an independent predictor after adjustment for potential confounders. Therefore, the observed pseudophakic advantage should be interpreted as a hypothesis-generating association warranting further research into the effect of pseudophakia on SLT response.

The Mediterranean diet (MedDiet) has emerged as a promising dietary strategy for the prevention and management of type 2 diabetes mellitus (T2DM). This narrative review provides a comprehensive synthesis linking the biological pathways of the MedDiet with established clinical evidence. Adherence to this traditional dietary pattern—characterized by a high intake of fiber, complex carbohydrates, antioxidants, and healthy fats—has demonstrated significant benefits in terms of glycemic control, enhanced insulin sensitivity, and overall metabolic health. Mechanistically, the review explains how the MedDiet improves health by modulating key physiological processes, including anti-inflammatory and antioxidant pathways, the regulation of branched-chain amino acid metabolism, the enhancement of short-chain fatty acid production via gut microbiota modulation, and upregulated incretin effects. Importantly, this review explains how the MedDiet complements modern medications, including glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT-2) inhibitors. By integrating molecular mechanisms with human clinical outcomes, this narrative review addresses multiple aspects of the MedDiet in both the prevention and management of T2DM including glycemic control, weight management, and cardiovascular risk reduction, rendering it a valuable dietary strategy for both the prevention and treatment of this chronic condition.

Diabetes is a global pandemic and, with its chronic complications, represents a major health issue worldwide, as 12

Background: R wave amplitude in the aVL ECG lead (R_aVL) has been identified as a marker of cardiovascular (CV) risk, hypertension-mediated target organ damage (HMOD), and mortality in patients with arterial hypertension (AH), where R_aVL > 1.1 mV suggests left ventricular hypertrophy. However, the exact threshold for identifying high-risk patients has yet to be determined. Therefore, we compared R_aVL values among hypertensive patients with and without hypertensive urgencies (HUs) and healthy subjects, aiming to identify the predictors of elevated R_aVL and to compare its prognostic value with the SCORE 2 model. Methods: This cross-sectional study included 339 participants divided into three groups according to ambulatory blood pressure monitoring results: 100 patients with AH and HU from the emergency department, 134 patients with AH without HU, and 105 healthy subjects recruited from four family medicine practices. Basic laboratory parameters were determined, SCORE 2 risk was calculated, PWV was measured using oscillometry, and a standard 12-lead ECG was recorded in all participants. Results: Participants with AH and HU had the highest R_aVL values compared to those with AH without HU and healthy subjects (averages of 0.76 ± 0.24 mV, 0.49 ± 0.27, 0.22 ± 0.25, respectively; p < 0.001). Significantly higher R_aVL values were observed in males compared to females (0.56 ± 0.31 vs. 0.41 ± 0.34 mV; p < 0.001) and in non-dippers compared to dippers (0.56 ± 0.34 mV vs. 0.41 ± 0.31 in dippers; p < 0.001). Age, mean arterial pressure, PWV, and SCORE 2 were shown as independent predictors of R_aVL. Compared with SCORE 2, individuals with R_aVL > 0.40 mV had high CV risk (sensitivity of 58.16%, specificity of 73.68%; p < 0.001). Conclusions: In this study, R_aVL demonstrated good prognostic value for CV risk stratification. However, larger studies are needed to determine a precise high-risk threshold to improve CV risk estimation and HMOD detection in patients with marginal SCORE 2 CV risk.

Background: Hypertrophic cardiomyopathy (HCM) is associated with an elevated risk of ventricular arrhythmias and sudden cardiac death (SCD) despite contemporary therapy. Cardiac myosin inhibitors directly target sarcomeric hypercontractility and have demonstrated consistent symptomatic, hemodynamic, and structural benefits in randomized controlled trials (RCTs). However, their effects on malignant ventricular arrhythmias and SCD remain uncertain. This meta-analysis aimed to evaluate the incidence of ventricular arrhythmias and SCD with cardiac myosin inhibitor therapy in HCM. Methods: We conducted a meta-analysis of RCTs evaluating mavacamten or aficamten in patients with HCM. PubMed was systematically searched through September 2025. Eligible trials randomized myosin inhibitors versus control and reported ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD. Results: Seven RCTs including 1519 patients (779 myosin inhibitor; 740 control) were analyzed. Eight composite VT/VF/SCD events (1.03%) occurred in the treatment group compared with twelve (1.62%) in controls. Time-standardized incidence rates were 1.48 versus 2.36 per 100 patient-years, respectively. The pooled RR was 0.69 (95% CI 0.27–1.74; I² = 0%), indicating no statistically significant difference. Sensitivity analyses yielded concordant results despite low event counts. Conclusions: No statistically significant increase in ventricular arrhythmia or SCD risk was observed. However, limited events and short follow-up preclude firm conclusions regarding the arrhythmic safety of myosin inhibitors.

Background/Objectives: We aimed to evaluate the diagnostic accuracy of the MONA.health artificial intelligence (AI) software (Version 1.0.0; MONA.health, Leuven, Belgium) and compare its advantages in screening for diabetic retinopathy (DR) and diabetic macular edema (DME) with standard fundus photography. Methods: This cross-sectional, real-life instrument validation study was conducted at the Vuk Vrhovac University Clinic in Zagreb during routine DR screening and included 296 patients (592 eyes) with diabetes. Following standard fundus photography using a 45° Zeiss VISUCAM NM/FA camera (Carl Zeiss Meditec AG, Jena, Germany), each patient also underwent imaging with an automated portable retinal camera (NFC-600, Crystalvue Ophthalmic Instruments, Taoyuan City, Taiwan). Two retina specialists independently graded images from the standard camera, while images from the NFC-600 were analyzed using the MONA.health AI software. Results: Among the 592 eyes, human grading identified 81 with any DR, including 17 with mild NPDR, 64 with referable DR (moderate/severe NPDR or PDR), and 13 with DME. The MONA.health AI software identified 65 eyes with referable DR and 19 with DME. For MONA DR screening compared to the standard fundus camera, the area under the curve, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, kappa agreement, diagnostic odds ratio, and diagnostic effectiveness were 99.74%, 100%, 99.81%, 99.33%, 100%, 528.00, 0.00, 0.99, infinity, and 99.85%, respectively. For MONA DME screening, these metrics were 97.97%, 100%, 98.95%, 85.93%, 100%, 95.67, 0.00, 0.81, infinity, and 99.02%, respectively. The MONA AI screening process required 1 day of training and approximately 5 min for image capture and analysis, compared to 7 days of training and 13 min for image acquisition and grading with the standard method. Conclusions: These findings demonstrate that the MONA.health AI software matches the accuracy of standard fundus photography for screening and early detection of referable DR and DME, while offering a faster, simpler, and more user-friendly workflow that significantly reduces the time to obtain screening results.

Diabetes is a global pandemic with almost 600 million adults living with diabetes in 2024 [1,2]. High blood glucose levels have harmful effects on small vessels and neuroretinal structures, leading to the development of diabetic retinopathy (DR), a microvascular complication of diabetes, which is currently a leading cause of preventable blindness in working-age adults [3]. While the majority of patients with diabetes will develop DR, it is important to stress that about 10% of them will develop vision-threatening forms of DR, such as proliferative DR (PDR) and diabetic macular edema (DME) [4]. While there is a trend of decreasing the incidence of the most severe forms of DR in developed countries, the risk of vision-threatening forms of DR is still high, and the overall prevalence of DR is increasing due to the global diabetes epidemic [5]. In light of these considerations, further action is required to minimize the burden of vision loss and disability among individuals with diabetes. This Research Topic, therefore, highlights current developments and recent progress in the understanding and management of DR and DME, bringing together 18 original research articles, 5 narrative reviews, and 3 systematic reviews.Chen et al. investigated the association between serum selenium levels and DR and collected data from 645 adults through the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016. While there was no statistically significant linear association between serum selenium levels and the probability of developing DR, a U-shaped relationship was observed. The incidence of DR is elevated in individuals with serum selenium levels that are either higher or lower than the optimal range, suggesting that selenium supplementation should be balanced to avoid excessive intake.In addition to selenium, vitamin D has been reported to be involved in DR pathogenesis, but results have been inconsistent. He et al. explore the relationship between vitamin D level and the risk of DR in 535 adult patients with type 2 diabetes mellitus (T2DM). The results suggest that males, but not females, with DR had significantly lower vitamin D levels and a higher proportion of severe vitamin D deficiency than those without DR. In addition, total testosterone levels were significantly lower in males with DR. The findings indicate a sexspecific association between serum vitamin D levels and the risk of DR in T2DM. A significant inverse relationship was observed exclusively in men, potentially driven by a substantial decline in total testosterone levels.Since emerging evidence suggests a potential association between depression and DR, Li et al. investigate the relationship between depression and DR using nationally representative data from the National Health and Nutrition Examination Survey (NHANES, 2011-2020).Depression was assessed using the PHQ-9, and among 1,653 participants, the weighted DR prevalence was 18.91%. Depression was independently associated with higher DR risk. These findings underscore the importance of an integrated approach that addresses both mental health and metabolic regulation in individuals with diabetes. Targeted management of depressive symptoms may help mitigate the burden of DR and enhance overall quality of life. Decision curve analysis supported its clinical usefulness over a wide range of risk thresholds.Overall, the model offers a practical, scalable tool for early referable DR risk stratification in both community and ophthalmic settings.Triglyceride-glucose index (TyG). Data from 3,750 patients were analyzed, and SHapley Additive exPlanations (SHAP) analysis identified TyG, insulin therapy, HbA1c, diabetes duration, and HDL as key predictors, with HDL protective. This model highlights TyG as a cost-effective, practical alternative to traditional insulin resistance measures, such as HOMA-IR, enabling accessible DR risk stratification in primary care.In addition, a systematic review and meta-analysis from Amirashov et al. examined the association between the TyG and DR. Sixteen observational studies involving over 33,000 participants were included. Higher TyG levels were associated with increased DR risk, particularly when analyzed as a continuous variable. However, substantial heterogeneity and potential publication bias were observed, especially in categorical analyses. Subgroup and meta-regression analyses identified male proportion as a key source of heterogeneity. These findings suggest a possible link between TyG and DR, though inconsistent thresholds and bias limit immediate clinical application. She et al. investigated the association between the albumin-to-neutrophil-lymphocyte ratio (ANLR), a marker of nutritional and inflammatory status, and DR using NHANES data Glucagon-like peptide-1 (GLP-1) receptor agonists are now a fundamental class of drugs used in the treatment of T2DM because of their cardiorenoprotective properties and weight-reducing effects [6]. However, their impact on DR appear to be neutral, or in some cases, even harmful [7]. A systematic review and meta-analysis from Alwafi et al. aimed to clarify the association between GLP-1 receptor agonist use and the development or progression of DR. Thirty-nine studies were reviewed, with 23 included in the meta-analysis. Overall, GLP-1 receptor agonist use was not significantly associated with DR risk compared with other therapies. Subgroup analyses by study design, sample size, and risk of bias yielded consistent non-significant results, with a modest trend toward reduced risk in randomized trials.The collective evidence presented in this Research Topic provides a comprehensive overview of recent advances in research on DR and DME in T2DM and emphasizes the need to improve our understanding and management of these vision-threatening complications."

Background/Objectives: Diabetic foot ulcers (DFUs) represent common and severe complications of diabetes mellitus (DM). The aim of our parallel-group, open-label, superiority, multicentre randomised controlled trial (RCT) was to evaluate the effectiveness of transcutaneous gaseous carbon dioxide therapy (hereinafter CO₂ therapy) in ulcer healing in patients with non-healing DFUs. Methods: A total of 115 participants (89 males and 26 females, aged 65.7 ± 10.9 years) with a non-healing DFU were randomised to the intervention (76 participants) and control (39 participants) group. Participants in the intervention group received standard of care, combined with CO₂ therapies administered every weekday for four consecutive weeks. Participants in the control group received only standard of care. Results: After 4 weeks, 49 (64.5%) ulcers in the intervention group healed, compared with three (7.7%) in the control group (primary outcome). The percentage ulcer area reduction from baseline (secondary outcome) was significantly larger (p ≤ 0.001) in patients from the intervention group, with the median value 100% (18.4–100%), compared to the patients from the control group, with the median value 40% (−300–100%). Patients receiving CO₂ therapy had 35.4-fold higher odds of ulcer healing versus controls (OR 35.4, 95% CI 6.68–187.53; p < 0.001), and in multivariate logistic regression, CO₂ therapy remained independently associated with healing, while larger baseline ulcer area was associated with lower odds of healing (OR 0.654, 95% CI 0.438–0.977; p = 0.038). No adverse effects were reported. Conclusions: CO₂ therapy significantly contributes to ulcer healing in patients with non-healing DFUs, with no observable adverse effects, demonstrating significant potential as an effective and safe complementary treatment of DFUs in conjunction with standard of care.