MEDLINE

Background and Objectives: Guideline-directed medical therapy (GDMT) remains a challenge due to its low rates worldwide. Adherence to GDMT in patients with heart failure (HF) and reduced ejection fraction (rEF) in the Baltics (Estonia, Latvia, and Lithuania) has been unknown. This is the first study to describe the characteristics of patients with HFrEF and their treatment patterns in the Baltics. Materials and Methods: The EVOLUTION-HF study was a longitudinal, real-world evidence study that enrolled patients with HFrEF following newly initiated sodium–glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin therapy. In total, 12 study sites (four from each country) were included. Patients were followed up for 12 months. A pooled data set including adherence to GDMT, dapagliflozin’s usage, and patients’ profiles was evaluated. Results: Between April and December 2022, 178 patients with a median left ventricular ejection fraction of 32% were enrolled. At baseline, 155 (87%) patients received renin–angiotensin–aldosterone system inhibitors (RAASi), 168 (94%) received beta-blockers (BB), and 106 (60%) received mineralocorticoid receptor antagonists (MRA); however, only 47.8% of the study population were found to be treated with GDMT (including RAASi, BB, MRA, and dapagliflozin) at the beginning of the study. At the end of the follow-up, the percentage of GDMT users decreased to 42.3%. The number of dapagliflozin discontinuations per 100 patient-years was found to be 13.2 (95% CI 8.2–18.2). Conclusions: The findings indicate a low rate of dapagliflozin discontinuation (13%) and an overall suboptimal proportion of patients receiving GDMT for HFrEF (almost half of the patients). The low rate of GDMT use in the Baltics prompts great attention. Additional research and incremental joint efforts are needed to ensure an increase in GDMT use across diverse HF patient populations.

Purpose: This clinical trial was carried out to compare the outcomes of immediate implants positioned 4 mm below free gingival margin versus deeper placement of 6 mm after a period of 1 year.

Background and objectives: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with endothelial glycocalyx injury and perioperative endothelial dysfunction. Syndecan-1 is commonly used as a biomarker of glycocalyx shedding, but data on its perioperative changes and their relationship with operative and patient-related factors remain limited. The aim of this study was to evaluate perioperative Syndecan-1 dynamics during coronary artery bypass grafting (CABG) with CPB and to assess associations with ischemia–reperfusion exposure and patient characteristics. Materials and methods: This prospective observational study included 147 patients undergoing elective CABG with CPB. Syndecan-1 concentrations were measured at five time points: before induction of anaesthesia, immediately after aortic cross-clamp application, immediately after aortic declamping, on arrival at the ICU and 24 h after surgery. Perioperative changes were analysed using non-parametric tests, Spearman’s rank correlation analysis and mixed-effects modelling. The study was registered at ClinicalTrials.gov (NCT03491163; registered on 29 March 2018). Results: Syndecan-1 concentrations changed significantly over time (p < 0.001), increasing from a baseline median of 49.74 ng/mL to a peak of 147.78 ng/mL at ICU admission, followed by a partial decline to 65.26 ng/mL at 24 h. Aortic cross-clamp duration was weakly but significantly associated with Syndecan-1 concentration at ICU admission (rs = 0.243, p = 0.003) and with perioperative increases from baseline to ICU admission (ΔS4-1: rs = 0.196, p = 0.017) and from aortic clamping to ICU admission (ΔS4-2: rs = 0.207, p = 0.012). No significant associations were observed between CPB duration and Syndecan-1 concentrations in univariable analyses. In the mixed-effects model, a significant non-linear temporal pattern of Syndecan-1 concentrations was observed (both linear and quadratic time terms, p < 0.001). Male sex (β = 0.247, p = 0.009) and aortic cross-clamp duration (β = 0.016, p = 0.005) were independently associated with higher Syndecan-1 concentrations, whereas smoking status, age, BMI, diabetes status, EuroSCORE II, and CPB duration were not independently associated. Conclusions: Syndecan-1 concentrations increase significantly during cardiac surgery with cardiopulmonary bypass, peaking at ICU admission and partially declining within 24 h. Aortic cross-clamping duration, but not total CPB duration, showed weak associations with glycocalyx shedding. Male sex was independently associated with higher Syndecan-1 concentrations. These findings support ischemia–reperfusion injury as an important contributor to endothelial glycocalyx shedding during cardiac surgery.

Purpose: To investigate sex-related differences in uveitis etiologies through a systematic review and meta-analysis.

Previous studies showed that orthodontic ligatures can change their color if the patient consumes certain foods, uses mouth rinses, or applies lipstick. Color changes are also influenced by factors such as ultraviolet radiation and thermal energy. Thus, the aim of this study was to investigate the influence of certain drinks on the color changes of esthetic orthodontic elastic ligatures. The study object consisted of standard-size clear orthodontic ligature sticks made from the same material as the ligatures themselves. In this study color changes were analyzed using a digital spectrometer. The results showed that all solutions caused changes in the light transmittance of the ligatures compared with the control group after 10 days. The transmittance values of the turmeric, coffee, and black tea groups were similar to one another, though coffee showed the lowest transmittance of all. When evaluating the effect of the solutions on color changes, it was determined that coffee and turmeric solution caused the greatest color changes in the ligatures, followed by tea and juices. The data from this experiment indicated that the most pronounced statistically significant color changes over 10 days were observed in the coffee, turmeric, and black tea groups, followed by green tea, carrot, beetroot juice, Fanta, and Coca-Cola.

Background and Objectives: Microscopic colitis (MC) encompasses two chronic inflammatory disorders of the large intestine: collagenous colitis (CC) and lymphocytic colitis (LC). Both conditions are characterised by chronic watery diarrhoea and substantially impaired quality of life. Diagnosis relies on colonoscopy with multiple biopsies, and no reliable non-invasive biomarker currently exists. This exploratory study aimed to investigate circulating fatty acid-binding protein 2 (FABP2), interleukin-10 (IL-10), and lipopolysaccharides (LPSs) as potential biomarkers for MC and to compare their profiles with those in ulcerative colitis (UC). Materials and Methods: Plasma samples were obtained from 45 patients with active CC, 16 patients with active LC, 52 healthy controls, 43 patients with active UC, and 43 patients with inactive UC. Concentrations of FABP2, IL-10, and LPS were measured by enzyme-linked immunosorbent assay (ELISA). Results: Plasma FABP2 concentrations differed significantly across groups (Kruskal–Wallis p = 0.008). CC patients exhibited the highest levels (median 1719.0 pg/mL, IQR 1364.0–2240.0) compared with active UC (median 1272.0 pg/mL, IQR 861.7–1727.5; p = 0.005) and inactive UC (median 1334.0 pg/mL, IQR 854.2–1702.0; p = 0.001), but did not differ significantly from controls (median 1364.5 pg/mL, IQR 982.6–2160.5; p = 0.076) or LC (median 1421.5 pg/mL, IQR 1207.0–2002.2; p = 0.171). IL-10 concentrations also differed across groups (Kruskal–Wallis p = 0.029 after removal of one extreme outlier in active UC). Active UC patients had significantly lower levels (median 2.6 pg/mL, IQR 1.4–4.6) than CC (median 4.0 pg/mL, IQR 3.0–7.2; p = 0.009) and controls (median 4.8 pg/mL, IQR 2.6–7.4; p = 0.005). LPS concentrations showed no overall differences across groups (Kruskal–Wallis p = 0.55), although CC patients had numerically higher levels (median 73.7 pg/mL, IQR 45.6–104.9) compared with controls (median 56.4 pg/mL, IQR 33.7–87.1; p = 0.124). No significant differences were observed between LC and other groups for any biomarker. Conclusions: In this exploratory study, plasma FABP2 and IL-10 showed limited diagnostic accuracy in differentiating CC from UC but failed to distinguish MC from healthy controls. LPS levels were not significantly different among study groups. None of the biomarkers reliably separated LC from other groups, possibly reflecting the small LC sample size. These preliminary findings suggest subtle differences in circulating biomarker profiles between CC and UC that warrant validation in larger cohorts.

Background: Severe asthma affects a minority of patients with asthma; however, it substantially impacts morbidity, health-care use, and systemic corticosteroid-related harm. Despite the increasing use of biological treatments, achievement of severe asthma remission remains elusive. Notably, real-world data on the disease burden and remission potential of severe asthma in Europe remain limited. We aimed to close this knowledge gap, offering insights with global relevance.

Background and Objectives: Recent studies suggest that remimazolam, a novel ultra-short-acting benzodiazepine, has an excellent pharmacokinetic and safety profile, favourable for ambulatory procedures. Although remimazolam has been studied as a sole agent for anaesthesia in day case gynaecological surgery, studies assessing its use in combination with other anaesthetics remain scarce. The aim of this study was to investigate the effects of a low-dose remimazolam adjunct on the characteristics of an intravenous propofol–remifentanil anaesthesia regimen. Materials and Methods: A single-centre retrospective observational cohort study was conducted on patients who underwent brief day case gynaecological surgery under general intravenous anaesthesia using remifentanil and propofol from November 2024 to January 2025. The patients were divided into two groups depending on whether they received remimazolam as an adjunct. To account for confounding, propensity scores (PSs) were estimated from baseline characteristics and used to derive stabilised inverse probability of treatment weights (IPTWs). Weighted regression models were then applied to estimate treatment effects on postoperative recovery time measures, consumption of anaesthetics, and incidence of any adverse effects intraoperatively and postoperatively. Cost effectiveness was evaluated using the incremental cost-effectiveness ratio (ICER). Results: The clinical data of 51 patients were retrospectively examined: 32 patients were assigned to the intervention group, and 19 patients were assigned to the reference group; after IPTW and PS trimming, the sum of weights was 22 in the intervention group and 58.8 in the reference group. The use of remimazolam as an adjunct was associated with 3.5 min shorter time to eye opening (p < 0.001) and 3.6 min shorter time to full consciousness (p = 0.002); the total consumption of propofol was decreased by 3 mg/kg (p < 0.001); the median dose of remimazolam adjunct was 0.12 mg/kg, or 10 mg per case. There were no statistically significant adverse effects. ICER was 2.35 € per minute of operating room (OR) time saved. Conclusions: In the setting of day case gynaecological surgery, the addition of remimazolam to a propofol–remifentanil regimen reduced propofol requirements and shortened recovery time without an increase in adverse effects. This may represent a more efficient anaesthetic approach for ambulatory procedures with a comparable safety profile.

Background and Objectives: Non-invasive biomarkers reflecting neurodegeneration are increasingly important in multiple sclerosis (MS). Optical coherence tomography (OCT) provides quantitative measures of retinal structure, most commonly peripapillary retinal nerve fiber layer (pRNFL) thickness. However, the potential clinical relevance of optic nerve head morphology, including cup-to-disc ratio (CDR), remains insufficiently explored. We investigated associations between OCT-derived parameters, subjective visual vertical (SVV), and disability in MS. Materials and Methods: In this retrospective study, 100 patients with MS were included. OCT parameters (pRNFL thickness and area-based CDR) were analyzed at baseline and follow-up. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Detailed optic neuritis history was not consistently available in the retrospective clinical records and therefore could not be systematically accounted for in the analyses. SVV was evaluated in 37 patients using a virtual reality–based protocol. Associations were assessed using Spearman correlation and linear regression analyses. Multivariable regression models were adjusted for age, sex, and follow-up duration. Results: pRNFL thickness was not associated with baseline EDSS (rho = −0.06, p = 0.55) or annualized EDSS change. Baseline CDR correlated with both baseline EDSS (rho = 0.30, p = 0.0065) and follow-up EDSS (rho = 0.46, p < 0.0001). In univariable regression analysis, baseline CDR was associated with follow-up EDSS (B = 3.33, R2 = 0.23, p < 0.0001), remaining significant after adjustment for age, sex, and follow-up duration (B = 2.59, 95% CI 1.26–3.92, p = 0.0002). No significant associations were observed between OCT parameters and SVV measures. Conclusions: Higher CDR values, but not pRNFL thickness, were associated with disability measures in this exploratory MS cohort. However, these findings should be interpreted cautiously because optic neuritis history could not be systematically accounted for and physiological optic disc variability may substantially influence CDR measurements.

In this study, we evaluated the impact of different in vitro 3D culture modelling methods on the activity of doxorubicin (DOX) and 5-fluorouracil (5-FU) in human melanoma spheroids. Human melanoma A375 and IGR39 spheroids were generated using the hanging drop and non-adhesive surface methods. Spheroid growth dynamics were assessed by measuring changes in spheroid diameter. To compare the effects of anticancer drugs in spheroids of different sizes, spheroids of approximately 200 and 400 µm were formed. Drug activity was evaluated based on spheroid growth and cell viability using the MTT assay. A375 spheroids formed using the non-adhesive surface method were more sensitive to DOX than spheroids formed using the hanging drop method. In smaller A375 spheroids, 10 µM 5-FU reduced cell viability more effectively in spheroids formed using the hanging drop method. In contrast, IGR39 spheroids formed by the hanging drop method were more resistant than those formed on a non-adhesive surface. However, in IGR39 spheroids, the effects of DOX and 5-FU on growth and viability did not significantly differ between formation methods. In conclusion, A375 spheroid growth was not significantly influenced by the formation method, whereas IGR39 spheroid growth depended on the method used. A375 spheroids formed on non-adhesive surfaces were more sensitive to DOX, whereas 5-FU activity depended on drug concentration and spheroid size. In IGR39 spheroids, the effects of DOX and 5-FU on growth and viability were largely independent of the spheroid formation method.