ABSTRACT Background and hypothesis Kidney replacement therapy (KRT) practices in Europe are heterogeneous, with apparent differences between Western and Central/Eastern Europe. However, time trends in KRT incidence and prevalence in Central and Eastern Europe have not been previously reported. Therefore, we aimed to describe trends in incidence and prevalence of KRT in Central and Eastern Europe from 2010 to 2021. Methods Data on incident and prevalent KRT patients from 19 Central and Eastern European countries between the years 2010 and 2021 were derived from the European Renal Association (ERA) Registry. Time trends were calculated using JoinPoint regression. Results Overall, KRT incidence increased at 1.5% [95% confidence interval (CI): +0.7 to +2.6%] per year from 106.3 per million population (pmp) in 2010 to 119.6 pmp in 2019. However, trends differed within the region. While in Bosnia and Herzegovina KRT incidence significantly decreased from 2010 to 2019, it remained stable in nine and increased in eight countries. The overall KRT prevalence increased at 5.1% (95% CI: +4.5 to +5.7%) per year from 426.2 pmp in 2010 to 651.2 pmp in 2019. KRT prevalence increased in all countries, except for Belarus where it remained stable, and was mainly attributable to increases in the prevalence of kidney transplantation. The COVID-19 pandemic did not have a major impact on KRT incidence and prevalence in the region, as most trends remained until 2021. Conclusions Although we found an overall increase in KRT incidence and prevalence in the region, large country variations remain, much larger than observed in Western Europe. The results of this study can help to define country-specific priorities for the optimization of KRT care in Central and Eastern Europe.

African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars, which poses severe threats to the global pork industry. Despite the promise of live attenuated vaccines (LAVs), their narrow margin between efficacy and residual virulence presents major safety challenges. This study bridges a critical knowledge gap in ASF vaccinology by identifying innate and adaptive correlates of protection. This was achieved by using an established model with two groups of pigs differing in baseline immunological status (farm and specific pathogen-free [SPF]). The animals were immunized with an attenuated ASFV strain and subsequently challenged with a related, highly virulent genotype II strain. By applying a systems immunology approach, we correlated kinetic data, including serum cytokines, blood transcription modules (BTMs), T-cell responses, and antibody levels, with clinical outcomes to track protective and detrimental immune responses to the virus over time. Key innate correlates of protection included early and sustained IFN-α response, activation of antigen presentation BTMs, and controlled IL-8 levels during immunization. Lower baseline immune activation observed in SPF pigs in steady state was linked to increased protection. Adaptive correlates encompassed cell cycle, plasma cell, and T-cell BTM responses lasting until day 15 post-immunization. Consequently, an effective response from ASFV-specific Th cells prior to challenge indicated protection. After the challenge, an early IFN-α response, along with low levels of pro-inflammatory cytokines and a strong induction of memory Th and Tc cells, correlated with improved clinical outcomes. The model highlights the critical role of host-specific factors in vaccine efficacy and provides a valuable framework for optimizing ASFV vaccine design while distinguishing between protective and detrimental immune responses.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality worldwide; however, precision oncology has fundamentally transformed its treatment landscape. In 2025, seven approvals by the U.S. Food and Drug Administration (FDA) further accelerated biomarker-driven care across critical molecular subsets. These include MET-directed and trophoblast cell-surface antigen-2 (TROP-2) antibody-drug conjugates (ADCs), expanded strategies targeting epidermal growth factor receptor (EGFR), notably those addressing exon 20 insertion mutations, a ROS proto-oncogene 1 (ROS1) inhibitor, and various human epidermal growth factor receptor 2 (HER2) options that encompass both tumor-agnostic and mutation-selected approaches. These advancements underscore the necessity for integrated diagnostics-such as next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC)-while also emphasizing ongoing challenges in biomarker selection, therapeutic sequencing, and equitable global implementation.

The growth of medical tourism has contributed to the expansion of dental tourism. With the rise of tourism in Albania, dental tourism has similarly progressed. This research aims to evaluate the quality of dental tourism services in Tirana, applying fuzzy methods such as CRITIC (CRiteria Importance Through Intercriteria Correlation) and CoCoSo (Combined Compromise Solution). These two methods were integrated into a hybrid approach, as described in this paper. Seven experts evaluated dental practices using linguistic values. The CRITIC method results indicated that, among the ten criteria, the most significant was the variety of services. According to the CoCoSo method, Biodent Denti e Sorrisi, Diamond Dental, and Dental Med Austria practices demonstrated the highest quality in dental tourism services. As research results indicate, these clinics could serve as models for improving dental tourism in Albania through a focus on quality development.

ABSTRACT Introduction Interindividual variability in drug response remains a significant clinical challenge, leading to therapeutic failure and toxicity. Much of this variability is unexplained by classical host-centric pharmacokinetic (PK) models, highlighting a critical gap in understanding of drug disposition. This review addresses this gap by establishing the gut microbiome as an important determinant of drug fate. Areas covered This narrative review with scoping approach examines how microbial enzymes affect therapeutics through comprehensive analysis of mechanistic and clinical studies. Key examples discussed include irinotecan, digoxin, and sulfasalazine. We highlight specific situations where the influence of gut bacteria is particularly significant, such as with low-bioavailability drugs and in patients with an ileocolonic anastomosis, where gut bacteria directly impact drug absorption and metabolism. Additionally, we address the limitations of current PK models and explore the potential of new integrated approaches. Expert opinion We propose that the gut microbiome should be recognized as a ‘fifth pillar’ of PKs. This shift in perspective is crucial for advancing personalized medicine. In this new model, a ‘PK profile card’ integrating microbial, genomic, and clinical data will help guide dosing. We anticipate microbiome analysis to become a standard clinical tool to optimize drug efficacy and safety.

Abstract Introduction Emergent intracranial stenting (EIS) is increasingly employed in the context of the acute ischaemic stroke treatment, but requires intraprocedural antiplatelet therapy (APT), which may raise haemorrhagic risk. This study aimed to evaluate the safety and effectiveness of different APT regimens during EIS. Patients and methods This is a subanalysis of the RESISTANT registry, which is a multicenter retrospective registry of patients with acute ischaemic stroke treated with intracranial EIS between 2016 and 2023. Patients receiving intraprocedural antithrombotics were included. Primary efficacy outcomes were stent patency (intraprocedural and within 24 hours) and 3-month mRS. Secondary outcome was successful reperfusion (modified thrombolysis in cerebral infarction ≥ 2b), and the safety outcome was sICH. Multivariable and propensity score-matched analyses were performed. Results Among 827 patients, 4 APT strategies were identified: single APT (n = 102), oral dual antiplatelet therapy (dAPT) (Aspirin + Clopidogrel or Ticagrelor; n = 83), Cangrelor (n = 92) and GP IIb/IIIa inhibitors (GPi) (n = 550). Intravenous agents (Cangrelor/GPi) showed a trend towards lower risk of intraprocedural stent occlusion compared to oral dAPT (adjusted odds ratio [aOR] 0.30, [95% CI, 0.09–1.01], P = .053), though this did not reach statistical significance. GP IIb/IIIa inhibitors continued to demonstrate a protective trend at 24 hours (aOR 0.25, [95% CI, 0.06–0.99], P = .047), without a significant increase in sICH. Both intravenous agents were independently associated with higher odds of successful final reperfusion (odds ratio [OR] 4.35, [95% CI, 1.57–12.09], P = .001). No significant differences emerged between GPi and Cangrelor in matched analysis. No significant difference was observed on good functional outcome between APT strategies. Conclusion In the setting of EIS, intravenous APT agents (Cangrelor or GPi) were associated with improved stent patency and higher rates of successful reperfusion, without a significant increase in symptomatic haemorrhage.

Abstract Rationale Intra-arterial fibrinolytics may be used for distal remaining vessel occlusions after incomplete mechanical thrombectomy (MT). However, their efficacy in improving reperfusion in this specific clinical scenario is unclear. While better reperfusion may lead to improved clinical outcomes, additional fibrinolytics could also increase the risk of hemorrhagic complications. Aim To assess the safety and reperfusion efficacy of intra-arterial tenecteplase (TNK) compared to no further interventional treatment in patients with incomplete reperfusion and mechanically non-amendable residual occlusions after MT. Methods and design This is an international, multicenter, randomized (1:1) controlled, two-arm, open, assessor-blinded, surrogate endpoint trial. The interventional arm receives 3 mg (not weight-adjusted) intra-arterial TNK, administered as close as possible to the residual occlusion. The control arm receives no further interventional treatment. Sample size TECNO will randomize 156 participants 1:1 to 3 mg intra-arterial tenecteplase or no further interventional treatment. This sample size is based on anticipated absolute improvements in early and late reperfusion with intra-arterial TNK of 25% and 30%, respectively. Outcomes The two co-primary imaging outcomes are early and late reperfusion. Early reperfusion is defined as an extended Thrombolysis in Cerebral Infarction (eTICI) score ⩾ 2a for residual occlusions on angiography 25 min after randomization. Late reperfusion is defined as the absence of a wedge-shaped perfusion delay on delay-sensitive perfusion maps assessed on 24 h ± 6 h perfusion imaging. Standard secondary clinical outcomes will be assessed at 24 h and 90 ± 15 days. Discussion The TECNO trial will provide evidence on the safety and reperfusion efficacy of locally administered intra-arterial TNK in patients with residual occlusions following MT.

Abstract Background The no-reflow phenomenon, characterized by impaired microvascular reperfusion despite successful macrovascular recanalization, has been identified as a potential contributor to poor outcomes in acute ischemic stroke (AIS) treated with endovascular therapy (EVT). This systematic review and meta-analysis aimed to assess the prevalence and clinical impact of no-reflow phenomenon in AIS patients undergoing EVT. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies reporting the no-reflow phenomenon after EVT. Databases searched included PubMed, Embase, and CENTRAL (inception to February 9, 2025). Outcomes included no-reflow prevalence, functional outcomes (mRS), early neurological recovery, infarct volume, hemorrhagic complications, and 90-day mortality. Pooled risk ratios (RR) or mean differences (MD) were calculated using random-effects meta-analysis, and heterogeneity was assessed with I2. Results Eight studies (n = 1483 patients) were included. The pooled prevalence of no-reflow was 20.5% (95% CI 6.2%–49.9%; I2 = 96.9%). Compared with controls, patients with no-reflow had reduced early neurological recovery (RR 0.76; 95% CI 0.64–0.90) and increased risk of hemorrhagic transformation (RR 1.82; 95% CI 1.18–2.79) and symptomatic intracranial hemorrhage (RR 1.88; 95% CI 1.00–3.56). Differences in functional independence (mRS 0–2) and mortality were not statistically significant. Subgroup analyses based on study design revealed divergent patterns, particularly for infarct volume, which was significantly greater in no-reflow patients in post-hoc RCTs but not in the overall analysis. Conclusion No-reflow affects one in five EVT-treated patients and is associated with adverse neurological and hemorrhagic outcomes. Findings highlight the need for standardized definitions and prospective trials to clarify its clinical impact.

Abstract Introduction Covert brain infarctions (CBIs) are associated with cardiovascular risk factors (cvRFs). We aimed to evaluate the presence and therapeutic implications of modifiable cvRFs in patients with incidentally discovered CBI on routine neuroimaging. Patients and methods The SILENT cohort (NCT05685069) is a prospective, multicentred European cohort recruiting patients with incidentally detected focal CBIs on routine MRI, without prior clinical stroke. Modifiable cvRFs and their control were assessed using applicable international guidelines during a dedicated outpatient visit, including a clinical examination and laboratory work-up. Associations between cvRF profiles and the number of CBIs were analysed using linear regression. Results We included 231 patients (mean age 65 years, n = 130 [56%] male) with a total of 445 CBI lesions. Most CBIs were of lacunar type (n = 226; 51%) and the most common location was the cerebellum (n = 220; 50%). One hundred and fifty (65%) patients had at least 1, 112 (49%) at least 2 and 56 (24%) at least 3 known modifiable cvRFs. Among hypertensive patients, 69 (53%) had uncontrolled hypertension; 22 (65%) of diabetics were insufficiently controlled and 74 (58%) patients with dyslipidaemia had poorly controlled low-density lipoprotein cholesterol. Therapeutic measures were made for 144 patients (62%), including antiplatelet initiation in 107 (46%) and a statin in 69 (30%). The number of cvRFs per patient was significantly associated with the number of CBIs, rate ratio 1.08 (95% Confidence Interval (CI), 1.04−1.13). Conclusion In patients with incidentally discovered CBI, we found a high burden of poorly controlled cvRFs. Our findings highlight the importance and yield of a dedicated clinical and laboratory assessment of cvRFs in patients with CBIs.

Objectives The COVID-19-associated hyperinflammatory syndrome (cHIS) score has been proposed as a tool for identifying patients at risk of clinical deterioration. This study evaluated the predictive accuracy of the admission cHIS score for invasive mechanical ventilation and ICU mortality in critically ill COVID-19 patients. Methods We conducted a single-center retrospective observational study including 85 adults with laboratory-confirmed COVID-19 who were admitted to the ICU. The cHIS score was calculated on admission, and patients were stratified into two groups (<3 and ≥3). Associations with mechanical ventilation and ICU mortality were examined using ROC curve analysis and multivariable logistic regression, adjusted for age and comorbidity burden. Results An admission cHIS score ≥3 demonstrated moderate discrimination for ICU mortality (AUROC = 0.70; sensitivity = 0.76; specificity = 0.66) and mechanical ventilation (AUROC = 0.71; sensitivity = 0.73; specificity = 0.65). Higher cHIS scores were significantly associated with both outcomes in unadjusted analyses. After adjustment, the associations were attenuated and became borderline for mortality and mechanical ventilation, suggesting potential confounding by age and underlying comorbidities. Key inflammatory markers within the cHIS score—CRP, LDH, and D-dimer—showed the strongest individual associations with adverse outcomes. Kaplan–Meier analysis demonstrated significantly reduced survival probabilities in patients with cHIS ≥3. Conclusion The admission cHIS score reflects the degree of systemic hyperinflammation and is associated with greater illness severity, ICU mortality, and the need for mechanical ventilation. Although its predictive value diminishes after adjusting for age and comorbidities, the score remains a useful adjunct for early risk stratification in critically ill COVID-19 patients. Larger multicenter studies are needed to determine its independent prognostic utility.