Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target.

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor ß signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model.

Comprehensive Analysis of the Role of Gene Variants in Matrix Metalloproteinases and Their Tissue Inhibitors in Retinopathy of Prematurity: A Study in the Polish Population.

This study was designed to investigate the relationship between variants of matrix metalloproteinases (MMP-1 rs179975, MMP-9 rs17576 and rs17577), their tissue inhibitors (TIMP-1 rs4898, TIMP-2 rs2277698 and rs55743137) and the development of retinopathy of prematurity (ROP) in infants from the Polish population. A cohort of 100 premature infants (47% female) was enrolled, including 50 ROP cases and 50 no-ROP controls. Patients with ROP were divided into those with spontaneous remission and those requiring treatment. A positive association between MMP-1 rs179975 1G deletion allele and ROP was observed in the log-additive model (OR = 5.01; p = 0.048). Furthermore, female neonates were observed to have a negative association between the TIMP-1 rs4898C allele and the occurrence of ROP and ROP requiring treatment (codominant models with respective p-values < 0.05 and 0.043). Two and three loci interactions between MMP-1 rs1799750 and TIMP1rs4989 (p = 0.015), as well as MMP-1 rs1799750, MMP-9 rs17576 and TIMP-1 rs4989 (p = 0.0003) variants influencing the ROP risk were also observed. In conclusion, these findings suggest a potential role of MMPs and TIMPs genetic variations in the development of ROP in the Polish population. Further studies using a larger group of premature infants will be required for validation.

Simultaneous Occurrence of Multiple Neoplasms in Children with Cancer Predisposition Syndromes: Collaborating with Abnormal Genes.

The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the BRCA2 gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the NF1 gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nephroblastoma, in whom a pathogenic variant in the DICER1 gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.

Outcomes of Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) Procedure for the Treatment of Extensive Aortoiliac Occlusive Disease Using the BeGraft Balloon-Expandable Covered Stent: A Multicenter Observational Study.

PURPOSE: The covered endovascular reconstruction of the aortic bifurcation (CERAB) technique offers an alternative for Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions involving the aortic bifurcation. The study aims to evaluate the outcomes of the CERAB technique for extensive aortoiliac occlusive disease (AIOD) using the BeGraft balloon-expandable covered stent (BECS). MATERIALS AND METHODS: This is a physician-initiated, multicenter, retrospective, observational study. Between June 2017 and June 2021, all consecutive patients who underwent the CERAB procedure using the BeGraft stent (Bentley InnoMed, Hechingen, Germany) in 3 clinics were enrolled. Patients' demographics, lesion characteristics, and procedural results were collected and retrospectively analyzed. Follow-up was done at 1, 6, and 12 months and then annually with clinical examination, ankle-brachial index (ABI), and duplex ultrasound. The primary endpoint was the patency at 12 months. Secondary endpoints included procedural-related complications, secondary patency, freedom from target lesion revascularization (TLR), and clinical improvement. RESULTS: In all, 120 patients (64 men) with a median age of 65 years (range: 34-84 years) were analyzed. Most patients had extensive AIOD classified as TASC II C (n=32; 26.7%) or TASC II D (n=81; 67.5%). The median duration of the procedure was 120 minutes (interquartile range [IQR]: 80-180 minutes). All 454 BeGraft stents (137 aortic and 317 peripheral) were successfully delivered and deployed. The overall procedural complication rate was 14 (11.7%). The median hospital length of stay was 5 days (IQR: 3-6 days). All patients improved clinically, and the ABI increased significantly (p<0.05). The median follow-up was 19 months (range: 6-56 months). The primary patency rate, secondary patency rate, and freedom from TLR at 12 months were 94.5%, 97.3%, and 93.5%, respectively. CONCLUSIONS: The CERAB procedure with BeGraft BECSs has a high technical success rate, favorable patency outcomes, and low morbidity, even in relatively ill patients with extensive AIOD. Prospective randomized studies on the CERAB technique are definitely recommended. CLINICAL IMPACT: This study evaluates the outcomes of BeGraft stents used during the covered endovascular reconstruction of the aortic bifurcation (CERAB) procedure. To date, several balloon-expandable covered stents have been used for this technique with satisfactory results. This study showed the safety and excellent patency of the CERAB technique in extensive AIOD using BeGraft balloon-expandable covered stents.

Hypoxia-Inducible Pathway Polymorphisms and Their Role in the Complications of Prematurity.

Excessive oxidative stress resulting from hyperoxia or hypoxia is a recognized risk factor for diseases of prematurity. However, the role of the hypoxia-related pathway in the development of these diseases has not been well studied. Therefore, this study aimed to investigate the association between four functional single nucleotide polymorphisms (SNPs) in the hypoxia-related pathway, and the development of complications of prematurity in relation to perinatal hypoxia. A total of 334 newborns born before or on the 32nd week of gestation were included in the study. The SNPs studied were HIF1A rs11549465 and rs11549467, VEGFA rs2010963, and rs833061. The findings suggest that the HIF1A rs11549465T allele is an independent protective factor against necrotizing enterocolitis (NEC), but may increase the risk of diffuse white matter injury (DWMI) in newborns exposed to hypoxia at birth and long-term oxygen supplementation. In addition, the rs11549467A allele was found to be an independent protective factor against respiratory distress syndrome (RDS). No significant associations with VEGFA SNPs were observed. These findings indicate the potential involvement of the hypoxia-inducible pathway in the pathogenesis of complications of prematurity. Studies with larger sample sizes are needed to confirm these results and explore their clinical implications.

SELENOP rs3877899 Variant Affects the Risk of Developing Advanced Stages of Retinopathy of Prematurity (ROP).

The significance of selenoproteins for the incidence of prematurity and oxidative-damage-related diseases in premature newborns is poorly understood. The latter are at risk for ROP as well as BPD, IVH, PDA, RDS, and NEC, which is particularly high for newborns with extremely low gestational age (ELGA) and extremely low birth weight (ELBW). This study evaluates the hypothesis that variation in the selenoprotein-encoding genes SELENOP, SELENOS, and GPX4 affects the risk of ROP and other comorbidities. The study included infants born ≤ 32 GA, matched for onset and progression of ROP into three groups: no ROP, spontaneously remitting ROP, and ROP requiring treatment. SNPs were determined with predesigned TaqMan SNP genotyping assays. We found the association of the SELENOP rs3877899A allele with ELGA (defined as <28 GA), ROP requiring treatment, and ROP not responsive to treatment. The number of RBC transfusions, ELGA, surfactant treatment, and coexistence of the rs3877899A allele with ELGA were independent predictors of ROP onset and progression, accounting for 43.1% of the risk variation. In conclusion, the SELENOP rs3877899A allele associated with reduced selenium bioavailability may contribute to the risk of ROP and visual impairment in extremely preterm infants.

Hemangioma-related gene polymorphisms in the pathogenesis of intraventricular hemorrhage in preterm infants.

PURPOSE: The aim of this study was to evaluate the possible relationship between four single nucleotide polymorphisms of hemangioma-linked genes encoding for anthrax toxin receptor 1 (ANTXR1 G976A), R kinase insert domain receptor (KDR T1444C), adrenoceptor beta 2 (ADRB C79CG), and insulin-like growth factor 1 receptor (IGF-1R G3174A) and the occurrence of IVH in a population of preterm infants. METHODS: The study includes a population of 105 infants born from 24 + 0 to 32 + 0 weeks of gestation and hospitalized at the Department of Neonatology (III level hospital) of Poznan University of Medical Science. Intraventricular hemorrhage was diagnosed with the use of cranial ultrasound. The classification of intraventricular bleeding was based on the Papile IVH classification. RESULTS: The incidence of IVH was higher in infants with lower birth weight, lower APGAR scores, and low birth weight. The study revealed that IVH was approximately two times less likely to occur in infants with the allele G of IGF-1R 3174G > A. CONCLUSION: Identifying susceptible premature infants through genetic analysis could be a potential way to alleviate severe IVH and its subsequent consequences. Further research examining a wider range of relevant gene polymorphisms could help highlight any genetic patterns in this deleterious bleeding complication.

Clinical characteristics of children with MIS-C fulfilling classification criteria for macrophage activation syndrome.

Background: Macrophage activation syndrome (MAS) is a potentially life-threatening complication of various inflammatory disorders, including multisystem inflammatory syndrome in children (MIS-C). MIS-C refractory to treatment should raise suspicion of MAS, which can be fatal if a definitive diagnosis is delayed. Unfortunately, there is a lack of data on MAS in children with MIS-C. Objective: Our study aims to analyze the risk factors for the development of MAS in MIS-C, its clinical course and response to treatment, and identify predictive factors for pediatric intensive care. Material and methods: We analyzed data from the Polish MIS-C registry of the MultiOrgan Inflammatory Syndromes COVID-19 Related Study. Patients were diagnosed according to the WHO MIS-C definition and treated according to national guidelines (Polish Pediatric Society) based on international consensus. MAS definition was based on 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Results: Two-hundred and seventy four children met the study inclusion criteria. Fifty-nine patients fulfilled MAS classification criteria, nine of which required admission to the pediatric intensive care unit (PICU). MIS-C patients with MAS were significantly older than patients without MAS (median 11.2 vs. 8.1 years). Multivariable analysis showed that age, symptoms characteristic of atypical Kawasaki disease, and skin erosions were significant factors associated with MAS in MIS-C patients. Analysis of laboratory parameters showed that on admission, MIS-C patients with MAS had significantly lower median lymphocyte and platelet counts, albumin and sodium levels, and higher median levels of C-reactive protein, procalcitonin, ferritin, D-dimers, triglycerides, serum creatinine, urea, and γ-glutamyl transpeptidase, and neutrophil count. Multivariate analysis showed that higher procalcitonin, ferritin, and fibrinogen levels at admission were predictive of MAS. Only elevated troponin level was a factor indicating a requirement of PICU hospitalization for children with MAS. MIS-C patients fulfilling MAS criteria were treated more often with intravenous immunoglobulins and steroids than children without MAS. Children with MAS more often required mechanical ventilation. None of the patients required biological agents. Conclusions: The clinical course of MAS in MIS-C seems milder, treatment less aggressive, and the prognosis better than expected based on the current knowledge on MAS complicating other rheumatological diseases.

Are There Any Limiting Factors of Minimally Invasive Adrenalectomy in Children? Over 20-Year Single-Center Experience.

<b> Introduction:</b> Laparoscopic adrenalectomy is more widely recognized as a valuable treatment method for benign and malignant tumours. </br></br> <b>Aim:</b> This study reviews over 20-year experience with laparoscopic adrenalectomy in children in Central-West Poland. </br></br> <b>Materials and methods:</b> During the last 21 years, 5041 laparoscopic procedures were performed, among them 39 adrenalectomies in children aged from 2 days to 17 years. The following data were analysed: patient's age at diagnosis and surgery, lesion volume in CT/MRI examination, duration of surgery, the incidence of complication after surgery, and length of hospitalization. </br></br> <b>Results:</b> The volume of adrenal lesion visualized by CT or MRI before surgery varied from 0.5 cm3 up to 490 cm3, with a median of 14 cm3. As many as 80% of adrenalectomies allowed radical removal of the lesion and 92% of those procedures were performed without any complications. From all data analysed, only age, both at diagnosis and at surgery, was significantly lower in patients with a malignant lesion. </br></br> <b>Conclusions:</b> Laparoscopic adrenalectomy is a valuable method to use in paediatric patients for both benign and malignant adrenal lesions. However, in patients with malignant adrenal lesions it may be expected that the procedure will be more difficult due to the lower age and larger lesion size.

Why Is Health Care for Children with Down Syndrome So Crucial from the First Days of Life? A Retrospective Cohort Study Emphasized Transient Abnormal Myelopoiesis (TAM) Syndrome at Three Centers.

Down syndrome (DS) is a common genetic disorder and is associated with an increased likelihood of many diseases, including defects of the heart, genitourinary system, gastrointestinal tract, and oncological diseases. The aim of this study was to analyze medical problems occurring in newborns with DS and to create a basic diagnostic and therapeutic algorithm intended primarily for neonatologists, pediatricians, family physicians, and physicians of other specialties caring for children with DS. Over a 5-year period, the medical records of 161 neonates with Down syndrome from four neonatology departments in Poznan, Poland, were examined. After applying exclusion criteria, 111 patients were analyzed. Data obtained from medical history included sex, week of gestation, birth weight, APGAR score, clinical symptoms, peripheral blood count with smear, and clinical features such as jaundice, hemorrhagic diathesis, ascites, hepato- or splenomegaly, pericardial or pleural effusion, respiratory failure, and other rare transient signs of abnormal myelopoiesis: fetal edema, hepatic fibrosis, renal failure, and rush. In the study group, 8% of children with Down syndrome were diagnosed with a heart and 1.8% with a genitourinary defect. Transient abnormal myelopoiesis syndrome (Transient abnormal myelopoiesis (TAM)) was found in 10% of newborns with DS. A blood count with blood smear, cardiology consultation with echocardiography, and an abdominal ultrasound should be performed in the first few days after birth in all newborns with Down syndrome. If this is not possible and the child's condition is stable, these tests can be performed within 2-3 months after birth.

Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease.

Currently, atherosclerosis, which affects the vascular bed of all vital organs and tissues, is considered as a leading cause of death. Most commonly, atherosclerosis involves coronary and peripheral arteries, which results in acute (e.g., myocardial infarction, lower extremities ischemia) or chronic (persistent ischemia leading to severe heart failure) consequences. All of them have a marked unfavorable impact on the quality of life and are associated with increased mortality and morbidity in human populations. Lower extremity artery disease (LEAD, also defined as peripheral artery disease, PAD) refers to atherosclerotic occlusive disease of the lower extremities, where partial or complete obstruction of peripheral arteries is observed. Decreased perfusion can result in ischemic pain, non-healing wounds, and ischemic ulcers, and significantly reduce the quality of life. However, the progressive atherosclerotic changes cause stimulation of tissue response processes, like vessel wall remodeling and neovascularization. These mechanisms of adapting the vascular network to pathological conditions seem to play a key role in reducing the impact of the changes limiting the flow of blood. Neovascularization as a response to ischemia induces sprouting and expansion of the endothelium to repair and grow the vessels of the circulatory system. Neovascularization consists of three different biological processes: vasculogenesis, angiogenesis, and arteriogenesis. Both molecular and environmental factors that may affect the process of development and growth of blood vessels were analyzed. Particular attention was paid to the changes taking place during LEAD. It is important to consider the molecular mechanisms underpinning vessel growth. These mechanisms will also be examined in the context of diseases commonly affecting blood vessel function, or those treatable in part by manipulation of angiogenesis. Furthermore, it may be possible to induce the process of blood vessel development and growth to treat peripheral vascular disease and wound healing. Reactive oxygen species (ROS) play an important role in regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. With regard to the repair processes taking place during diseases such as LEAD, prospective therapeutic methods have been described that could significantly improve the treatment of vessel diseases in the future. Summarizing, regenerative medicine holds the potential to transform the therapeutic methods in heart and vessel diseases treatment.

Mid-Term Results of Endovascular Aneurysm Sealing in the Treatment of Abdominal Aortic Aneurysm With Unfavorable Morphology.

PURPOSE: To report mid-term results of endovascular aneurysm sealing (EVAS) of abdominal aortic aneurysms (AAA) deemed unsuitable for a standard endovascular aneurysm repair (EVAR). METHODS: A prospectively maintained database of 42 patients with EVAR-unfavorable anatomy treated by EVAS combined with chimney grafts in case of the proximal AAA neck shorter than 5 mm was analyzed. Early outcomes included final angiographic result, intra- and early post-operative deaths, and complications. Mid-term outcomes included all-cause mortality (ACM), aneurysm-related mortality (ARM), patency of the stents, occurrence of endoleaks, serious complications and graft failures defined as the AAA growth of more than 5 mm, type I endoleak, occlusion of the stent-graft or chimney graft, aorto-duodenal fistula, or aneurysm rupture. RESULTS: The procedure was completed in all patients. Twenty-eight chimney grafts were implanted in 19 patients. Patients were followed for a median of 24 months (range 12-34 months). There were 2 intraoperative ruptures and 1 patient died in an early postoperative period. The cumulative ACM was 15, 21, and 36% at 12, 24, and 36 months, respectively, and the cumulative ARM was 8, 11, and 27% at 12, 24, and 36 months, respectively. Three out of 5 aneurysm-related deaths were due to a secondary aorto-duodenal fistula. The cumulative incidence of graft failure was 20, 27, and 42% at 12, 24, and 36 months, respectively. The cumulative incidence of an endoleak was 5, 9, and 23% at 12, 24, and 36 months, respectively. The graft failure increased significantly both ACM (p = .012) and ARM (p = .00003). The implantation of chimney grafts at the initial procedure increased ARM significantly (p = .008). The presence of an endoleak did not have any significant influence on ACM and ARM. CONCLUSION: Patients treated with EVAS for AAAs with EVAR-unfavorable anatomy, especially those with chimney grafts, exhibit a high risk of graft failure and subsequent death.

Midterm Results of the Treatment of Penetrating Abdominal Aortic or Iliac Artery Ulcer with the BeGraft Balloon-Expandable Covered Stent-A Single-Center Experience.

BACKGROUND: The purpose of the study was to evaluate the feasibility and efficacy of the novel BeGraft covered stent for the treatment of abdominal penetrating aortic ulcer (PAU) or penetrating ulcers of the iliac arteries (PUIAs). METHODS: This was a single-center observational study, which included 24 consecutive patients who underwent endovascular surgery due to abdominal PAU or PUIA between June 2017 and September 2019. Demographics of patients, lesion characteristics, diameter and length of the BeGraft stents, and postoperative events were prospectively collected and retrospectively analyzed. Follow-up examinations were performed at 1, 6, 12, and 24 months with clinical and hemodynamic evaluation. Outcome measures included technical success, perioperative complications, and stent patency. RESULTS: A total of 24 patients (13 men and 11 women), with a median age of 67 years (range, 42-81 years), were analyzed. Among them, 20 patients were symptomatic, and 4 patients underwent elective surgery because of the size of PAU. A total of 54 BeGraft stents (26 aortic and 28 peripheral) were successfully delivered and deployed to cover 13 aortic and 13 common iliac artery ulcer lesions. The technical success rate was 100%. The average procedural time was 53.8 ± 12.8 min. Complications included one case of the access-site pseudoaneurysm, which was successfully treated by thrombin injection. During a median follow-up of 20.5 months (range, 6-33 months), all stents remained patent, without endoleak or ulcer recurrence. CONCLUSIONS: BeGraft stents used during endovascular treatment of abdominal PAU and PUIA lesions are associated with favorable outcomes regarding technical success and patency. The primary use of BeGraft covered stents provides a valid option for patients with abdominal PAU. Long-term follow-up is required to confirm these promising results.

Angio PLanewave UltraSensitive Imaging (Angio PL.U.S.) as an Innovative Doppler Ultrasound Technique with a Potential to follow up Endoleaks after Endovascular Aneurysm Repair (EVAR).

The aim of the study was to evaluate the effectiveness of Angio PLanewave UltraSensitive imaging (Angio PL.U.S.) as an alternative to contrast-enhanced ultrasound (CEUS) and computed tomography angiography (CTA) for endoleak detection and classification in patients after endovascular aneurysm repair. A total of 28 patients underwent a post-endovascular aneurysm repair follow-up with color Doppler ultrasound, power Doppler ultrasound, CEUS, Angio PL.U.S and CTA examinations. CTA revealed 17 endoleaks in 14 patients (50%): 3 type Ia, 13 type II and 1 type III. There were no differences between Angio PL.U.S. and CEUS in terms of sensitivity, specificity or accuracy (93%, 100% and 97%). We did not observe any statistically significant differences between CTA, CEUS and Angio PL.U.S. in terms of the endoleak identification ability. Angio PL.U.S. may be considered as a potential tool to follow-up patients after endovascular aneurysm repair implantation, especially in patients who cannot be examined with CTA or CEUS.

The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis.

Neovascularization and angiogenesis are vital processes in the repair of damaged tissue, creating new blood vessel networks and increasing oxygen and nutrient supply for regeneration. The importance of Adipose-derived Mesenchymal Stem Cells (ASCs) contained in the adipose tissue surrounding blood vessel networks to these processes remains unknown and the exact mechanisms responsible for directing adipogenic cell fate remain to be discovered. As adipose tissue contains a heterogenous population of partially differentiated cells of adipocyte lineage; tissue repair, angiogenesis and neovascularization may be closely linked to the function of ASCs in a complex relationship. This review aims to investigate the link between ASCs and angiogenesis/neovascularization, with references to current studies. The molecular mechanisms of these processes, as well as ASC differentiation and proliferation are described in detail. ASCs may differentiate into endothelial cells during neovascularization; however, recent clinical trials have suggested that ASCs may also stimulate angiogenesis and neovascularization indirectly through the release of paracrine factors.

The role of proprotein convertase subtilisin-kexin type 9 (PCSK9) in the vascular aging process - is there a link?

Lately there are many new, promising low-density lipoprotein cholesterol reducing therapies with PCSK9 inhibitors. We performed selected sampling of the publications in PubMed and made a review according to selected keywords. It summarizes the effect of PCSK9 on vascular aging, directly associated with lipid and glucose metabolism, chronic inflammation, atherosclerosis and hypertension. Serum level of PCSK9 is different in patients affected by certain illnesses (whose risk increases with age) than in healthy individuals. The same could be observed in the case of chronic inflammation. In this review we summarize what is known about the role PCSK9 in human metabolism and how this could affect the vascular aging process. Based on the available sources, we prove that PCSK9 is involved in many biochemical pathways associated with vascular aging. In the future, treatments using PCSK9 inhibition may not only reduce the cardiovascular risk but also slow down this process.

Associations and interactions between variants in selenoprotein genes, selenoprotein levels and the development of abdominal aortic aneurysm, peripheral arterial disease, and heart failure.

BACKGROUND: Little is known on the role of selenoprotein genes in cardiovascular disease. This study examines the associations of the SEPP1, SELENOS, TXNRD1, TXNRD2, GPX4, and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin concentrations with the development of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AOID), as well as their influence on cardiac phenotype. METHODS: 564 patients with AAA, 400 patients with AIOD, and 543 controls were enrolled and characterized for coronary artery disease, myocardial infarction, and systolic heart failure (HF) occurrence. In AAA, the coexistence of peripheral arterial disease (PAD) was examined. Genotypes were determined using TaqMan-based assays. Selenoprotein concentration was assessed using the ELISA method. RESULTS: The SELENOS rs34713741T, SEPP1 rs3877899A, and GPX4 rs713041T alleles were related to a 30-60% increase in the AIOD/PAD risk in the recessive or dominant model (all associations at P < .05). The SEPP1 rs3877899A allele was a protective factor for the development of AAA without concomitant PAD (OR = 0.68 for the dominant model, P = .014), but not AAA with concomitant PAD. The cumulative two-locus effects of selenoprotein genes on the AAA/AIOD risk were observed, including the multiplicative interaction between the SELENOS rs34713741T and GPX4 rs713041T alleles (both in the recessive model) affecting the AIOD risk (OR = 5.27, P = .001) and its clinical phenotype. Coexistence of HF in aortic diseases was related to both the SEPP1 rs7579A allele (OR = 1.83 for carriers, P = .013) and increased SeP concentrations; SeP level ≥8.5 mg/mL caused a 3.5-fold increase in the risk of HF. In AAA, SeP levels were correlated with BMI (r = -0.575, P < .0001). CONCLUSIONS: Our results provide evidence that selenoprotein polymorphisms constitute a risk factor for HF and peripheral atherosclerosis, but prevent the development of AAA. Excessive weight might result in reduced antioxidant reserve efficiency in AAA. Validation studies are required to establish whether SeP concentration may be a marker for HF.

Superb Micro-vascular Imaging (SMI): a Doppler ultrasound technique with potential to identify, classify, and follow up endoleaks in patients after Endovascular Aneurysm Repair (EVAR).

PURPOSE: The aim of the study was to assess the effectiveness of Superb Micro-vascular Imaging (SMI) as an alternative to Contrast-Enhanced Ultrasound (CEUS) and Computed Tomography Angiography (CTA) for endoleak detection and classification in patients followed up after endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS AND METHODS: From May 2015 to January 2017, 30 patients underwent post-EVAR follow-up with Color Doppler Ultrasound (CDUS), CEUS, SMI, and CTA examinations. Aneurysmal sac diameter and graft patency were evaluated; endoleaks were identified and classified. Sensitivity, specificity, and accuracy values were calculated for each of the four diagnostic methods of endoleak detection. A percentage of agreement and Cohen's Kappa coefficient were calculated for comparison of methods in terms of endoleak identification. RESULTS: CTA revealed fifteen endoleaks (50%): three type Ia, nine type II, and three type III. The sensitivity of CDUS, CEUS, and SMI relative to CTA was 27%, 100%, and 100%, respectively. Specificity was 93%, 93%, and 93%, respectively. Accuracy was 60%, 97%, and 97%, respectively. There were no differences between SMI and CEUS in terms of sensitivity, specificity, or accuracy (100%, 93%, and 97%). We do not observe statistically significant differences between CTA, CEUS, and SMI concerning endoleak identification ability. The weakest method in endoleak identification was CDUS. CONCLUSIONS: The analysis showed that SMI is effective, repeatable, and comparable with the CEUS modality in identification endoleaks after EVAR; it may be considered as a potential tool to monitor patients after EVAR implantation, especially those with renal insufficiency or with an allergy to any contrast media.

Morphology-Related Limitations of Endovascular Aneurysm Repair Applicability in the Treatment of Abdominal Aortic Aneurysm in West-Central Poland.

BACKGROUND: Morphology is one of the most important factors influencing the long-term durability of endovascular repair of an infrarenal abdominal aortic aneurysm (AAA). The knowledge of morphological characteristics of AAA that may differ in various populations seems to be important for further development of a technology of endovascular repair as well as for planning of treatment strategies. To analyze the current applicability of endovascular aneurysm repair (EVAR) in patients with an infrarenal AAA with an indication for elective treatment in west-central Poland. METHODS: Computed tomography angiograms of 100 consecutive patients with infrarenal AAA deemed to require treatment were analyzed with an OsiriX DICOM viewer in 3D-multiplanar reconstruction mode. Proximal neck diameter, length, angulation, shape, the presence of thrombus and calcification, distal neck diameter, and morphology of the iliac arteries were determined. Three sets of morphological criteria were established. The optimal criteria consisted of a nonconical proximal neck without moderate or severe calcification or thrombus, with a diameter of 18-28 mm, length of ≥15 mm, and ß angulation of <60%; a distal neck with a diameter of ≥20 mm; a landing zone in the common iliac arteries (CIAs) with a length of ≥10 mm and diameter of ≤20 mm; and external iliac arteries with diameters of ≥7 mm. The suboptimal criteria included proximal neck diameters of 18-32 mm, neck lengths ≥10 mm, infrarenal neck angulations of up to 75°, and CIA diameters of up to 25 mm. Finally, the extended suboptimal criteria included proximal neck diameters of 16-34 mm and infrarenal neck angulations ≤90°, without limits in the maximal diameter of the CIAs. RESULTS: The median maximum aneurysm diameter was 61 mm. The optimal, suboptimal, and extended suboptimal criteria were met by 23%, 32%, and 53% of patients, respectively. The most common deviations were wide, conical, and angulated proximal necks and aneurysmal iliac arteries. CONCLUSIONS: The majority of patients with AAA deemed to be candidates for elective repair do not meet the most favorable criteria for EVAR. Availability of better endovascular solutions for conical, angulated, and wide necks and aneurysmal iliac arteries would likely expand EVAR applicability. Open repair remains a valid option.

How many single-nucleotide polymorphisms (SNPs) must be tested in order to prove susceptibility to bacterial meningitis in children? Analysis of 11 SNPs in seven genes involved in the immune response and their effect on the susceptibility to bacterial meningitis in children.

The aim of this study is to describe the prevalence of single single-nucleotide polymorphisms (SNPs) as well as their combinations in genes encoding proteins involved in the immune response in children with bacterial meningitis. The prospective study group consisted of 39 children with bacterial meningitis and 49 family members surveyed between 2012 and 2016. Eleven SNPs in seven genes involved in immune response were analysed. The mean number of minor frequency alleles (MAF) of studied SNPs was lowest in the control group and highest in patients with pneumococcal meningitis. We found that carrying ≥6 MAF of studied SNPs was associated with an increased risk of pneumococcal meningitis. The prevalence of risky variants was noted to be higher in patients with pneumococcal meningitis as compared to the control group. In conclusion, genetic factors are a relevant factor in determining the susceptibility to bacterial meningitis. A statistically significant cumulative effect of mutated variants on increasing the risk of bacterial meningitis was detected. Combining all three SNPs in MBL2 improves the prediction of susceptibility to pneumococcal meningitis. Analysis of risky alleles can help indicate people prone to the disease who are 'gene-immunocompromised'.