Bivalirudin as an anticoagulation strategy for acute hemodialysis in children: Two cases with a summary of recent literature.

Unfractionated heparin is the most used anticoagulative agent for extracorporeal settings in children, including acute hemodialysis modalities. In certain situations, such as heparin-induced thrombocytopenia, alternatives must be applied. The direct thrombin inhibitor bivalirudin has come forth as an attractive substitute. Bivalirudin is currently only approved for adult use in specific percutaneous coronary intervention settings. However, it has a growing off-label popularity in different contexts for both adult and pediatric patients. Experience with bivalirudin in children is mainly limited to extracorporeal membrane oxygenation, ventricular assist devices and during cardiopulmonary bypass surgery. Literature about its use as anticoagulation strategy for pediatric hemodialysis is very scarce. Here, we present two pediatric cases where bivalirudin was used during acute hemodialysis, followed by a short summary of recent literature.

Myhre syndrome in adulthood: clinical variability and emerging genotype-phenotype correlations.

Myhre syndrome (MS, MIM 139210) is a rare multisystemic disorder caused by recurrent pathogenic missense variants in SMAD4. The clinical features have been mainly documented in childhood and comprise variable neurocognitive development, recognizable craniofacial features, a short stature with a pseudo-muscular build, hearing loss, thickened skin, joint limitations, diverse cardiovascular and airway manifestations, and increased fibrosis often following trauma or surgery. In contrast, adults with MS are underreported obscuring potential clinical variability. Here, we describe 24 adults with MS, including 17 diagnosed after the age of 18 years old, and we review the literature on adults with MS. Overall, our cohort shows a milder phenotype as well as lower mortality rates compared to what has been published in literature. Individuals with a codon 500 variant in SMAD4 present with a more pronounced neurodevelopmental and systemic phenotype. However, in contrast to the literature, we observe cardiovascular abnormalities in individuals with the p.(Arg496Cys) variant. In addition, we describe scoliosis as a new manifestation and we report fertility in two additional males with the p.(Arg496Cys). In conclusion, our study contributes novel insights into the clinical variability of MS and underscores the importance of variant-specific considerations, and we provide recommendations for the management of MS in adulthood.

Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum.

Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination. Single-cell analysis indicates that the responsive T cell population is polyclonal and exhibits the near-entire spectrum of T cell differentiation states, including a naive-like state, but excluding exhausted cell states. Three of six vaccinated patients experience disease recurrence during the follow-up period of 2 years. Collectively, these data support the feasibility, safety, and immunogenicity of this treatment in resected NSCLC.

The use of AVF.SIM system for the surgical planning of arteriovenous fistulae in routine clinical practice.

BACKGROUND: The number of patients treated with hemodialysis (HD) in Europe is more than half a million and this number increases annually. The arteriovenous fistula (AVF) is the vascular access (VA) of first choice, but the clinical outcome is still poor. A consistent number of AVFs fails to reach the desired blood flow rate for HD treatment, while some have too high flow and risk for cardiac complications. Despite the skill of the surgeons and the possibility to use Ultrasound investigation for mapping arm vasculature, it is still not possible to predict the blood flow volume that will be obtained after AVF maturation. METHODS: We evaluated the potential of using a computational model (AVF.SIM) to predict the blood flow volume that will be achieved after AVF maturation, within a multicenter international clinical investigation aimed at assessing AVF.SIM predictive power. The study population included 231 patients, with data on AVF maturation in 124 patients, and on long-term primary patency in 180 patients. RESULTS: At 1 year of follow-up, about 60% of AVFs were still patent, with comparable primary patency in proximal and distal anastomosis. The correlation between predicted and measured blood flow volume in the brachial artery at 40 days after surgery was statistically significant, with an overall correlation coefficient of 0.58 (p < 0.001). The percent difference between measured and predicted brachial blood flow 40 days after surgery was less than 30% in 72% of patients investigated. CONCLUSIONS: The results indicate that the use of the AVF.SIM system allowed to predict with a good accuracy the blood flow volume achievable after VA maturation, for a given location and type of anastomosis. This information may help in AVF surgical planning, reducing the AVFs with too low or too high blood flow, thus improving AVF patency rate and clinical outcome of renal replacement therapy.