Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists.

XAF1 as a modifier of p53 function and cancer susceptibility.

Cancer risk is highly variable in carriers of the common R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns.

Unraveling the Relationship Between Itching, Scratch Scales, and Biomarkers in Children With Alagille Syndrome.

Pruritus is a debilitating symptom for patients with Alagille syndrome (ALGS). In a previously reported trial of maralixibat, an investigational antipruritic agent, itching was assessed using a digital diary based on twice-daily caregiver observation of itching severity (Itch Reported Outcome, ItchRO[Observer]). The goal of this study was to characterize pruritus in participants with ALGS at baseline in this trial, as assessed by the ItchRO instrument and the physician-observed clinician scratch scale (CSS), relative to biomarkers putatively associated with pruritus and health-related quality of life assessment.

TNFAIP8 family gene expressions in the mouse tail intervertebral disc injury model.

Introduction: The TNF-α-induced protein-8 (TNFAIP8, also known as TIPE) family of molecules comprises four members: TNFAIP8 and TIPEs1-3. Since the first description of these proteins, their roles in fine-tuning inflammation and in directing leukocyte migration have been described in several organ systems. However, their relationship with intervertebral disc (IVD) is unknown.

Epidemiology, Natural History, and Treatment of Hepatitis Delta Virus Infection in HIV/Hepatitis B Virus Coinfection.

Purpose Of Review: Limited data exist on the prevalence, determinants, and outcomes of hepatitis delta virus (HDV) infection among HIV/hepatitis B virus (HBV)-coinfected persons. This review provides current evidence on the epidemiology, natural history, and treatment of HDV infection in patients with HIV/HBV coinfection and highlights future research needs.

Recent Findings: Cross-sectional studies in Europe, Africa, South America, and Asia show that the prevalence of HDV among HIV/HBV-coinfected patients ranges from 1.

Advanced imaging tools for childhood tuberculosis: potential applications and research needs.

Tuberculosis is the leading cause of death globally that is due to a single pathogen, and up to a fifth of patients with tuberculosis in high-incidence countries are children younger than 16 years. Unfortunately, the diagnosis of childhood tuberculosis is challenging because the disease is often paucibacillary and it is difficult to obtain suitable specimens, causing poor sensitivity of currently available pathogen-based tests. Chest radiography is important for diagnostic evaluations because it detects abnormalities consistent with childhood tuberculosis, but several limitations exist in the interpretation of such results.

Identification and characterization of calyceal diverticula with MR urography (MRU) in children.

Purpose: To determine the MRU imaging findings of calyceal diverticula in a large cohort of children and to compare the frequency of calyceal diverticula in our cohort with what has been previously reported.

Methods: This was a HIPAA-compliant, IRB-approved retrospective study of all patients with suspected CD based on their medical records. All patients in this study underwent MRU at our institution between 2010 and 2017.

Maternal and neonatal response to COVID-19.

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to maternal and newborn health has yet to be determined. Several reports suggest pregnancy does not typically increase the severity of maternal disease; however, cases of preeclampsia and preterm birth have been infrequently reported. Reports of placental infection and vertical transmission are rare.

A retrospective analysis of venous thromboembolism trends in chemotherapy-induced anemia: Red blood cell transfusion versus erythrocyte stimulating agent administration.

Background: Patients receiving a variety of chemotherapy regimens often develop chemotherapy-induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs).

Management of Lupus Nephritis in Children.

Lupus nephritis affects 50-75% of all children with systemic lupus erythematosus with a higher prevalence in Asians. It remains a major contributor to morbidity and mortality in childhood onset lupus. Proliferative lupus nephritis (class III and class IV) warrants aggressive treatment to prevent progression to end stage renal disease.

Impact of PTFE-covered stent position and extension on TIPS patency.

Purpose: The objectives of this study were to determine the effects of expanded polytetrafluoroethylene (PTFE)-covered stent location and TIPS extension on primary patency.

Methods: This retrospective cohort study examined patients with PTFE-covered TIPS creation between 07/2002 and 06/2016. Clinical information and patency outcomes at 24 months were extracted.

Whole-Exome Sequencing in NF1-Related West Syndrome Leads to the Identification of KCNC2 as a Novel Candidate Gene for Epilepsy.

Patients with neurofibromatosis type 1 (NF1) have an increased risk for West syndrome (WS), but the underlying mechanisms linking NF1 and WS are unknown. In contrast to other neurocutaneous syndromes, intracerebral abnormalities explaining the course of infantile spasms (IS) are often absent and the seizure outcome is usually favorable. Several studies have investigated a potential genotype-phenotype correlation between and seizure susceptibility, but an association was not identified.

In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity.

Nanotechnologies are considered to be of growing importance to the vaccine field. Through decoration of immunogens on multivalent nanoparticles, designed nanovaccines can elicit improved humoral immunity. However, significant practical and monetary challenges in large-scale production of nanovaccines have impeded their widespread clinical translation.

Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure.

Background: Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear.

Research Question: Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure?

Study Design And Methods: This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study.

Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure.

Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models.

Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA).

Pre-existing heterologous T-cell immunity and neoantigen immunogenicity.

Neoantigens are tumor-specific mutated proteins that are exempt from central tolerance and are therefore capable of efficiently eliciting effective T-cell responses. The identification of immunogenic neoantigens in tumor-specific mutated proteins has promising clinical implications for cancer immunotherapy. However, the factors that may contribute to neoantigen immunogenicity are not yet fully understood.

Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis.

Background: The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children.

Methods: A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed.

Intraoperative Cardiac Arrest During Adult Liver Transplantation: Incidence and Risk Factor Analysis From 7 Academic Centers in the United States.

Background: Intraoperative cardiac arrest (ICA) has a reported frequency of 1 in 10,000 anesthetics but has a much higher estimated incidence in orthotopic liver transplantation (OLT). Single-center studies of ICA in OLT are limited by small sample size that prohibits multivariable regression analysis of risks.

Methods: Utilizing data from 7 academic medical centers, we performed a retrospective, observational study of 5296 adult liver transplant recipients (18-80 years old) between 2000 and 2017 to identify the rate of ICA, associated risk factors, and outcomes.