Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

Background: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied.

Methods: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018.

Cell-based cccDNA reporter assay combined with functional genomics identifies YBX1 as HBV cccDNA host factor and antiviral candidate target.

Objectives: Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and hepatocellular carcinoma. A key feature of HBV replication is the synthesis of the covalently close circular (ccc)DNA, not targeted by current treatments and whose elimination would be crucial for viral cure. To date, little is known about cccDNA formation.

2022 Update of indications and contraindications for lung transplantation in France.

Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process.

A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity.

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family.

Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy.

Eukaryotic initiation factor-4A2 (EIF4A2) is an ATP-dependent RNA helicase and a member of the DEAD-box protein family that recognizes the 5' cap structure of mRNAs, allows mRNA to bind to the ribosome, and plays an important role in microRNA-regulated gene repression. Here, we report on 15 individuals from 14 families presenting with global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies, all of whom have extremely rare de novo mono-allelic or inherited bi-allelic variants in EIF4A2. Neurodegeneration was predominantly reported in individuals with bi-allelic variants.

Fusion and clinical outcomes of lumbar interbody fusion for low-grade isthmic spondylolisthesis.

Introduction: Low-grade isthmic spondylolisthesis (ISPL) is generally treated by circumferential fusion with interbody graft, although there is no consensus on technique.

Hypothesis: The various interbody fusion strategies provide satisfactory fusion rates and clinical results.

Methods: A multicenter retrospective study analyzed lumbar interbody fusion for low-grade ISPL performed between March 2016 and March 2019.

Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study.

Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM.

Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use.

Gender differences in psychosocial function and self-reported health status in late-diagnosed autistic adults: results from the FACE-ASD national cohort.

Background: While adult outcome in autism spectrum disorder (ASD) is generally measured using socially valued roles, it could also be understood in terms of aspects related to health status - an approach that could inform on potential gender differences.

Methods: We investigated gender differences in two aspects of outcome related to health-status, i.e.

The Autoinflammatory Diseases Alliance Registry of monogenic autoinflammatory diseases.

Objective: The present manuscript aims to describe an international, electronic-based, user-friendly and interoperable patient registry for monogenic autoinflammatory diseases (mAIDs), developed in the contest of the Autoinflammatory Diseases Alliance (AIDA) Network.

Methods: This is an electronic platform, based on the Research Electronic Data Capture (REDCap) tool, used for real-world data collection of demographics, clinical, laboratory, instrumental and socioeconomic data of mAIDs patients. The instrument has flexibility, may change over time based on new scientific acquisitions, and communicate potentially with other similar registries; security, data quality and data governance are corner stones of the platform.

Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.

Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation.

Effects of Adaptive Servo-Ventilation on Nocturnal Ventricular Arrhythmia in Heart Failure Patients With Reduced Ejection Fraction and Central Sleep Apnea-An Analysis From the SERVE-HF Major Substudy.

Background: The SERVE-HF trial investigated the effect of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with heart failure with reduced ejection fraction (HFrEF).

Objective: The aim of the present ancillary analysis of the SERVE-HF major substudy (NCT01164592) was to assess the effects of ASV on the burden of nocturnal ventricular arrhythmias as one possible mechanism for sudden cardiac death in ASV-treated patients with HFrEF and CSA.

Methods: Three hundred twelve patients were randomized in the SERVE-HF major substudy [no treatment of CSA (control) vs.

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers.

Hemostats in Spine Surgery: Literature Review and Expert Panel Recommendations.

Bleeding in spine surgery is a common occurrence but when bleeding is uncontrolled the consequences can be severe due to the potential for spinal cord compression and damage to the central nervous system. There are many factors that influence bleeding during spine surgery including patient factors and those related to the type of surgery and the surgical approach to bleeding. There are a range of methods that can be employed to both reduce the risk of bleeding and achieve hemostasis, one of which is the adjunct use of hemostatic agents.

A partial form of inherited human USP18 deficiency underlies infection and inflammation.

Human USP18 is an interferon (IFN)-stimulated gene product and a negative regulator of type I IFN (IFN-I) signaling. It also removes covalently linked ISG15 from proteins, in a process called deISGylation. In turn, ISG15 prevents USP18 from being degraded by the proteasome.

Association Between Endometriosis Phenotype and Preterm Birth in France.

Importance: Endometriosis is an inflammatory disease with a heterogeneous presentation that affects women of childbearing age. Given the limitations of previous retrospective studies, it is still unclear whether endometriosis has adverse implications for pregnancy outcomes.

Objective: To evaluate the association between the presence of endometriosis and preterm birth and whether the risk varied according to the disease phenotype.

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes.

Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial.

Background: Single-agent nivolumab showed durable responses, manageable safety, and promising survival in patients with advanced hepatocellular carcinoma in the phase 1-2 CheckMate 040 study. We aimed to investigate nivolumab monotherapy compared with sorafenib monotherapy in the first-line setting for patients with advanced hepatocellular carcinoma.

Methods: In this randomised, open-label, phase 3 trial done at medical centres across 22 countries and territories in Asia, Australasia, Europe, and North America, patients at least 18 years old with histologically confirmed advanced hepatocellular carcinoma not eligible for, or whose disease had progressed after, surgery or locoregional treatment; with no previous systemic therapy for hepatocellular carcinoma, with Child-Pugh class A and Eastern Cooperative Oncology Group performance status score of 0 or 1, and regardless of viral hepatitis status were randomly assigned (1:1) via an interactive voice response system to receive nivolumab (240 mg intravenously every 2 weeks) or sorafenib (400 mg orally twice daily) until disease progression or unacceptable toxicity.

Validation of an Intelligibility Test Based on Acoustic-Phonetic Decoding of Pseudo-Words: Overall Results from Patients with Cancer of the Oral Cavity and the Oropharynx.

Objectives: Loss of intelligibility is a major complaint for patients with speech disorders, as it affects their everyday communication and thus contributes to a decrease in their quality of life. Several tests are available to measure intelligibility, but these tests do not take into account the evaluators' ability to restore distorted sequences. Due to this ability, the evaluator will tend to recognize words despite phonetic distortions, and speech production deficit can go undetected.

Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section.

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm.

Recurrent missense variants in can cause syndromic intellectual disability.

Purpose: Binding proteins (G-proteins) mediate signalling pathways involved in diverse cellular functions and comprise Gα and Gβγ units. Human diseases have been reported for all five Gβ proteins. A missense variant in was recently reported in one individual with developmental delay/intellectual disability (DD/ID) and dysmorphism.