Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances.

Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway.

Genome sequencing identify chromosome 9 inversions disrupting ENG in 2 unrelated HHT families.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a dominant inherited vascular disorder. The clinical diagnosis is based on the Curaçao criteria and pathogenic variants in the ENG and ACVRL1 genes are responsible for most cases of HHT. Four families with a negative targeted gene panel and selected by a multidisciplinary team were selected and whole-genome sequencing was performed according to the recommendations of the French National Plan for Genomic Medicine.

Pro-angiogenic changes of T-helper lymphocytes in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare inherited disease due to heterozygous loss-of-function mutations on the BMP9/10 pathway ( or mainly). HHT endothelial cells are prone to lose their quiescence, leading to progressive appearance of numerous telangiectases on skin and mucosa (complicated by epistaxis and anemia), and to larger arteriovenous malformations in lungs, liver and brain. HHT is also associated with T lymphocyte abnormalities, which are currently poorly understood.

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL).

Background: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents.

Objectives: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT.

Seven cases of hereditary haemorrhagic telangiectasia-like hepatic vascular abnormalities associated with pathogenic variants.

Background: loss of function is associated with type 2 capillary malformation-arteriovenous malformation syndrome, an autosomal dominant vascular disorder. The phenotype partially overlaps with hereditary haemorrhagic telangiectasia (HHT) due to epistaxis, telangiectases and cerebral arteriovenous malformations, but a similar liver involvement has never been described.

Methods: Members of the French HHT network reported their cases of mutation identified after an initial suspicion of HHT.

T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients.

Introduction: This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection.

Patients And Methods: Patients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not.

Altered expressions of CXCR4 and CD26 on T-helper lymphocytes in hereditary hemorrhagic telangiectasia.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (muco-cutaneous telangiectases, arteriovenous malformations), a specific risk of infection is suggested by case series of severe and atypical infections as well as by reports of decreased T and natural killer (NK) lymphocyte counts. As some evidence supports a dysregulation of the CXCR4/CXCL12 chemotactic axis of HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes.

The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.

Background: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.

Methods: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care.

Intra-venous bevacizumab in hereditary hemorrhagic telangiectasia (HHT): A retrospective study of 46 patients.

Background: Bevacizumab, an anti-VEGF monoclonal antibody, has recently emerged as a new option for severe forms of hereditary hemorrhagic telangiectasia (HHT). Its utilization in this orphan disease has rapidly spread despite the lack of randomized trials and international guidelines. The objective of this study is to report the main clinical data (baseline characteristics, dose schedule, efficacy, adverse events and deaths) of HHT patients treated by intravenous bevacizumab in France.

Efficacy and safety of dapsone as second line therapy for adult immune thrombocytopenia: A retrospective study of 42 patients.

Dapsone is recommended as a second line therapy in immune thrombocytopenia (ITP), but is underused because of its potential side effects. The medical charts of 42 ITP patients treated with dapsone (100 mg/day) were retrospectively reviewed in order to assess its efficacy and safety in daily clinical practice. The overall response rate was 54.

Immunological abnormalities associated with hereditary haemorrhagic telangiectasia.

Objective: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder related to mutations in one of the coreceptors to the transforming growth factor-β superfamily (ALK1 or endoglin). Besides the obvious vascular symptoms (epistaxis and arteriovenous malformations), patients have an unexplained high risk of severe bacterial infections. The aim of the study was to assess the main immunological functions of patients with HHT using the standard biological tests for primary immunodeficiencies.

[Radiation pneumonitis: a rare and potentially severe pneumonia. Usefulness of corticosteroids].

We report a 80-year-old woman who presented with asthenia, confusion and abdominal pain, leading to a diagnosis of severe pneumonia complicated by a colonic pseudo-obstruction. The unfavourable outcome with antibiotic treatment and a recent past medical history of thoracic radiotherapy pointed to a possible diagnosis of radiation pneumonitis. Absence of other explanation and the rapid improvement with corticosteroids confirmed this rare and potentially serious diagnosis, especially among elderly people.

Nonvolcanic tremor evolution and the San Simeon and Parkfield, California, earthquakes.

Nonvolcanic tremors occur adjacent to locked faults and may be closely related to the generation of earthquakes. Monitoring of the San Andreas Fault in the Parkfield, California, region revealed that after two strong earthquakes, tremor activity increased in a nearly dormant tremor zone, increased and became periodic in a previously active zone, and has remained elevated and periodic for over 4 years. Static shear- and Coulomb-stress increases of 6 to 14 kilopascals from these two earthquakes are coincident with sudden increases in tremor rates.

Histomorphometric comparison of three bioabsorbable GTR barrier membranes in the canine model.

Guided tissue regeneration (GTR) using bioabsorbable barrier membranes has shown promising and somewhat predictable clinical results. However, limited information is available on the stages of histologic healing when these types of barriers are used. Therefore, the aim of this study was to compare three currently available bioabsorbable GTR barriers (type 1 collagen, polylactide/polyglycolide copolymer, and citric acid copolymer) for the treatment of surgically created periodontal dehiscences in dogs.

[Tartrate-resistant acid phosphatases (TRAP) and cytology of pseudosynovial membranes].

Pseudo-synovial membranes are found at the interface between bone and aseptically lost prostheses. They are supposed to be due to the release of material debris at the interface with bone. They are mostly composed of macrophages and giant cells, and some fibrocytes in the deep layer of the membrane.

[Engineering of osseous cells and bioartificial tissues].

The association of osteogenic stem cells to a synthetic carrier makes possible the elaboration of bioartificial tissue. Numerous phosphocalcic ceramics does not trigger a foreign body reaction when implanted in bone tissue and thus, a number of materials are available osteogenic stem cell carriers to replace the bone tissue. Several methods can be used to harvest these cells.

Degradation of hydroxylapatite, fluorapatite, and fluorhydroxyapatite coatings of dental implants in dogs.

Calcium phosphate coatings on dental implants enhance integration of the material. Resorption of the ceramic coatings has raised some concern about the behavior of the bone-implant interfaces after the coating disappearance. Substitution of the OH- ions by fluoride in the hydroxylapatite (HA) lattice makes the calcium phosphate more stable.

A study of structure and degradation of nonpolymeric biomaterials implanted in bone using reflected and transmitted light microscopy.

Orthopedic biomaterials currently are made of metal alloy coated with one or more thin layers of dense or porous ceramic or metal. Sections of these materials implanted in human bone were made without altering the implant or bone-implant interfaces. Bone containing an implant was fixed and then embedded in polymethylmethacrylate.

[Histological analysis of the bone/prosthesis interface in man after implantation of a hip prosthesis coated with plasma-sprayed hydroxyapatite].

Thin coatings of calcium phosphate hydroxyapatite on metal alloys provide to these materials biological properties of calcium phosphates. We have analysed, using histological techniques or newly developed scanning electronic microscopy techniques, hip prostheses implanted into humans for periods from a few days up to twenty six months. The results of these analyses confirm the good osteointegration of these prostheses observed during clinical studies.

New observations on middle term hydroxyapatite-coated titanium alloy hip prostheses.

HA-coated hip prostheses were retrieved from elderly patients after death. Histological analysis, scanning electron microscopy and microanalysis by energy-dispersive X-ray spectrometry were performed on the same sections. These revealed good osseointegration of the implant material and evolution of bone and material.

Bonding of hydroxyapatite-coated femoral prostheses. Histopathology of specimens from four cases.

We examined specimens of hydroxyapatite-coated femoral prostheses from four patients who had died within nine months of implantation for fractured neck of femur. Histology showed newly formed immature bone overlying the hydroxyapatite coating with new trabeculae bridging to the endosteal bone layer. In the diaphysis, where there had been contact between the hydroxyapatite and the cortex, there was dense, firmly anchored bone with an haversian architecture.