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Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. β-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a β-blocker (atenolol) during murine peritonitis.Ivabradine (3 μg/g), atenolol (3 μg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile).As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224).Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.

Introduction: Langerhans cell histiocytosis (HL) is a rare disease that can affect all tissues. Oral manifestations such as mucosal ulcer and tooth mobility are often the first signs of the disease. We report a rare case of mandibular condyle unifocal HL mimicking a temporomandibular joint disorder.Case report: A 44-year-old patient presented with a left temporomandibular disorder with painful left preauricular swelling. The imaging assessment found a bone lesion of the left mandibular condyle. A curettage with biopsy was used to diagnose HL. Six months later, the patient had no more pain.Discussion: The craniofacial clinical expressions of HL mainly concern the bones, which can cause: pain, swelling, fracture, compression of noble organs. The other sites are: oral cavity, skin, lymph nodes, or eyes. Isolated forms are generally benign, and their treatment is discussed between abstention and non-aggressive surgery.Keywords: Condyle mandibulaire; Désordre temporo-mandibulaire; Eosinophilic granuloma; Granulome éosinophile; Histiocytose langerhansienne; Langerhans-cell histiocytosis; Mandibular condyle; Temporomandibular joint disorder; Trismus., IntroductionL’histiocytose langerhansienne (HL) est une maladie rare pouvant toucher tous les tissus. Les premières manifestations de l’HL sont souvent orales (ulcérations buccales, mobilités dentaires). Nous rapportons un cas rare d’HL unifocale localisée au condyle mandibulaire et mimant un désordre de l’appareil manducateur.ObservationUne femme de 44 ans présentait un tableau de désordre temporo-mandibulaire gauche associé à un œdème pré-auriculaire gauche douloureux. Le bilan d’imagerie retrouvait une lésion ostéolytique du condyle mandibulaire gauche. Un curetage avec biopsie a permis de faire le diagnostic d’HL. Six mois plus tard, la patiente n’avait plus de douleur.DiscussionLes atteintes crâniofaciales de l’HL concernent majoritairement les os, pouvant provoquer : douleur, œdème, fracture, compressions d’organes nobles. Les autres atteintes sont buccales, cutanée, ganglionnaire ou oculaire. Les formes isolées sont généralement bénignes, et leur traitement se discute entre abstention et chirurgie non agressive.

International audience; Rationale: Promoting endogenous pulmonary regeneration is crucial after damage to restore normal lungs and prevent the onset of chronic adult lung diseases.Objectives: To investigate whether the cell-cycle inhibitor p16INK4a limits lung regeneration after newborn bronchopulmonary dysplasia (BPD), a condition characterized by the arrest of alveolar development, leading to adult sequelae.Methods: We exposed p16INK4a-/- and p16INK4a ATTAC (apoptosis through targeted activation of caspase 8) transgenic mice to postnatal hyperoxia, followed by pneumonectomy of the p16INK4a-/- mice. We measured p16INK4a in blood mononuclear cells of preterm newborns, 7- to 15-year-old survivors of BPD, and the lungs of patients with BPD.Measurements and Main Results: p16INK4a concentrations increased in lung fibroblasts after hyperoxia-induced BPD in mice and persisted into adulthood. p16INK4a deficiency did not protect against hyperoxic lesions in newborn pups but promoted restoration of the lung architecture by adulthood. Curative clearance of p16INK4a-positive cells once hyperoxic lung lesions were established restored normal lungs by adulthood. p16INK4a deficiency increased neutral lipid synthesis and promoted lipofibroblast and alveolar type 2 (AT2) cell development within the stem-cell niche. Besides, lipofibroblasts support self-renewal of AT2 cells into alveolospheres. Induction with a PPARγ (peroxisome proliferator-activated receptor γ) agonist after hyperoxia also increased lipofibroblast and AT2 cell numbers and restored alveolar architecture in hyperoxia-exposed mice. After pneumonectomy, p16INK4a deficiency again led to an increase in lipofibroblast and AT2 cell numbers in the contralateral lung. Finally, we observed p16INK4a mRNA overexpression in the blood and lungs of preterm newborns, which persisted in the blood of older survivors of BPD.Conclusions: These data demonstrate the potential of targeting p16INK4a and promoting lipofibroblast development to stimulate alveolar regeneration from childhood to adulthood.

Purpose Nasomaxillary fractures can be mistaken for fractures confined to the nasal bones, resulting in inappropriate treatments that jeopardize patient outcomes. Our purpose here was to provide information on nasomaxillary fractures via a retrospective study and literature review. Material and methods We retrospectively collected clinical, computed tomography (CT), therapeutic, and outcome data in consecutive patients managed for unilateral impacted nasomaxillary fractures at our centre over a 5-year period (2013–2017). Long-term outcomes were further assessed by administering scoring tools for subjectively assessed cosmesis, nasal obstruction, and pain during a telephone interview. Results The 11 included patients had a mean age of 33.4 years. The clinical manifestations included nasal asymmetry in all 11 patients and infra-orbital rim step-off deformity in 9 patients. Consistent CT findings were involvement of the nasal bone, canine pillar, and anterior maxillary bone; and presence of blood within the maxillary sinus. The treatment in 8 patients consisted in open reduction and internal fixation via the intraoral approach, with or without an added infra-orbital approach; 1 patient was managed by endonasal reduction and 2 patients declined reduction. Almost 1 year after surgery, the cosmetic outcome was good (mean score, 22/25) and few patients reported nasal obstruction (mean score, 3.6/20) or pain (mean score, 1.6/10). Conclusion Nasomaxillary fracture is a specific entity that must be differentiated from nasal bone fracture. Open reduction and internal fixation via the intraoral approach, with an added infra-orbital approach if needed, provides good outcomes.

BACKGROUND & AIM The canalicular bile salt export pump (BSEP/ABCB11) of hepatocytes is the main adenosine triphosphate (ATP)-binding cassette (ABC) transporter responsible for bile acid secretion. Mutations in ABCB11 cause several cholestatic diseases, including progressive familial intrahepatic cholestasis type 2 (PFIC2) often lethal in absence of liver transplantation. We investigated in vitro the effect and potential rescue of a BSEP mutation by ivacaftor, a clinically approved cystic fibrosis transmembrane conductance regulator (CFTR/ABCC7) potentiator. METHODS The p.T463I mutation, identified in a PFIC2 patient and located in a highly conserved ABC transporter motif, was studied by 3D structure modelling. The mutation was reproduced in a plasmid encoding a rat Bsep-green fluorescent protein. After transfection, mutant expression was studied in Can 10 cells. Taurocholate transport activity and ivacaftor effect were studied in Madin-Darby canine kidney (MDCK) clones co-expressing the rat sodium-taurocholate co-transporting polypeptide (Ntcp/Slc10A1). RESULTS As the wild-type protein, BsepT463I was normally targeted to the canalicular membrane of Can 10 cells. As predicted by 3D structure modelling, taurocholate transport activity was dramatically low in MDCK clones expressing BsepT463I . Ivacaftor treatment increased by 1.7-fold taurocholate transport activity of BsepT463I (P

Les 40es Journées de la SFSPM se sont tenues à Avignon du 7 au 9 novembre 2018. Le thème abordé—Cancer du sein : optimisation du parcours de soins — a réuni plus de 1 200 participants sous les voûtes du Palais des Papes. La fluidité de chaque segment du parcours a été analysée en termes de risques de rupture de continuité des soins tant au sein du segment lui-même qu’en amont et en aval. Dans un parcours par essence pluridisciplinaire et plurimétiers, la nécessité d’une réflexion globale et d’une coordination active réalisées par des professionnels formés a été rappelée à chaque session. Chacun des intervenants a esquissé de potentiels indicateurs de qualité tenant compte à la fois de son implication dans son segment d’intervention, mais tenant compte aussi d’une vision plus globale de ce que devrait être le parcours au travers de la maladie et des soins. La parole a été très largement partagée entre soignants et associations de malades, entre paramédicaux et acteurs en sciences humaines et sociales, entre responsables de la santé publique HAS, ARS, CNAM–CPAM 84 et représentants des différents modes d’hospitalisation publique/privée et ESPIC. La session grand public a été l’occasion d’échanges fructueux et instructifs sur la perception des difficultés comme des satisfactions rencontrées que nous ont fait partager les malades, leurs proches et les représentantes des associations. Au total, un congrès de réflexion partagé par de nombreux acteurs qui cherchent tous à améliorer le parcours de soins des malades atteintes de cancer du sein. La publication le 21 janvier par l’INCa de dix indicateurs de qualité du parcours de soins pour les malades atteints de cancer du sein est une étape importante qu’attendaient tous les participants d’Avignon — SFSPM 2018.

Whether the systemic manifestations observed in Chronic Obstructive Pulmonary Disease (COPD) are ascribable to lung dysfunction or direct effects of smoking is in debate. Structural Equations Modeling (SEM), a causal-oriented statistical approach, could help unraveling the pathways involved, by enabling estimation of direct and indirect associations between variables. The objectives of the study was to investigate the relative impact of smoking and COPD on systemic manifestations, inflammation and telomere length. In 292 individuals (103 women; 97 smokers with COPD, 96 smokers without COPD, 99 non-smokers), we used SEM to explore the pathways between smoking (pack-years), lung disease (FEV1, KCO), and the following parameters: arterial stiffness (aortic pulse wave velocity, PWV), bone mineral density (BMD), appendicular skeletal muscle mass (ASMM), grip strength, insulin resistance (HOMA-IR), creatinine clearance (eGFR), blood leukocyte telomere length and inflammatory markers (Luminex assay). All models were adjusted on age and gender. Latent variables were created for systemic inflammation (inflammatory markers) and musculoskeletal parameters (ASMM, grip strength, BMD). SEM showed that most effects of smoking were indirectly mediated by lung dysfunction: e.g. via FEV1 on musculoskeletal factor, eGFR, HOMA-IR, PWV, telomere length, CRP, white blood cells count (WBC) and inflammation factor, and via KCO on musculoskeletal factor, eGFR and PWV. Direct effects of smoking were limited to CRP and WBC. Models had excellent fit. In conclusion, SEM highlighted the major role of COPD in the occurrence of systemic manifestations while smoking effects were mostly mediated by lung function.

Nitric oxide (NO) donors may be useful for treating pulmonary hypertension (PH) complicating sickle cell disease (SCD), as endogenous NO is inactivated by hemoglobin released by intravascular hemolysis. Here, we investigated the effects of the new NO donor NCX1443 on PH in transgenic SAD mice, which exhibit mild SCD without severe hemolytic anemia. In SAD and wild-type (WT) mice, the pulmonary pressure response to acute hypoxia was similar and was abolished by 100 mg/kg NCX1443. The level of PH was also similar in SAD and WT mice exposed to chronic hypoxia (9% O2) alone or with SU5416 and was similarly reduced by daily NCX1443 gavage. Compared with WT mice, SAD mice exhibited higher levels of HO-1, endothelial NO synthase, and PDE5 but similar levels of lung cyclic guanosine monophosphate. Cultured pulmonary artery smooth muscle cells from SAD mice grew faster than those from WT mice and had higher PDE5 protein levels. Combining NCX1443 and a PDE5 inhibitor suppressed the growth rate difference between SAD and WT cells and induced a larger reduction in hypoxic PH severity in SAD than in WT mice. By amplifying endogenous protective mechanisms, NCX1443 in combination with PDE5 inhibition may prove useful for treating PH complicating SCD.

Introduction Oral metastases from hepatocellular carcinoma (HCC) are very rare, and predominate in the mandible. We report an exceptional case of maxillary metastasis revealing HCC. Case report A 56-year-old man with a previous medical history of alcohol abuse presented to our department with a 3-week evolving oral mass. Physical examination showed a left maxillary tumor. The biopsy revealed a HCC and a multi-metastatic HCC with portal thrombosis and a pulmonary embolism was discovered following a CT-scan. A state of advanced malnutrition contraindicated sorafenib chemotherapy. Thus, external irradiation was proposed, without success. The patient subsequently died 50 days later. Discussion Maxillary HCC metastases are extremely rare. The average age of HCC jaw metastases appearance in patients has been reported to be approximately 57 years, men are more affected than women are, and the mean life expectancy is 12 months following the diagnosis. These patients require palliative treatment. Local recurrences occur very early after possible surgery, and expose the patient to life-threatening bleeding.