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Introduction: In recent years, several preliminary reports have suggested that the robot-assisted approach may decrease the surgical morbidity of artificial urinary sphincter (AUS) implantation in female patients with stress urinary incontinence (SUI). However, for now, only short-term outcomes have been reported. The present study aimed to report the 5-year outcomes of robot-assisted AUS implantation in female patients.Patients and methods: All female patients who underwent a robot-assisted AUS implantation between January 2014 and September 2019 at a single academic center were included in a retrospective study. All robot-assisted female AUS implantations performed after September 2019 were excluded to ensure a 5-year minimum follow-up duration. The indication for AUS implantation was SUI due to intrinsic sphincter deficiency. The primary endpoint was the explantation-free survival and revision-free survival.Results: Forty-two patients were included. The median age was 66 years (28-84), and 83.8% of the patients had a history of previous anti-incontinence procedure. After a median follow-up of 64 months (16-110), 8 patients were lost to follow-up before the 5-year time point. The 5-year estimated revision-free survival was 89.2 and the 5-year estimated explantation-free survival was 88%. Five AUS explantations were needed (11.9%), and six revisions were required (14.3%). The median time to explantation was 14 months. Four explantations (80%) occurred within the first 18 months, and all of them within the first 27 months. Thirty patients (71.42%) had a complete or improved continence with a complete continence rate of 59.52% and an improved continence rate of 11.9%. There were 10 intraoperative complications (23.8%): 5 bladder injuries and 5 vaginal injuries. Thirteen patients had postoperative complications (30.9%), but only two were Clavien grade ⩾3.Conclusion: The 5-year outcomes of robot-assisted AUS implantation seem to confirm the promising short-term outcomes that have been reported so far, although revision rates increased with time, which warrants further investigation.

PurposeNeurogenic bladder associated with spina bifida disease remains a major cause for mortality or morbidity due to kidney damages. However, we currently do not know which urodynamic findings are associated with an higher risk of upper tract damages in spina bifida patients. The objective of the present study was to evaluate urodynamic findings associated with functional kidney failure and/or with morphological kidney damages.MethodsA large single-center restrospective study was conducted in our national referral center for spina bifida patients using our patients’ files. All urodynamics curves were assessed by the same examinator. Functional and/or morphological evaluation of the upper urinary tract were done at the same moment as the urodynamic exam (between 1 week before and 1 month after). Kidney function was assessed using creatinine serum levels or 24 h urinary creatinine levels (creatinine clearance) for walking patients, or with the 24 h urinary creatinine level for wheelchair‐users.ResultsWe included 262 spina bifida patients in this study. Fifty-five patients had a poor bladder compliance (21.4%) and 88 of them had detrusor overactivity (33.6%). Twenty patients had a stage 2 kidney failure (eGFR < 60 ml/min) and 81 patients out of 254 (30.9%) had an abnormal morphological examination. There were three urodynamic findings significantly associated with UUTD: bladder compliance (OR = 0.18; p = 0.007), Pdetmax (OR = 14.7; p = 0.003) and detrusor overactivity (OR = 1.84; p = 0.03).ConclusionIn this large series of spina bifida patients, maximum detrusor pressure and bladder compliance are the main urodynamic findings determinants of UUTD risk.

Background The Spina Bifida and other Dysraphisms working group (SBoD WG) is an interdisciplinary group, comprising experts on spinal dysraphism from 11 European countries. In 2022, the SBoD WG was tasked by 2 European Rare Disease Networks (ERN ITHACA and ERN eUROGEN) to revise the Orphanet classification of spinal dysraphism. Over the past two decades numerous subcategories of spinal dysraphism have been described in the medical literature resulting in a proliferation of terms, numerous synonyms and variously applied definitions. In the light of this, a revision of all terms and definitions was conducted by a Delphi approach in 3 steps by neurosurgeons (fetal/paediatric/adult), urologists (paediatric/adult), rehabilitation medicine specialists, fetal medicine and perinatal imaging specialists, geneticists, pathologists, nephrologists and patient representatives, all members of the International Federation for Spina Bifida and Hydrocephalus (IFSBH). Results In the first instance, 39 experts reviewed and refined the terminology that could be used to describe the anatomical characteristics of all forms of SBoD. At the second stage, 24 experts established terms and unambiguous definitions for 16 skin findings, 7 bone findings and 33 spinal cord findings that were considered essential features capable of describing all forms of spinal dysraphism. In the third stage, 29 experts validated 24 spinal dysraphic anomalies using these pre-agreed findings. All terms and definitions were validated by vote with a threshold of 80% approval (abstention was permitted). No terms with disagreement were retained in the subsequent classification. The revised SBoD classification was transferred to the Orphanet nomenclature ( ORPHA:823 ). 16 existing ORPHAcodes were deemed obsolete, 10 ORPHAcodes were updated (terms and/or textual definitions) and 25 new ORPHAcodes were created. The SBoD working group also developed a ‘decision tree’ for new users, to assist them in the practical aspects of applying the revised classification and designating appropriate ORPHAcodes. Conclusions An update of the Orphanet Classification of spinal dysraphism was conducted by a European interdisciplinary group of experts encompassing all aspects of healthcare for patients with these disorders. This new classification, based on essential skin, bone and spinal cord findings offers a more logical and reproducible means to categorise SBoD. It is hoped that this will permit more precise disease delineation, consistent diagnostic accuracy and better prognostication.

Background Vaccination is currently the most effective means of preventing influenza infection. Yet evidence of vaccine performance, and the impact and value of seasonal influenza vaccination across risk groups and between seasons, continue to generate much discussion. Moreover, vaccination coverage is below recommended levels. Methods A model was generated to assess the annual public health benefits and economic importance of influenza vaccination in 5 WHO recommended vaccination target groups (children 6 – 23 months of age; persons with underlying chronic health conditions; pregnant women; health care workers; and, the elderly, 65 years of age) in 27 countries of the European Union. Model estimations were based on standard calculation methods, conservative assumptions, age-based and country-specific data. Results Out of approximately 180 million Europeans for whom influenza vaccination is recommended, only about 80 million persons are vaccinated. Seasonal influenza vaccination currently prevents an annual average of between 1.6 million and 2.1 million cases of influenza, 45,300 to 65,600 hospitalizations, and 25,200 to 37,200 deaths. To reach the 75% vaccination coverage target set by the EU Council Recommendation in 2009, an additional 57.4 million person would need to be vaccinated in the elderly and other risk groups. By achieving the 75% target rate set in EU-27 countries, average annual influenza- related events averted would increase from current levels to an additional +1.6 to +1.7 million cases, +23,800 to +31,400 hospitalization, +9,800 to +14,300 deaths, +678,500 to +767,800 physician visits, and +883,800 to +1,015,100 lost days of work yearly. Influenza-related costs averted because of vaccination would increase by an additional + €190 to + €226 million yearly, in vaccination target groups. Conclusions Full implementation of current influenza vaccination recommendations of 75% vaccination coverage rate (VCR) in Europe by the 2014–2015 influenza season could immediately reduce an important public health and economic burden.

Bone Morphogenetic Protein 9 (BMP9) has been recently found to be the physiological ligand for the activin receptor-like kinase 1 (ALK1), and to be a major circulating vascular quiescence factor. Moreover, a soluble chimeric ALK1 protein (ALK1-Fc) has recently been developed and showed powerful anti-tumor growth and anti-angiogenic effects. However, not much is known concerning BMP9. This prompted us to investigate the human endogenous sources of this cytokine and to further characterize its circulating form(s) and its function. Analysis of BMP9 expression reveals that BMP9 is produced by hepatocytes and intrahepatic biliary epithelial cells. Gel filtration analysis combined with ELISA and biological assays demonstrate that BMP9 circulates in plasma (1) as an unprocessed inactive form that can be further activated by furin a serine endoprotease, and (2) as a mature and fully active form (composed of the mature form associated with its prodomain). Analysis of BMP9 circulating levels during mouse development demonstrates that BMP9 peaks during the first 3 weeks after birth and then decreases to 2 ng/mL in adulthood. We also show that circulating BMP9 physiologically induces a constitutive Smad1/5/8 phosphorylation in endothelial cells. Taken together, our results argue for the role of BMP9 as a hepatocyte-derived factor, circulating in inactive (40%) and active (60%) forms, the latter constantly activating endothelial cells to maintain them in a resting state.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease’s pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes’ subsets were analyzed by flow cytometry, with analysis of TH1/TH2/TH17, TFH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren’s syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, TH2, TH17, and CD4+CXCR5+PD1+ TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of TFH2 (CCR6−CXCR3−), and to a lesser extent of TFH17 (CCR6+CXCR3−) cells. Interestingly, CD4+CXCR5+PD1+ TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a TH2/TFH2 and TH17/TFH17 polarization. This immunological imbalance might be implicated in the disease’s pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocyte's subsets were analyzed by flow cytometry, with analysis of T(H)1/T(H)2/T(H)17, T-FH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjogren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, T(H)2, T(H)17, and CD4(+)CXCR5(+)PD1(+) TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of T(FH)2 (CCR6(-)CXCR3(-)), and to a lesser extent of (T(FH)17 (CCR6(+)CXCR3(-))) cells. Interestingly, CD4(+)CXCR5(+)PD1(+) TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a T(H)2/T(FH)2 and T(H)17/T(FH)17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.

The deep-sea floor encompasses more than half of the surface of our planet, yet the extent and distribution of deep-sea biodiversity and its contribution to large biogeochemical cycles remain poorly understood. This knowledge gap stems from several factors, including sampling issues, the magnitude of the work required for morphological inventories, and the difficulty of integrating results from disparate local studies. The application of meta-omics to environmental DNA now makes it possible to assemble interoperable datasets at different spatial scales to move towards a global assessment of deep-sea biodiversity. We present a large-scale dataset on deep-sea biodiversity, with data and metadata openly accessible at ENA and Zenodo. The resource was generated using standardized protocols developed according to FAIR principles, covering fieldwork through bioinformatic analysis, within “ Pourquoi Pas les Abysses? ” and eDNAbyss projects. Together with information ensuring reproducibility, this dataset —combining metagenomics, metabarcoding across the Tree of Life and capture-by-hybridization— contributes to the international concerted effort to achieve a holistic view of the biodiversity in the largest biome on Earth.

Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome. One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection. While its precise function in the virus cycle is still unclear, the viral protein PB1-F2 is proposed to exert a deleterious activity within the infected host. Using an engineered recombinant virus unable to express PB1-F2 and its wild-type homolog, we analyzed and compared the pathogenicity and host response developed by the two viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the virus less virulent. The global transcriptomic analyses of the infected lungs revealed a potent impact of PB1-F2 on the response developed by the host. Thus, after two days post-infection, PB1-F2 invalidation severely decreased the number of genes activated by the host. PB1-F2 expression induced an increase in the number and level of expression of activated genes linked to cell death, inflammatory response and neutrophil chemotaxis. When generating interactive gene networks specific to PB1-F2, we identified IFN-γ as a central regulator of PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes was evidenced using an apoptosis assay, confirming the pro-apoptotic properties of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify in vivo the implication of NF-kB in the inflammation mediated by the influenza virus infection; we found that PB1-F2 expression intensifies the NF-kB activity. Finally, we quantified the neutrophil recruitment within the airways, and showed that this type of leukocyte is more abundant during the infection of the wild-type virus. Collectively, these data demonstrate that PB1-F2 strongly influences the early host response during IAV infection and provides new insights into the mechanisms by which PB1-F2 mediates virulence.