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The Psychosocial Impact of Assistive Devices Scale (PIADS) is commonly used to assess the psychosocial effects of an assistive device. Given its growing use, an appraisal of the evidence regarding its psychometric properties is required. We conduct a systematic review using validated critical appraisal scales to analyze both the quality and content of the evidence on the psychometric properties of the PIADS. PubMed/Medline, Embase, and CINAHL were systematically searched for identification of studies. Two independent reviewers appraised the retrieved studies using MacDermid and COSMIN-RoB checklists, and extracted data regarding the psychometric measurements reported. MacDermid scores showed that 8 out of 11 studies were, at least, of good methodological quality. COSMIN-RoB scores ranged from inadequate to very good. Except criterion and construct validity, which have presented a moderate level of evidence, the other psychometric properties assessed have demonstrated a high level of evidence. Cross‐cultural validity, measurement error, and responsiveness have not been studied. Few studies have yet evaluated the psychometric properties of the PIADS. However, the quality of the evidence that they provide is mostly adequate. Therefore, this review supports the use of the PIADS, which has overall good psychometric properties. [ABSTRACT FROM AUTHOR]

Background: Recent studies reported a link between high salt diet (HSD) and clinical exacerbation in mouse models of autoimmune diseases, mainly through the induction of pathogenic Th17 cells and/or HSD-induced dysbiosis. However, the topic remains controversial and not fully understood., Purpose: In this study, we investigated the effects of HSD on the development of experimental autoimmune uveitis (EAU) in C57BL/6J mice., Methods and Results: Unexpectedly, our data showed a significant attenuating effect of HSD on disease severity of native EAU, induced by direct immunization with IRBP peptide. That said, HSD had no effect on EAU disease severity induced by adoptive transfer of semi-purified auto-reactive IRBP-specific T lymphocytes. Accordingly, HSD did not affect IRBP-specific systemic afferent immune response as attested by no HSD-linked changes in T lymphocytes proliferation, cytokine production and Treg proportion. Gut microbiota analysis from cecal samples in naïve and EAU mice demonstrated that HSD affected differentially α-diversity between groups, whereas β-diversity was significantly modified in all groups. Unknown Tannerellaceae was the only taxon associated to HSD exposure in all treatment groups. Interestingly, a significantly higher abundance of unknown Gastranaerophilales , with potential anti-inflammatory properties, appeared in HSD-fed native EAU mice, only., Discussion: In conclusion, our study suggests a possible impact of HSD on gut microbiota composition and consequently on development and clinical severity of EAU. Further studies are required to investigate the potential beneficial role of Gastranaerophilales in EAU., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Derluyn, Foucart, Verce, Abdo, Vaudoisey, Lipski, Flamand, Everard, Bruyns and Willermain.)

Assistive devices are designed to enhance individuals with disabilities' functional abilities. The rise of 3D printing technology enabled the production of individualized assistive devices (IADs). A REHAB-LAB is intended for IAD provision involving technical referents and occupational therapists. This study aimed to develop the REHAB-LAB logic model; to explore its fidelity and desirability; and to explore the characteristics of arising initiatives of IAD production. The REHAB-LAB logic model development involved stakeholders throughout the research process. A pragmatic multimethod approach followed two phases 1) logic model development and 2) exploration of its fidelity and desirability. The REHAB-LAB logic model presented the resources (equipment, space, human) required to implement IAD provision in a rehabilitation center, and the expected deliverables (activities and outputs). The REHAB-LAB logic model highlights the interdisciplinarity of IAD provision including occupational therapists, doctors, engineers, managers, and technical referents and places the users at the center of the IAD production. Results confirmed the fidelity and desirability of the REHAB-LAB logic model. The REHAB-LAB logic model can be used as a reference for future healthcare organizations wishing to implement an IAD provision. This research highlighted the interest of IAD provision based on the REHAB-LAB model involving users and transdisciplinary practices.

This work identifies the protein "macrophage infectivity potentiator" of Trypanosoma cruzi trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h in vitro culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18. rTcMIP activity is totally abolished by protease treatment and is not associated with its peptidyl-prolyl cis-trans isomerase enzymatic activity. The ability of rTcMIP to act as adjuvant was studied in vivo in neonatal mouse immunization models, using acellular diphtheria-tetanus-pertussis-vaccine (DTPa) or ovalbumin, and compared to the classical alum adjuvant. As compared to the latter, rTcMIP increases the IgG antibody response towards several antigens meanwhile skewing antibody production towards the Th-1 dependent IgG2a isotype. The amplitude of the rTcMIP adjuvant effect varied depending on the antigen and the co-presence of alum. rTcMIP did by contrast not increase the IgE response to OVA combined with alum. The discovery of the rTcMIP immunostimulatory effect on neonatal cells opens new possibilities for potential use as pro-type 1 adjuvant for neonatal vaccines. This, in turn, may facilitate the development of more efficient vaccines that can be given at birth, reducing infection associated morbidity and mortality which are the highest in the first weeks after birth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Radwanska, de Lemos Esteves, Linsen, Coltel, Cencig, Widart, Massart, Colson, Di Paolo, Percier, Ait Djebbara, Guillonneau, Flamand, De Pauw, Frère, Carlier and Truyens.)

Gut microbiota plays a role in the neonatal immune education and could influence susceptibility to Th2-type immune disorders, such as allergies, the most prevalent chronic diseases in early childhood. We studied the impact of oral Lactobacillus rhamnosus ( L.rhamnosus ) supplementation to pregnant/breastfeeding C57BL/6 mice on the development of allergic airways disease in their offspring. We observed that mice, from L.rhamnosus -treated mothers, inoculated with ovalbumin (OVA)-Aluminium hydroxide (ALUM) at 3 days of life and challenged intranasally 4 weeks later showed decreased Th2-associated cytokines, IgE and IgG1, lung eosinophilia and airway hyper-reactivity compared to OVA-sensitized mice from untreated mothers. In that setting, the L.rhamnosus treatment increased the number and maturation of splenic neonatal type 1 conventional dendritic cells (cDC1) that remained largely dominant over the cDC2 and favored their OVA-specific Th1 differentiation. In response to inhaled house dust mite (HDM) allergen, the maternal L.rhamnosus supplementation increased the number of neonatal pulmonary cDC1 expressing lower amount of costimulatory molecules compared with no supplementation and decreased the number of cDC2 without affecting their costimulatory molecules expression. An HDM-specific Foxp3 + RORγt + Treg polarization was monitored in the lung draining lymph nodes. Finally, we confirmed the inhibitory effect of maternal L.rhamnosus treatment on all the measured features of the HDM allergic airways reaction in their offspring. We conclude that maternal L.rhamnosus administration prevents Th2-type allergic airways disease in their neonates by favoring splenic cDC1/Th1 responses against ALUM-adjuvanted OVA or by promoting a pulmonary Foxp3 + RORγt + Treg activation against inhaled HDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Smout, Valentin, Delbauve, Pauwels, Köhler and Flamand.)

In utero exposure to maternally-derived antigens following chronic infection is associated with modulation of infants 'immune response, differential susceptibility to post-natal infections and immune response toward vaccines. The maternal environment, both internal (microbiota) and external (exposure to environmental microbes) also modulates infant's immune response but also the clinical phenotype after birth. Vertical transmission of ubiquitous respiratory pathogens such as influenza and COVID-19 is uncommon. Evidence suggest that in utero exposure to maternal influenza and SARS-CoV-2 infections may have a significant impact on the developing immune system with activation of both innate and adaptive responses, possibly related to placental inflammation. Here in, we review how maternal respiratory infections, associated with airway, systemic and placental inflammation but also changes in maternal microbiota might impact infant's immune responses after birth. The clinical impact of immune modifications observed following maternal respiratory infections remains unexplored. Given the high frequencies of respiratory infections during pregnancy (COVID-19, influenza but also RSV and HMPV), the impact on global child health could be important., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Dauby and Flamand.)

Cytotoxic T cell (CTL) infiltration of the tumor carries the potential to limit cancer progression, but their exclusion by the immunosuppressive tumor microenvironment hampers the efficiency of immunotherapy. Here, we show that expression of the axon guidance molecule Plexin-A4 ( Plxna4 ) in CTLs, especially in effector/memory CD8 + T cells, is induced upon T-cell activation, sustained in the circulation, but reduced when entering the tumor bed. Therefore, we deleted Plxna4 and observed that Plxna4 -deficient CTLs acquired improved homing capacity to the lymph nodes and to the tumor, as well as increased proliferation, both achieved through enhanced Rac1 activation. Mice with stromal or hematopoietic Plxna4 deletion exhibited enhanced CTL infiltration and impaired tumor growth. In a melanoma model, adoptive transfer of CTLs lacking Plxna4 prolonged survival and improved therapeutic outcome, which was even stronger when combined with anti-programmed cell death protein 1 (PD-1) treatment. PLXNA4 abundance in circulating CTLs was augmented in melanoma patients versus healthy volunteers but decreased after the first cycle of anti-PD-1, alone or in combination with anti-cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4), in those patients showing complete or partial response to the treatment. Altogether, our data suggest that Plxna4 acts as a "checkpoint," negatively regulating CTL migration and proliferation through cell-autonomous mechanisms independent of the interaction with host-derived Plxna4 ligands, semaphorins. These findings pave the way toward Plxna4-centric immunotherapies and propose Plxna4 detection in circulating CTLs as a potential way to monitor the response to immune checkpoint blockade in patients with metastatic melanoma., (©2021 The Authors; Published by the American Association for Cancer Research.)

Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with Brucella in C57BL/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using RNA sequencing, we identified the aconitate decarboxylase 1 gene (Acod1; also known as Immune responsive gene 1), as one of the genes most upregulated in murine AMs in response to B. melitensis infection at 24 hours post-infection. Upregulation of Acod1 was confirmed by RT-qPCR in lungs infected with B. melitensis and B. abortus. We observed that Acod1-/- C57BL/6 mice display a higher bacterial load in their lungs than wild-type (wt) mice following B. melitensis or B. abortus infection, demonstrating that Acod1 participates in the control of pulmonary Brucella infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. Dimethyl itaconate (DMI), a chemically-modified membrane permeable form of itaconate, has a dose-dependent inhibitory effect on Brucella growth in vitro. Interestingly, structural analysis suggests the binding of itaconate into the binding site of B. abortus isocitrate lyase. DMI does not inhibit multiplication of the isocitrate lyase deletion mutant ΔaceA B. abortus in vitro. Finally, we observed that, unlike the wt strain, the ΔaceA B. abortus strain multiplies similarly in wt and Acod1-/- C57BL/6 mice. These data suggest that bacterial isocitrate lyase might be a target of itaconate in AMs., Competing Interests: The authors have declared that no competing interests exist.

The liver ischemia-reperfusion (IR) injury that occurs consequently to hepatic resection performed in patients with metastases can lead to tumor relapse for not fully understood reasons. We assessed the effects of liver IR on tumor growth and the innate immune response in a mouse model of colorectal (CR) liver metastasis. Mice subjected to liver ischemia 2 days after intrasplenic injection of CR carcinoma cells displayed a higher metastatic load in the liver, correlating with Kupffer cells (KC) death through the activation of receptor-interating protein 3 kinase (RIPK3) and caspase-1 and a recruitment of monocytes. Interestingly, the immunoregulatory mediators, tumor necrosis factor-α (TNF-α) and heme oxygenase-1 (HO-1) were strongly upregulated in recruited monocytes and were also expressed in the surviving KC following IR. Using TNF flox/flox LysM cre/wt mice, we showed that TNF deficiency in macrophages and monocytes favors tumor progression after IR. The antitumor effect of myeloid cell-derived TNF involved direct tumor cell apoptosis and a reduced expression of immunosuppressive molecules such as transforming growth factor-β, interleukin (IL)-10, inducible nitric oxyde synthase (iNOS), IL-33 and HO-1. Conversely, a monocyte/macrophage-specific deficiency in HO-1 (HO-1 flox/flox LysM cre/wt ) or the blockade of HO-1 function led to the control of tumor progression post-liver IR. Importantly, host cell RIPK3 deficiency maintains the KC number upon IR, inhibits the IR-induced innate cell recruitment, increases the TNF level, decreases the HO-1 level and suppresses the tumor outgrowth. In conclusion, tumor recurrence in host undergoing liver IR is associated with the death of antitumoral KC and the recruitment of monocytes endowed with immunosuppressive properties. In both of which HO-1 inhibition would reinforce their antitumoral activity., (© 2020 UICC.)

Objective: Induction of immune protection against pathogens is particularly crucial during the neonatal period dominated by anti-inflammatory and tolerance immunity. The preclinical study was carried out to determine whether environmental factors such as microbiota may influence early life immunity by impacting the development and the functional maturation of precursors of type 1 conventional dendritic cells (pre-cDC1), endowed with regulatory properties., Design: Pre-cDC1 phenotype and cytokine expression in the spleen of neonates from antibiotic-treated mothers were established. The role of myeloid-derived tumour necrosis factor (TNF) was tested in vitro and in vivo. RNA sequencing analysis on neonatal sorted pre-cDC1 was performed. The early life protective CD8 + T-cell response against Listeria monocytogenes was monitored., Results: We observed that first exposure to microbiota promotes TNF secretion by monocytes and macrophages shortly after birth. We demonstrated that this myeloid-derived inflammatory cytokine is crucial to induce the maturation of these neonatal regulatory pre-cDC1. Myeloid TNF signalling acts on C1q and β-catenin pathway and modifies the fatty acid metabolism in neonatal pre-cDC1. Furthermore, we showed that during neonatal L. monocytogenes infection, microbiota-associated myeloid TNF promotes the capacity of these pre-cDC1 to induce protective CD8 + T-cell responses, by modulating their ability to secrete interleukin-10 (IL-10) and IL-12p40., Conclusion: Our findings emphasise the role of microbiota-derived TNF to kick-start the differentiation and the functional maturation of the neonatal splenic pre-cDC1 compartment. They bring a better understanding of potential mechanisms underlying some microbiota-linked immune dysfunction in early life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Graft-versus-host disease (GVHD) remains a major clinical drawback of allogeneic hematopoietic stem cell transplantation (HSCT). Here, we investigated how the stress responsive heme catabolizing enzyme heme oxygenase-1 (HO-1, encoded by HMOX1 ) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the Hmox1 allele, specifically in the myeloid compartment of mouse donor bone marrow, promotes the development of aggressive GVHD after allogeneic transplantation. The mechanism driving GVHD in mice transplanted with allogeneic bone marrow lacking HO-1 expression in the myeloid compartment involves enhanced T cell alloreactivity. The clinical relevance of these observations was validated in two independent cohorts of HSCT patients. Individuals transplanted with hematopoietic stem cells from donors carrying a long homozygous (GT) n repeat polymorphism (L/L) in the HMOX1 promoter, which is associated with lower HO-1 expression, were at higher risk of developing severe acute GVHD as compared to donors carrying a short (GT) n repeat (S/L or S/S) polymorphism associated with higher HO-1 expression. In this study, we showed the unique importance of donor-derived myeloid HO-1 in the prevention of lethal experimental GVHD and we corroborated this observation by demonstrating the association between human HMOX1 (GT) n microsatellite polymorphisms and the incidence of severe acute GVHD in two independent HSCT patient cohorts. Donor-derived myeloid HO-1 constitutes a potential therapeutic target for HSCT patients and large-scale prospective studies in HSCT patients are necessary to validate the HO-1 L/L genotype as an independent risk factor for developing severe acute GVHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Spilleboudt, De Wilde, Lewalle, Cabanne, Leclerc, Beckerich, Bories, Cardoso, Soares, Vokaer, Hougardy, Flamand, Racapé, Abramowicz, Maury and Le Moine.)

Partial hepatectomy (PH) is the main treatment for early-stage hepatocellular carcinoma (HCC). Yet, a significant number of patients undergo recursion of the disease that could be linked to the fate of innate immune cells during the liver regeneration process. In this study, using a murine model, we investigated the impact of PH on HCC development by bioluminescence imaging and flow cytometry. While non-resected mice were able to control and reject orthotopic implanted Hepa1-6 hepatocarcinoma cells, resected liver underwent an increased tumoral proliferation. This phenomenon was associated with a PH-induced reduction in the number of liver-resident macrophages, i.e., Kupffer cells (KC). Using a conditional ablation model, KC were proved to participate in Hepa1-6 rejection. We demonstrated that in the absence of Hepa1-6, PH-induced KC number reduction was dependent on tumor necrosis factor-alpha (TNF-α), receptor-interacting protein kinase (RIPK) 3, and caspase-8 activation, whereas interleukin (IL)-6 acted as a KC pro-survival signal. In mice with previous Hepa1-6 encounter, the KC reduction switched toward a TNF-α-RIPK3-caspase-1 activation. Moreover, KC disappearance associated with caspase-1 activity induced the recruitment of monocyte-derived cells that are beneficial for tumor growth, while caspase-8-dependent reduction did not. In conclusion, our study highlights the importance of the TNF-α-dependent death pathway induced in liver macrophages following partial hepatectomy in regulating the antitumoral immune responses., (Copyright © 2020 Hastir, Delbauve, Larbanoix, Germanova, Goyvaerts, Allard, Laurent, Breckpot, Beschin, Guilliams and Flamand.)

Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). IRI-induced AKI releases proinflammatory cytokines (e.g. IL-1β, TNF-α, IL-6) that induce a systemic inflammatory response, resulting in proinflammatory cells recruitment and remote organ damage. AKI is associated with poor outcomes, particularly when extrarenal complications or distant organ injuries occur. Acute lung injury (ALI) is a major remote organ dysfunction associated with AKI. Hence, kidney-lung cross-talk remains a clinical challenge, especially in critically ill population. The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against renal IRI and may be preventively induced using hemin prior to renal insult. However, the use of hemin-induced HO-1 to prevent AKI-induced ALI remains poorly investigated. Mice received an intraperitoneal injection of hemin or sterile saline 1 day prior to surgery. Twenty-four hours later, mice underwent bilateral renal IRI for 26 min or sham surgery. After 4 or 24 h of reperfusion, mice were sacrificed. Hemin-induced HO-1 improved renal outcomes after IRI (i.e. fewer renal damage, renal inflammation, and oxidative stress). This protective effect was associated with a dampened systemic inflammation (i.e. IL-6 and KC). Subsequently, mitigated lung inflammation was found in hemin-treated mice (i.e. neutrophils influx and lung KC). The present study demonstrates that hemin-induced HO-1 controls the magnitude of renal IRI and the subsequent AKI-induced ALI. Therefore, targeting HO-1 represents a promising approach to prevent the impact of renal IRI on distant organs, such as lung.

Acute kidney injury (AKI) is a major public health concern, which is contributing to serious hospital complications, chronic kidney disease (CKD) and even death. Renal ischemia-reperfusion injury (IRI) remains a leading cause of AKI. The stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against renal IRI and may be preventively induced using hemin prior to renal insult. This HO-1 induction pathway called hemin preconditioning is largely known to be effective. Therefore, HO-1 might be an interesting therapeutic target in case of predictable AKI (e.g. partial nephrectomy or renal transplantation). However, the use of hemin to mitigate established AKI remains poorly characterized. Mice underwent bilateral renal IRI for 26 min or sham surgery. After surgical procedure, animals were injected either with hemin (5 mg/kg) or vehicle. Twenty-four hours later, mice were sacrificed. Despite strong HO-1 induction, hemin-treated mice exhibited significant renal damage and oxidative stress as compared to vehicle-treated mice. Interestingly, higher dose of hemin is associated with more severe IRI-induced AKI in a dose-dependent relation. To determine whether hemin preconditioning remains efficient to dampen postoperative hemin-amplified IRI-induced AKI, we pretreated mice either with hemin (5 mg/kg) or vehicle 24 h prior to surgical procedure. Then, all mice (hemin- and vehicle-pretreated) received postoperative injection of hemin (5 mg/kg) to amplify IRI-induced AKI. In comparison to vehicle, prior administration of hemin to renal IRI mitigated hemin-amplified IRI-induced AKI as attested by fewer renal damage, inflammation and oxidative stress. In conclusion, hemin may have a dual effect on renal IRI, protective or deleterious, depending on the timing of its administration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Focal ablative therapy may be a suboptimal option for anterior prostate cancers (APCs) reaching the prostate apex due to concerns for thermal injury to the external sphincter., Objective: To explore the technical feasibility of anterior partial prostatectomy (APP) for isolated APCs detected by magnetic resonance imaging (MRI), and to report short-term oncologic and functional outcomes., Design, Setting, and Participants: Following institutional review board approval, over an 8-yr period (2008-2015) 17 consenting patients were enrolled in a prospective single-arm single-center Innovation, Development, Exploration, Assessment, Long-term (IDEAL) phase 2a study. Inclusion criteria comprised preurethral, low- to intermediate-risk APC diagnosed by MRI, and targeted biopsies. Robotic template APP was performed; posterolateral aspect of the submontanal urethra, peripheral zone, and periprostatic tissues were preserved intact. Median follow-up was 30 mo (interquartile range [IQR]: 25-70)., Outcome Measurements and Statistical Analysis: We noted the incidence of perioperative complications and examined reports of pathology, prostate-specific antigen (PSA), imaging, biopsies, and questionnaires., Results and Limitations: Preoperatively, median PSA was 9.8 ng/ml, Gleason score was 6-7 (3 + 4), and cancer volume was 3.7cm 3 (IQR: 1.7-4.6). The technique was feasible in all cases. Perioperative complications included anastomotic leak (12%; G2), urinary tract infection (6%; G2), and transient intestinal ileus in one case (6%; G2). At 3 mo, continence and potency rates were 100% and 83%, respectively. Median nadir PSA was 0.4 ng/ml (IQR: 0.3-0.7). All margins and posterolateral margins rates were 55% and 35%, respectively. APC recurrence-free survival at 2 yr was 0.86 (95% confidence interval [CI], 0.55-0.96). Four patients (24%) who recurred underwent an uncomplicated completion of robot-assisted prostatectomy. Regarding limitations, CIs are quite wide for reported outcomes., Conclusions: Robotic partial prostatectomy for isolated APC is feasible with good functional results. While promising, much more research is needed to verify our initial outcomes and appropriately position APP in the treatment paradigms for APC., Patient Summary: We explored a novel approach for partial prostatic surgical ablation for prostate cancer located in the anterior part of the prostate as an alternative to other focal ablative techniques., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To describe a step-by-step guide to robot-assisted anterior partial prostatectomy (RA-APP) for isolated magnetic resonance imaging (MRI)-detected anterior prostate cancer (APC)., Patients and Methods: After Institutional Review Board approval, over an 8-year period (2008-2015), 17 consenting patients were enrolled in a prospective, single-arm, single-centre, Idea, Development, Evaluation, Assessment and Long-term evaluation of innovative surgery (IDEAL) phase 2a study. The inclusion criteria comprised pre-urethral, low-intermediate risk APC diagnosed by MRI and targeted biopsies. Patient position and port placement were identical to the transperitoneal RA radical prostatectomy procedure. Three steps of dissection were identified in the following order: (i) retrograde apical, after dorsal venous plexus division, transition zone (TZ) enucleation, and distal peripheral zone (PZ) sectioning; (ii) antegrade, at the bladder neck (BN) after anterior BN sectioning, TZ enucleation up to the verumontanum; and (iii) lateral dissections, including anterolateral PZ sectioning without incision of the endopelvic fascia. We report the incidence of perioperative complications. The RA completion of prostatectomy in four cases with cancer recurrence was performed at 0.3, 2.5, 2 and 2 years, respectively., Results: The RA-APP comprised en bloc excision of the anterior part of the prostate comprising of the anterior fibromuscular stroma, BN, prostate adenoma (TZ and median lobe) along with the proximal prostate urethra, PZ apical anterior horns, anterior aspect of the distal (sub-montanal) urethra, and anterior BN. The posterolateral parts of the PZ and distal (sub-montanal) urethra and peri-prostatic tissues were preserved intact. The bladder opening was sutured to the anterior sphincteric urethra wall and PZ lateral edges. The technique was feasible in all cases with no conversion to an open procedure. Perioperative complications were only Clavien-Dindo grade II. RA completion of prostatectomy was feasible in the four cases with cancer recurrence., Conclusion: PZ prostate-sparing RA-APP for isolated APC is feasible and safe, and represents an option for highly selected men with APCs as an alternative to other focal ablative therapy., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Competing Interests: V. Flamand et N. Lamandé déclarent n’avoir aucun lien d’intérêts.

Competing Interests: Service d’urologie, hôpital Claude-Huriez, CHU de Lille, 59037 Lille Cedex, France

Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1 M-KO ), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1 M-KO exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1 M-KO mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b + F4/80 lo subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1 + CD11b + F4/80 lo myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1 M-KO mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.

Purpose: Kupffer cells (KCs), the liver resident macrophages, are important mediators of tissue homeostasis and pathogen clearance. However, depending on the inflammatory stimuli, KCs have been involved in divergent hepato-protective or hepato-destructive immune responses. The versatility of KCs in response to environmental triggers, in combination with the specific biomarkers they express, make these macrophages attractive in vivo targets for non-invasive monitoring of liver inflammation or pathogenicity. This study aims to determine whether V-set and Ig domain-containing 4 (Vsig4) and C-type lectin domain family (Clec) 4, member F (Clec4F) can be used as imaging biomarkers for non-invasive monitoring of KCs during distinct liver inflammation models., Procedure: Flow cytometry (FACS), immuno-histochemistry (IHC), and single-photon emission computed tomography (SPECT) with Tc-99m labeled anti-Vsig4 or anti-Clec4F nanobodies (Nbs) was performed to evaluate in mice KC dynamics in concanavalin A (ConA)-induced hepatitis and in non-alcoholic steatohepatitis induced via methionine choline deficiency (MCD)., Results: In homeostatic mice, Nbs targeting Clec4F were found to accumulate and co-localize with Vsig4-targeting Nbs only in the liver. Upon induction of acute hepatitis using ConA, down-regulation of the in vivo Nb imaging signal was observed, reflecting reduction in KC numbers as confirmed by FACS and IHC. On the other hand, induction of steatohepatitis resulted in higher signals in the liver corresponding to higher density of KCs. The Nb-imaging signals returned to normal levels after resolution of the investigated liver diseases., Conclusions: Anti-Clec4F and anti-Vsig4 Nbs targeting KCs as molecular imaging biomarkers could allow non-invasive monitoring/staging of liver pathogenesis.

Objective: To evaluate the oncologic outcomes of nephron-sparing surgery (NSS) for localized chromophobe renal cell carcinoma (cRCC)., Material and Methods: We performed a multicenter international study involving the French Network for Research on Kidney Cancer (UroCCR) and 5 international teams. Data from 808 patients treated with NSS between 2004 and 2014 for non-clear cell RCCs were analyzed., Results: We included 234 patients with cRCC. There were 123 (52.6%) females. Median age was 61 (23-88) years. Median tumor size was 3 (1-11)cm. A positive surgical margin was identified in 14 specimens (6%). Pathologic stages were T1, T2, and T3a in 202 (86.3%), 9 (3.8%), and 23 (9.8%) cases, respectively. After a mean follow-up of 46.6 ± 36 months, 2 (0.8%) patients experienced a local recurrence. No patient had metastatic progression, and no patient died from cancer. Three-years estimated cancer-free survival and cancer-specific survival were 99.1% and 100%, respectively., Conclusion: Oncological results of NSS for localized cRCC are excellent. In this series, only 2 patients had a local recurrence, and no patient had metastatic progression or died from cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To present a systematic review of the different therapeutic sequences in metastatic castration-resistant prostate cancer (mCRPC)., Methods: Evidence acquisition on therapeutic sequences in mCRPC was performed by a MEDLINE search using combination of the following key words: "prostate cancer," "metastatic," "castration resistant," "enzalutamide," "abiraterone," "treatment sequencing," "cabazitaxel," "docetaxel." A total of 17 studies were included for analysis., Results: Different sequences have been reported for the treatment of mCRPC: docetaxel after abiraterone, cabazitaxel after docetaxel and abiraterone, abiraterone after cabazitaxel and docetaxel, abiraterone after docetaxel and enzalutamide, and enzalutamide after docetaxel and abiraterone. There are arguments from the preclinical observations suggesting a cross-resistance between docetaxel and abiraterone, and between abiraterone and enzalutamide in mCRPC. Despite limitations, several retrospective clinical reports support these data., Conclusion: No study of high level of evidence is available to support any recommendation on sequential treatment for mCRPC. There are only clues that prospective clinical studies need to confirm.

Infection by Listeria monocytogenes (Lm) causes serious sepsis and meningitis leading to mortality in neonates. This work explored the ability of CD11c(high) lineage DCs to induce CD8+ T-cell immune protection against Lm in mice before 7 days of life, a period symbolized by the absence of murine IL-12p70-producing CD11c(high)CD8α+ dendritic cells (DCs). We characterized a dominant functional Batf3-dependent precursor of CD11c(high) DCs that is Clec9A+CD205+CD24+ but CD8α- at 3 days of life. After Lm-OVA infection, these pre-DCs that cross-present Ag display the unique ability to produce high levels of IL-12p40 (not IL-12p70 nor IL-23), which enhances OVA-specific CD8+ T cell response, and regulatory IL-10 that limits OVA-specific CD8+ T cell response. Targeting these neonatal pre-DCs for the first time with a single treatment of anti-Clec9A-OVA antibody in combination with a DC activating agent such as poly(I:C) increased the protection against later exposure to the Lm-OVA strain. Poly(I:C) was shown to induce IL-12p40 production, but not IL-10 by neonatal pre-DCs. In conclusion, we identified a new biologically active precursor of Clec9A+ CD8α- DCs, endowed with regulatory properties in early life that represents a valuable target to augment memory responses to vaccines.

Objectives: To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death., Materials and Methods: An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014., Results: We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1-120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p < 0.001) and less grade III (20 vs. 41 %; p < 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three-year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03)., Conclusion: Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival.

Modulating the activity of tumor-infiltrating dendritic cells (TiDC) provides opportunities for novel cancer interventions. In this article, we report on our study of the uptake of mRNA by CD8α(+) cross-presenting TiDCs upon its intratumoral (i.t.) delivery. We exploited this property to deliver mRNA encoding the costimulatory molecule CD70, the activation stimuli CD40 ligand, and constitutively active Toll-like receptor 4, referred to as TriMix mRNA. We show that TiDCs are reprogrammed to mature antigen-presenting cells that migrate to tumor-draining lymph nodes (TDLN). TriMix stimulated antitumor T-cell responses to spontaneously engulfed cancer antigens, including a neoepitope. We show in various mouse cancer models that i.t. delivery of TriMix mRNA results in systemic therapeutic antitumor immunity. Finally, we show that the induction of antitumor responses critically depends on TiDCs, whereas it only partially depends on TDLNs. As such, we provide a platform and a mechanistic rationale for the clinical testing of i.t. administration of TriMix mRNA., (©2015 American Association for Cancer Research.)