[Which indications for inpatient admission of a patient with an addiction? Application of the chronic disorders model. A face validity study]. / Quelles indications d'hospitalisation d'un patient avec addiction ? Application du modèle des pathologies chroniques. Une étude de validité apparente.

INTRODUCTION: The medical identification of an addiction (use disorder) often results in inpatient admission with a view to its definitive suspension. However, for other chronic diseases, inpatient admission is indicated for specific situations and the objective is not the definitive suspension of the chronic disease. Our goal was to clarify addiction as a chronic disease and to determine explicit indications for inpatient admission. METHOD: Three-stage face validity study: (1) from the analysis of consensual definitions, search by the subset theory whether addiction can be considered as a chronic disease; (2) Develop generic indications for inpatient admissions based on the analysis of chronic disease care pathways validated by the HAS (French Health Agency) and apply them to addiction; (3) Validate by Delphi expert consensus method the determined indications. RESULTS: Step (1) showed that the definition of addiction allowed to include it in that of chronic disease. Step (2) determined 7 indications for inpatient admission of a patient with a chronic disease, and its application to addiction identified 15 indications for inpatient admission of a patient with addiction. In step (3), the Delphi method yielded consensus on 14 of the 15 indications. CONCLUSION: By clarifying addiction as a chronic disease, we were able to determine 14 indications for inpatient admission of a person with an addiction and to distinguish them from the long-term care of addiction. These explicit indications can help the general practitioner or community psychiatrist to better manage patients with addiction on the basis of their expertise with chronic diseases management.

Characterization of five associations of F8 missense mutations containing FVIII B domain mutations.

INTRODUCTION: Haemophilia A (HA) is a bleeding disorder due to an absence or a reduced activity of coagulation factor VIII (FVIII) caused by mutations in F8 gene. Missense mutations represent approximately 45% of the reported molecular defects in HA. However, only few missense mutations in FVIII B domain have been described. AIM: The aim of this study was to characterize five genetic variations (three novels and two previously reported) localized in the FVIII B domain. In all cases, an additional missense variation located outside the FVIII B domain was found. We investigated each of these variations separately and in combination too for their contribution to HA phenotype. METHODS: F8 variants were transiently expressed in COS-1 cells. Media and cell lysates were collected after 72 h. Then, FVIII activity, secretion and thermostability were analysed and compared to FVIII wild-type. RESULTS: The 5 FVIII B domain variants showed normal FVIII: C (98.5-128.5%) and FVIII: Ag (97.7-154%). No synergistic effect was observed between the B domain variant and their associated mutations. In contrast, the variants located outside the B domain, p.V682L, p.S714L, p.V592D and p.C573F revealed significantly decrease of FVIII: C with values in the range 3.5-44.5% (p < 0.05). However, the p.G224R variant showed FVIII: C and FVIII: Ag values no significantly different from FVIII-WT. CONCLUSION: The FVIII B domain variants, p.D963N, p.S806T, p.G873D, p.H998Q and p.Q1225R may be considered as polymorphism or non-pathologic mutations. In five patients, clinical phenotype could be explained by the additional causative missense mutation. For the p.G224T variant further splicing studies are necessary to determine its pathogenicity.

Seroprevalence of West Nile and Usutu viruses in military working horses and dogs, Morocco, 2012: dog as an alternative WNV sentinel species?

A serosurvey of 349 military working horses and 231 military working dogs was conducted in ten sites in Morocco in 2012. This survey revealed a high level of exposure of these animals to flaviviruses: seroprevalence rates of 60% in horses and of 62% in dogs were observed using a competitive West Nile virus (WNV) enzyme-linked immunosorbent assay (cELISA). Seroneutralization test results showed that the majority of cELISA-positive results were due to exposure to WNV. Further assays conducted in vaccinated horses with a DIVA (Differentiating Infected from Vaccinated Animals) test indicated that anti-WNV antibodies had been stimulated through WNV natural infection. Moreover, in both species, seroneutralization tests suggested an exposure to Usutu virus (USUV). Data analysis did not show any significant difference of cELISA seropositivity risk between horses and dogs. Dogs may thus represent an interesting alternative to equines for the serological surveillance of WNV or USUV circulation, especially in areas where equine vaccination precludes passive surveillance (based on the detection of West Nile fever cases) in horses.

Toxoplasma gondii infection in pork produced in France.

The aim of this study was to assess the seroprevalence of the Toxoplasma gondii parasite in pork produced in France, and to determine infection risk factors. An innovative survey was designed based on annual numbers of slaughtered pigs from intensive and outdoor farms in France. A total of 1549 samples of cardiac fluids were collected from pig hearts to determine seroprevalence using a Modified Agglutination Test. Of those, 160 hearts were bio-assayed in mice to isolate live parasites. The overall seroprevalence among fattening pigs was 2·9%. The adjusted seroprevalence in pigs from intensive farms was 3·0%; the highest in sows (13·4%); 2·9% in fattening pigs and 2·6% in piglets. Adjusted seroprevalence in fattening animals from outdoor farms was 6·3%. Strains were isolated from 41 animals and all were genotyped by Restriction Fragment Length Polymorphism as type II. Risk-factor analysis showed that the risk of infection was more than three times higher for outdoor pigs, and that sows' risk was almost five times higher than that of fattening animals. This study provides further evidence of extensive pork infection with T. gondii regardless of breeding systems, indicating that farm conditions are still insufficient to guarantee 'Toxoplasma-free pork'.

West Nile virus epizootics in the Camargue (France) in 2015 and reinforcement of surveillance and control networks.

West Nile virus (WNV) infection is a non-contagious disease mainly transmitted by the bites of infected mosquitoes from the genus Culex. The virus is maintained in a mosquito-bird-mosquito cycle, and can accidentally be transmitted to mammalian hosts. Among mammalian hosts, equines and humans are the most sensitive to WNV infection and can develop severe meningoencephalitis. As WNV infections are zoonotic and can be severe in humans and equines, West Nile fever is considered to be a public and animal health concern. After a silent period of almost ten years, WNV re-emerged in France at the periphery of the Camargue area during the summer of 2015, underlining the fact that the Camargue area creates favourable conditions for WNV emergence and amplification in France. The French Network for Epidemiological Surveillance of Equine Diseases (Réseau d'Épidémio-Surveillance en Pathologie Équine [RESPE]) facilitated the early detection of WNV cases in horses. In total, 49 horses were found to be infected; among them, 44 presented clinical signs, 41 with meningoencephalitis and three with hyperthermia only. Six horses among the 41 with nervous symptoms died from the disease or were euthanised (a case fatality rate of 14.6%). The authors describe the characteristics of the 2015 WNV epizootics, the early detection of the first WNV equine cases via the RESPE network and the coordination of WNV surveillance in France.

L'infection par le virus de West Nile est une maladie non contagieuse essentiellement transmise lors de piqûres de moustiques infectés appartenant au genre Culex ; le virus se maintient dans la nature au moyen d'un cycle moustique­ oiseau­moustique ; la transmission à des hôtes mammifères a lieu de manière accidentelle. Parmi les mammifères hôtes, les plus sensibles à l'infection par le virus de West Nile sont les équidés et l'homme, chez qui l'infection peut se manifester sous forme d'une méningo-encéphalite sévère. Les infections par le virus de West Nile étant des zoonoses potentiellement graves chez l'homme et chez les équidés, la fièvre de West Nile doit être considérée comme une priorité de santé publique et animale. Resté silencieux pendant plus d'une décennie, le virus de West Nile est réapparu en France à l'été 2015 en bordure de la Camargue, confirmant que les conditions de cette région sont favorables à l'émergence et à l'amplification du virus. Le réseau français d'épidémiosurveillance en pathologie équine (RESPE) a contribué à la détection précoce du virus de West Nile chez les chevaux. Au total, 49 chevaux étaient infectés, parmi lesquels 44 présentaient des signes cliniques, correspondant à une méningo-encéphalite pour 41 d'entre eux et à une hyperthermie seule pour les trois autres. Six chevaux parmi les 41 qui présentaient des signes neurologiques ont succombé à la maladie ou ont été euthanasiés (taux de létalité de 14,6 %). Les auteurs de cet article décrivent les principales caractéristiques de l'épizootie de 2015 due au virus de West Nile ainsi que la détection précoce des premiers cas équins grâce au réseau RESPE et la coordination des activités de surveillance du virus en France.

La infección por el virus West Nile es una enfermedad no contagiosa que se transmite básicamente por la picadura de mosquitos infectados del género Culex. El virus, que se instala en un ciclo mosquito­ave­mosquito, también puede transmitirse accidentalmente a mamíferos, de entre los cuales los más sensibles a la infección son los equinos y el ser humano, que pueden contraer graves meningoencefalitis. Puesto que las infecciones por este virus son zoonóticas y pueden revestir gravedad en personas y equinos, se considera que la fiebre West Nile es una enfermedad de importancia sanitaria y zoosanitaria. En Francia, tras un periodo silente de más de diez años, el virus reapareció en verano de 2015 en la periferia de la zona de la Camarga, poniendo así de manifiesto que esta zona genera condiciones propicias al surgimiento y la amplificación del virus en el país. La red francesa de vigilancia epidemiológica de patologías equinas (Réseau d'Épidémio-Surveillance en Pathologie Équine: RESPE]) facilitó la rápida detección de caballos infectados por el virus West Nile. Se detectaron en total 49 animales infectados, entre ellos 44 con signos clínicos, de los que 41 sufrían meningoencefalitis y tres solo presentaban hipertermia. Seis de los 41 caballos que mostraban signos neurológicos murieron a causa de la enfermedad o fueron sacrificados con métodos de eutanasia (lo que supone una tasa de letalidad del 14,6%). Los autores describen las principales características de la epizootia causada por el virus West Nile en 2015, la pronta detección de los primeros casos de caballos infectados gracias a la red RESPE y la coordinación de las labores de vigilancia del virus en Francia.

Assessment of Chlamydia psittaci Shedding and Environmental Contamination as Potential Sources of Worker Exposure throughout the Mule Duck Breeding Process.

Chlamydia psittaci is an obligate intracellular bacterium responsible for avian chlamydiosis, otherwise known as psittacosis, a zoonotic disease that may lead to severe atypical pneumonia. This study was conducted on seven mule duck flocks harboring asymptomatic birds to explore the circulation and persistence of C. psittaci during the entire breeding process and assess the potential sources of worker exposure. Cloacal swabs and air samples were taken on each occasion requiring humans to handle the birds. In parallel, environmental samples, including dust, water, and soil, were collected. Specific real-time PCR analyses revealed the presence of C. psittaci in all flocks but with three different shedding patterns involving ducks about the age of 4, 8, and 12 weeks with heavy, moderate, and low excretion levels, respectively. Air samples were only positive in flocks harboring heavy shedders. Dust in flocks with heavy or moderate shedders carried chlamydial loads strongly associated with the loads detected in avian and soil samples. Environmental contamination, significantly correlated with shedding dynamics, was considered to be the most probable source of exposure. The high prevalence of bacteriophage Chp1 in all flocks, mostly jointly present with chlamydia, suggests an important factor in C. psittaci persistence, thus creating a greater risk for humans. A survey conducted in these flocks regarding farming practices and activities showed that disinfection seems to be the most promising practice for reducing C. psittaci prevalence in ducks and that the place and the duration of action during operations seem to be potential risk factors. Strict adherence to good practices is strongly recommended.

Usefulness of an in vitro cellular expression model for haemophilia A carrier diagnosis: illustration with five novel mutations in the F8 gene in women with isolated factor VIII:C deficiency.

This study aims to determine the way to predict the haemophilia A (HA) carrier status and the potential severity in six females with low FVIII: C levels (<0.50 IU mL(-1) ), F8 gene variations and without family history of HA. Except p.Ser577Tyr, F8 gene variations that we reported have never been described (p.Leu107His, p.Pro521Leu, p.Val682Leu, p.Leu2032Pro, p.Ala315dup). Prediction of their potential causal impact was studied by two strategies: bioinformatics approaches and site-directed mutagenesis followed by FVIII cellular expression into COS-1 cell. FVIII clotting assay ( FVIII: C) and antigen ( FVIII: Ag) were assayed in vitro. In silico analysis showed the probably damaging effect of all substitutions and the full conservation of the residues across mammalian species, except for p.Leu2032Pro. The in vitro variant expression model showed abnormal intra and/or extracellular FVIII: C and FVIII: Ag levels for five mutations, which suggest their causality in HA and provide informations about the involved mechanism. We suspect a defect in synthesis and secretion for p.Leu107His, p.Ala315dup and p.Pro521Leu. The mutation p.Val682Leu only affects the FVIII function while p.Ser577Tyr alters function and synthesis. The variant p.Leu2032Pro is probably a polymorphism because no alteration of the FVIII protein expression was observed in vitro. In vitro results suggest that mutations p.Ser577Tyr and p.Ala315dup could led to a severe HA in men. This study demonstrates the ability of this in vitro cellular expression model to contribute to the diagnosis strategy for female suspected of being HA carrier, without HA family history and with a novel F8 gene variation and to provide new criteria for the genetic counselling.

Poor long-term stability of the Corvita abdominal stentgraft.

INTRODUCTION: The endovascular treatment of abdominal aortic aneurysms was introduced in the early 1990s, with different generations of devices using various options for either the stent skeleton or the membrane. REPORT: Corvita generated one of these devices using braided stainless steel and a porous spun polycarbonate urethane membrane. DISCUSSION: In this report, we describe a case involving Corvita stentgraft explantation for complete aneurysm reperfusion after 13 years, demonstrating major degradation of the polyurethane membrane.

Unravelling direct and indirect contact patterns between duck farms in France and their association with the 2016-2017 epidemic of Highly Pathogenic Avian Influenza (H5N8).

Live animal movements generate direct contacts (via the exchange of live animals) and indirect contacts (via the transit of transport vehicles) between farms, which can contribute to the spread of pathogens. However, most analyses focus solely on direct contacts and can therefore underestimate the contribution of live animal movements in the spread of infectious diseases. Here, we used French live duck movement data (2016-2018) from one of the largest transport companies to compare direct and indirect contact patterns between duck farms and evaluate how these patterns were associated with the French 2016-2017 epidemic of highly pathogenic avian influenza H5N8. A total number of 614 farms were included in the study, and two directed networks were generated: the animal introduction network (exchange of live ducks) and the transit network (transit of transport vehicles). Following descriptive analyses, these two networks were scrutinized in relation to farm infection status during the epidemic. Results showed that farms were substantially more connected in the transit network than in the animal introduction network and that the transit of transport vehicles generated more opportunities for transmission than the exchange of live animals. We also showed that animal introduction and transit networks' statistics decreased substantially during the epidemic (January-March 2017) compared to non-epidemic periods (January-March 2016 and January-March 2018). We estimated a probability of 33.3 % that a farm exposed to the infection through either of the two live duck movement networks (i.e. that was in direct or indirect contact with a farm that was reported as infected in the following seven days) becomes infected within seven days after the contact. However, we also demonstrated that the level of exposure of farms by these two contact patterns was low, leading only to a handful of transmission events through these routes. As a consequence, we showed that live animal movement patterns are efficient transmission routes for HPAI but have been efficiently reduced to limit the spread during the French 2020-2021 epidemic. These results underpin the relevance of studying indirect contacts resulting from the movement of animals to understand their transmission potential and the importance of accounting for both routes when designing disease control strategies.

Neoadjuvant treatment of pancreatic adenocarcinoma: Chemoradiation or stereotactic body radiation therapy?

Despite recent advances, the prognosis of pancreatic adenocarcinomas remains poor, even for patients with resectable tumors. For these latter, new approaches based on neoadjuvant treatment have been developed. Two components are used: chemotherapy and radiation therapy (RT). Indeed, pre-operative RT has many advantages in terms of efficacy and tolerance. It increases notably the chances of subsequent complete tumor resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal. Another crucial question is to know which is the best RT technique: conventional normofractionated chemoradiotherapy or hypofrationated stereotactic body RT?

Spread of West Nile virus in Iran: a cross-sectional serosurvey in equines, 2008-2009.

We report the first large-scale serosurvey for West Nile virus (WNV) conducted in the equine population in Iran. Blood samples were obtained in 2008-2009 from 1054 equines collected from 260 districts located in 27 provinces. The overall seroprevalence rate for WNV neutralizing antibodies was 23·7%. Marked geographical variations were observed as province-specific seroprevalence rates ranged from 1% to 88%, the highest values being observed in the southern and western parts of the country. The presence of IgM-positive animals (n=9) indicated a recent circulation of WNV in several provinces. Logistic modelling confirmed this result with a significant effect of age on seropositivity. This study revealed extensive circulation of WNV in Iran particularly in southwestern provinces where the virus probably circulates every year.

A qualitative risk assessment methodology for scientific expert panels.

Risk assessment can be either quantitative, i.e. providing a numeric estimate of the probability of risk and the magnitude of the consequences, or qualitative, using a descriptive approach. The French Agency for Food, Environmental and Occupational Health and Safety (ANSES), formerly the French Food Safety Agency (AFSSA), bases its assessments on the opinions of scientific panels, such as the ANSES Animal Health Scientific Panel (AH-SP). Owing to the lack of relevant data and the very short period of time usually allowed to assess animal health risks on particular topics, this panel has been using a qualitative risk method for evaluating animal health risks or crises for the past few years. Some experts have drawn attention to the limitations of this method, such as the need to extend the range of adjectives used for the lower probabilities and to develop a way to assess consequences. The aim of this paper is to describe the improved method now established by the AH-SP, taking into account the limitations of the first version. The authors describe a new set of levels for probabilities, as well as the items considered when addressing either animal or human health consequences.

Combination of radiation therapy-immunotherapy for head and neck cancers: Promises kept?

Chemoradiotherapy with concurrent cisplatin has been the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) for over 20 years. Recently, immunotherapy, a new therapeutic class, has emerged for patients with recurrent or metastatic HNSCC and has significantly extended their survival. Will it bring the same benefit to patients with localized tumors? There is a strong rationale for combining radiation therapy and checkpoint inhibitors for HNSCC. Indeed, radiation therapy can have both immunostimulatory and immunomodulatory effects. This is what explains the famous abscopal effect. The aim of this review is to present the data available on the combination of radiation therapy and immunotherapy for HNSCC.

A novel stent for percutaneous heart valve implantation: first in vitro results.

Percutaneous aortic valve implantation has become an alternative technique to surgical valve replacement in patients with high risk for surgery. This technique is at its beginning and stents used for valve prostheses remain standard vascular stents. These stents are, however, not designed to undergo heart valve stress. They do not match the aortic environment geometry, and induce exaggerated tissue traumatism. Reduced implant lifetime may therefore be expected. The purpose of the present work is to evaluate in vitro the technical feasibility of noninvasive aortic valve replacement with a novel more specific stent. This stent is especially adapted to its implantation environment with a design that matches the shape of the aortic root while respecting the valve functions. We present a design, a manufacturing process and in vitro performances for the stent under static pressure loading and pulsatile flow. The stent shows good dynamic behavior in keeping position imposed at implantation time and in matching the aortic root dimensions changes. Prosthesis static and dynamic regurgitation are evaluated and show values close to those obtained with other commercially available prostheses.

[Gastric and pancreatic cancers: Will neoadjuvant (chemo)radiotherapy replace adjuvant chemoradiotherapy?] / Cancers gastriques et pancréatiques : la (chimio)radiothérapie néoadjuvante remplacera-t-elle la chimioradiothérapie adjuvante ?

For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal.

Modelling the time-dependent transmission rate for porcine circovirus type 2 (PCV2) in pigs using data from serial transmission experiments.

Six successive transmission trials were carried out from 4 to 39 days post inoculation (DPI) to determine the features of the infectious period for PCV2-infected pigs. The infectiousness of inoculated pigs, assessed from the frequency of occurrence of infected pigs in susceptible groups in each contact trial, increased from 4 to 18 DPI (0, 7 and 8 infected pigs at 4, 11 and 18 DPI, respectively) and then decreased slowly until 39 days post infection (4, 2 and 1 pigs infected at 25, 32 and 39 DPI, respectively). The estimated time-dependent infectiousness was fitted to three unimodal function shapes (gamma, Weibull and lognormal) for comparison. The absence of infected pigs at 4 DPI revealed a latency period between 4 and 10 DPI. A sensitivity analysis was performed to test whether the parametric shape of the transmission function influenced the estimations. The estimated time-dependent transmission rate was implemented in a deterministic SEIR model and validated by comparing the model prediction with external data. The lognormal-like function shape evidenced the best quality of fit, leading to a latency period of 8 days, an estimated basic reproduction ratio of 5.9 [1.8,10.1] and a mean disease generation time of 18.4 days [18.2, 18.5].

Spatiotemporal prediction of Escherichia coli and Enterococci for the Commonwealth Games triathlon event using Bayesian Networks.

A number of Bayesian Networks were developed in order to nowcast and forecast, up to 4 days ahead and in different locations, the likelihood of water quality within the 2018 Commonwealth Games Triathlon swim course exceeding the critical limits for Enterococci and Escherichia coli. The models are data-driven, but the identification of potential inputs and optimal model structure was performed through the parallel contribution of several stakeholders and experts, consulted through workshops. The models, whose main nodes were discretised with a customised discretisation algorithm, were validated over a test set of data and deployed in real-time during the Commonwealth Games in support to a traditional water quality monitoring program. The proposed modelling framework proved to be cost-effective and less time-consuming than process-based models while still achieving high accuracy; in addition, the added value of a continuous stakeholder engagement guarantees a shared understanding of the model outputs and its future deployment.

Land cover, landscape structure, and West Nile virus circulation in southern France.

The transmission of West Nile virus (WNV) is strongly influenced by environmental factors. In France, two endemic areas for WNV have been identified: Camargue and Var. The objective of our study was to test whether landscape characteristics could be associated with the risk of endemic circulation of WNV in these two ecologically different areas. Equine serological data collected during outbreaks in Var (2003) and Camargue (2004) were used. Both areas were marked out in cells of 5 km(2), and data were aggregated for each cell. Sixteen cells, classified as "high" level viral circulation, and 28 cells, classified as "low" level viral circulation were used for the analysis. The Corine Land Cover database (European Environment Agency) was used to evaluate, for each geographic cell, the area covered by 12 land cover classes, as well as the value of 5 landscape metrics (patch richness and density, edge density, the Shannon's diversity index, and interspersion and juxtaposition index (IJI). Multivariate linear generalized regression showed that IJI as well as the surface covered by heterogeneous agricultural areas were significantly higher in high level WNV circulation cells than in low level ones (p = 0.01 and 0.05 respectively). Both variables are indicators of a complex spatial biotope configuration that may favor the co-existence of competent vectors and reservoir hosts: the structure of the landscape thus appeared as a key element in WNV circulation. An internal validation was performed and the model was used to compute a risk map for the French Mediterranean coast. Cells with a probability > 0.8 of having a high level of viral circulation were found near Aix-en-Provence, Beziers, and Perpignan, areas where no serological study has yet been conducted. Equine cases reported in 2006 were all located in the neighborhood of cells having a > 0.8 probability for high WNV circulation status.

Patterns of lesions of bovine tuberculosis in wild red deer and wild boar.

The data obtained from a survey of Mycobacterium bovis infection in wild red deer (Cervus elaphus) and wild boar (Sus scrofa) conducted in France in the 2005/06 hunting season were used to describe and quantify the pathological findings in the two species. The red deer had caseous abscessed lesions in their organs and lymph nodes, whereas in the wild boar the lesions were predominantly caseocalcareous and occurred mainly in the lymph nodes. The severity of the gross tuberculosis-like lesions was estimated on the basis of a numerical score. The significant difference between the distribution of the scores in the two species indicated that the disease was more serious in the red deer than in the wild boar. Unlike the red deer, the wild boar did not show a generalised pattern of disease. Among the lymph nodes examined systematically, gross lesions were most frequently observed in the mesenteric lymph nodes in the red deer and in the retropharyngeal lymph nodes in the wild boar. In both species, the presence of gross lesions showed the closest agreement with the isolation of M bovis from the same lymph nodes. The different patterns of the lesions of tuberculosis in the two species suggest that red deer might play an important role in the intraspecies and interspecies dissemination of the infection, whereas in wild boar the spread of the infection would be more likely to be restricted to other wild boar.

Combining radiation therapy and cancer immune therapies: From preclinical findings to clinical applications.

Besides its direct cytotoxic effect on the tumor cells, radiation therapy is also able to elicit an immune-mediated systemic anti-tumor response, resulting in tumor regression in irradiated sites but also within distant out of field secondary lesions and providing a long-term anti-tumor response. It is now clear that associating ionizing radiation with immune therapies can enhance radio-induced anti-tumor immune responses. Over the last decade, such a combination aroused considerable interest among the scientific community, with many preclinical models and clinical trials, using many types of immune therapies and radiation regimens. In this article, we summarize the main mechanisms underlying radio-induced anti-tumor responses. We will then present an extended overview of the recent preclinical and clinical research built on this background of combined radiation and immune therapy, shedding light on what we know so far about such a promising strategy.