L’incidence des fistules anales est comprise entre 12 et 28 sur 100 000 habitants en Europe. L’âge moyen de survenue se situe entre 30 et 50 ans. La majorité des fistules anales surviennent sous la ...forme d’un abcès anorectal et ont pour origine une infection cryptogénétique des glandes d’Hermann et Desfosses. Le diagnostic est principalement clinique. L’abcès est la plupart du temps facile à repérer, car il se présente sous la forme d’une tuméfaction érythémateuse, plus ou moins volumineuse, chaude, tendue, luisante et hyperalgique à la palpation. Lorsqu’il est intramural ou ischioanal profond, l’inspection de la marge anale est alors normale, et le toucher rectal permet de faire le diagnostic en palpant une voussure douloureuse du bas rectum. En cas de fistulisation, l’aspect est variable, l’examen clinique permet de repérer le ou les orifices secondaires, il peut palper un trajet fistuleux superficiel sous la forme d’un cordon roulant sous la peau. Il doit rechercher l’orifice interne palpable sous la forme d’une dépression ou d’une granulation située au niveau pectinéal, plus rarement visible en anuscopie. Plusieurs techniques d’imagerie permettent de caractériser les fistules anales, notamment complexes, en repérant le trajet fistuleux principal et le ou les trajets fistuleux secondaires, les abcès et diverticules. Les techniques de référence sont l’échoendoscopie anale et l’IRM pelvienne. L’IRM s’impose de plus en plus dans la caractérisation préopératoire des fistules notamment complexes. En pratique, dans la plupart des cas, les fistules anales peuvent être opérées sans examen d’imagerie, mais devant la disponibilité de celle-ci et ses performances, elle est de plus en plus utilisée. Il paraît indispensable de réaliser une IRM préopératoire dans la prise en charge des fistules complexes.
The incidence of anal fistula is between 12 and 28 per 100,000 inhabitants in Europe. The average age of onset is between 30 and 50 years. The majority of anal fistulas occur in the form of anorectal abscess and originate from cryptogenic infection of the Hermann and Desfosses glands. The diagnosis is mainly clinical. The abscess is most of the time easy to spot because it is in the form of erythematous swelling, more or less voluminous, hot, tense, shiny and hyperalgic to palpation. When it is intramural or deep ischio-anal, the inspection of the anal margin is then normal and the rectal examination makes it possible to make the diagnosis by palpating a painful groove of the lower rectum. In case of fistulization, the aspect is variable, the clinical examination makes it possible to locate the secondary orifice or orifices, it can palpate a superficial fistular course in the form of a cord rolling under the skin. The clinical examiner must look for the palpable internal orifice in the form of a depression or granulation located at the pectineal level, more rarely visible in anuscopy. Several imaging techniques make it possible to characterize the anal fistula in particular complex by locating the main fistulous path and the secondary fistulous path(s), abscesses and diverticula. Reference techniques are anal echoendoscopy and pelvic MRI. MRI is becoming increasingly important in the preoperative characterization of particularly complex fistulas. In practice, in most cases, anal fistulas can be operated without imaging examination, however because of the availability and its performance, it is been increasingly used. It seems essential to perform a preoperative MRI in the management of complex fistulas.
Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful ...development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies.
Introduction L'ipilimumab (anticorps anti-CTLA4) et le pembrolizumab (anticorps anti-PD1) permettent de restaurer l'immunité anti-tumorale des lymphocytes. Initialement développés dans le traitement ...du mélanome malin métastatique, ils sont maintenant testés dans d'autres néoplasies. Ces traitements sont connus des endocrinologues pour leurs effets secondaires thyroïdiens et hypophysaires auto-immuns. Nous rapportons le cas d'un diabète de type 1 probablement induit chez un patient de 65 ans. Patients et Méthodes : Observations Mr B., 65 ans, (IMC = 23), est suivi en dermatologie depuis 2010 pour un mélanome de la cuisse gauche métastatique au niveau ganglionnaire, pulmonaire et surrénalien. Le patient bénéficie de 4 injections mensuelles d'ipilimumab en avril, mai, juin et juillet 2014. En juin 2014, juste après la 3e injection, il développe une hyperthyroïdie de type Basedow avec anticorps anti-récepteurs de la TSH (30mUI/l) et hyperfixation diffuse à la scintigraphie, traitée par irathérapie. Les glycémies à jeun sont normales. En raison de l'apparition de métastases cérébrales en juillet 2014, l'ipilimumab est remplacé par le pembrolizumab avec une première injection le 09/ 09/2014. La glycémie à jeun est normale. Le 29/09/2014, le patient se présente avec un syndrome polyuropolydipsique brutal, la glycémie est à 23 mmol/l avec des bicarbonates à 25 mmol/l et une cétonémie à 1,8 mmol/l. L'HbA1c est paradoxalement peu élevée à 7 %. Le scanner pancréatique est normal. Les anticorps anti GAD sont très positifs à plus de 250 U/ml. Le taux de C-peptide est indosable après repas test et test au glucagon. Le patient est HLA DR3 et DQ2. Les anticorps anti-GAD, dosés de façon rétrospective sur un sérum antérieur au traitement par ipilimumab étaient déjà positifs à plus de 250U/ml. Le patient reste actuellement insulino-dépendant. Conclusions Plusieurs cas de diabète fulminant ont été décrits après utilisation de pembrolizumab. La physiopathologie reste encore peu élucidée puisque seulement une partie des patients ont des anticorps anti GAD positifs. Notre patient présentait déjà un taux élevé d'anticorps antiGAD avant le début des thérapies mais le développement brutal de l'hyperglycémie chez ce patient de 65 ans peut évoquer une maladie fulminante déclenchée par les traitements sur un terrain prédisposé.
Aim
There are few data evaluating the long‐term outcomes of intersphincteric resection (ISR), especially the impact of inclusion of more juxtapositioned and intra‐anal tumours on oncological and ...functional outcomes. We compared the oncological and functional results of patients treated by total mesorectal excision and ISR for low rectal cancer over a 25‐year period.
Method
This is a retrospective study from a single institution evaluating results of ISR over three periods: 1990–1998, 1999–2006 and 2007–2014. Patients treated by partial or total ISR, with or without neoadjuvant chemoradiotherapy, for low rectal cancer (≤ 6 cm from the anal verge) were included. We compared postoperative morbidity, quality of surgery and oncological and functional outcomes in the time periods studied.
Results
Of 813 patients operated on for low rectal cancer, 303 had ISR. Tumour stage did not differ; however, the distance of the tumour from the anorectal junction decreased from 1 to 0 cm (P < 0.001) and the distal resection margin shortened from 25 to 10 mm (P < 0.001) from 1990 to 2014. The postoperative morbidity and quality of surgery did not change significantly over time. The 5‐year local recurrence (4.3% vs 5.9% vs 3.5%; P = 0.741) and disease‐free survival (72% vs 71% vs 75%; P = 0.918) did not differ between the three time periods. Functional results improved during the last period; however, overall 42% of patients experienced major bowel dysfunction.
Conclusion
Pushing the envelope of sphincter‐saving resection in ultra‐low rectal cancer reaching or invading the anal sphincter did not compromise oncological and functional outcomes. The main limitation of the ISR procedure appears to be functional rather than oncological, suggesting that bowel rehabilitation programmes should be developed.
Every step of microplastic analysis (collection, extraction and characterization) is time-consuming, representing an obstacle to the implementation of large scale monitoring. This study proposes a ...semi-automated Raman micro-spectroscopy method coupled to static image analysis that allows the screening of a large quantity of microplastic in a time-effective way with minimal machine operator intervention. The method was validated using 103 particles collected at the sea surface spiked with 7 standard plastics: morphological and chemical characterization of particles was performed in <3h. The method was then applied to a larger environmental sample (n=962 particles). The identification rate was 75% and significantly decreased as a function of particle size. Microplastics represented 71% of the identified particles and significant size differences were observed: polystyrene was mainly found in the 2–5mm range (59%), polyethylene in the 1–2mm range (40%) and polypropylene in the 0.335–1mm range (42%).
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•Semi-automated micro-spectroscopy Raman method coupled to static image analysis•Time-effective and reproducible method requiring minimum operator intervention•High particles identification rate (>70%)•Fast morphological and chemical characterization of environmental particles•Efficient method for microplastics monitoring in marine environment
Schizophrenia is a chronic, severe and highly complex mental illness. Current treatments manage the positive symptoms, yet have minimal effects on the negative and cognitive symptoms, two prominent ...features of the disease with critical impact on the long-term morbidity. In addition, antipsychotic treatments trigger serious side effects that precipitate treatment discontinuation. Here, we show that activation of the trace amine-associated receptor 1 (TAAR1), a modulator of monoaminergic neurotransmission, represents a novel therapeutic option. In rodents, activation of TAAR1 by two novel and pharmacologically distinct compounds, the full agonist RO5256390 and the partial agonist RO5263397, blocks psychostimulant-induced hyperactivity and produces a brain activation pattern reminiscent of the antipsychotic drug olanzapine, suggesting antipsychotic-like properties. TAAR1 agonists do not induce catalepsy or weight gain; RO5263397 even reduced haloperidol-induced catalepsy and prevented olanzapine from increasing body weight and fat accumulation. Finally, TAAR1 activation promotes vigilance in rats and shows pro-cognitive and antidepressant-like properties in rodent and primate models. These data suggest that TAAR1 agonists may provide a novel and differentiated treatment of schizophrenia as compared with current medication standards: TAAR1 agonists may improve not only the positive symptoms but also the negative symptoms and cognitive deficits, without causing adverse effects such as motor impairments or weight gain.
Traumatic stress in early-life increases the risk for cognitive and neuropsychiatric disorders later in life. Such early stress can also impact the progeny even if not directly exposed, likely ...through epigenetic mechanisms. Here, we report in mice that the offspring of males subjected to postnatal traumatic stress have decreased gene expression in molecular pathways necessary for neuronal signaling, and altered synaptic plasticity when adult. Long-term potentiation is abolished and long-term depression is enhanced in the hippocampus, and these defects are associated with impaired long-term memory in both the exposed fathers and their offspring. The brain-specific gamma isoform of protein kinase C (Prkcc) is one of the affected signaling components in the hippocampus. Its expression is reduced in the offspring, and DNA methylation at its promoter is altered both in the hippocampus of the offspring and the sperm of fathers. These results suggest that postnatal traumatic stress in males can affect brain plasticity and cognitive functions in the adult progeny, possibly through epigenetic alterations in the male germline.
Universal prophylaxis for cytomegalovirus (CMV) prevention is viable but, compared with a preemptive strategy, leads to higher incidence of late‐onset disease (LOD) associated with poor patient and ...graft survival. The purpose of this study was to compare LOD with early onset disease (EOD), with a focus on the highest risk kidney transplant recipients (KTRs): CMV seronegative recipients transplanted from seropositive donors (D+R−). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vδ2‐negative (Vδ2neg) γδ T cell expansion involved in CMV infection resolution. EOD was defined as occurring <3 mo and LOD as occurring >3 mo after transplantation. Depending on the period, universal prophylaxis or preemptive treatment was used. Overall, 168 D+R− KTRs were included between 2003 and 2011. LOD was associated with a lower peak DNAemia (p = 0.04), fewer recurrences (odds ratio 0.16; 95% confidence interval 0.05–0.55; p = 0.01) and shorter anti‐CMV curative treatment (40 vs. 60 days, p < 0.0001). As a corollary, we found that Vδ2neg γδ T cell expansion was faster in LOD than in EOD (31 vs. 168 days after the beginning of CMV disease, p < 0.0001). In D+R− KTRs, universal prophylaxis is associated with more LOD, which had better infection management and a faster immune response. These results support the use of universal prophylaxis over a preemptive strategy and reappraise outcomes of LOD.
In a comparison of the prognosis of early‐ and late‐onset cytomegalovirus (CMV) disease in donor‐positive, recipient‐negative kidney transplant patients, patients with late‐onset CMV disease occurring at the end of universal prophylaxis had better infection management and a faster immune response than patients with earlyonset CMV disease, often occurring in cases of preemptive strategy, supporting the use of universal prophylaxis in these high‐risk patients.
Flow-diverter stents are an alternative treatment for challenging and recurrent aneurysms. Thrombosis of the sac is thought to induce perianeurysmal brain inflammation, but such phenomena have never ...been studied in flow-diverter devices. We developed imaging data to explain the clinical exacerbation of symptoms after flow-diversion treatment.
Seventeen patients with unruptured aneurysms were treated by using a flow-diverter device. Clinical symptoms and angiographic and MR imaging features were recorded before and after treatment, during both the acute and chronic phases, to look for inflammatory reaction.
Seven of the 17 patients (41%) showed a delayed clinical aggravation of symptoms posttreatment consisting of a headache (n = 7) with aggravation of pre-existing compressive symptoms (n = 4) and the appearance of compressive symptoms (n = 1). This clinical deterioration was transient; it was observed between 3 and 15 days posttreatment and resolved by day 30. MR imaging revealed signs highly suggestive of perianeurysmal inflammation with vasogenic edema and blood-brain barrier breakdown. The association between MR imaging inflammatory features and clinical aggravation was statistically significant. Large aneurysmal size and its proximity to surrounding brain tissue were predictive of this inflammatory reaction after flow diversion.
The main finding of the series is that MR imaging-defined perianeurysmal inflammation is observed with a high frequency after treatment of unruptured aneurysms with flow diverters and is, in most cases, associated with a transient clinical deterioration.
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