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Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan.

BackgroundIntraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, a widespread parasite which infects the gut epithelium. IFN-γ producing CD4+ T IELs provide an efficient and a long-term protection against cryptosporidiosis while intraepithelial type 1 innate lymphoid cells limits pathogen spreading during early stages of infection in immunodeficient individuals. Yet, the role of T-cell like innate IELs, the most frequent subset of innate lymphocytes in the gut, remains unknown.MethodsTo better define functions of innate IELs in cryptosporidiosis, we developed a co-culture model with innate IELs isolated from Rag2-/- mice and 3D intestinal organoids infected with C. parvum using microinjection.ResultsThanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IELs secrete IFN-γ in response to C. parvum, the cytokine was not sufficient to inhibit parasite proliferation at early stages of the infection. The rapid protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis of the Cryptosporidium-infected organoids revealed that epithelial cells down regulated Serpinb9b, a granzyme inhibitor, which may increase their sensitivity to cytolytic attack by innate IELs.ConclusionBased on these data we conclude that innate IELs, most likely T-cell-like innate IELs, provide a rapid protection against C. parvum infection through a perforin/granzymes-dependent mechanism. C. parvum infection. The infection may also increase the sensitivity of intestinal epithelial cells to the innate IEL-mediated cytotoxic attack by decreasing the expression of Serpin genes.

Despite their high productivity and their key role in coastal processes, microphytobenthic biofilm studies remain relatively scarce because in situ, meteorological hazards make it difficult to acquire reproducible measurements, also due to difficulties in properly reproducing field conditions in the laboratory. Therefore, in order to better understand the processes of microphytobenthic primary production, we have developed an automated laboratory system and procedure with variable light intensity, with a large number of replicates. This article aims to provide a description of the creation of a P-I curve based on a total of 128 vertical profiles recorded on a sediment core taken in situ, placed in the automated system and studied under controlled conditions of temperature and air humidity while light intensity was varied automatically, thus allowing to work in standard and replicable conditions. With measured production levels of up to 14.68 ± 3.70 mmol O2.m-2.h-1 and a productivity of 0.06 ± 0.01 mmol O2.m-2.h-1 per gram of Chl a corresponding to what is generally found in temperate environments, we have shown that our system is suitable for high frequency measurements and, by combining surficial measurements of modulated fluorescence and oxygen microprofiling in sediments, complementary information from a large dataset on photosynthetic and microphytobenthic migratory activity may be obtained under standard conditions. The development of this tool has made it possible to highlight a stabilization time for oxygen fluxes. For our study conducted in a temperate environment, we observed a time lag of a few minutes that should be considered when acquiring PE curves in the laboratory to study microphytobenthic photosynthetic capacities. This tool also allowed to describe microphytobenthic migration in response to light exposure, with successive steps observed through fluorescence and oxygen profiles. First, microphytobenthos migrated towards the surface until the optimal intensity of production at 475 µmol photons.m-2.s-1, then from this intensity as well as towards 780 µmol photons.m-2.s-1, downwards migratory movements were detected. This system is a working basis which can open interesting perspectives for the study of the effect of other abiotic (or biotic) parameters.

Abstract Background The lateral chest wall is intimately associated with the esthetics of the breast. Patients with massive weight loss often have excess skin and fat in the lateral thoracic region causing functional, esthetic, and psychological discomfort. In addition, the breasts exhibit extreme ptosis after weight loss due to a reduction in volume and projection that is exacerbated by qualitative changes in the skin, with loss of its natural elasticity. This article describes a reliable new technique for simultaneous autologous breast augmentation and lateral thoracic dermolipectomy to provide autologous tissue for breast augmentation and simultaneous rejuvenation of the chest wall. Case presentation A 30-year-old Caucasian woman who had lost 58 kg after bariatric surgery had major skin excess sequelae combined with major breast ptosis. She wanted to correct her brachial and lateral thoracic skin and fat excess, as well as rejuvenate her breasts. The lateral thoracic panicle present was harvested and transposed in the retroglandular plane to perform autologous breast augmentation with lateral thoracic dermolipectomy. Results The patient was totally healed and complication-free at day 15. Both esthetic results and patient satisfaction were good at 6 months post-surgery. Conclusions Superolateral thoracic flap augmentation mammaplasty during thoracic dermolipectomy is a simple and safe procedure for selected patients. Durable and natural autologous breast augmentation may be achieved in a single step without the need for a breast implant, while rejuvenating the thoracic region.

Summary:. Breast implant reconstructions increasingly incorporate meshes like the synthetic nonresorbable titanium-coated polypropylene mesh commercialized as Tiloop (Pfm medical). We report the case of a 48-year-old woman, with a medical history of nickel allergy, who presented with an extensive erythematous eruption, a periprosthetic reaction, and an axillary node reaction, 18 months after a unilateral prophylactic mastectomy. We excluded infectious, sarcoidosis and carcinomatosis. The patient’s medical history, the clinical evolution, and the particularly fast and complete healing after removal of the mesh were suggestive of an unusual allergic reaction to the titanium in the titanium-coated polypropylene mesh. Titanium allergies are very rare events, predominantly described in the dental and orthopedic fields. We also discussed the hypothesis of a tardive red breast syndrome related to a synthetic mesh, also mediated by immunological response as described recently in another case report.

Abstract Background Soft tissue sarcomas affecting the root of an upper extremity raise the question of limb amputation depending on their location, size, and malignancy. Malignant triton tumors are a rare subtype of neurofibrosarcomas that have been poorly reported in the literature. We report the case of a challenging reconstruction of the upper extremity using a pedicled latissimus dorsal flap. Case presentation A 25-year-old Occidental man was referred to our sarcoma unit for the management of a large, high-grade malignant peripheral nerve sheath tumor with no regional or distant extension and very fast progression. He was treated first by concomitant neoadjuvant radiotherapy and chemotherapy. Carcinologic excision was performed “en bloc” including the skin, the tumor, and the flexor muscles of our patient’s elbow. Coverage of the skin defect and elbow flexion restoration were achieved by using a homolateral pedicled musculocutaneous latissimus dorsi flap. Histological analysis showed an R0 resection. The reconstruction process recovered a complete bending of his elbow. He is still in remission at 26 months follow-up. Conclusions A malignant triton tumor is a rare, aggressive, and high-grade sarcoma. It was successfully treated and this case report describes an effective treatment modality. Reconstructive surgery, allowing large, complete tumor removal, is indispensable after neoadjuvant chemotherapy and radiotherapy.

The NKG2 family of NK receptors includes activating and inhibitory members. With the exception of the homodimer-forming NKG2D, NKG2 receptors recognize the nonclassical MHC class I molecule HLA-E, and they can be subdivided into two groups: those that associate with and signal through DAP12 to activate cells, and those that contain an ITIM motif to promote inhibition. The function of NKG2 family member NKG2E is unclear in humans, and its surface expression has never been conclusively established, largely because there is no Ab that binds specifically to NKG2E. Seeking to determine a role for this molecule, we chose to investigate its expression and ability to form complexes with intracellular signaling molecules. We found that NKG2E was capable of associating with CD94 and DAP12 but that the complex was retained intracellularly at the endoplasmic reticulum instead of being expressed on cell surfaces, and that this localization was dependent on a sequence of hydrophobic amino acids in the extracellular domain of NKG2E. Because this particular sequence has emerged and been conserved selectively among higher order primates evolutionarily, this observation raises the intriguing possibility that NKG2E may function as an intracellular protein.

This paper seeks to consider games — and more particularly card games and gambling — as an American form of resistance in Thomas Pynchon’s novels. As opposed to agôn, a category of games that Roger Caillois delineates in Man, Play and Games (1958) as “a combat in which equality of chances is artificially created, in order that the adversaries should confront each other under ideal conditions,” alea encompasses games of chance which are “a strict negation of controlled effort, […] efficacious resort to skill, power, and calculation, and self-control; respect for the rules; the desire to test oneself under conditions of equality.” It will be my contention that alea, in Pynchon’s novels, offers the possibility of an alternative world and becomes a necessary mode of resistance in the face of a plenty-flushed adversity which threatens to hold sway over the American continent. For Pynchon’s players, more often than not cheaters and fraudsters, use such games of chance to fulfil their longing for emancipation and flight, at a time in history when the American continent is about to be mapped by the abstractions of colonial companies and Enlightenment science. Gaming clubs — ranging from taverns in Mason & Dixon to casinos and gambling dens in Gravity’s Rainbow (1973), Against the Day (2006), and Inherent Vice (2009) — can be recognized as heterotopian sites where otherwise dispersed groups of people momentarily gather in order to gain freedom from the ruling few. Although the moralism of Puritan ministers sternly reminded their flocks to refrain from wasting their earnings on rash bets, gambling can thus be envisioned as a way to escape from the hyper-productivity expounded by modernity, intersecting with Walter Benjamin’s discourse on the materialist form of gambling within industrial capitalism. Following Gerda Reith’s and Susan Strange’s arguments in The Age of Chance (1999) and Casino Capitalism (1986), I will further argue that, in the new capitalist economy, Pynchon anticipates in his novels the attention of late capitalism to new areas for capitalization, overseeing both the commodification of idleness and the insinuation into the fabric of existence of the same risk assessment strategy as that applied by capitalism.

Book Reviews, of:Dalsgaard (ed) – Thomas Pynchon in ContextChetwynd, Freer, Maragos (eds) – Thomas Pynchon, Sex, and GenderMogultay – The Ruins of Urban Modernity: Thomas Pynchon’s Against the DayAlworth – Site Reading: Fiction, Art, Social FormMullins – Postmodernism in Pieces: Materializing the SocialHenry – New Media and the Transformation of Postmodern American Literature: From Cage to Connectionden Dulk – Existentialist Engagement in Wallace, Eggers, and Foer: A Philosophical Analysis of Contemporary American LiteratureAnderson – Postmodern Artistry in Medievalist Fiction: An International StudyHouser – Ecosickness in Contemporary U.S. Fiction: Environment and AffectPalleau-Papin (ed) – Under Fire; William T. Vollmann, The Rifles: A Critical Study [a note from the Book Reviews Editor: if you’re interested in reviewing a book on any aspect of unconventional post-1945 US literature, please send an email proposing a review to reviews@pynchon.net]

Abstract Objectives Assessment of the adaptive immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is crucial for studying long‐term immunity and vaccine strategies. We quantified IFNγ‐secreting T cells reactive against the main viral SARS‐CoV‐2 antigens using a standardised enzyme‐linked immunospot assay (ELISpot). Methods Overlapping peptide pools built from the sequences of M, N and S viral proteins and a mix (MNS) were used as antigens. Using IFNγ T‐CoV‐Spot assay, we assessed T‐cell and antibody responses in mild, moderate and severe SARS‐CoV‐2 patients and in control samples collected before the outbreak. Results Specific T cells were assessed in 60 consecutive patients (mild, n = 26; moderate, n = 10; and severe patients, n = 24) during their follow‐up (median time from symptom onset [interquartile range]: 36 days [28;53]). T cells against M, N and S peptide pools were detected in n = 60 (100%), n = 56 (93.3%), n = 55 patients (91.7%), respectively. Using the MNS mix, IFNγ T‐CoV‐Spot assay showed a specificity of 96.7% (95% CI, 88.5–99.6%) and a specificity of 90.3% (75.2–98.0%). The frequency of reactive T cells observed with M, S and MNS mix pools correlated with severity and with levels of anti‐S1 and anti‐RBD serum antibodies. Conclusion IFNγ T‐CoV‐Spot assay is a reliable method to explore specific T cells in large cohorts of patients. This test may become a useful tool to assess the long‐lived memory T‐cell response after vaccination. Our study demonstrates that SARS‐CoV‐2 patients developing a severe disease achieve a higher adaptive immune response.

Abstract Background Ideally, monoclonal antibodies provide selective treatment by targeting the tumour, without affecting normal tissues. Therefore, antibody imaging is of interest, preferably in early stages of drug development. However, the imaging signal consists of specific, as well as non-specific, uptake. The aim of this study was to assess specific, target-mediated uptake in normal tissues, with immuno-PET in a phase I dose escalation study, using the anti-CD44 antibody RG7356 as example. Results Data from thirteen patients with CD44-expressing solid tumours included in an imaging sub-study of a phase I dose escalation clinical trial using the anti-CD44 antibody RG7356 was analysed. 89Zirconium-labelled RG7356 (1 mg; 37 MBq) was administered after a variable dose of unlabelled RG7356 (0 to 675 mg). Tracer uptake in normal tissues (liver, spleen, kidney, lung, bone marrow, brain and blood pool) was used to calculate the area under the time antibody concentration curve (AUC) and expressed as tissue-to-blood AUC ratios. Within the dose range of 1 to 450 mg, tissue-to-blood AUC ratios decreased from 10.6 to 0.75 ± 0.16 for the spleen, 7.5 to 0.86 ± 0.18 for the liver, 3.6 to 0.48 ± 0.13 for the bone marrow, 0.69 to 0.26 ± 0.1 for the lung and 1.29 to 0.56 ± 0.14 for the kidney, indicating dose-dependent uptake. In all patients receiving ≥ 450 mg (n = 7), tumour uptake of the antibody was observed. Conclusions This study demonstrates how immuno-PET in a dose escalation study provides a non-invasive technique to quantify dose-dependent uptake in normal tissues, indicating specific, target-mediated uptake.

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gamma-producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.

An amendment to this paper has been published and can be accessed via the original article.

Toxoplasma gondii is an intracellular parasite that frequently infects a large spectrum of warm-blooded animals. This parasite induces abortion and establishes both chronic and silent infections, particularly in the brain. Parasite penetration into the host activates a strong anti-parasite immune response. In the present paper, we will discuss the interplay between innate and adaptive immunity that occurs within the infected intestine to clear the parasite and to maintain intestinal homeostasis despite the exacerbation of an inflammatory immune response.

Background and objectivesAnti-hypertensive treatment with the angiotensin II receptor antagonist olmesartan is a rare cause of severe Sprue-like enteropathy. To substantiate the hypothesis that olmesartan interferes with gut immune homeostasis, clinical, histopathological and immune features were compared in olmesartan-induced-enteropathy (OIE) and in autoimmune enteropathy (AIE).MethodsMedical files of seven patients with OIE and 4 patients with AIE enrolled during the same period were retrospectively reviewed. Intestinal biopsies were collected for central histopathological review, T cell Receptor clonality and flow cytometric analysis of isolated intestinal lymphocytes.ResultsAmong seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies. Small intestinal lesions and signs of intestinal lymphocyte activation were thus reminiscent of the four cases of AIE diagnosed during the same period. Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two.ConclusionThis case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals.

Background: The prevalence of pterygium colli (“webbed neck”) is 75% in patients with Turner syndrome. This congenital deformity manifests as a bilateral cervical skin fold stretching from the mastoid to the acromion. Although the visibility of this skin fold varies among patients, it frequently has negative social effects. The surgical management of this malformation remains challenging as it requires the achievement of a harmonious neck profile and natural hairline implantation. Methods: We describe a series of 5 girls with Turner syndrome who were managed in our department at the University Hospital Center of Toulouse-Rangueil, France. All patients benefited from a surgical approach based on a new posterior technique, including half-moon resection of the skin fold with an inferior back-cut and suturing of the superficial lamina of the cervical fascia. To ensure solidity, the fascia was fastened to the nuchal ligament. Results: Patients’ mean age at surgery was 10 years (range, 6–13 y). The mean duration of follow-up was 13.7 years (range, 2–20 y). No scar enlargement or recurrence was remotely authenticated. The patients were satisfied with the cosmetic results, including an esthetic neck profile and recovery of hairline implantation. Conclusion: The “posterior cervical lift,” an innovative surgical technique for the management of pterygium colli, achieved satisfying cosmetic outcomes and stability over time.

PurposeAromatase inhibitor therapy (AI) significantly improves survival in breast cancer patients. Little is known about adherence and persistence to aromatase inhibitors and about the causes of treatment discontinuation among older women.MethodsWe constituted a cohort of women over 65 receiving a first AI therapy for breast cancer between 2006 and 2008, and followed them until June 2011. Women were selected in the population-based French National Health Insurance databases, and data was collected on the basis of pharmacy refills, medical records and face-to-face interviews. Non-persistence to treatment was defined as the first treatment discontinuation lasting more than 3 consecutive months. Time to treatment discontinuation was studied using survival analysis techniques.ResultsOverall among the 382 selected women, non-persistence to treatment went from 8.7% (95%CI: 6.2-12.1) at 1 year, to 15.6% (95%CI: 12.2-19.8) at 2 years, 20.8% (95%CI: 16.7-25.6) at 3 years, and 24.7% (95%CI: 19.5-31.0) at 4 years. In the multivariate analysis on a sub-sample of 233 women with available data, women using complementary or alternative medicine (CAM) (HR = 3.2; 95%CI: 1.5-6.9) or suffering from comorbidities (HR = 2.2; 95%CI: 1.0-4.8) were more likely to discontinue their treatment, whereas women with polypharmacy (HR = 0.4; 95%CI: 0.2-0.91) were less likely to discontinue. In addition, 13% of the women with positive hormonal receptor status did not fill any prescription for anti-hormonal therapy.ConclusionAI therapy is discontinued prematurely in a substantial portion of older patients. Some patients may use CAM not as a complementary treatment, but as an alternative to conventional medicine. Improving patient-physician communication on the use of CAM may improve hormonal therapy adherence.

Structural and biophysical studies of protein complexes require multi-milligram quantities of soluble material. Subunits are often unstable when expressed separately so co-expression strategies are commonly employed since in vivo complex formation can provide stabilising effects. Defining constructs for subunit co-expression experiments is difficult if the proteins are poorly understood. Even more problematic is when subunit polypeptide chains co-fold since individually they do not have predictable domains. We have developed CoESPRIT, a modified version of the ESPRIT random library construct screen used previously on single proteins, to express soluble protein complexes. A random library of target constructs is screened against a fixed bait protein to identify stable complexes. In a proof-of-principle study, C-terminal fragments of the influenza polymerase PB2 subunit containing folded domains were isolated using importin alpha as bait. Separately, a C-terminal fragment of the PB1 subunit was used as bait to trap N-terminal fragments of PB2 resulting in co-folded complexes. Subsequent expression of the target protein without the bait indicates whether the target is independently stable, or co-folds with its partner. This highly automated method provides an efficient strategy for obtaining recombinant protein complexes at yields compatible with structural, biophysical and functional studies.

BackgroundThe clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences.MethodologyMRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4+/-3.6) was performed. All met the DSM-IV and ADI -R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0+/-4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable.Principal findingsMRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients).ConclusionsAn unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism.

O autismo é um transtorno de neurodesenvolvimento com diversas apresentações clínicas. Essas apresentações variam em gravidade (leves a graves) e são denominadas transtornos do espectro do autismo. O sinal mais comum aos transtornos desse espectro é o déficit de interação social, que está associado a déficits de comunicação verbal e não-verbal e a comportamentos estereotipados e repetitivos. Graças a estudos recentes que utilizam métodos de imagem cerebral, os cientistas obtiveram uma idéia melhor dos circuitos neurais envolvidos nos transtornos do espectro do autismo. De fato, os exames de imagem cerebral funcionais, como tomografia por emissão de pósitrons, tomografia por emissão de fóton único e ressonância magnética funcional abriram uma nova perspectiva para o estudo do funcionamento cerebral normal e patológico. Três estudos independentes encontraram anormalidades da anatomia e do funcionamento em repouso do lobo temporal em pacientes autistas. Essas alterações estão localizadas bilateralmente nos sulcos temporais superiores. Essa região anatômica é de grande importância para a percepção de estímulos sociais essenciais. Além disso, estudos funcionais demonstraram hipoativação da maior parte das áreas envolvidas na percepção social (percepção de faces e voz) e cognição social (teoria da mente). Esses dados sugerem um funcionamento anormal da rede de pensamentos do cérebro social no autismo. A compreensão das alterações nesse importante mecanismo pode estimular a elaboração de novas e mais adequadas estratégias sociais de reeducação para pacientes autistas.Autism is a neurodevelopmental disorder with a range of clinical presentations. These presentations vary from mild to severe and are referred to as autism spectrum disorders. The most common clinical sign of autism spectrum disorders is social interaction impairment, which is associated with verbal and non-verbal communication deficits and stereotyped and repetitive behaviors. Thanks to recent brain imaging studies, scientists are getting a better idea of the neural circuits involved in autism spectrum disorders. Indeed, functional brain imaging, such as positron emission tomography, single foton emission tomographyand functional MRI have opened a new perspective to study normal and pathological brain functioning. Three independent studies have found anatomical and rest functional temporal lobe abnormalities in autistic patients. These alterations are localized in the superior temporal sulcus bilaterally, an area which is critical for perception of key social stimuli. In addition, functional studies have shown hypoactivation of most areas implicated in social perception (face and voice perception) and social cognition (theory of mind). These data suggest an abnormal functioning of the social brain network in autism. The understanding of the functional alterations of this important mechanism may drive the elaboration of new and more adequate social re-educative strategies for autistic patients.

The advent of free flaps has made it possible to undertake increasingly complex reconstructive surgeries. Many of the patients have already undergone extensive prior surgery, primary free flap reconstruction and/or cervical irradiation. These treatments strongly impact anatomy and tissue quality. The reconstructive surgeon may be faced with a situation where the choice of recipient vessels is limited; in 7% of cases, no cervical vessels are available at all. For venous anastomosis, branches of the internal and external jugular vein are preferentially used, but may have been ligated or be unusable. Venous congestion is one of the most common causes of failure in these situations. The cephalic vein has been described as an alternative for second anastomosis in first line, but is rarely used for early free-flap salvage. Based on a case study, the technique of cephalic vein transposition is illustrated for early salvage of a double free flap for head-and-neck reconstruction. This technique is simple, reliable and rapid. It should be part of the armamentarium of the head and neck reconstructive surgeon. [ABSTRACT FROM AUTHOR]

Limb lymphoedema is common in patients who have undergone inguinal or axillary lymph node dissection. Lymphoedema seriously impacts the patient's quality of life by inducing adipogenesis, fibrosis and repeated episodes of lymphangitis and cellulitis. Following failure of compression therapies, several curative or symptomatic surgical options have been proposed over recent decades, such as liposuction or lymphovenous anastomosis. Vascularized lymph node transfer techniques have recently been described, with promising results. Vascularized lymph node transfer with submental free flap appears to be the most reliable of these technique, associated with the lowest morbidity. The flap harvesting technique presents several specific differences compared to conventional submental free flap. A good knowledge of neck anatomy is essential and multimodal and multidisciplinary management is often required. In the light of a case report, we describe the basic submental free flap technique for vascularized lymph node transfer for the treatment of lower limb lymphoedema. This technique may be used by head and neck surgeons performing flap harvest, as well as plastic surgeon surgeons or gynaecologists ensuring long-term management of these patients. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is booming in the medical field. This technology increases the possibilities of personalized treatment for patients, while lowering manufacturing costs. To facilitate mandibular reconstruction with fibula free flap, some companies propose cutting guides obtained by CT-guided moulding. However, these guides are prohibitively expensive (€ 2,000 to € 6,000). Based on a partnership with the CNRS, engineering students and a biomedical company, the authors have developed cutting guides and 3D-printed mandible templates, deliverable in 7 days and at a lower cost. The novelty of this project is the speed of product development at a significantly lower price. In this technical note, the authors describe the logistic chain of production of mandible templates and cutting guides, as well as the results obtained. The goal is to allow access to this technology to all patients in the near future. [ABSTRACT FROM AUTHOR]

Background & Aims: CD4+ T cells specific for dietary gluten and interleukin 15 (IL15) contribute to the pathogenesis of celiac disease. We investigated whether and how they interact to damage the intestine using mice that overexpress human IL15 in the intestinal epithelium and have CD4+ T cells specific for ovalbumin, a dietary antigen. Methods: We crossed mice with CD4+ T cells specific for ovalbumin (OTII) with mice that overexpress human IL15 under an intestine-specific promoter (B6 × IL15Tge). The offspring (OTII × IL15Tge mice) received control or ovalbumin-containing diets until 3 months of age. Enteropathy was monitored by weight, ratio of villous:crypt length, and the number of intestinal lymphocytes. Phenotype, cytokine production, and degranulation of mucosal and spleen lymphocytes were analyzed by multicolor flow cytometry or enzyme-linked immunosorbent assay. Regulatory T-cell function and CD8+ T-cell activation were analyzed in co-culture assays. Results: Exposure to ovalbumin reduced growth and led to enteropathy in OTII × IL15Tge mice but not in control OTII × B6 littermates. Enteropathy was associated with expansion of mucosal granzyme B+ CD8+ T cells, and developed despite increased frequency of functional ovalbumin-specific regulatory T cells. Ovalbumin-activated CD4+ T cells secreted IL2, which along with IL15 stimulated expansion of noncognate intestinal cytotoxic CD8+ T cells, which did not respond to regulatory T cells and induced epithelial damage. Conclusions: We observed that in mice given food antigen, cooperation between IL15 and CD4+ T cells is necessary and sufficient to activate CD8+ T cells and damage the small intestine. We propose that this process is involved in the development of celiac disease. [Copyright &y& Elsevier]

Background & Aims: Refractory celiac disease (RCD) was recently subdivided into 2 subtypes (RCD I and II) based on a normal or abnormal phenotype of intraepithelial lymphocytes (IELs), respectively. It is not clear, however, if these 2 entities differ in their presentation at diagnosis or long-term outcome. We compared the clinical and biological characteristics of RCD I and RCD II at diagnosis, the risk of developing an overt lymphoma, and the predictive factors of survival. Methods: Medical files of 14 patients with RCD I and 43 with RCD II were analyzed retrospectively. Predictive factors of overt lymphoma and survival were studied in univariate and multivariate analyses. Results: At diagnosis, malnutrition, ulcerative jejunitis, and lymphocytic gastritis were more common in patients with RCD II than RCD I (P < .05). Overt lymphomas occurred in 2 patients with RCD I and 16 with RCD II. In the univariate analysis, abnormal IEL phenotype and increased age at diagnosis of RCD were predictive factors for overt lymphoma. Abnormal IEL phenotype (P < .01), clonality (P = .01), and overt lymphoma (P = .001) predicted short survival time. Only abnormal IEL phenotype (P = .03) and overt lymphoma (P = .04) were predictive in the multivariate analysis. The 5-year survival rate was 93% in patients with RCD I and 44% with RCD II. Conclusions: RCD II has a much more severe presentation and prognosis than patients with RCD I; <44% of patients with RCD II survive 5 years after diagnosis. Abnormal IEL phenotype is a predictive factor but not a necessary condition for the development of overt lymphoma. [Copyright &y& Elsevier]

Background & Aims: Interleukin (IL)-15 delivers signals that drive chronic inflammation in several diseases, including celiac disease. Smad3–transforming growth factor-beta (TGF-β) signaling is instrumental to counteract proinflammatory signals and maintain immune homeostasis. Our goal has been to investigate why the proinflammatory effects of IL-15 cannot be efficiently controlled by TGF-β in celiac disease. Methods: The impact of IL-15 on TGF-β signaling in T cells and in the intestinal mucosa of celiac disease patients was analyzed by combining cell and organ cultures, immunohistochemistry, flow cytometry, real-time polymerase chain reaction, electromobility gel shift, and Western blot. Results: IL-15 impaired Smad3-dependent TGF-β signaling in human T lymphocytes downstream from Smad3 nuclear translocation. IL-15-mediated inhibition was associated with a long-lasting activation of c-jun-N-terminal kinase and reversed by c-jun antisense oligonucleotides, consistent with the demonstrated inhibitory effect of phospho-c-jun on the formation of Smad3–DNA complexes. In active celiac disease, intestinal lymphocytes showed impaired TGF-β–Smad3-dependent transcriptional responses and up-regulation of phospho-c-jun. Anti-IL-15 antibody and c-jun antisense both downmodulated phospho-c-jun expression and restored TGF-β–Smad-dependent transcription in biopsies of active celiac disease. c-jun antisense decreased interferon gamma transcription. Conclusions: Impairment of TGF-β-mediated signaling by IL-15 might promote and sustain intestinal inflammation in celiac disease. More generally, our data provide a new rationale for the potent proinflammatory effects of IL-15, and further support the concept that IL-15 is a meaningful therapeutic target in inflammatory diseases associated with irreducible elevation of IL-15. [Copyright &y& Elsevier]