Young porcine endocrine pancreatic islets cultured in fibrin and alginate gels show improved resistance towards human monocytes.

AIM: To investigate the protective function of alginate and fibrin gels used to embed porcine endocrine pancreatic islets towards human monocytes. METHODS: Groups of 200 islet equivalents from young pigs were embedded in either a fibrin or in an alginate gel, and as a control seeded in tissue culture polystyrene (TCPS) well plates. The islet cultures were incubated with 2×10(5) human monocytes for 24h. In addition, both islets and monocytes were separately cultured in TCPS, fibrin and alginate. Islet morphology, viability and function were investigated as well as the secretion of cytokines TNFα, IL-6, and IL-1ß. RESULTS: When freely-floating in TCPS, non-encapsulated islets were surrounded by monocytes and started to disperse after 24h. In fibrin, monocytes could be found in close proximity to embedded islets, indicating monocyte migration through the gel. In contrast, after 24h, few monocytes were found close to islets in alginate. Immunofluorescence staining and manual counting showed that integrin expression was higher in fibrin-embedded islet cultures. A TUNEL assay revealed elevated numbers of apoptotic cells for islets in TCPS wells compared to fibrin and alginate cultures. Insulin secretion was higher with islets embedded in fibrin and alginate when compared to non-encapsulated islets. TNFα, IL-6 and IL-1ß were found in high concentrations in the media of co-cultures and monocyte mono-culture in fibrin. CONCLUSION: Both alginate and fibrin provide key structural support and offer some protection for the islets towards human monocytes. Fibrin itself triggers the cytokine secretion from monocytes.

Cross talk between the extracellular matrix and the immune system in the context of endocrine pancreatic islet transplantation. A review article.

This review aims to highlight the importance of the bidirectional influence of the extracellular matrix (ECM) and immune cells in the context of type 1 diabetes mellitus (T1DM) and endocrine pancreatic islet transplantation. We introduced the main classes of molecules and proteins constituting the ECM as well as cells and cytokines of the immune system with the aim to further examine their roles in T1DM and islet transplantation. Integrins expressed by immune cells and their functions are detailed. Finally, this article reviews the roles of the ECM and the immune system in islet transplantation as well as ECM-related cytokines and their influence on the ECM and immune cells.

Strongyloides hyper-infection in a lung transplant recipient: Case report and review of the literature.

CASE PRESENTATION: A 63-year-old man with a left single lung transplant for end-stage combined restrictive and obstructive lung disease developed persistent pulmonary infiltrates and recurrent gram-negative bacteremia post-transplant. Bronchoalveolar lavage fluid revealed a nematode on Papanicolau staining compatible with Strongyloides stercoralis larvae on day 50 post-transplant. Although Strongyloides serology performed post-transplant was negative, a retrospective review of the medical record revealed marked peripheral blood eosinophilia on several occasions before transplantation. Despite reduction in immunosuppression and treatment with albendazole and ivermectin, the patient developed another episode of Escherichia coli bacteremia. He died 3 months post-transplant from pulmonary and neurological complications. DIAGNOSIS: Strongyloides hyper-infection. DISCUSSION: Strongyloides hyper-infection syndrome is known to occur in immunocompromised patients, but it has only been reported once in a lung transplant recipient. This case illustrates the importance of screening for parasitic infections before transplantation in patients with marked eosinophilia, especially among immigrants from countries in which Strongyloides is endemic. Hyper-infection syndrome may appear years after infection in the context of immunosuppression or immunodeficiency. This case also highlights the association between Strongyloides hyper-infection and bacteremia with enteric organisms.

PRÉSENTATION DU CAS: Un homme de 63 ans ayant subi une transplantation du poumon gauche à cause d'une pneumopathie en phase terminale à la fois restrictive et obstructive a développé des infiltrats pulmonaires persistants et une bactériémie à Gram négatif récurrente après la transplantation. À la coloration de Papanicolau, le liquide du lavage bronchoalvéolaire a révélé un nématode compatible avec des larves de Strongyloides stercoralis le cinquantième jour après la transplantation. Même si la sérologie du Strongyloides effectuée après la transplantation était négative, une analyse rétrospective de son dossier médical a révélé une éosinophilie sanguine périphérique marquée à plusieurs occasions avant la transplantation. Malgré la diminution de l'immunodépression et un traitement à l'albendazole et à l'ivermectine, le patient a contracté une nouvelle bactériémie à Escherichia coli. Il est décédé de complications pulmonaires et neurologiques trois mois après la transplantation. DIAGNOSTIC: Hyperinfestation à Strongyloides. DISCUSSION: On sait que le syndrome d'hyperinfestation à Strongyloides se déclare chez des patients immunodéprimés, mais il n'a été signalé qu'une fois chez un transplanté du poumon. Ce cas démontre l'importance du dépistage d'infections parasitaires avant la transplantation chez des patients atteints d'éosinophilie marquée, notamment chez des immigrants de pays où le Strongyloides est endémique. Le syndrome d'hyperinfestation peut se manifester des années après l'infection en cas d'immunodépression ou d'immunodéficience. Ce cas fait également ressortir l'association entre l'hyperinfestation à Strongyloides et la bactériémie causée par des organismes entériques.

Invasive aspergillosis and endocarditis.

INTRODUCTION: Aspergillusfumigatus can cause a systemic infection called invasive aspergillosis causing pulmonary and extra-pulmonary damage. Aspergillus endocarditis (AE) is a relatively rare disease but can be life-threatening. CASE REPORTS: We report here on five cases of endocarditis due to invasive aspergillosis: a 58-year-old man receiving immunosuppressive medication following a kidney graft, a 58-year-old man undergoing chemotherapy for chronic lymphocytic leukaemia, a 55-year-old man receiving corticosteroids for IgA vasculitis, a 52-year-old HIV-infected woman under no specific treatment and a 17-year-old boy under immunosuppressive therapy for auto-immune chronic neutropenia. DISCUSSION: Aspergillus accounts for 25-30% of fungal endocarditis and 0.25% to 8.5% of all cases of infectious endocarditis. Aspergillus endocarditis results from invasion of the lung arterioles by hyphae and blood dissemination. It is associated with a very high mortality rate (42-68%). Diagnosing Aspergillus endocarditis is mainly problematic because blood cultures are almost always negative, and fever may be absent. Immunosuppression, haematological malignancies, recent cardiothoracic surgery, negative blood cultures with endocarditis and/or systemic or pulmonary emboli are predictors of AE. In the setting of endocarditis, some clinical characteristics may raise early suspicions of aspergillosis rather than a non-fungal agent: no fever, vegetations affecting the mitral valve, non-valve or aortotomy sites, aortic abscess or pseudo-aneurysm. The identification of invasive aspergillosis is based on a chest CT scan, microscopy/culture or other serological and molecular tests. The treatment of Aspergillus endocarditis requires triazole antifungal drugs, and frequently additional surgical debridement. CONCLUSION: Aspergillus endocarditis is rare but is associated with a very high mortality rate. Knowledge of its predictive factors and key clinical features can help to differentiate aspergillosis from non-fungal endocarditis and may enable improved survival rates.

Cryptosporidiosis and microsporidiosis as causes of diarrhea in kidney and/or pancreas transplant recipients.

INTRODUCTION: Gastrointestinal disorders in solid organ recipients may have various origins including cryptosporidiosis and microsporidiosis. The prevalence of these infections is poorly known in solid organ transplant (SOT) patients in industrialized countries. METHODS: We prospectively assessed the infectious causes of diarrhea in SOT patients. Secondary objectives were to gain further insight into the main characteristics of cryptosporidiosis, and to assess risk factors for this infection. All adult kidney and/or pancreas recipients presenting with diarrhea and admitted to our facility between May 1, 2014 and June 30, 2015 were enrolled. A stool sample was analyzed using a standardized protocol including bacteriological, virological, and parasitological investigations. Data related to clinical symptoms, immunosuppression, and environmental potential risk factors were collected through a self-administered questionnaire and computerized medical records. RESULTS: Out of 73 enrolled patients, 36 had infectious diarrhea (49.3%). Viruses ranked first (17/36), followed by parasites and fungi (11/17). Cryptosporidiosis was the most common parasitic disease (n=6 patients). We observed four microsporidiosis cases. The estimated prevalence of cryptosporidiosis and microsporidiosis in this cohort was 3.7 and 2.40/00, respectively. No significant risk factor for cryptosporidiosis or microsporidiosis, neither environmental nor immunological, could be evidenced. CONCLUSION: Both cryptosporidiosis and microsporidiosis represent a significant cause of diarrhea in kidney transplant recipients.

[Organ Donation from the Perspective of Certified Anesthesiology Nurses]. / Organspende aus Sicht der diplomierten Anästhesiepflege.

Organ Donation from the Perspective of Certified Anesthesiology Nurses Abstract. Abstract: The certified experts in anesthesia nursing are responsible for a holistic process of anesthesia care. This includes demanding, high-quality and safety-oriented service in the field of anesthesia and pain medicine for patients of all age groups and health conditions. Depending on their institution and working environment, these experts will also deliver patient care in the case of organ donation and/or transplantation. In this highly specialized field, certified anesthesiology nurses take on many coordi-native, planning, preparatory and technical tasks in addition to direct patient care. Long-term success of organ donation and transplantation requires an extraordinarily close and careful cooperation between many different disciplines and professions. Only in this way will patients benefit from optimal results, i.e. gain many additional years with high quality of life.

[Caracterization of HLA allo-immunization and clinical impact in transfusion and organ transplantation]. / Caractérisation de l'allo-immunisation anti-HLA et impact clinique en transfusion et en transplantation d'organe.

Allo-immunizations against HLA antigens are known to be deleterious in transfusion and organ transplantation. The development of new tests based on solid phase assays for screening and identification of HLA antibodies in particular those using Luminex® bead based technology has completely changed the way of allo-immunization monitoring because of their extreme sensitivity. They allow a better characterization of these antibodies, identification of acceptable antigens and the use of virtual cross-matches. All these new possibilities improve the managing of patients before and after platelets transfusion or organ transplantation. However, this technology displays some limits that should be known in order to interpret correctly the results. Beside these bead based assays, cellular cross-matches based on Complement Dependent Cytotoxicity (CDC) and flow cytometry are still used and useful in organ transplantation since beads are produced in vitro and do not reflected exactly what happens physiologically. Moreover, differences of sensitivity between these methods make results interpretation and decision making difficult in some cases.

An overview of EU and USA intestinal transplant current activity.

AIM OF THE STUDY: To report the current activity of intestinal transplantation in Europe (EU) and Unites States of America (USA), underlining outcomes in the last 5 years and discussing possible trends. PATIENTS AND METHODS: Data review of results was performed through analysis of ITR and UNOS registries, Eurotransplant and newsletter transplant reports, congress abstracts, international published literature, personal communications and hospital web sites. RESULTS: The absence in Europe of a sole organization collecting donors and the presence of many low-volume centers (less than 5 cases/year) makes the difference with USA: in the last 5 years (2010-2014), 222 intestinal/multivisceral transplants have been performed in EU countries (most of them in the UK), while in USA, the number of transplants achieved 634 procedures in the same period of time. Waiting list mortality remains unacceptable in both continents. Improved short-term results, with over 80% survival at 1 year, have been achieved in the busiest transplant centers likely due to immune-induction agents, more recently to innovative cross match strategies and optimizing organ allocation, but long term outcomes are still inferior to other organ transplants. Most long-term survivors were reintegrated to society with self-sustained socioeconomic status. The economic burden for the society is high and related costs are different between USA and EU (and inside Europe between member state's health-care systems), but cost-effectiveness for intestinal transplantation still needs to be proved. CONCLUSION: Overall intestinal transplantation continues to develop in EU and USA together with surgical and medical rehabilitation of patients affected by short gut syndrome.

Predictive patterns of sensory evoked potentials in comatose brain injured patients evolving to brain death.

OBJECTIVE: To assess whether Somatosensory Evoked Potentials (SEPs), recorded within 24h after ICU admission, are reliable predictors of brain death (BD) in comatose patients with acquired brain injury of various aetiologies. METHODS: SEPs were classified as absent (A), pathological (P), and normal (N). Considering SEP recordings from both hemispheres, 6 patterns were identified: NN, NP, PP, NA, AP, and AA. The final endpoint was BD. RESULTS: Of the 203 patients included in the study, 70 (34%) evolved toward BD. The survival analysis indicated that the combination of SEP patterns in a two-graded scale (grade 1: NN-NP-PP-NA, and grade 2: AP-AA), allowed for prediction of BD with the best accuracy. This aggregation predicted BD with a sensitivity of 75.7% (CI: 64-84), a specificity of 76.6% (CI: 68-83), a positive predictive value of 64.2% (CI: 53-74) and a negative predictive value of 84.3% (CI: 77-90) in overall patients, and with a sensitivity of 75.0% (CI: 63-84), a specificity of 84.9% (CI: 75-90), a positive predictive value of 77.5% (CI: 63-88) and a negative predictive value of 84.3% (CI: 74-91) when excluding cardiac arrest. CONCLUSION: It is worth including SEPs, in association with other investigations and clinical signs, in prognostic scores of BD. The early identification of patients at high risk of evolving towards BD could help physicians to optimise management.

Is brain computed tomography combined with somatosensory evoked potentials useful in the prediction of brain death after cardiac arrest?

BACKGROUND: Brain death (BD) in coma after cardiac arrest (CA) is difficult to predict. Basal ganglia gray matter/white matter (GM/WM) ratio density and somatosensory evoked potentials (SEPs) may differentiate patients evolving toward BD. METHODS: We used SEPs and brain computed tomography (CT) after coma onset, within the first 24hours. RESULTS: Of the 160 patients included in the study, 22 (14%) evolved toward BD. SEP patterns predicted BD (ROC area=0.82, P<0.0001). The combination of SEP patterns, bilaterally absent (AA) and absent on one hemisphere and pathological on the other (AP), predicted BD with a sensitivity of 100% and a specificity of 62.3%, with a positive likelihood ratio of 2.65. The GM/WM ratio predicted BD (ROC area=0.68, P=0.01). A GM/WM ratio <1.07 had a sensitivity of 30.4%, a specificity of 94.9%, and a positive likelihood ratio of 6.27. The combination of SEP and CT findings did not increase the prediction of BD. CONCLUSION: SEPs and brain CT within 24hours predicted BD after CA. Severe SEP findings (SEP patterns: AA, AP) identified a subset of patients in whom BD could occur. Brain CT (GM/WM ratio in basal ganglia) predicted an early evolution toward BD with high specificity but lower sensitivity.

[Pneumocystosis in non-HIV-infected immunocompromised patients]. / Pneumocystose chez les patients immunodéprimés non infectés par le VIH.

Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected patients differs from AIDS-associated pneumocystosis in mostly two aspects: diagnosis is more difficult, and prognosis is worse. Hence, efforts should be made to target immunocompromised patients at higher risk of pneumocystosis, so that they are prescribed long-term, low-dose, trimethoprime-sulfamethoxazole, highly effective for pneumocystosis prophylaxis. Patients at highest risk include those with medium and small vessels vasculitis, lymphoproliferative B disorders (chronic or acute lymphocytic leukaemia, non-Hodgkin lymphoma), and solid cancer on long-term corticosteroids. Conversely, widespread use of prophylaxis in all patients carrier of inflammatory diseases on long-term corticosteroids is not warranted. The management of pneumocystosis in non-AIDS immunocompromised patients follows the rules established for AIDS patients. The diagnosis relies on the detection of P. jiroveci cyst on respiratory samples, while PCR does not reliably discriminate infection from colonization, in 2015. High-doses trimethoprim-sulfamethoxazole is, by far, the treatment of choice. The benefit of adjuvant corticosteroid therapy for hypoxic patients, well documented in AIDS patients, has a much lower level of evidence in non-HIV-infected patients, most of them being already on corticosteroid by the time of pneumocystosis diagnosis anyway. However, based on its striking impact on morbi-mortality in AIDS patients, adjuvant corticosteroid is recommended in hypoxic, non-HIV-infected patients with pneumocystosis by many experts and scientific societies.

[The educational website Dermaguard to prevent the incidence of skin cancer after transplantation]. / Die edukative Website Dermaguard zur Prävention von Hautkrebs nach Organtransplantation.

Solid organ transplant recipients are highly susceptible to skin cancer. The major driving factors are immunosuppressive medication and ultraviolet light. Appropriate sun protection markedly reduces the development of skin cancer. Skin cancer recognized at an early stage can reliably be cured, and fatal outcomes can be prevented. The aim of this work is to educate organ transplant recipients and health care professionals involved in their care, to increase awareness of skin cancer in this high-risk population and thus to optimize the long-term outcome of patients with skin cancer. Our newly developed website provides free access to various educational materials, including leaflets, presentations and interactive elements using edutainment.

Les patients ayant eu une transplantation d'organe sont à risque accru de développer un/des cancer(s) de la peau. Les facteurs favorisants sont principalement les médicaments immunosuppresseurs et le rayonnement UV. L'utilisation appropriée d'un écran solaire peut réduire la survenue de cancers de la peau. La détection précoce d'un cancer de la peau permet un traitement adéquat et une réduction de la mortalité. Malheureusement, de nombreux patients ne sont pas suffisamment conscients de ce risque qui nécessite la mise en œuvre de mesures de protection solaire. L'objectif de ce document est d'informer les transplantés d'organe et le personnel soignant afin d'augmenter leur connaissance des risques de cancer de la peau et d'améliorer la prévention, la prise en charge et la survie des patients. Un site web a été créé à cet effet, permettant un libre accès aux sources d'informations telles que brochures et présentations, en plus d'un contenu interactif divertissant.