[Assessment of the Internal Medicine Multidisciplinary Team meetings at the Grenoble University Hospital]. / Évaluation des réunions de concertation pluridisciplinaire de médecine interne au CHU Grenoble Alpes.

INTRODUCTION: Multidisciplinary team (MDT) meetings purpose is to optimize the disease management regarding state of science. While cancer MDT has proven its effectiveness, this is not yet the case with internal medicine MDT. METHODS: We performed a descriptive monocentric retrospective study. Data were collected from 247 MDT meeting reports which took place at the Grenoble University Hospital over a 5 years period. We investigated the data related to patient, MDT features, and decision-making process and reporting. Discussions were classified as diagnostic and/or therapeutic. RESULTS: Three specialties, among which at least internal medicine, attended to meetings. While 12% of cases were considered as "complex", a specialist opinion was required in 18% of diagnostic discussions. With regards to therapeutic discussions, 35% were supported by guidelines, 50% of therapeutic implementation involved innovating and expensive drugs, with off-label prescription in 75% of them. The decision-making process was described in 6% of the reports. Treatment recommendations were actually implemented in 72% of the patients. CONCLUSION: MDT meetings in Internal medicine meets a real need of physicians, in the ultimate interest of the patient. A prospective analysis would be interesting for a better definition of the evaluation criteria of these MDT meetings, meeting the physicians' needs, in patient management best interest. Prospective analyses are needed to better define MDT meetings assessment criteria.

[Severe MDA5 dermatomyositis associated with cancer and controlled by JAK inhibitor]. / Dermatomyosite à anticorps anti-MDA5 sévère associée à un cancer et contrôlée par inhibiteur de JAK.

Dermatomyositis is an idiopathic inflammatory myopathy with various clinical and serological profiles, including poor prognosis forms for which aggressive immunosuppressive treatment is warranted. We report the case of a 60-year-old woman referred to our hospital for an anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis (MDA5 DM) with rapidly progressive interstitial pneumonia, typical cutaneous features and muscular impairment. Treatment with high-dose methylprednisolone, cyclophosphamide and gamma globulin was performed, but the patient remained corticodependant. Blood detection of positive interferon signature justified the administration of an anti-JAK1/2, leading to the clinical remission and the regression of the interferon signature. After 12 months of follow up, a small cell carcinoma was discovered, raising the question of a paraneoplastic syndrome, for which the most recent datas are quite reassuring for this kind of MDA5 DM. The presentation of this case is of twofold interest: describing one of the first report of successful treatment of intereronopathy MDA5 DM with ruxolitinib and highlighting an association with a cancer, which is not expected for this phenotype of dermatomyositis.

[Acute respiratory distress syndrome as the presenting manifestation of an antisynthetase syndrome]. / Pneumopathie aiguë sévère révélatrice d'un syndrome des anticorps antisynthétases.

The antisynthetase syndrome is a subgroup of idiopathic inflammatory muscle diseases. Its characteristics are interstitial lung disease, myositis, polyarthritis, mechanic's hand like cutaneous involvement, and the presence of antisynthetase antibodies (anti-Jo1). The lung disease is the presenting feature in 50% of cases. We report a patient with an antisynthetase syndrome, revealed by an acute respiratory distress syndrome. This patient was already followed-up for a scleroderma and presented a probable overlap syndrome. The disease course was favourable with anti-CD20 therapy.

[Amoebosis: May sexual transmission be an underestimated way of contamination?] / Amibiase : au cours de rapports sexuels, un mode de transmission sous-estimé ?

INTRODUCTION: Amoebiasis is a cosmopolitan disease and the third most deadly of parasitic diseases. Entamoeba histolytica is the only one to be pathogenic. Its transmission is not only related to the faecal peril but also sexual, with cases described among men who have sex with men. A case of unusual sexual transmission is described in this article, aiming to discuss the impact of these ways of transmitting amoebiasis on patient management. CASE REPORT: We describe the case of an amebic liver abscess in a 27-years-old man who did not travel in endemic areas. After patient interrogation, it seems that the contamination mode was sexual, related to a heterosexual relationship with a new female partner 4 months before the diagnosis. HIV and hepatitis B serologies were negative. CONCLUSION: The diagnosis of amoebiasis should be suspected in case of dysentery or liver abscess even if there is no history of travel in endemic areas or of sexual intercourse between men.

The changing pattern of Fusobacterium infections in humans: recent experience with Fusobacterium bacteraemia.

A retrospective study was conducted of 26 adult cases of fusobacterium bacteraemia that occurred between 1998 and 2003 at Center Hospitalier Universitaire de Grenoble, France. Most patients presented with pre-existing adverse medical conditions, including evolving malignant diseases (eight patients), recent surgery (four patients), and chronic organ failure (six patients). Only one patient presented with a classic Lemierre's syndrome. These results suggest an opportunistic pattern of modern fusobacterium infections.

An analysis of discrepancies in HLA phenotypes of cadaver donors in the united network for organ sharing registry.

BACKGROUND: HLA matching is an important component of the United Network for Organ Sharing algorithm for kidney allocation and is the primary factor in the mandatory sharing of kidneys that have zero HLA antigens mismatched with specific patients on the waiting list. An assessment of the HLA-A, -B, and -DR antigen discrepancy rate in the Organ Procurement and Transplantation Network database is desirable to judge the adequacy of the HLA typing data upon which the allocation program is based. METHODS: A subset of the Organ Procurement and Transplantation Network database, composed of 10,047 cadaver donor HLA phenotypes that have been repeated by laboratories affiliated with organ recipient centers, was analyzed for the overall rate of HLA phenotype discrepancy and for the type and frequency of discrepancies of the individual HLA antigen assignments. The United Network for Organ Sharing HLA antigen equivalences were applied to the data. RESULTS: Fourteen percent of 12,419 HLA typing comparisons were discrepant in at least one HLA antigen of six possible antigens per phenotype. Of a possible 74,514 individual HLA antigen assignments, 2.7% were discrepant. For African-American donors, the discrepancy rate was 5.1% as compared with 2.4% for Caucasian donors. The most frequent type of discrepancy was the assignment of an antigen blank versus a named antigen. CONCLUSIONS: The discrepancy rate is comparatively low and can be expected to improve as more laboratories adopt methods for HLA typing by DNA typing techniques. It is recommended that the HLA data be further reviewed by the laboratories for possible typographical errors and that centers review the UNOS listing of HLA antigen equivalences and encourage laboratories to split HLA antigens.

Prediction of donor-specific transfusion sensitization. I. A linear logistic model.

Using linear logistic regression, six factors were identified as important predictors of risk of DST sensitization in a group of 195 patients. Factors increasing the risk were: percent panel reactive antibody (PRA), previous transplants, and pregnancy; those decreasing the risk were HLA antigens matched, third-party blood transfusions, and Imuran administration. From this analysis, the magnitude of the effect of each factor on the risk of sensitization was obtained. An equation was then obtained that can be used to compute an estimated probability of sensitization (PS) for each patient. As a test of predictive ability of the model, the PS was calculated for 66 patients in an independent patient group. These observations were arranged according to the estimated probability and then divided into intervals of risk. Overall, for each interval, a very high level of agreement was found between the predicted and actual number of sensitized patients. A total of 16.13 patients were predicted to become sensitized and 17 actually did.

Two patterns of sensitization demonstrated by recipients of donor-specific transfusion. Limitations to control by Imuran.

Characteristics of the sensitization response to donor-specific transfusion (DST) have been studied in the context of the pretransfusion panel reactive antibody (PRA) status of the recipient. Two distinct patterns of response to DST and Imuran treatment have been found. In patients with one-haplotype-matched donors, the panel nonreactive patient (PRA less than 10%) has a 19% incidence of DST sensitization that is further reduced by Imuran treatment to 6%; antibodies are both anti-T cell and anti-B cells, are transient, and are specific to the mismatched HLA antigens of the blood donor. Panel-reactive patients (PRA greater than 10%) have a 56% incidence of DST sensitization; the antibodies appear within 2 weeks of the first transfusion, are anti-T cell, and are generally of broad specificity and persistent duration consistent with amplification of a previous antigenic exposure; Imuran seems to have little or no effect in reducing the incidence of sensitization in these panel-reactive patients. However, panel reactive patients whose PRA levels spontaneously fall to panel-nonreactive levels immediately prior to DST therapy have an exceedingly low (0-8%) incidence of sensitization with or without Imuran coverage.

Identification of high- and low-risk second kidney grafts.

The purpose of this study was to identify recipients who are at low or high risk of early cadaveric regraft failure by segregating results of the flow cytometric crossmatch (FCXM) test with previous graft survival time (PGST). Early immunologic kidney regraft failure was analyzed in 103 multicenter recipients by cross-stratifying FCXM negative/positive status with < or =3- and >3-month PGST. T cell and B cell cytotoxicity crossmatches were negative. All were tested retrospectively in the T cell FCXM and 60 of the 103 were also tested in the B cell FCXM. A positive T and B cell FCXM was defined as a mean channel shift of > or = 9 (256 channel log scale) or > or = 40 (1024 channel log scale) for pretransplant crossmatch serum above negative control serum. Recipients received triple immunosuppression therapy and limited-use antilymphocyte induction therapy. Early cadaveric regraft losses were biopsied. Comparably good rates of second kidney graft survival at 3 years were found among three ow risk subsets: 78% for 18 FCXM-positive patients with PGST >3 months, 78% for 49 FCXM-negative patients with PGST >3 months, and 84% for 19 FCXM-negative patients with PGST < or =3 months. in contrast, 53% 3-month and 44% 3-year regraft survival rates occurred in 17 high-risk FCXM-positive recipients with a PGST < or =3 months. The odds ratio for increased relative risk of early second graft loss was 4.5 (confidence interval: 1.32-1.67) for the high-risk versus low-risk subsets (P = 0.009). Within the high-risk subset, 56% (5 of 9) of those who were FCXM T negative B positive experienced early regraft loss. A positive B cell FCXM has an adverse clinical impact only for high-risk regraft recipients. Pretransplant panel reactive antibody levels, pregnancy, number of blood transfusions between grafts, repeat donor HLA mismatches, and regraft recipient HLA mismatches did not correlate with early regraft loss. We conclude that kidney regraft survival rates in low-risk recipients (PGST >3 months/FCXM negative or positive [T and/or B cell] and PGST < or = 3 months/FCXM negative) approach primary graft survival rates and justify retransplantation, but the rate in high-risk regraft candidates (PGST < or =3 months/FCXM positive T and/or B cell) suggests that retransplantation should be performed only with a negative FCXM.

HLA-DR antigens in Chinese-American families.

This paper contains results of a study on HLA-DR antigens in Chinese-American families. DR2, DR4, DRw9, and DRw6Y were the most common DR specificities encountered, and DR1 occurred with the lowest frequency. All recognized DR antigens were observed. The frequency of a blank allele was 6.4-12.8%. Weak serologic reactions with sera primarily of Caucasian origin were not infrequently observed. These findings suggested that ethnic-related antigens were present in this population. Two families showed segregation of a new serologic pattern based on polyspecific sera. The gene frequencies of the BfF allele and the GLO1 allele were low as compared to Caucasians. A method is described for improving the yield of viable B cells from frozen B-lymphocyte preparations.

Detection of panel-reactive anti-HLA class I antibodies by enzyme-linked immunosorbent assay or lymphocytotoxicity. Results of a blinded, controlled multicenter study.

A soluble HLA ELISA for the detection of anti-HLA class I IgG antibodies was developed and compared to complement-dependent microlymphocytotoxicity. ELISA plates were coated with a panel of sHLA class I antigens isolated from the culture supernatants of 46 different EBV-transformed phenotyped B-cell lines. After the incubation of the coated plates with test serum, bound antibodies were detected using a peroxidase-conjugated anti-human IgG antibody. Absorbance was read using an ELISA plate reader and assay results were analyzed by computer. Antibody specificities were determined by Fisher's exact test tail analysis. The reproducibility of ELISA assay results was evaluated in a blinded, controlled multicenter study. A total of 102 serum specimens from patients on waiting lists to receive kidney transplants were tested five times by ELISA in five different laboratories. The correlation coefficients (r) of %PRA values determined by ELISA ranged from 0.89 to 0.96, and the average agreement on qualitative assay results (antibody positive vs antibody negative) was 98%. Endpoint titration of several serum specimens demonstrated equivalent sensitivity of ELISA and microlymphocytotoxicity (using the anti-globulin antibody protocol). Most of the antibody specificities determined by ELISA were in agreement with specificities determined by microlymphocytotoxicity. To evaluate the correlation of ELISA and microlymphocytotoxicity (CDC) assay results the same 102 specimens were tested six times by CDC in five different laboratories. The interlaboratory correlation coefficient (r) of %PRA values determined by microlymphocytotoxicity ranged from 0.57 to 0.94, and the average agreement on qualitative assay results was 85%. A comparison of ELISA with microlymphocytotoxicity was performed using consensus microlymphocytotoxicity results. This showed a high correlation (r = 0.81) of %PRA values determined by ELISA and microlymphocytotoxicity. This demonstrates that the detection of anti-HLA class I antibodies by soluble HLA ELISA is a reliable alternative to microlymphocytotoxicity testing.

"Anti-idiotypic" antibodies to HLA in transiently sensitized DST patients.

To test the hypothesis whether "anti-idiotypic" antibodies (Ab2) were involved in the loss of sensitization following donor-specific blood transfusions (DST), we investigated nine potential kidney graft recipients who became transiently sensitized after DST. Inhibiting "anti-idiotypic" activity of post-DST sera was determined using a complement-dependent cytotoxicity inhibition assay. The follow-up after DST ranged from 9 to 66 months. The nine patients developed 12 different anti-HLA antibodies (Ab1). Inhibiting post-DST serum activity was found in relation to four of them, while enhancement of cell killing caused by post-DST sera was observed in relation to six anti-HLA antibodies. In two patients presenting with more than one anti-HLA antibody inhibition was found with only one of the antibodies, indicating that the blocking of Ab1 was specific for the respective antibody. Enhancement was associated with a significantly prolonged sensitization of the patients. On the average, 5.7 +/- 5.0 months were necessary before "anti-idiotypic" activity was developed after the loss of sensitization, whereas enhancement was found immediately thereafter. Testing by flow cytometry indicated that enhancing sera still contained subthreshold levels of Ab1. Our results indicate that DST can induce the development of "anti-idiotypic" antibodies following a short period of sensitization. This finding provides further evidence that anti-idiotypic antibodies might be relevant factors in the eventual disappearance of sensitization to HLA antigens.

Development of tolerance after haplocompatible T-depleted bone marrow transplantation.

We evaluated proliferative responses in mixed lymphocyte cultures (MLC) following bone marrow transplantation (BMT) in 14 recipients of T cell-depleted haplo-compatible parental marrow: 11 for the treatment of severe combined immunodeficiency (SCID), 2 for leukemia and 1 for Wiskott-Aldrich syndrome (WAS). We compared the results obtained in 9 SCID patients and 1 WAS patient with split chimerism (T cells of donor origin, B cells and monocytes of recipient origin) to 4 patients (2 SCID and 2 leukemias) who were full chimeras (T, B and monocytes of donor origin). In the full chimeras, as with the fresh donor PBMC, fresh donor T cells did not proliferate in the MLC to recipient non-T cells (E-). In this group there were no differences (p > 0.2) between the responses of engrafted T and fresh donor T to recipient E- cells. We found tolerance of engrafted donor T cells to residual mismatched T cell-depleted (E-) recipient cells in the split chimera group. In this group the engrafted T cells had low or no responses in MLC to HLA mismatched E- host cells compared with fresh donor cells (p < 0.001). In 3 of 8 split chimera patients that we tested the addition of small numbers (5000-10,000) of freshly isolated donor T cells, irradiated or not, resulted in a two fold increase in the engrafted T cell response to recipient E- cells. In contrast, in 3 of 3 full chimeras tested, the addition of fresh donor T cells had no demonstrable effect on the response of engrafted T cells to recipient E-.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful immunomodulation with intravenous gamma globulin and cyclophosphamide in an alloimmunized heart transplant recipient.

A highly human leukocyte antigen-sensitized heart transplant candidate underwent immunomodulation with intravenous gamma globulin and cyclophosphamide. His panel reactive antibody screen fell from 64% to 14%. He underwent successful orthotopic heart transplantation with a histoincompatible, T-cell cross-match-negative heart without the development of hyperacute rejection. The combination of intravenous gamma globulin and cyclophosphamide may be a simple and effective means to overcome the human leukocyte antigen-barrier in sensitized heart transplant candidates.

Heritable factors distinguish two types of alopecia areata.

Alopecia areata (AA) has been shown to be associated with the inheritance of HLA class II alleles. HLA-DQ3 appears to be the general susceptibility allele for AA. Patients with long-standing disease patterns, namely, longterm patchy AA and long-term alopecia totalis and alopecia universalis (AT/AU), can be differentiated by their particular HLA associations. Long-standing AT/AU patients have unique and highly significant associations with HLA antigens DR4, DR11, and DQ7. A complex of early onset, disease severity, family incidence, and associations with HLA DR antigens are characteristic of long-standing AT/AU as distinct from long-standing patchy AA.

[Chronic meningitis: aetiologies, diagnosis and treatment]. / Méningites chroniques : étiologies, diagnostic et thérapeutique.

PURPOSE: Chronic meningitis are very uncommon and account for less than 10% of all meningitis cases. Their symptoms are uncunth and there outcome is insidious. Therefore, they remain often unknown. There are only a few published reports on this disease, so diagnosis and therapeutic approachs are difficult. CURRENT KNOWLEDGE AND KEY POINTS: Positive chronic meningitis diagnosis is easy. However, determining the cause of chronic meningitis remains dilemma, as many infectious and noninfectious processes (including inflammatory, neoplastic or autoimmune aetiologies or as a result of a chemical exposure) can result in the chronic meningitis syndrome. In order to institute a pertinent treatment, sometimes urgently needed, diagnostic approach must be extremely rigourous and accutely orientated. Nevertheless, although extensive investigations, 30% of the aetiologies remain undetermined. Only two choices are left for the medical physician: an aggressive attitude based on complementary investigations or a contemplated therapy with a close clinical and biological control. On the other hand, when the patient's condition is quickly deterioring without a clear and proved aetiology, it is sometimes necessary to institute an empirical treatment, not always properly determined and sometimes contreversial. Besides, few reports on prognosis and outcome od idiopathic chronic meningitis have been published. FUTURE PROSPECTS AND PROJECTS: After a review of aetiologies and diagnostic investigations chronic meningitis, we propose a practical experience attitude about management and treatment of chronic meningitis. Thus, large-scale studies about the follow up chronic meningitis in long term, in particular those without aetiology, treated or no, should improve the outcome of this chronic syndrome.

[Thrombotic microangiopathy with anti-ADAMTS 13 antibodies revealing an acute Q fever]. / Micro-angiopathie thrombotique avec anticorps anti-ADAMTS 13 révélant une fièvre Q aiguë

INTRODUCTION: Q fever can commonly mimic systemic diseases, leading to several immunological manifestations. Thrombotic micro-angiopathies manifest as a spectrum of related disorders in the form of thrombocytopenic purpura and hemolytic uremic syndrome. CASE REPORT: We report a 77-year-old woman, who presented an acquired thrombotic microangiopathy with renal expression associated with the presence of anti-ADAMTS 13 antibodies, which occurred during an acute infection by Coxiella burnetii (acute Q fever). CONCLUSION: Auto-immune disorders are well-known in chronic or acute Q fever but to our knowledge, this is the first reported observation of thrombotic microangiopathy with anti-ADAMTS 13 antibodies.