Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

Astrocyte-neuron lactate transport is required for long-term memory formation.

We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation.

Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials.

The purpose of this study was to assess the outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (EGPA) enrolled in 2 prospective, randomized, open-label clinical trials (1994-2005), with or without Five-Factor Score (FFS)-defined poor-prognosis factors, focusing on survival, disease-free survival, relapses, clinical and laboratory findings, therapeutic responses, and factors predictive of relapse. Forty-four patients with FFS ≥ 1 were assigned to receive 6 or 12 cyclophosphamide pulses plus corticosteroids and the seventy-four with FFS = 0 received corticosteroids alone, with immunosuppressant adjunction when corticosteroids failed. Patients were followed (2005-2011) under routine clinical care in an extended study and data were recorded prospectively. Mean ± SD follow-up was 81.3 ± 39.6 months. Among the 118 patients studied, 29% achieved long-term remission and 10% died. Among the 115 patients achieving a first remission, 41% experienced ≥1 relapses, 26.1 ± 26.8 months after treatment onset, with 57% of relapses occurring when corticosteroid-tapering reached <10 mg/day. Treatment achieved new remissions in >90%, but relapses recurred in 38%. Overall survival was good, reaching 90% at 7 years, regardless of baseline severity. Age ≥65 years was the only factor associated with a higher risk of death during follow-up. The risk of relapse was higher for patients with anti-myeloperoxidase antibodies and lower for those with >3000 eosinophils/mm(3). Sequelae remained frequent, usually chronic asthma and peripheral neuropathy. In conclusion, EGPA patients' survival rate is very good when treatment is stratified according to the baseline FFS. Relapses are frequent, especially in patients with anti-myeloperoxidase antibodies and baseline eosinophilia <3000/mm(3).

Le triangle primaire : le père, la mère, le bébé

Préface de Daniel N. Stern - Préface d'Édith Goldbeter Merinfeld - Introduction à la deuxième édition - Comment aborder la famille - Le modèle familial de Lausanne: présentation générale - Typologie des alliances - Les fondements structuraux des alliances familiales - Les fondements dynamiques des alliances familiales - La petite enfance du processus triangulaire - Alliance de travail et interventions d'encadrement - Consultations avec des thérapeutes et des familles - Du développement du nourrisson à la dynamique - Le triangle primaire - Annexe A : Résultats du LTP - Annexe B : Consigne du jeu trilogique de Lausanne

KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients.

Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR) genes with protection from cytomegalovirus (CMV) replication after organ transplantation. Whether KIR-associated protection is operating in the context of primary infection, re-activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus at the time of transplantation with rates of CMV viremia in 517 heart (n=57), kidney (n=223), liver (n=165) or lung (n=72) allograft recipients reported to the Swiss Transplant Cohort Study. Across the entire cohort we found B haplotypes-which in contrast to A haplotypes may contain multiple activating KIR genes-to be protective in the most immunosuppressed patients (receiving anti-thymocyte globulin induction and intensive maintenance immunosuppression) (hazard ratio after adjustment for covariates 0.46, 95% confidence interval 0.29-0.75, P=0.002). Notably, a significant protection was detected only in recipients who were CMV-seropositive at the time of transplantation (HR 0.45, 95% CI 0.26-0.77, P=0.004), but not in CMV seronegative recipients (HR 0.59, 95% CI 0.22-1.53, P=0.28). These data indicate a prominent role for KIR-and presumably natural killer (NK) cells-in the control of CMV replication in CMV seropositive organ transplant recipients treated with intense immunosuppression.

Texte et contexte dans la communication

DES FRONTIERES ENTRE TEXTE ET CONTEXTE : POINTS DE VUE THEORIQUES - Sur la métacommunication / C. Sluzki - De l'amour du texte à l'amour du contexte / J. Cosnier - Le dialogue entre l'intra-psychique et l'interpersonnel : une perspective développmentale / D. Stern - Texte et contexte. La perspective thermodynamique / R. Fivaz - Une position constructiviste pour la thérapie familiale / L. Hoffman MICROPROCESSUS DANS LES CONVERSATIONS : POINTS DE VUE EMPIRIQUES ET DEVELOPPEMENTAUX - Le contrat comme relation. Une étude des cadres sociaux du consentement / M. Modak - Recherche sur les axiomes de "Une logique de la communication" / J. Beavin-Bavelas - Distance physique ou distance psychique ? Les formations corporelles parents-bébé comme contextes de l'autonomisation dans la famille / C. Gertsch-Bettens - L'encadrement parental dans le jeu à trois. Une recherche exploratoire d'inspiration systémique / A. Corbosz-Warnery - L'évolution des formations corporelles lors de thérapies familiales en fonction de l'alliance thérapeutique / S. Serpa-Rusconi, P.-A. Doudin - Genèse de la négociation interpersonnelle des conflits : point de vue pragmatique / H. Jisa LES RECONTEXTUALISATIONS EN THERAPIE FAMILIALE - De l'ajustement du cadre en thérapie familiale / F. Seywert, E. Fivaz Depeursinge - Les questions réflexives, source d'autoguérison / K. Tomm...[et al.] - Langage et changement. L'usage de paroles-clés en thérapie / J. Pereira - Texte et contexte en psychosomatique : des modèles réductionnistes à une épistémologie de la complexité / L. Onnis

Ornament of Reason : an annoted english translation of rMa bya Byang chub brtson 'grus's : commentary to the Mūlamadhyamakakārikā

The present work contains an English translation of the Ornament of Reason (Tib. dBu ma'i rtsa ba shes rab kyi 'grel ba thad pa'i rgyan), an influential 12th century Tibetan commentary to a classic of Indian Buddhism, Nàgàrjuna's Root of the Middle Way (Skt. Mûlamadhyamaka-kârikâ Tib. dBu ma'i rtsa ba shes rab ces bya ba). The author, rMa bya byang chub brtson 'grus's, was among the first Tibetans to explicitly align themselves with the philosophical project of the 7th century Indian Madhyamaka teacher, CandrakTrti. With his stern revision and transformative re-employment of the epistemological framework that CandrakTrti otherwise scorns, rMa bya was however to develop an original and highly influential Madhyamaka interpretation.¦rMa bya's "topical outline" (Tib. sa bead) of his commentary is contained in the first appendix to the translation. The second appendix contains a digitalized version of the Rumtek edition of rMa bya's commentary, cross-referenced to the page numbers of the translation. The annotations contain concise explanatory remarks and suggestions for further reading, as well as identifications of the passages that rMa bya cites.

Low incidence of severe respiratory syncytial virus infections in lung transplant recipients despite the absence of specific therapy.

BACKGROUND: Respiratory syncytial virus (RSV) infections in lung transplant recipients (LTRs) have been associated with significant morbidity and mortality. Immunoglobulins, ribavirin, and palivizumab are suggested treatments for both pre-emptive and therapeutic purposes. However, in the absence of randomized, placebo-controlled trials, efficacy is controversial and there is toxicity as well as cost concerns. METHODS: We retrospectively reviewed cases of lower respiratory tract RSV infections in adult LTRs. Diagnosis was based on clinical history, combined with a positive polymerase chain reaction (PCR) and/or viral cultures of bronchoalveolar lavage (BAL) specimens. RESULTS: Ten symptomatic patients were identified (7 men and 3 women, age range 28 to 64 years). All were hospitalized for community-acquired respiratory tract infections. Two patients had a concomitant acute Grade A3 graft rejection, and 1 patient had a concomitant bacterial pneumonia. Eight patients did not receive a specific anti-RSV treatment because of clinical stability and/or improvement at the time of RSV diagnosis. Only 2 patients (1 with Grade A3 allograft rejection and 1 requiring mechanical ventilation) received ribavirin and palivizumab. All patients recovered without complications and with no persistent RSV infection. However, bronchiolitis obliterans (BOS) staging worsened in 6 patients during the mean follow-up of 45 months. CONCLUSIONS: Our data suggest that mild RSV infections in LTRs might evolve favorably in the absence of specific anti-viral therapy. However, this observation needs confirmation in a large clinical trial specifically investigating the development of BOS in untreated vs treated patients.