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Background Fat mass distribution, especially in the abdominal visceral region, has been rarely evaluated in patients with PsA or psoriasis (PsO). Methods Patients with PsA and patients with PsO alone were evaluated and compared with control subjects (1:1 ratio in each patient group) matched for age, sex and BMI category. Body composition and fat distribution (android and visceral fat) were evaluated by DXA. Anthropometric measurements, disease activity and the systematic coronary risk evaluation (SCORE) cardiovascular risk were assessed. Metabolic parameters (insulin, homeostasis model assessment for insulin resistance), serum adipokines [total and high-molecular-weight adiponectin, leptin, resistin and retinol-binding protein-4 (RBP4)] were measured. Results Data for 52 patients with PsA and 52 patients with PsO and their respective paired controls were analysed. Android fat and visceral fat were found to be significantly higher in patients with PsO compared with their controls, while these measurements did not differ between patients with PsA and their controls. By multivariate analysis, after adjusting for age, sex and BMI, visceral fat was higher in PsO patients compared with PsA patients (P = 0.0004) and the whole group of controls (P = 0.0013). Insulin levels and HOMA-IR were increased in both PsA and PsO groups. High-molecular-weight/total adiponectin ratio was decreased in patients with PsO. RBP4 was significantly higher in both PsA and PsO patients. In patients with PsO, visceral fat strongly correlated with SCORE (r = 0.61). Conclusion Visceral fat accumulates more in PsO alone than in PsA. Visceral adiposity may be a more pressing concern in PsO relative to PsA. Trial registration The ADIPSO study (Évaluation du tissu ADIpeux et des adipokines dans le PSOriasis et le rhumatisme psoriasique et analyse de ses relations avec le risque cardiovasculaire) is a case–control study conducted in Besançon, France, and is registered on ClinicalTrials.gov under the number NCT02849795.

Extracellular vesicles (EVs) are active components of red blood cell (RBC) concentrates and may be associated with beneficial and adverse effects of transfusion. Elucidating controllable factors associated with EV release in RBC products is thus important to better manage the quality and properties of RBC units. Erythrocyte-derived EVs (EEVs) and platelet-derived EVs (PEVs) were counted in 1226 RBC units (administered to 280 patients) using a standardized cytometry-based method. EV size and CD47 and annexin V expression were also measured. The effects of donor characteristics, processing methods, and storage duration on EV counts were analyzed by using standard comparison tests, and analysis of covariance was used to determine factors independently associated with EV counts. PEV as well as EEV counts were higher in whole-blood–filtered RBC units compared with RBC-filtered units; PEV counts were associated with filter type (higher with filters associated with higher residual platelets), and CD47 expression was higher on EEVs in RBC units stored longer. Multivariate analysis showed that EEV counts were strongly associated with filter type (P < .0001), preparation, and storage time (+25.4 EEV/µL per day [P = .01] and +42.4 EEV/µL per day [P < .0001], respectively). The only independent factor associated with PEV counts was the residual platelet count in the unit (+67.1 PEV/µL; P < .0001). Overall, processing methods have an impact on EV counts and characteristics, leading to large variations in EV quantities transfused into patients. RBC unit processing methods might be standardized to control the EV content of RBC units if any impacts on patient outcomes can be confirmed. The IMIB (Impact of Microparticles in Blood) study is ancillary to the French ABLE (Age of Transfused Blood in Critically Ill Adults) trial (ISRCTN44878718).

Objective Taenia solium (Ts) cysticercosis is a neglected zoonotic disease particularly prevalent in Madagascar. Few data are available for children, current data mainly rely on antibody prevalence. We sought to determine the Ts-antigen seroprevalence–determining active cysticercosis—amongst school children from various cities in Madagascar (excluding the capital) and evaluated associated risk factors. Methods In seven cities in Madagascar, the presence of cysticercosis in school children (n = 1751) was investigated in 2007 using the B158/B60 antigen (Ag)-ELISA. Results The overall prevalence based on Ag detection was 27.7% [95%CI: 10–37%]. Risk factors associated with Ag positivity were age, biotope, altitude and annual average rainfall. Conclusion These results highlight the high prevalence of active cysticercosis in Madagascar among school children in an urban setting. This high prevalence as well as the risk factors unraveled point to the emergency to implement appropriate Public Health measure son a national scale.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

BackgroundThe strong geographic variations in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease are not solely related to variations in the population's needs, such as the prevalence of diabetes or the deprivation level. Inequitable geographic access to health services has been involved in different countries but never in France, a country with a generous supply of health services and where the effect of the variability of medical practices was highlighted in an analysis conducted at the geographic scale of districts. Our ecological study, performed at the finer scale of townships in a French area of 8,370,616 inhabitants, investigated the association between RRT incidence rates, socioeconomic environment and geographic accessibility to healthcare while adjusting for morbidity level and medical practice patterns.MethodsUsing data from the Renal Epidemiology and Information Network registry, we estimated age-adjusted RRT incidence rates during 2010-2014 for the 282 townships of the area. A hierarchical Bayesian Poisson model was used to examine the association between incidence rates and 18 contextual variables describing population health status, socioeconomic level and health services characteristics. Relative risks (RRs) and 95% credible intervals (95% CrIs) for each variable were estimated for a 1-SD increase in incidence rate.ResultsDuring 2010-2014, 6,835 new patients ≥18 years old (4231 men, 2604 women) living in the study area started RRT; the RRT incidence rates by townships ranged from 21 to 499 per million inhabitants. In multivariate analysis, rates were related to the prevalence of diabetes [RR (95% CrI): 1.05 (1.04-1.11)], the median estimated glomerular filtration rate at dialysis initiation [1.14 (1.08-1.20)], and the proportion of incident patients ≥ 85 years old [1.08 (1.03-1.14)]. After adjusting for these factors, rates in townships increased with increasing French deprivation index [1.05 (1.01-1.08)] and decreased with increasing mean travel time to reach the closest nephrologist [0.92 (0.89-0.95]).ConclusionThese data confirm the influence of deprivation level, the prevalence of diabetes and medical practices on RRT incidence rates across a large French area. For the first time, an association was found with the distance to nephrology services. These data suggest possible inequitable geographic access to RRT within the French health system.

Database set-up directly impacts the quality and viability of research data, and therefore is a crucial part of the quality of clinical research. Setting up a quality database implies following a strict data-management process. Too much collected information threatens the quality of the information required to achieve the objectives of the study. Therefore, the data that will be collected and managed have to be cautiously discussed and selected. Case report forms (CRF) are the tools the most frequently used to collect the data specified by the protocol. An informative and well-structured document simplifies database design and data validation. Key elements are about choice of sequential or thematic structuring, information and type of information that should be entered and the importance of data standards and coding guide. Final database must be structured with unique ID patient, with one record per subject or per measure. Specific information must be provided for each variable according to the database specifications. The quality of the results is directly related to the quality of the collected data. The CRF should then be completed as fully and accurately as possible. Data validation relies on three key points: the CRF completion guidelines, the Edit Checks process and the Data clarification process. Various open source or business software applications provide all functionalities to set up a clinical data base and CRF. The General Data Protection Regulation (GDPR) standardizes and strengthens the protection of personal data across the EU and for other country’s data being “processed” within the EU. The General principles include lawfulness, fairness and transparency, restricted use of data, data minimization, accuracy, limited storage, confidentiality and probity, and accountability.

International audience; Objectives: Several studies have reported that patients operated on for non-small cell lung cancer (NSCLC) are at high risk of second primary lung cancer (SPLC). However, widely varying estimates of this risk have been reported, with very few studies taking into account that these patients are at particularly high competing risk of death, due to recurrence of the initial disease and to comorbidities. Risk factor evaluation over time has significant repercussions on the post-surgery surveillance strategy offered for NSCLC. This study primarily sought to measure the risk of SPLC in a long-term follow-up series, using statistical methods considering competing risks of death.Materials and methods: The cumulative SPLC risk was estimated using the cumulative incidence of patients with completely resected Stage I-III NSCLC diagnosed between 2002 and 2015 based on the Doubs and Belfort cancer registry (France). A proportional sub-distribution hazard model (sdRH) was used to investigate factors associated with SPLC risk in the presence of competing risks.Results: Among the 522 patients, adenocarcinoma and Stage I or II disease accounted for 52.3% and 75.7% of patients, respectively. Overall, 84 patients developed SPLC (16.1%). The cumulative risk of SPLC was 20.2% at 10 years post-surgery (95% confidence interval [CI]: 15.3-23.2), and 25.2% (CI: 19.4-31.3) at 14 years post-surgery. On multivariate analysis, the SPLC risk was significantly higher in patients with postoperative thoracic radiotherapy (sdRH 2.79; 95% CI: 1.41-5.52; p = 0.003).Conclusion: This study using appropriate statistical methods to consider competing risks showed that after complete NSCLC resection, the cumulative incidence function of SPLC was high, with patients receiving postoperative thoracic radiotherapy at higher risk. These data support the need for life-long follow-up of patients who undergo NSCLC surgery, with the objective of screening for SPLC.

Background:current data regarding areal bone mineral density (aBMD) in patients with psoriasis (PsO) or psoriatic arthritis (PsA) are conflicting. Results on Trabecular Bone Score (TBS) in these patients are lacking. 3D-analysis of cortical and trabecular bone from hip DXA is a new method for non-invasive bone structure assessment, providing separate assessment of the cortical layer and trabecular macrostructure.Objectives:Case-control study (NCT02849795)Methods:52 PsO and 52 PsA cases (CASPAR criteria) were each paired to a control subject matched for age, sex and body mass index (BMI). aBMD measurements at (L2-4) lumbar spine (LS), femoral neck (FN) and total hip (TH) were performed using DXA, Lunar GE. TBS was calculated from antero-posterior L2-L4 BMD image using TBS iNsight V1.8 (Med-Imaps, Pessac, France). 3D-SHAPER software (version 2.10, Galgo Medical S.L, Barcelona, Spain) was used to derive a 3D analysis from the hip DXA scans.Results:LS and TH aBMD measurements did not differ between patients with PsO or PsA and their respective controls (Table 1). Left FN BMD was higher in patients with PsO compared to controls (p = 0.028), a difference not observed on the right FN. TBS was similar in PsA patients and their controls while decreased values were observed in PsO patients (p = 0.04). In 3D analysis, none of the parameters differed between patients with PsA and their controls. For patients with PsO, no difference was found with the controls for 3D-DXA parameters from the right FN, while total hip cortical surface BMD (sBMD) of the left FN was higher in PsO compared to their controls (p = 0.037). Similarly, cortical thickness (Cth) of the intertrochanteric and shaft regions of the left FN was also higher in PsO (p = 0.032 and p = 0.033). Finally, analysis by region (neck, intertrochanteric and shaft) showed higher values for cortical sBMD from each region of the left FN in the patients with PsO (all p Conclusion:Our results showed comparable aBMD, TBS and 3D proximal femur parameters in patients with PsA and controls. This supports that PsA population is not at increased risk of osteoporosis. In patients with PsO, while LS bone microarchitecture seems impaired, FN displayed better cortical parameters than the controls. Although these results seem marginal, they support the fact that patients with PsO are not at high risk for osteoporosis and hip fracture.Table 1.PsA: psoriatic arthritis; PsO: psoriasis; M: male; F: female; BMI: body mass index; PASI: psoriasis area severity index; CPDAI: composite psoriatic disease activity index; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; aBMD: areal bone mineral density; LS: lumbar spine; FN: femoral neck; TH: total hip; TBS: trabecular bone score; sBMD: surface bone mineral density; Cth: cortical thickness; quantitative data are mean ± standard deviation; * and ***: paired t test comparing patients with psoriatic arthritis or psoriasis alone to their respective controls; * p < 0.05; *** p < 0.001).PsAPsA controlsPsOPsO controlsN52525252Age (years)52.5 ± 11.752.8 ±11.150.5 ± 12.850.7 ± 12.8Sex (M/F)25/2725/2738/1436/16Menopausal women18 (67%)16 (59%)5 (36%)8 (50%)BMI (Kg/m2)27.4 ± 5.927.7 ± 6.428.4 ± 5.828.2 ± 6.1PASI2.4 ± 4.18.4 ± 4.9CPDAI7.4 ± 3.3ESR (mm/h)19.8 ± 16.6 ***6.9 ± 5.810.7 ± 8.8 ***6.4 ± 6.4CRP (mg/L)10.5 ± 11.7 ***3.9 ± 4.86.0 ± 9.04.7 ± 5.5LS (L2-4) aBMD (g/cm2)1.27 ± 0.491.20 ± 0.201.25 ± 0.211.20 ± 0.18FN aBMD (g/cm2) right0.96 ± 0.120.94 ± 0.140.98 ± 0.150.98 ± 0.15 left0.96 ± 0.160.93 ± 0.121.0 ± 0.14 *0.97 ± 0.13TH aBMD (g/cm2)1.01 ± 0.161.00 ± 0.151.11 ± 0.221.06 ± 0.21L2-L4 TBS1.32 ± 0.111.32 ± 0.151.23 ± 0.15 *1.30 ± 0.16Cortical sBMD (left FN) (mg/cm2)169.7 ± 32.8163.1 ± 29.7182.0 ± 31.0 *173.5 ± 30.3Cth intertrochanteric (left FN) (mm)1.91 ± 0.201.94 ± 0.182.03 ± 0.23 *1.97 ± 0.19Cth shaft (left FN) (mm)2.98 ± 0.313.01 ± 0.283.19 ± 0.36 *3.09 ± 0.29Cortical sBMD (left FN) (mg/cm2)neck135.27 ± 26.9129.67 ± 21.9140.29 ± 24.2 *134.6 ± 22.5intertrochanteric162.32 ± 31.1155.34 ± 29.3171.39 ± 29.1 *163.1 ± 28.9shaft cort269.20 ± 49.0257.12 ± 47.3286.2 ± 47.5 *272.7 ± 45.2Disclosure of Interests:ERIC TOUSSIROT: None declared., Renaud Winzenrieth Employee of: GALGO MEDICAL, maxime DESMARETS: None declared., Daniel Wendling: None declared., Francois AUBIN: None declared., Gilles DUMOULIN: None declared.

BACKGROUND Blood products use has increased in France between 2000 and 2011. To understand the reasons for this increase, data about transfused patients and transfusion practices needed to be updated. STUDY DESIGN AND METHODS A nationwide cross-sectional survey was performed with health care establishments. Diagnoses and indication for the transfusion, pretransfusion laboratory results, and blood products used were collected during a randomly selected 24-hour period in 2011. All patients who received at least one blood product delivered on the survey day were included. RESULTS A total of 10,794 blood products were requested for 4720 patients: 8688 red blood cell (RBC) units, 842 platelet (PLT) concentrates, and 1264 fresh-frozen plasma (FFP) units. Hematologic and cancer pathologies included 46% of transfused patients, 34% of the patients had transfusions in a surgical context, and 32.4% of transfused patients were receiving medication with an impact on transfusion. Nearly half of RBC transfusions were performed with hemoglobin levels of less than 8 g/dL. PLT transfusions for prophylactic indication were prescribed with PLT counts of less than 20 × 109 and 50 × 109/L in 56.9 and 86.6% of patients, respectively. RBCs and PLTs transfusion practices were in agreement with national guidelines. FFP units were involved in 8.0% of all prescriptions. Among these, 57.4% were requested in the context of an acute hemorrhage and 8.4% for plasma exchange. The median of FFP use (n = 2) in a nonsurgical context, excluding plasma exchange, suggests an insufficient dosing of FFP. CONCLUSION Except for insufficient FFP dosing per patient and limitations on assessment of indications for prescribing, transfusion practices were in agreement with national guidelines.

BACKGROUND Red blood cell (RBC) storage lesions and RBCs from females transfused into male recipients may have adverse effects on transfusion recipients' survival. We hypothesized that the effect of donor sex and the effect of age of blood on mortality would be most apparent in cardiac surgery patients. STUDY DESIGN AND METHODS Using data from French Blood Services and two university hospitals, we conducted a retrospective cohort study on cardiac surgery patients whose first transfusion occurred between 2007 and 2011. The age of blood and donor sex effects on 1-year survival were studied using Cox regression modeling, with time-dependent stratification on the number of RBCs and adjustments for the type of surgery and other products transfused. RESULTS Among the 2715 cardiac surgery patients, 85.1% were alive after 1 year. Age of blood and donor sex were associated with survival before adjustments (p

Background:Obesity is a leading comorbidity in both psoriasis (Pso) and psoriatic arthritis (PsA) and is associated with common metabolic complications and increased cardiovascular (CV) risk. Obesity is also a risk factor for the onset of these diseases. Body composition and fat distribution have been rarely evaluated in Pso and PsA.Objectives:In this study, we aimed to characterize the fat mass distribution in patients with Pso or PsA compared to a control group, with a special emphasis on the android/visceral region.Methods:case-control study (NCT02849795). Patients with Pso (plaque psoriasis) or PsA (CASPAR criteria) were evaluated. Each patient was paired to a control subject, recruited in the same outpatient population, and matched for sex, age and body mass index (BMI) category. Clinical assessment included BMI, anthropometric measurements (waist circumference, waist /hip ratio), disease activity (PASI for Pso, CPDAI for PsA) and the SCORE CV risk score. Laboratory parameters of inflammation (ESR, CRP, IL-6), lipid parameters (total cholesterol, LDL and HDL cholesterol, triglycerides), metabolic parameters (glycemia, insulin, HOMA), serum adipokines (total and high molecular weight [HMW] adiponectin, leptin, resistin and retinol binding protein 4 [RBP4]) were measured. Body composition (lean mass, fat mass) and fat distribution (android/gynoid regions and visceral fat) were evaluated (DEXA, Lunar GE, CoreScan). Our primary criteria was the fat mass in the android/visceral region. Comparisons between patients and controls were performed with paired t tests, between all groups with ANCOVA (adjusted for age, sex, and BMI category) and Tukey post-hoc tests. Pearson correlations between CV risk and fat mass were calculated within groups.Results:52 patients with Pso and 52 patients with PsA and their respective paired-control were evaluated. Total fat mass was increased in Pso but not in PsA. Android fat and visceral fat were found higher in Pso (pConclusion:visceral fat is increased in patients with Pso but not in PsA. In parallel, both groups showed an elevation of circulating RBP4. Patients with Pso and PsA were also characterized by metabolic disturbances as showed by the increase in HOMA, and specific adipokine changes. In the Pso group, visceral fat is associated with CV risk evaluated by SCORE. Weight control and reduction of fat mass, especially visceral fat mass, may thus be an important concern in patients with Pso and appears less relevant in PsA.Disclosure of Interests:None declared

Background A better knowledge of the connections between platelet concentrate (PC) characteristics and transfusion outcomes in day-to-day practice would help improve the selection process of the most appropriate PC. Study design and methods In this study of prophylactic platelet transfusions in patients with hematologic malignancies between 2002 and 2012, outcome criteria were corrected count increments (CCIs) and platelet transfusion intervals (TIs, in days). Studied characteristics were ABO matching status, platelet source, dose, storage duration, irradiation, washing, and transfusion sequence number (TSN). The analysis consisted of multivariable linear mixed-effects models with adjustments for patient diagnosis, sex, and type of treatment. Results Overall, 869 patients and 6662 platelet transfusions were analyzed. For each day after the second day of storage, the CCI and TI decreased by 0.88 and 0.06 day, respectively. Compared to ABO-identical, transfusion with major ABO-incompatible PCs decreased the CCI and TI by 0.79 and 0.21 day, respectively. Platelet washing reduced the CCI and TI by 2.28 and 0.24 day, respectively. There was no significant association between platelet source or irradiation and CCI or TI. TI increased as the platelet dose per kg increased. Both CCI and TI decreased as the TSN increased. Conclusion Transfusion outcomes were significantly related to several PC-related factors. Associations for ABO matching status and storage duration were stronger than previously reported. Taking into account such factors when selecting a PC for transfusion could be beneficial to the recipient.

Sickle cell disease (SCD) is a chronic inflammatory disease associated with multiple organ damage, chronic anemia, and infections. SCD patients have a high rate of alloimmunization against red blood cells (RBCs) following transfusion and may develop autoimmune diseases. Studies in mouse models have suggested that regulatory T cells (Treg) play a role in alloimmunization against RBC antigens. We characterized the phenotype and function of the Treg cell population in a homogeneous cohort of transfused SCD patients. We found that the distribution of Treg subpopulations differed significantly between SCD patients and healthy blood donors. SCD patients have a particular Treg phenotype, with strong CTLA-4 and CD39 expression and weak HLA-DR and CCR7 expression. Finally, we show that this particular phenotype is related to SCD rather than alloimmunization status. Indeed, we observed no difference in Treg phenotype or function in vitro using autologous feeder cells between strong and weak responders to alloimmunization.

HLA-matched bone marrow transplantation (BMT) is a cure for nonmalignant hematological disorders; however, rejection rates are high and correlate with the number of antecedent transfusions. Recently, using murine models, we reported that minor antigens (mHAs) in transfused leukoreduced red blood cell (RBC) or platelet units induce rejection of subsequent BMT. To study RBCs as an immunogen, we utilized transgenic donors that express a model mHA selectively on RBCs (HOD mouse). Transfusion of HOD blood did not induce BMT rejection of marrow that shared mHAs with the HOD RBCs. Similarly, no endogenous anti-HOD CD8(+) T-cell response was detected with antigen-specific tetramer reagents. Adoptively transferred OT-I T cells rapidly expanded after HOD blood transfusion; however, only a semi-effector phenotype was observed (tumor necrosis factor-α and interferon-γ secretion, but essentially no Granzyme B). After initial expansion, OT-I T cells contracted rapidly to very low levels. A similar trend was observed by in vivo CTL assay, with only transient lytic activity. Together, these data indicate that RBCs may not be the component of RBC units that induces BMT rejection, and suggest that contaminating platelets or leukocytes may be responsible.

When successful, human leukocyte antigen (HLA)–matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization to antigens on transfused blood may prime BMT rejection. Using a novel mouse model of red blood cell (RBC) transfusion and major histocompatibility complex–matched bone marrow transplantation, we report that transfusion of RBC products induced BMT rejection across minor histocompatibility antigen (mHA) barriers. It has been proposed that contaminating leukocytes are responsible for transfusion-induced BMT rejection; however, filter leukoreduction did not prevent rejection in the current studies. Moreover, we generated a novel transgenic mouse with RBC-specific expression of a model mHA and demonstrated that transfusion of RBCs induced a CD8+ T-cell response. Together, these data suggest that mHAs on RBCs themselves are capable of inducing BMT rejection. Cellular immunization to mHAs is neither monitored nor managed by current transfusion medicine practice; however, the current data suggest that mHAs on RBCs may represent an unappreciated and significant consequence of RBC transfusion.

A number of studies have demonstrated that non-neuronal acetylcholine can play a role in the regulation of T cell function. Recently, we reported that CD8(+) T cells, from mice with a targeted deletion of the M(1) muscarinic receptor, had a defect in differentiating into cytolytic T lymphocytes when stimulated in vitro. In the current report, we analyze the in vivo function of CD8(+) T cells from mice with targeted deletions of either M(1) or M(5) muscarinic receptors. M(1) or M(5) knockout mice were infected with either lymphocytic choriomeningitis virus or vesicular stomatitis virus. Expansion of anti-viral CD8(+) T cells was monitored by staining with tetramer reagents specific for the immunodominant peptides of the viruses. No defect in expansion of CD8(+) T cells was observed in either M(1) or M(5) knockout mice. The extent to which one can draw a generalized conclusion that M(1) and M(5) are not involved in anti-viral immunity depends upon issues of antigen strength, genetic background, induction of redundant receptors, and the potential for qualitative defects in the expanded CD8(+) T cells.

Purpose To compare graft survival between 3 10-year periods and according to surgical techniques performed in the last years. Design Cohort study. Methods setting: Regional center (Besancon University Hospital, France). patients: All 1132 patients operated on between 1983 and 2014. Graft and patient baseline characteristics, risk factors for failure, surgical procedures, and postoperative corneal status were collected. main outcome measures: Five-year survival rate in the whole cohort; 1-year and 3-year survival rates, respectively, among 88 patients with endothelial dystrophy (ED) or postoperative bullous keratopathy (PBK) operated on using endothelial lamellar keratoplasty (ELK) or penetrating keratoplasty (PK), and among 56 patients with keratoconus operated on using anterior lamellar keratoplasty (ALK) or PK. Results Between the 1983–1993 and the 2004–2014 periods, overall 5-year graft survival rate increased from 61.4% to 76.5% ( P = .0004). The main prognostic factors were preoperative diagnosis, graft endothelial density, and postoperative lens status. After adjusting for these factors, difference in survival rates was no longer significant (hazard ratio 0.90 for the second and 1.17 for the third period, compared to the first, P = .4191). Only 1 graft failure, after PK, occurred among the 56 patients with keratoconus. Among the 88 patients with ED or PBK, the 1-year graft survival was higher with PK (90.6%) than with ELK (60.8%) ( P = .0025) but no significance remained after adjustment (hazard ratio 3.22, P = .1304). Conclusions Despite numerous changes in graft procedures and surgical techniques, no noticeable improvement in graft survival was found during the last 30 years while taking into account other prognostic factors.

BACKGROUND: Most alloantigens on transfused red blood cells (RBCs) are weakly immunogenic, with only a 2 to 6 percent overall immunization rate even in patients receiving multiple transfusions. Although recipient genetics may contribute to responder and/or nonresponder status, in most cases HLA type does not predict humoral response to RBC antigens. In contrast, rates of alloimmunization do correspond to the underlying disease status of transfusion recipients, suggesting that acquired host factors may play an important role. In this context, it was hypothesized that the inflammatory status of a transfusion recipient would influence immunization to transfused RBCs. STUDY DESIGN AND METHODS: A novel murine model for alloimmunization to RBC antigens was developed with the mHEL mouse, which expresses hen egg lysozyme (HEL) as a model blood group antigen. Leukoreduced mHEL RBCs were transfused into wild-type recipient mice, and anti-HEL responses were monitored. To test the stated hypothesis, some recipient animals were injected with polyinosinic polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA molecule that induces viral-like inflammation. RESULTS: Similar to the immunogenicity of most RBC antigens in humans, transfusion of mHEL RBCs into uninflamed mice was only a weak immunogen. In contrast, poly(I:C)-treated mice had a significant increase in both the frequency and the magnitude of alloimmunization to the mHEL antigen. CONCLUSIONS: These findings demonstrate that recipient inflammation with poly(I:C) significantly enhances humoral immunization to transfused alloantigens in a murine model. Moreover, these data suggest that the inflammatory status of human transfusion recipients may regulate the immunogenicity of transfused RBCs.

PURPOSE: This longitudinal study aimed at comparing heart rate variability (HRV) in elite athletes identified either in 'fatigue' or in 'no-fatigue' state in 'real life' conditions. METHODS: 57 elite Nordic-skiers were surveyed over 4 years. R-R intervals were recorded supine (SU) and standing (ST). A fatigue state was quoted with a validated questionnaire. A multilevel linear regression model was used to analyze relationships between heart rate (HR) and HRV descriptors [total spectral power (TP), power in low (LF) and high frequency (HF) ranges expressed in ms(2) and normalized units (nu)] and the status without and with fatigue. The variables not distributed normally were transformed by taking their common logarithm (log10). RESULTS: 172 trials were identified as in a 'fatigue' and 891 as in 'no-fatigue' state. All supine HR and HRV parameters (Beta+/-SE) were significantly different (P

Background: Transfusion immunology research has traditionally focused on humoral immunity to RBC antigens, with study of CD4+ T cell and B cell responses. However, minor histocompatibility antigens (mHAs) on transfused RBCs in theory can also be cross-presented by recipient APCs to CD8+ T cells. This has clinical relevance in the context of transfusion patients who undergo transplantation, as several lines of evidence suggest that immunization to mHAs can lead to rejection of bone marrow and solid organ transplants. To test the hypothesis that mHAs on RBCs are capable of inducing immune responses through cross priming of CD8+ T cells, we created a novel transgenic mouse (HOD mouse), which expresses Ovalbumin (OVA) on RBCs but neither on leukocytes nor platelets. Methods: 1×107 OT-I splenocytes (TCR transgenic for the OVA derived peptide SIINFEKL presented by H-2Kb) were adoptively transferred into B6.Thy1.1 mice. 100μl of packed HOD RBCs from whole or leukoreduced blood were then transfused intravenously. Control mice were transfused with FVB whole blood (HOD mice are on a FVB background). Three to 4 days post transfusion the OT-I T cells were visualized in the spleen by staining with anti-CD8 antibody and the Kb/SIINFEKL tetramer. Proliferation was evaluated by CFSE dilution. The activation phenotype was studied by staining with antibodies against CD44 and CD62L. Expression of effector molecules was studied by staining with antibodies against CD107a, Granzyme B, IFNγ, and IL-2. Results: Compared to background analysis of OT-I T cells in control mice that received FVB blood, OT-I T cells in HOD recipients had a maximal expansion 24 fold higher in mice transfused with HOD leukoreduced blood (p=.0001), and 26 fold in mice transfused with HOD whole blood (p=.0672). Compared to naïve OT-I T cells, cross-primed OT-I T cells were CD44high, CD62Llow, CD107ahigh, suggesting activation and degranulation. Expression of IFNγ was also increased. However, cross-primed OT-I T cells were Granzyme Blow and did not have increased IL-2 expression. Lack of increased Granzyme B and IL-2 was not an artifact of the assay not working, as strong expression of both Granzyme B and IL-2 were detected in OT-I T cells stimulated with OVA in vitro. Discussion: Overall these results demonstrate that RBC antigens can be cross-primed into the MHC class I pathway by recipient APCs. However, activation of CD8+ T cells specific for the RBC antigen demonstrates differentiation into an incomplete effector phenotype. The effect is unlikely due to contaminating donor leukocytes in the transfused unit since OVA is not expressed by WBCs. Moreover, we did not see any differences in proliferation or activation phenotype between the mice transfused with whole blood and leukoreduced blood. Activation was not due to direct presentation by residual cells, as the HOD donor mice are on an FVB (H-2q) background and cannot directly present mHAs to the H-2b restricted OT-I T cells. The reason for an incomplete effector profile is unclear, but may be because transfused RBCs are a sterile introduction of foreign antigen. These results also suggest better leukoreduction is not a viable solution to the problem of transfusion-induced immunization to mHAs, as the antigen is coming from the RBCs themselves. Matching for relevant mHAs or use of immunomodulatory treatments may be required.