Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial.

Infections remain the leading cause of death after major burns. Trace elements are involved in immunity and burn patients suffer acute trace element depletion after injury. In a previous nonrandomized study, trace element supplementation was associated with increased leukocyte counts and shortened hospital stays. This randomized, placebo-controlled trial studied clinical and immune effects of trace element supplements. Twenty patients, aged 40 +/- 16 y (mean +/- SD), burned on 48 +/- 17% of their body surfaces, were studied for 30 d after injury. They consumed either standard trace element intakes plus supplements (40.4 micromol Cu, 2.9 micromol Se, and 406 micromol Zn; group TE) or standard trace element intakes plus placebo (20 micromol Cu, 0.4 micromol Se, and 100 micromol Zn; group C) for 8 d. Demographic data were similar for both groups. Mean plasma copper and zinc concentrations were below normal until days 20 and 15, respectively (NS). Plasma selenium remained normal for group TE but decreased for group C (P < 0.05 on days 1 and 5). Total leukocyte counts tended to be higher in group TE because of higher neutrophil counts. Proliferation to mitogens was depressed compared with healthy control subjects (NS). The number of infections per patient was significantly (P < 0.05) lower in group TE (1.9 +/- 0.9) than in group C (3.1 +/- 1.1) because of fewer pulmonary infections. Early trace element supplementation appears beneficial after major burns; it was associated with a significant decrease in the number of bronchopneumonia infections and with a shorter hospital stay when data were normalized for burn size.

Low-dose radiotherapy (2x2 Gy) in indolent lymphoma

Dans la prise en charge des maladies oncologiques, la priorité est évidemment d'assurer le contrôle de la maladie (soit le taux de récidive local et la survie globale), surtout lorsque celle-ci est diagnostiquée tôt, à un stade précoce. Cependant, lorsque la maladie est plus avancée et que ce contrôle ne peut être assuré de façon raisonnable, l'accent de la prise en charge est surtout axé sur le confort du patient. Le principe est de fournir à celui-ci, dans la mesure du possible, une qualité de vie acceptable, avec notamment des douleurs bien contrôlées.Dans le cadre de ce travail de thèse, nous nous sommes intéressés à la prise en charge palliative des lymphomes non hodgkiniens (LNH) de bas grade. La survie de ces patients peut être relativement longue (de 5 à 10 ans selon les séries), cependant, le traitement est rarement à visée curative, contrairement aux lymphomes de haut grade, dont la survie est bien moindre, mais avec une chance de guérison après un traitement intensif.Plusieurs études cliniques, à la fois prospectives et rétrospectives, ont démontré l'intérêt d'une irradiation à faible dose {2x2 Gy) lors d'atteintes tymphomateuses à l'origine de symptômes gênants (douleurs, compression par une masse, dyspnée, entre autres). Etant donné la facilité d'administration de ce traitement (seulement 2 séances de radiothérapie sont nécessaires), et sa quasi absence de survenue d'effets secondaires avec cette faible dose totale (4 Gy), nous avons voulu y apporter une contribution suisse.Notre étude rétrospective a permis d'inclure 43 patients entre le CHUV et les HUG. Les résultats que nous avons obtenus sont également dans la ligne des autres études parues, avec un excellent contrôle local, soit un soulagement rapide et durable des symptômes dans la majorité des cas.Nous espérons que ce travail de thèse, publié sous forme d'un article dans « International Journal of Radiation Oncology, Biology, Physics », permettra une prise en charge plus optimale des ces patients en leur apportant un traitement facile à administrer, efficace, sans effets secondaires dans la majorité des cas, et pouvant être répété un grand nombre de fois si nécessaire.

La programmmation foetale de la dysfonction vasculaire pulmonaire chez la souris : rôle des mécanismes épigénétiques = Fetal programming of pulmonary vascular dysfunction in mice : role of epigenetic mechanisms

Rapport de synthèseDes événements pathologiques survenant pendant la période foetale prédisposent la descendance aux maladies cardiovasculaires systémiques. Il existe peu de connaissances au sujet de la circulation pulmonaire et encore moins quant aux mécanismes sous-jacents. La sous-alimentation maternelle pendant la grossesse peut représenter un modèle d'investigation de ces mécanismes, parce que chez l'animal et l'homme elle est associée à une dysfonction vasculaire systémique chez la progéniture. Chez le rat, la diète restrictive pendant la grossesse induit une augmentation du stress oxydatif dans le placenta. Les dérivés de l'oxygène sont connus pour induire des altérations épigénétiques et peuvent traverser la barrière placentaire. Nous avons dès lors spéculé que chez la souris la diète restrictive pendant la grossesse induit une dysfonction vasculaire pulmonaire chez sa progéniture qui serait liée à un mécanisme épigénétique.Pour tester cette hypothèse, nous avons examiné la fonction vasculaire pulmonaire et la méthylation de l'ADN pulmonaire à la fin de 2 semaines d'exposition à l'hypoxie chez la progéniture de souris soumises à une diète restrictive pendant la grossesse et des souris contrôles. Nous avons trouvé que la vasodilatation endothélium-dépendante de l'artère pulmonaire in vitro était défectueuse, et que l'hypertension pulmonaire et l'hypertrophie ventriculaire droite induites par l'hypoxie in vivo étaient exagérées chez la progéniture de souris soumises à une diète restrictive pendant la grossesse. Cette dysfonction vasculaire pulmonaire était associée avec une altération de la méthylation de l'ADN pulmonaire. L'administration d'inhibiteurs de la déacétylase des histones, le Butyrate et la Trichostatine-A à la progéniture de souris soumises à une diète restrictive pendant la grossesse a normalisé la méthylation de l'ADN et la fonction vasculaire pulmonaire. Finalement, l'administration du nitroxyde Tempol aux mères durant la diète restrictive pendant la grossesse a prévenu la dysfonction vasculaire et la dysméthylation chez la progéniture.Ces découvertes démontrent que chez la souris la sous-alimentation pendant la gestation induit une dysfonction vasculaire chez la progéniture qui est causée par un mécanisme épigénétique. Il est possible qu'un mécanisme similaire soit impliqué dans la programmation foetale de la dysfonction vasculaire chez les humains.

Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial.

BACKGROUND: Multislice CT (MSCT) combined with D-dimer measurement can safely exclude pulmonary embolism in patients with a low or intermediate clinical probability of this disease. We compared this combination with a strategy in which both a negative venous ultrasonography of the leg and MSCT were needed to exclude pulmonary embolism. METHODS: We included 1819 consecutive outpatients with clinically suspected pulmonary embolism in a multicentre non-inferiority randomised controlled trial comparing two strategies: clinical probability assessment and either D-dimer measurement and MSCT (DD-CT strategy [n=903]) or D-dimer measurement, venous compression ultrasonography of the leg, and MSCT (DD-US-CT strategy [n=916]). Randomisation was by computer-generated blocks with stratification according to centre. Patients with a high clinical probability according to the revised Geneva score and a negative work-up for pulmonary embolism were further investigated in both groups. The primary outcome was the 3-month thromboembolic risk in patients who were left untreated on the basis of the exclusion of pulmonary embolism by diagnostic strategy. Clinicians assessing outcome were blinded to group assignment. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00117169. FINDINGS: The prevalence of pulmonary embolism was 20.6% in both groups (189 cases in DD-US-CT group and 186 in DD-CT group). We analysed 855 patients in the DD-US-CT group and 838 in the DD-CT group per protocol. The 3-month thromboembolic risk was 0.3% (95% CI 0.1-1.1) in the DD-US-CT group and 0.3% (0.1-1.2) in the DD-CT group (difference 0.0% [-0.9 to 0.8]). In the DD-US-CT group, ultrasonography showed a deep-venous thrombosis in 53 (9% [7-12]) of 574 patients, and thus MSCT was not undertaken. INTERPRETATION: The strategy combining D-dimer and MSCT is as safe as the strategy using D-dimer followed by venous compression ultrasonography of the leg and MSCT for exclusion of pulmonary embolism. An ultrasound could be of use in patients with a contraindication to CT.

The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism.

Background: The Pulmonary Embolism Rule-out Criteria (PERC) rule is a clinical diagnostic rule designed to exclude pulmonary embolism (PE) without further testing. We sought to externally validate the diagnostic performance of the PERC rule alone and combined with clinical probability assessment based on the revised Geneva score. Methods: The PERC rule was applied retrospectively to consecutive patients who presented with a clinical suspicion of PE to six emergency departments, and who were enrolled in a randomized trial of PE diagnosis. Patients who met all eight PERC criteria [PERC(-)] were considered to be at a very low risk for PE. We calculated the prevalence of PE among PERC(-) patients according to their clinical pretest probability of PE. We estimated the negative likelihood ratio of the PERC rule to predict PE. Results: Among 1675 patients, the prevalence of PE was 21.3%. Overall, 13.2% of patients were PERC(-). The prevalence of PE was 5.4% [95% confidence interval (CI): 3.1-9.3%] among PERC(-) patients overall and 6.4% (95% CI: 3.7-10.8%) among those PERC(-) patients with a low clinical pretest probability of PE. The PERC rule had a negative likelihood ratio of 0.70 (95% CI: 0.67-0.73) for predicting PE overall, and 0.63 (95% CI: 0.38-1.06) in low-risk patients. Conclusions: Our results suggest that the PERC rule alone or even when combined with the revised Geneva score cannot safely identify very low risk patients in whom PE can be ruled out without additional testing, at least in populations with a relatively high prevalence of PE.

Hyponatremia and short-term outcomes in patients with acute pulmonary embolism

BACKGROUND: Hyponatremia, a marker of neurohormonal activation, is associated with poor outcomes in acute cardiorespiratory diseases such as myocardial infarction, right and left ventricular heart failure, and pneumonia. The prognostic value of hyponatremia in patients with acute pulmonary embolism (PE) is unknown. We sought to assess whether hyponatremia at presentation was associated with mortality and hospital readmission in patients hospitalized with PE. METHODS: We studied patient discharges with a primary diagnosis of PE from 185 acute care hospitals in Pennsylvania (1/2000-11/2002). We defined hyponatremia as a serum sodium level ≤135 mmol/l, measured at the time of patient presentation. The study outcomes were 30-day all-cause mortality and hospital readmission. We used random-intercept logistic regression to examine the association between hyponatremia and mortality. We adjusted for baseline patient (race, insurance, severity of illness using the Pulmonary Embolism Severity Index) and hospital characteristics (region, hospital size and teaching status). We used the same approach to examine the association between hyponatremia and readmission among patients who were discharged alive. RESULTS: Among 13,728 patient discharges with PE, 2907 (21.1%) had hyponatremia at the time of presentation. Patients with hyponatremia were older (P<0.001) and more likely to have a history of cancer (P<0.001), heart failure (P<0.001), or chronic lung disease (P=0.002) than patients without hyponatremia. Patients with hyponatremia had a higher unadjusted cumulative 30-day mortality (15.2% vs 8.0%;P<0.001) and readmission rate (15.9% vs 11.8%; P< 0.001) than patients without hyponatremia (Figure). After adjustment for race, insurance, severity of illness, and hospital factors, hyponatremia was associated with a significantly greater odds of death (OR 1.71, 95% CI: 1.50-1.95) and hospital readmission (OR 1.29, 95% CI: 1.14-1.46). CONCLUSIONS: In this large, statewide sample of unselected patients with acute PE, hyponatremia was relatively common and was an independent predictor of short-term mortality and hospital readmission. Given that sodium is a low-cost, easily available laboratory parameter, it may be potentially useful in risk-stratifying patients with PE.

Primary Sjögren's syndrome (SS) and malignant lymphoma. A retrospective cohort study of 55 patients with SS.

The aim of this study was to assess the prevalence of malignant lymphomas in patients with long-standing primary Sjögren's syndrome (pSS). We retrospectively studied a cohort of 55 patients with pSS over a mean follow-up period of 12 years. Five patients (9%) developed malignant lymphoma. The interval between the diagnoses of SS and lymphoma ranged from four to 12 years (mean = 6.5 years). The lymphoma arose in the lymph nodes in two cases, the parotid gland in one case, the lacrimal gland in one case, and the lung in one case. All five cases were B-cell low-grade lymphomas. Among our SS patients, those with extraglandular manifestations and/or a mixed cryoglobulin were at increased risk for lymphoma development. Secondary lymphoma carried a poor prognosis in our study. Three of the six SS patients who died during the follow-up period had lymphoma.

Lymphome et grossesse: quelle prise en charge [Management of lymphoma and pregnancy]

With an incidence of 1/6000 pregnancies, per-partum lymphoma is a rare but not an exceptional event, which gynaecologists and family physicians can be confronted in the course of their career The diagnosis, without a peripheral adenopathy, can be challenging because symptoms, such as fatigue or dyspnoea, can easily be attributed to the pregnancy. Although the therapeutic management is complex, because it involves the mother and her embryos, it can be optimal in the majority of cases. The multidisciplinary management, with modern diagnostic and therapeutic approaches, greatly improved the prognosis of these young women. Today, it generally allows the safekeeping of the baby with an outcome for the mother identical to the one observed in the population at large.

Neurodevelopmental outcome of neonates treated with nitric oxide for persistent pulmonary hypertension

Persistent pulmonary hypertension of the newborn (PPHN) is a life threatening condition associated with an increased risk of neurodevelopmental impairment. The recommended treatment for this condition is inhaled nitric oxide (iNO) and has been used in our Neonatal Intensive Care Unit since 1998. We prospectively offered neurodevelopmental follow-up to children treated with iNO for PPHN, including extensive neurological evaluation, developmental/cognitive evaluation at 18 months and 3.5-5 years old, and evaluated the rate of severe and moderate handicap and normal neurodevelopmental outcome, compared to a control group and the literature. Population consisted of 29 patients treated only with iNO, born between 01.01.1999 and 31.12.2005 (study group), and 32 healthy term infants born in 1998 in our maternity (control group). During those seven years, 65 infants were admitted in our Unit with PPHN, of whom 40 were treated with iNO alone. 34 children survived (85%) and were offered neurodevelopmental follow-up, 7 children were lost to follow-up due to various reasons. 22 children were examined at the age of 18 months (76%) with a rate of moderate handicap of 22% (2 with expressive language delay, 2 with difficult behavior, and 1 child with moderate hearing loss), and a rate of major handicap of 4.5% (1 child with cerebral palsy due to perinatal stroke, and moderate hearing loss). At preschool age, 17 (50%) were examined, the rate of moderate handicap was 22% (4 borderline intelligence, 1 hearing loss), and the rate of major handicap was 4.5% (one child with cerebral palsy and hearing loss), compared to 26.9% and 0% in the control group. Mean developmental quotient at 18 months was 100.3 ± 8.7 (control group 118.3), and at preschool age mean cognitive indices were within normal limits for the 2 tests performed at 3.5 or 5 years (108 ± 21, 94.4 ± 17). Most of the children with a less favorable neurodevelopmental outcome suffered from birth asphyxia (ruptured uterus, placental abruption, maternal hypotension, diabetic cardiomyopathy), and notably, the 2 children with sensorineural hearing loss both suffered from severe hypoxic-ischemic enkelopathy. Treatment with iNO was not the direct cause of the neurodevelopmental impairments observed in children treated for PPHN.

Malignant lymphoma cells induce tolerance of T cells

Inhibitory receptors are involvedin the induction of T cell dysfunctionand exhaustion in chronic viral infectionsand in tumors. In the presentstudy, we analyzed the expressionpattern of 3 different inhibitory receptors(PD-1, Lag-3, 2B4) in a murine Bcell lymphoma model. Furthermore,we functionally characterized CD8+T cells expressing inhibitory receptorsfor cytokine production and proliferation.Expansion and secretion ofpro-inflammatory cytokines of CD8+T cells from lymphoma-bearing E-myc mice were significantly reducedcompared to the healthy controls.Similarly, expansion and effectorfunction of CD8+ TCR transgenic(p14) Tcells specific for the gp-33 antigenof lymphocytic choriomeningitisvirus (LCMV) was reduced inlymphoma-bearing E-myc mice afteractivation with LCMV. The functionalimpairment of CTL in the presenceof lymphoma was reversible aftertransfer to naive C57BL/6 recipients.In vitro co-culture experimentsrevealed that the proliferation ofanti-CD3-activated CD8+ T cellsfrom WT mice was significantly inhibitedby CD19+ lymphoma cellsfrom E-myc mice, whereas no inhibitionwas observed after co-culturewith normal B cells. Supernatants ofin vitro cultured lymphoma B cellsand blood sera from lymphoma-bearingE-myc mice significantly reducedT cell proliferation in vitro, ascompared to supernatants from normalB cells cultures or sera of healthyanimals. These experiments indicatethat the lymphoma B cells inactivateCTL by a soluble factor. Expressionanalysis of different important immunologicalcytokines revealed that themacrophage migration inhibitory factor(MIF) is selectively overexpressedin malignant B cells. This finding wasconfirmed by analyzing MIF proteinin culture supernatants and in celllysates. Therefore, lymphoma B cellsmay reduce T cell function and suppresslymphoma surveillance by secretionof MIF.

Les calcifications pulmonaires métastatiques [Pulmonary metastatic calcification].

INTRODUCTION: The lung is the organ most frequently involved by metastatic calcification. This condition is probably under-diagnosed, the patients usually being asymptomatic. This article summarizes the current knowledge concerning pulmonary metastatic calcification. BACKGROUND: The pathogenesis of pulmonary metastatic calcification is not well known, but it involves phosphate-calcium balance, renal function and pH. The most frequently encountered aetiologies are hyperparathyroidism, neoplastic bony lesions, and renal failure. The definitive diagnosis is achieved by histology, radiological examinations being insensitive. The clinical manifestations are various and can include a pulmonary restrictive syndrome, diffusion abnormalities, hypoxaemia and respiratory failure. The latter can be severe and influence the prognosis adversely: 19 cases of fatal pulmonary metastatic calcification have been reported. The treatment is aetiological and symptomatic. VIEWPOINT: The prognostic factors for a poor outcome of this potentially lethal condition remain to be determined. The management of asymptomatic patients is also uncertain. CONCLUSIONS: Pulmonary metastatic calcification is a rare condition of complex pathogenesis. The clinical manifestations are varied, ranging from asymptomatic to severe, even fatal.

Mortality, complications and loss of pulmonary function after pneumonectomy vs. sleeve lobectomy in patients younger and older than 70 years.

Retrospective single institution analysis of all patients undergoing sleeve lobectomy or pneumonectomy between 2000 and 2005. Seventy-eight patients underwent pneumonectomy (65 patients <70 years, 13 patients >70 years) and 69 sleeve lobectomy (50 patients <70 years, 19 patients >70 years). Pre-existing co-morbidity, surgical indication and induction therapy was similarly distributed between treatment by age-groups. In patients <70 years, pneumonectomy and sleeve lobectomy resulted in a 30-day mortality of 3% vs. 0 and an overall complication rate of 26% vs. 44%, respectively. In patients >70 years, pneumonectomy and sleeve lobectomy resulted in a 30-day mortality of 15% vs. 0 and an overall complication rate of 23% vs. 32%. In both age groups, pneumonectomy was associated with more airway complications (NS) and a significantly higher postoperative loss of FEV(1) than sleeve lobectomy (P<0.0001, P<0.03). Age per se did not influence the loss of FEV(1) and DLCO for a given type of resection. Sleeve lobectomy may have a therapeutic advantage over pneumonectomy in the postoperative course of elderly patients.

Pulmonary thrombembolism as cause of death on unenhanced postmortem 3T MRI.

OBJECTIVES: To investigate unenhanced postmortem 3-T MR imaging (pmMRI) for the detection of pulmonary thrombembolism (PTE) as cause of death. METHODS: In eight forensic cases dying from a possible cardiac cause but with homogeneous myocardium at cardiac pmMRI, additional T2w imaging of the pulmonary artery was performed before forensic autopsy. Imaging was carried out on a 3-T MR system in the axial and main pulmonary artery adapted oblique orientation in situ. In three cases axial T2w pmMRI of the lower legs was added. Validation of imaging findings was performed during forensic autopsy. RESULTS: All eight cases showed homogeneous material of intermediate signal intensity within the main pulmonary artery and/or pulmonary artery branches. Autopsy confirmed the MR findings as pulmonary artery thrombembolism. At lower leg imaging unilateral dilated veins and subcutaneous oedema with or without homogeneous material of intermediate signal intensity within the popliteal vein were found. CONCLUSIONS: Unenhanced pmMRI demonstrates pulmonary thrombembolism in situ. PmMR may serve as an alternative to clinical autopsy, especially when consent cannot be obtained. KEY POINTS: ? Postmortem MRI (pmMRI) provides an alternative to clinical autopsy ? Fatal pulmonary thrombembolism (PTE) can now be diagnosed using postmortem MRI (pmMRI). ? Special attention has to be drawn to the differentiation of postmortem clots.