Radioimmunotherapy combined with maintenance anti-CD20 antibody may trigger long-term protective T cell immunity in follicular lymphoma patients.

Growing evidence suggests that the patient's immune response may play a major role in the long-term efficacy of antibody therapies of follicular lymphoma (FL). Particular long-lasting recurrence free survivals have been observed after first line, single agent rituximab or after radioimmunotherapy (RIT). Rituximab maintenance, furthermore, has a major efficacy in prolonging recurrence free survival after chemotherapy. On the other hand, RIT as a single step treatment showed a remarkable capacity to induce complete and partial remissions when applied in recurrence and as initial treatment of FL or given for consolidation. These clinical results strongly suggest that RIT combined with rituximab maintenance could stabilize the high percentages of patients with CR and PR induced by RIT. While the precise mechanisms of the long-term efficacy of these 2 treatments are not elucidated, different observations suggest that the patient's T cell immune response could be decisive. With this review, we discuss the potential role of the patient's immune system under rituximab and RIT and argue that the T cell immunity might be particularly promoted when combining the 2 antibody treatments in the early therapy of FL.

Clinical predictors for Legionella in patients presenting with community-acquired pneumonia to the emergency department.

BACKGROUND: Legionella species cause severe forms of pneumonia with high mortality and complication rates. Accurate clinical predictors to assess the likelihood of Legionella community-acquired pneumonia (CAP) in patients presenting to the emergency department are lacking. METHODS: We retrospectively compared clinical and laboratory data of 82 consecutive patients with Legionella CAP with 368 consecutive patients with non-Legionella CAP included in two studies at the same institution. RESULTS: In multivariate logistic regression analysis we identified six parameters, namely high body temperature (OR 1.67, p < 0.0001), absence of sputum production (OR 3.67, p < 0.0001), low serum sodium concentrations (OR 0.89, p = 0.011), high levels of lactate dehydrogenase (OR 1.003, p = 0.007) and C-reactive protein (OR 1.006, p < 0.0001) and low platelet counts (OR 0.991, p < 0.0001), as independent predictors of Legionella CAP. Using optimal cut off values of these six parameters, we calculated a diagnostic score for Legionella CAP. The median score was significantly higher in Legionella CAP as compared to patients without Legionella (4 (IQR 3-4) vs 2 (IQR 1-2), p < 0.0001) with a respective odds ratio of 3.34 (95%CI 2.57-4.33, p < 0.0001). Receiver operating characteristics showed a high diagnostic accuracy of this diagnostic score (AUC 0.86 (95%CI 0.81-0.90), which was better as compared to each parameter alone. Of the 191 patients (42%) with a score of 0 or 1 point, only 3% had Legionella pneumonia. Conversely, of the 73 patients (16%) with > or =4 points, 66% of patients had Legionella CAP. CONCLUSION: Six clinical and laboratory parameters embedded in a simple diagnostic score accurately identified patients with Legionella CAP. If validated in future studies, this score might aid in the management of suspected Legionella CAP.

Manipulating sex ratio to increase population growth: the example of the Lesser Kestrel

Small or decreasing populations call for emergency actions like, for example, captive breeding programs. Such programs aim at rapidly increasing population sizes in order to reduce the loss of genetic variability and to avoid possible Allee effects. The Lesser Kestrel Falco naumanni is one of the species that is currently supported in several captive breeding programs at various locations. Here, we model the demographic and genetic consequences of potential management strategies that are based on offspring sex ratio manipulation. Increased population growth could be achieved by manipulating female conditions and/or male attractiveness in the captive breeders and consequently shifting the offspring sex ratio towards more female offspring, which are then used for reintroduction. Fragmenting populations into wild-breeding and captive-breeding demes and manipulating population sex ratio both immediately increase the inbreeding coefficient in the next generation (i.e. decrease N-e) but may, in the long term, reduce the loss of genetic variability if population growth is restricted by the number of females. We use the Lesser Kestrel and the wealth of information that is available on this species to predict the long-term consequences of various kinds of sex-ratio manipulation. We find that, in our example and possibly in many other cases, a sex-ratio manipulation that seems realistic could have a beneficial effect on the captive breeding program. However, the possible long-term costs and benefits of such measures need to be carefully optimized.

Accès des patients agés aux urgences: evolution démographique et perspectives médico-ethiques [Access of elderly patients in the emergency department: demographic evolution and ethical perspectives].

Due to actual demographic evolution, emergency departments have to face a dramatic increase in admissions of elderly people. The peculiar medical and socio-demographic characteristics of these old patients emphasize the need of specific decision processes and resources allocation. An individual-based approach, related to significant ethical values, should allow better diagnostic and therapeutic attitudes. Such a way to admit, evaluate and treat older patients implies an active collaboration with patients and their relatives, but also with all medical interveners, including in particular primary care physicians.

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism.

Background:Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown.Methods:IUGR was induced through maternal dexamethasone infusion (100 μg/kg during last gestational week) in rats. Maternal supplementation with bLf (0.85% in food pellet) was provided during both gestation and lactation. Pup growth was monitored, and Pup brain metabolism and gene expression were studied using in vivo (1)H NMR spectroscopy, quantitative PCR, and microarray in the hippocampus at postnatal day (PND)7.Results:Maternal bLf supplementation did not change gestational weight but increased the birth body weight of control pups (4%) with no effect on the IUGR pups. Maternal bLf supplementation allowed IUGR pups to recover a normalized weight at PND21 (weaning) improving catch-up growth. Significantly altered levels of brain metabolites (γ-aminobutyric acid, glutamate, N-acetylaspartate, and N-acetylaspartylglutamate) and transcripts (brain-derived neurotrophic factor (BDNF), divalent metal transporter 1 (DMT-1), and glutamate receptors) in IUGR pups were normalized with maternal bLf supplementation.Conclusion:Our data suggest that maternal bLf supplementation is a beneficial nutritional intervention able to revert some of the IUGR-induced sequelae, including brain hippocampal changes.

Helicopter rescue operations involving winching of an emergency physician.

OBJECTIVE: We sought to study the epidemiologic and medical aspects of alpine helicopter rescue operations involving the winching of an emergency physician to the victim. METHODS: We retrospectively reviewed the medical and operational reports of a single helicopter-based emergency medical service. Data from 1 January 2003 to 31 December 2008 were analysed. RESULTS: A total of 921 patients were identified, with a male:female ratio of 2:1. There were 56 (6%) patients aged 15 or under. The median time from emergency call to helicopter take-off was 7 min (IQR = 5-10 min). 840 (91%) patients suffered from trauma-related injuries, with falls from heights during sports activities the most frequent event. The most common injuries involved the legs (246 or 27%), head (175 or 19%), upper limbs (117 or 13%), spine (108 or 12%), and femur (66 or 7%). Only 81 (9%) victims suffered from a medical emergency, but these cases were, when compared to the trauma victims, significantly more severe according to the NACA index (p<0.001). Overall, 246 (27%) patients had a severe injury or illness, namely, a potential or overt vital threat (NACA score between 4 and 6). A total of 478 (52%) patients required administration of major analgesics: fentanyl (443 patients or 48%), ketamine (42 patients or 5%) or morphine (7 patients or 1%). The mean dose of fentanyl was 188 micrograms (range 25-750, SD 127). Major medical interventions such as administration of vasoactive drugs, intravenous perfusions of more than 1000 ml of fluids, ventilation or intubation were performed on 39 (4%) patients. CONCLUSIONS: The severity of the patients' injuries or illnesses along with the high proportion of medical procedures performed directly on-site validates emergency physician winching for advanced life support procedures and analgesia.

A road map toward a globally harmonized approach for occupational health surveillance and epidemiology in nanomaterial workers

OBJECTIVE: Few epidemiological studies have addressed the health of workers exposed to novel manufactured nanomaterials. The small current workforce will necessitate pooling international cohorts. METHOD: A road map was defined for a globally harmonized framework for the careful choice of materials, exposure characterization, identification of study populations, definition of health endpoints, evaluation of appropriateness of study designs, data collection and analysis, and interpretation of the results. RESULTS: We propose a road map to reach global consensus on these issues. The proposed strategy should ensure that the costs of action are not disproportionate to the potential benefits and that the approach is pragmatic and practical. CONCLUSIONS: We should aim to go beyond the collection of health complaints, illness statistics, or even counts of deaths; the manifestation of such clear endpoints would indicate a failure of preventive measures.

Screening for post-traumatic stress disorder (PTSD) in a psychiatric emergency setting

Background and Objectives: (i) to assess the prevalence of PTSD in a psychiatric emergency setting by means of a diagnostic instrument and to compare it with PTSD-prevalence of a clinically evaluated, historical sample; and (ii) to assess psychiatric residents' perception of the systematic use of this diagnostic instrument. Methods: A consecutive sample of patients (N = 403) evaluated for a psychiatric emergency was assessed with the module J (PTSD) of the MINI, the historical sample (N = 350), assessed by chart review, consisted of consecutive patients of the same setting evaluated one year prior to the study period. Residents' perceptions were assessed by means of a focus group. Results: While in only 0.57% of the historical sample (N = 350) a diagnosis of PTSD was recorded, 20.3% (N = 64) of the patients assessed with the diagnostic instrument (N = 316) qualified for a diagnosis of PTSD. Higher prevalence rates were observed in refugees and those without legal residency status (50%); patients from countries with a recent history of war (47.1%); those with four (44.4%) or three psychiatric co-morbidities (35.3%); migrants (29.8%) and patients without professional income (25%). Residents felt that the systematic use of the tool was not adequate in the psychiatric emergency setting for various reasons (e.g.: not suitable for a first or single consultation, negative impact on the clinical evaluation). Conclusions: The study confirms that PTSD is underdiagnosed in the psychiatric emergency setting. To improve the situation, targeted screening or educational and institutional strategies are needed.

Percutaneous drainage versus emergency cholecystectomy for the treatment of acute cholecystitis in critically ill patients: does it matter?

Background The aim if this study was to compare percutaneous drainage (PD) of the gallbladder to emergency cholecystectomy (EC) in a well-defined patient group with sepsis related to acute calculous/acalculous cholecystitis (ACC/AAC).Methods Between 2001 and 2007, all consecutive patients of our ICU treated by either PD or EC were retrospectively analyzed. Cases were collected from a prospective database. Percutaneous drainage was performed by a transhepatic route and EC by open or laparoscopic approach. Patients' general condition and organ dysfunction were assessed by two validated scoring systems (SAPS II and SOFA, respectively). Morbidity, mortality, and long-term outcome were systematically reviewed and analyzed in both groups.Results Forty-two patients [median age = 65.5 years (range = 32-94)] were included; 45% underwent EC (ten laparoscopic, nine open) and 55% PD (n = 23). Both patient groups had similar preoperative characteristics. Percutaneous drainage and EC were successful in 91 and 100% of patients, respectively. Organ dysfunctions were similarly improved by the third postoperative/postdrainage days. Despite undergoing PD, two patients required EC due to gangrenous cholecystitis. The conversion rate after laparoscopy was 20%. Overall morbidity was 8.7% after PD and 47% after EC (P = 0.011). Major morbidity was 0% after PD and 21% after EC (P = 0.034). The mortality rate was not different (13% after PD and 16% after EC, P = 1.0) and the deaths were all related to the patients' preexisting disease. Hospital and ICU stays were not different. Recurrent symptoms (17%) occurred only after ACC in the PD group.Conclusions In high-risk patients, PD and EC are both efficient in the resolution of acute cholecystitis sepsis. However, EC is associated with a higher procedure-related morbidity and the laparoscopic approach is not always possible. Percutaneous drainage represents a valuable intervention, but secondary cholecystectomy is mandatory in cases of acute calculous cholecystitis.

Tests diagnostiques rapides (TDR): la panacée pour le praticien [Rapid diagnostic tests (RDT): the cure-all for the practitioner?].

Many rapid diagnostic tests (RDT) for the diagnosis of infectious diseases have been developed over the last 20 years. These allow (1) administering a treatment immediately in case of a potentially fatal disease, (2) prescribing a specific rather than presumptive treatment, (3) quickly introducing measures aimed at interrupting the transmission of the disease, (4) avoiding useless antibiotic treatments and (5) implementing a sequential diagnostic strategy to avoid extensive investigations. Using the example of malaria, a new strategy that includes a RDT as first-line emergency diagnostic tool and, when negative, delayed microscopy at the laboratory opening time is implemented in Lausanne since 1999. This strategy has been shown to be safe. Each TDR has its own characteristics that imperatively need to be known by the practitioner if he/she wants to use it in a rational way.

Regulation of protective immunity against Leishmania major in mice.

Resolution of lesions induced by Leishmania major in mice results from the development of Th1 responses. Cytokines produced by Th1 cells activate macrophages to a parasiticidal state. The development of Th2 responses in mice from a few strains underlies susceptibility to infection. Cytokines produced by Th2 cells exacerbate the development of lesions because of their deactivating properties for macrophages. This murine model of infection has provided significant insight into the mechanisms intrinsic to the differentiation of disparate CD4+ T cell subsets in vivo in animals from different genetic backgrounds.