To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.
A review of English literature on childhood ...ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups.
With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia chromosome-like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL.
The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.
Background More attention should be paid to rare serious adverse events such as anaphylaxis to increase the safety of anesthesia. Objective To report the results of an 8-year survey of anaphylaxis ...during anesthesia in France. Methods Data from patients who experienced anaphylaxis between January 1, 1997, and December 31, 2004, were analyzed. Estimated incidences were obtained by combining this database with data from the French pharmacovigilance system by using a capture-recapture method. The number of patients exposed to the offending agents was obtained from data collected during the national survey of anesthesia practice. Results A total of 2516 patients was included. A diagnosis of IgE-mediated reaction was established in 1816 cases (72.18%). The most common causes were neuromuscular blocking agents (NMBAs; n = 1067; 58.08%), latex (n = 361; 19.65%), and antibiotics (n = 236; 12.85%). The median annual incidence per million procedures was higher for females 154.9 (5th-95th percentile, 117.2-193.1) than for males 55.4 (5th-95th percentile, 42.0-68.0). It reached 250.9 (5th-95th percentile, 189.8-312.9) for women in cases of allergic reactions to NMBAs. In children, a diagnosis of IgE-mediated reactions was obtained in 122 cases (45.9%). The most common causes were latex (n = 51; 41.8%), NMBAs (n = 39; 31.97%), and antibiotics (n = 11; 9.02%). In contrast with adults, no female predominance was observed. Conclusion The incidence of allergic reactions during anesthesia, estimated on a national basis, is higher than previously estimated. These results should be taken into account in the evaluation of the benefit-to-risk ratio of the various anesthetic techniques in individuals. The similar incidence of reactions according to sex before adolescence suggests a role for sex hormones in the increase of anaphylaxis observed in women.
The hygienic quality of urban surfaces can be impaired by multiple sources of microbiological contaminants. These surfaces can trigger the development of multiple bacterial taxa and favor their ...spread during rain events through the circulation of runoff waters. These runoff waters are commonly directed toward sewer networks, stormwater infiltration systems or detention tanks prior a release into natural water ways. With water scarcity becoming a major worldwide issue, these runoffs are representing an alternative supply for some usage like street cleaning and plant watering. Microbiological hazards associated with these urban runoffs, and surveillance guidelines must be defined to favor these uses. Runoff microbiological quality from a recently implemented city center rainwater harvesting zone was evaluated through classical fecal indicator bacteria (FIB) assays, quantitative PCR and DNA meta-barcoding analyses. The incidence of socio-urbanistic patterns on the organization of these urban microbiomes were investigated. FIB and DNA from Human-specific Bacteroidales and pathogens such as Staphylococcus aureus were detected from most runoffs and showed broad distribution patterns. 16S rRNA DNA meta-barcoding profilings further identified core recurrent taxa of health concerns like Acinetobacter, Mycobacterium, Aeromonas and Pseudomonas, and divided these communities according to two main groups of socio-urbanistic patterns. One of these was highly impacted by heavy traffic, and showed recurrent correlation networks involving bacterial hydrocarbon degraders harboring significant virulence properties. The tpm-based meta-barcoding approach identified some of these taxa at the species level for more than 30 genera. Among these, recurrent pathogens were recorded such as P. aeruginosa, P. paraeruginosa, and Aeromonas caviae. P. aeruginosa and A. caviae tpm reads were found evenly distributed over the study site but those of P. paraeruginosa were higher among sub-catchments impacted by heavy traffic. Health risks associated with these runoff P. paraeruginosa emerging pathogens were high and associated with strong cytotoxicity on A549 lung cells. Recurrent detections of pathogens in runoff waters highlight the need of a microbiological surveillance prior allowing their use. Good microbiological quality can be obtained for certain typologies of sub-catchments with good hygienic practices but not all. A reorganization of Human mobility and behaviors would likely trigger changes in these bacterial diversity patterns and reduce the occurrences of the most hazardous groups.
•Socio-urbanistic differentiation of rainwater harvesting urban sub-catchments.•Recurrent high counts of fecal bacteria and pathogens among downtown runoff waters.•Use of DNA meta-barcoding approaches for inferring urban surface hygienic status.•16S rRNA and tpm metabarcoding profiles of urban runoff match traffic intensity.•Highly cytotoxic Pseudomonas paraeruginosa bacterial cells found over city surfaces.
Dexamethasone could be more effective than prednisolone at similar anti-inflammatory doses in the treatment of childhood acute lymphoblastic leukemia. In order to check if this "superiority" of ...dexamethasone might be dose-dependent, we conducted a randomized phase III trial comparing dexamethasone (6 mg/m(2)/day) to prednisolone (60 mg/m(2)/day) in induction therapy. All newly diagnosed children and adolescents with acute lymphoblastic leukemia in the 58951 EORTC trial were randomized on prephase day 1 or day 8. The main endpoint was event-free survival; secondary endpoints were overall survival and toxicity. A total of 1947 patients with acute lymphoblastic leukemia were randomized. At a median follow-up of 6.9 years, the 8-year event-free survival rate was 81.5% in the dexamethasone arm and 81.2% in the prednisolone arm; the 8-year overall survival rates were 87.2% and 89.0% respectively. The 8-year incidences of isolated or combined central nervous system relapse were 2.9% and 4.5% in the dexamethasone and prednisolone arms, respectively. The incidence of grade 3-4 toxicities during induction and the frequency of osteonecrosis were similar in the two arms. In conclusion, dexamethasone and prednisolone, used respectively at the doses of 6 and 60 mg/m(2)/day during induction, were equally effective and had a similar toxicity profile. Dexamethasone decreased the 8-year central nervous system relapse incidence by 1.6%. This trial was registered at www.clinicaltrials.gov as #NCT00003728.
Healthcare-associated infections due to third-generation cephalosporin-resistant Enterobacteriaceae (CRE) have become a major public health threat, especially in intensive care units (ICUs). We ...assessed and compared β-lactam use, the prevalence of colonization with CRE at admission and the incidence of CRE acquisition across ICUs.
A cohort study was conducted in 10 ICUs of the Paris (France) metropolitan area between November 2005 and February 2006. Antibiotic use was recorded prospectively in all patients admitted during the study period. Rectal swabs were collected at admission, twice weekly thereafter, before β-lactam prescription and before discharge.
A total of 893 patients provided 3453 rectal swabs; 793 of the patients were newly admitted, mostly for medical reasons (80.7%). On admission, 74 patients (9.6%) were colonized with CRE, including 32 with an extended-spectrum β-lactamase (ESBL)-producing strain. Among the remaining 694 naive patients, 94 acquired CRE during their follow-up, including 31 with an ESBL-producing strain. Incidence rates of colonization ranged from 8.8 to 21.0/1000 patient-days for all CRE, and from 1.4 to 10.9/1000 patient-days for ESBL producers. A majority of patients (68.3%) were prescribed β-lactams during their ICU stay, with defined daily doses ranging from 428 to 985/1000 patient-days. Across ICUs, prescriptions of all antibiotics, β-lactams and carbapenems were significantly correlated to incidence rates of colonization with ESBL-producing CRE.
The standardized and systematic follow-up of patients in 10 ICUs revealed great heterogeneity in the rates of colonization with ESBL- and non-ESBL-producing CRE, as well as in antimicrobial prescription practices.
Magmatic intrusions and volcanic eruptions are intimately related phenomena. Shallow magma intrusion builds subsurface reservoirs that are drained by volcanic eruptions. Thus, the long-held view is ...that intrusions must precede and feed eruptions. Here we show that explosive eruptions can also cause magma intrusion. We provide an account of a rapidly emplaced laccolith during the 2011 rhyolite eruption of Cordón Caulle, Chile. Remote sensing indicates that an intrusion began after eruption onset and caused severe (>200 m) uplift over 1 month. Digital terrain models resolve a laccolith-shaped body ∼0.8 km
. Deformation and conduit flow models indicate laccolith depths of only ∼20-200 m and overpressures (∼1-10 MPa) that likely stemmed from conduit blockage. Our results show that explosive eruptions may rapidly force significant quantities of magma in the crust to build laccoliths. These iconic intrusions can thus be interpreted as eruptive features that pose unique and previously unrecognized volcanic hazards.
Summary Background Critically ill patients often require emergency intubation. The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible ...adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients. Methods In this randomised, controlled, single-blind trial, 655 patients who needed sedation for emergency intubation were prospectively enrolled from 12 emergency medical services or emergency departments and 65 intensive care units in France. Patients were randomly assigned by a computerised random-number generator list to receive 0·3 mg/kg of etomidate (n=328) or 2 mg/kg of ketamine (n=327) for intubation. Only the emergency physician enrolling patients was aware of group assignment. The primary endpoint was the maximum score of the sequential organ failure assessment during the first 3 days in the intensive care unit. We excluded from the analysis patients who died before reaching the hospital or those discharged from the intensive care unit before 3 days (modified intention to treat). This trial is registered with ClinicalTrials.gov , number NCT00440102. Findings 234 patients were analysed in the etomidate group and 235 in the ketamine group. The mean maximum SOFA score between the two groups did not differ significantly (10·3 SD 3·7 for etomidate vs 9·6 3·9 for ketamine; mean difference 0·7 95% CI 0·0–1·4, p=0·056). Intubation conditions did not differ significantly between the two groups (median intubation difficulty score 1 IQR 0–3 in both groups; p=0·70). The percentage of patients with adrenal insufficiency was significantly higher in the etomidate group than in the ketamine group (OR 6·7, 3·5–12·7). We recorded no serious adverse events with either study drug. Interpretation Our results show that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in critically ill patients, and should be considered in those with sepsis. Funding French Ministry of Health.
Allergic or pseudoallergic reactions that occur during anesthesia have been increasing for the last few years. To date, the diagnosis of allergy to muscle relaxants remains difficult. In this ...respect, we developed a flow cytometric method for the study of drug-induced basophil degranulation using CD63 and CCR3. Fifty patients who developed clinical features evocative of allergic reactions immediately after induction of anesthesia were included and classified into two groups. Group 1 (n = 39) comprised true allergic patients, who developed typical signs of shock associated to positive skin testing. Group 2 (n = 11) consisted of patients whose clinical history was not typical and skin testing was negative or nonconclusive. Seventeen control subjects were also studied in this report. We compared data from flow cytometry to skin tests, specific IgE, and histamine release results. Flow cytometry showed a sensitivity of 54%, while that of specific IgE was similar, at 62%. Interestingly, when considering the sensitivity of IgE + CD63 for diagnosis, we reached a sensitivity value of 80%. Of 15 negative results for specific IgE, we found 7 positive CD63 tests, while histamine release gave positive results in only 2 cases. Furthermore, the CD63 protocol showed good specificity (100%). We conclude that our flow cytometry protocol is a promising tool in allergy diagnosis since it is specific and complementary to specific IgE detection.
IMPORTANCE: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this ...indication remains unclear. OBJECTIVE: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015. INTERVENTIONS: Patients were randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). MAIN OUTCOMES AND MEASURES: The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay. RESULTS: At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, −3.2 95% CI, −12.1 to 5.6; P = .47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, −6.6 95% CI, −16.6 to 3.4; P = .20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. CONCLUSIONS AND RELEVANCE: Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01915719
In this randomized, controlled trial involving critically ill patients not receiving early parenteral nutrition, tight glucose control did not affect the length of time that ICU care was needed or ...mortality.
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