Hôpital Fleurimont

BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. METHODS: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. RESULTS: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). CONCLUSIONS: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Quantitative extraction of high-dimensional mineable data from medical images is a process known as radiomics. Radiomics is foreseen as an essential prognostic tool for cancer risk assessment and the quantification of intratumoural heterogeneity. In this work, 1615 radiomic features (quantifying tumour image intensity, shape, texture) extracted from pre-treatment FDG-PET and CT images of 300 patients from four different cohorts were analyzed for the risk assessment of locoregional recurrences (LR) and distant metastases (DM) in head-and-neck cancer. Prediction models combining radiomic and clinical variables were constructed via random forests and imbalance-adjustment strategies using two of the four cohorts. Independent validation of the prediction and prognostic performance of the models was carried out on the other two cohorts (LR: AUC = 0.69 and CI = 0.67; DM: AUC = 0.86 and CI = 0.88). Furthermore, the results obtained via Kaplan-Meier analysis demonstrated the potential of radiomics for assessing the risk of specific tumour outcomes using multiple stratification groups. This could have important clinical impact, notably by allowing for a better personalization of chemo-radiation treatments for head-and-neck cancer patients from different risk groups.

BACKGROUND: -L) to standard therapy for newly diagnosed glioblastoma. METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. CONCLUSIONS: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.

BACKGROUND: Cardiac surgery is frequently complicated by coagulopathic bleeding that is difficult to optimally manage using standard hemostatic testing. We hypothesized that point-of-care hemostatic testing within the context of an integrated transfusion algorithm would improve the management of coagulopathy in cardiac surgery and thereby reduce blood transfusions. METHODS: We conducted a pragmatic multicenter stepped-wedge cluster randomized controlled trial of a point-of-care-based transfusion algorithm in consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at 12 hospitals from October 6, 2014, to May 1, 2015. Following a 1-month data collection at all participating hospitals, a transfusion algorithm incorporating point-of-care hemostatic testing was sequentially implemented at 2 hospitals at a time in 1-month intervals, with the implementation order randomly assigned. No other aspects of care were modified. The primary outcome was red blood cell transfusion from surgery to postoperative day 7. Other outcomes included transfusion of other blood products, major bleeding, and major complications. The analysis adjusted for secular time trends, within-hospital clustering, and patient-level risk factors. All outcomes and analyses were prespecified before study initiation. RESULTS: Among the 7402 patients studied, 3555 underwent surgery during the control phase and 3847 during the intervention phase. Overall, 3329 (45.0%) received red blood cells, 1863 (25.2%) received platelets, 1645 (22.2%) received plasma, and 394 (5.3%) received cryoprecipitate. Major bleeding occurred in 1773 (24.1%) patients, and major complications occurred in 740 (10.2%) patients. The trial intervention reduced rates of red blood cell transfusion (adjusted relative risk, 0.91; 95% confidence interval, 0.85-0.98; P=0.02; number needed to treat, 24.7), platelet transfusion (relative risk, 0.77; 95% confidence interval, 0.68-0.87; P<0.001; number needed to treat, 16.7), and major bleeding (relative risk, 0.83; 95% confidence interval, 0.72-0.94; P=0.004; number needed to treat, 22.6), but had no effect on other blood product transfusions or major complications. CONCLUSIONS: Implementation of point-of-care hemostatic testing within the context of an integrated transfusion algorithm reduces red blood cell transfusions, platelet transfusions, and major bleeding following cardiac surgery. Our findings support the broader adoption of point-of-care hemostatic testing into clinical practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02200419.

BACKGROUND: Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness. METHODS: Computerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes. RESULTS: Thirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I (2) = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I (2) = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists. CONCLUSION: Probiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.

UNLABELLED: Respiratory motion may reduce the sensitivity of (18)F-FDG PET for the detection of small pulmonary nodules close to the base of the lungs. This motion also interferes with attempts to use fused PET/CT images through software or combined PET/CT devices. This study was undertaken to assess the feasibility of respiratory gating for PET of the chest and the impact of respiratory motion on quantitative analysis. METHODS: Ten healthy subjects were enrolled in this study. Three-dimensional studies were acquired with 8 gates per respiratory cycle on a commercial PET scanner with a temperature-sensitive respiratory gating device built in-house. All scans were obtained over 42 cm of body length with 3 bed positions of 10 min each after injection of (18)F-FDG at 4.5 MBq/kg. The reconstructed images were assembled to produce gated whole-body volumes and maximum-intensity projections. The amplitude of respiratory motion of the kidneys (as a surrogate for diaphragmatic incursion) as well as the apex of the heart was measured in the coronal plane. Phantom studies were acquired to simulate the impact of respiratory motion on quantitative uptake measurements. RESULTS: The respiratory gating device produced a consistent, reliable trigger signal. All acquisitions were successful and produced reconstructed volumes with excellent image quality. Mean +/- SD motion amplitude and maximal motion amplitude values were 6.7 +/- 3.0 and 11.9 mm for the heart, 12.0 +/- 3.7 and 18.8 mm for the right kidney, and 11.1 +/- 4.8 and 17.1 mm for the left kidney, respectively. In phantom studies, the standardized uptake value for a 1-mL lesion was underestimated by 30% and 48% for the average and maximal respiratory motion values, respectively. CONCLUSION: Respiratory gating of PET of the thorax and upper abdomen is a practical and feasible approach that may improve the detection of small pulmonary nodules. Further work is planned to assess prospectively the diagnostic accuracy of this new method.

Fabry disease is an X-linked, hereditary, lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A, which results in the accumulation of the neutral glycosphingolipid globotriaosylceramide (Gb3) in the walls of small blood vessels, nerves, dorsal root ganglia, renal glomerular and tubular epithelial cells, and cardiomyocytes. It is a complex, multisystem disorder that is characterized clinically by chronic pain and acroparesthesia, gastrointestinal disturbances, characteristic skin lesions (angiokeratomata), progressive renal impairment, cardiomyopathy, and stroke. Enzyme replacement therapy (ERT) with intravenous infusions of recombinant human alpha-galactosidase A consistently decreases Gb3 levels in plasma and clears lysosomal inclusions from vascular endothelial cells. The effects of ERT on other tissues are not as obvious, suggesting that treatment must be initiated early in the course of the disease to be optimally effective or that some complications of the disease are not responsive to enzymes delivered intravenously.

Aims: Guidelines recommend warfarin continuation rather than heparin bridging for pacemaker and defibrillator surgery, after the BRUISE CONTROL trial demonstrated an 80% reduction in device pocket haematoma with this approach. However, direct oral anticoagulants (DOACs) are now used to treat the majority of patients with atrial fibrillation. We sought to understand the best strategy to manage the DOACs at the time of device surgery and specifically hypothesized that performing device surgery without DOAC interruption would result in a reduced haematoma rate. Methods and results: We randomly assigned patients with atrial fibrillation and CHA2DS2-VASc score ≥2, to continued vs. interrupted DOAC (dabigatran, rivaroxaban, or apixaban). The primary outcome was blindly evaluated, clinically significant device pocket haematoma: resulting in re-operation, interruption of anticoagulation, or prolonging hospital stay. In the continued arm, the median time between pre- and post-operative DOAC doses was 12 h; in the interrupted arm the median time was 72 h. Clinically significant haematoma occurred in of 7 of 328 (2.1%; 95% CI 0.9-4.3) patients in the continued DOAC arm and 7 of 334 (2.1%; 95% CI 0.9-4.3) patients in the interrupted DOAC arm (P = 0.97). Complications were uncommon, and included one stroke and one symptomatic pericardial effusion in each arm. Conclusions: These results suggest that, dependent on the clinical scenario, either management strategy (continued DOAC or interrupted DOAC) might be reasonable, at least for patients similar to those enrolled in our trial.

Enlargement of the cell wall requires separation of cellulose microfibrils, mediated by proteins such as expansin; according to the multi-net growth hypothesis, enlargement passively reorients microfibrils. However, at the molecular scale, little is known about the specific movement of microfibrils. To find out, we examined directly changes in microfibril orientation when walls were extended slowly in vitro under constant load (creep). Frozen-thawed cucumber hypocotyl segments were strained by 20-30% by incubation in pH 4.5 buffer or by incubation of heat-inactivated segments in alpha-expansin or a fungal endoglucanase (Cel12A). Subsequently, the innermost layer of the cell wall was imaged, with neither extraction nor homogenization, by field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM). AFM images revealed that sample preparation for FESEM did not appreciably alter cell wall ultrastructure. In both FESEM and AFM, images from extended and non-extended samples appeared indistinguishable. To quantify orientational order, we used a novel algorithm to characterize the fast Fourier transform of the image as a function of spatial frequency. For both FESEM and AFM images, the transforms of non-extended samples were indistinguishable from those of samples extended by alpha-expansin or Cel12A, as were AFM images of samples extended by acidic buffer. We conclude that cell walls in vitro can extend slowly by a creep mechanism without passive reorientation of innermost microfibrils, implying that wall loosening agents act selectively on the cross-linking polymers between parallel microfibrils, rather than more generally on the wall matrix.

G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric heptahelical glycoproteins that recognize a broad array of extracellular mediators including cationic amines, lipids, peptides, proteins, and sensory agents. Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE(2) and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.

The brain reacts to injury or disease by cascades of cellular and molecular responses. Evidence suggests that immune-inflammatory processes are key elements in the physiopathological processes associated with brain injury or damage. Cytokines are among major mediators implicated in these processes. Cytokine responses in the initial phase of brain injury might have a role in aggravating brain damage. However, in later stages, these molecular mediators might contribute to recovery or repair. Hemodynamic stabilization and optimalization of oxygen delivery to the brain remain cornerstones in the management of acute brain injury. New approaches might use anticytokine therapy to limit progression and halt or attenuate secondary brain damage. Progress toward such novel neuroprotection strategies, however, awaits better understanding of the optimal timing and dosing of those neuromodulatory therapies and better knowledge of the numerous interactions of those mediators. This also requires understanding of how and when precisely immune mechanisms shift from noxious to protective or restorative actions.

Objective: To investigate the cytokine-related molecular cascade leading to neural cell death in periventricular leukomalacia (PVL). Methods: The authors explored potential tumor necrosis factor (TNF) signaling pathways in human brains with PVL and conducted in situ immunohistochemical investigations to search for possible expression of cytokine receptors in these brains. They also investigated likely links to molecules potentially involved in neurocytotoxicity, particularly pathways involving nitrosative-induced apoptosis. Results: TNF overexpression was associated with immune reactivity for p75TNFR2 and p55TNFR1 receptors in affected PVL areas. p75TNFR2 labeling was intense on cerebrovascular endothelial cells in PVL areas, whereas no vascular p55TNFR1 immunoreactivity was detected therein. Immune labeling for both receptors was detected on many white matter parenchymal cells. In contrast, there was no immune reactivity for either receptor in tissues taken from non-PVL areas. Additionally, in situ overexpression of inducible nitric oxide synthase was found in PVL brain regions where apoptotic cell death was detected. Conclusions: Both p75TNFR2 and p55TNFR1 receptors and nitric oxide may be implicated in the pathogenesis of periventricular leukomalacia.

There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.

INTRODUCTION: Published in 2018, the 5C scale is psychometrically validated to assess five psychological antecedents of vaccination (confidence, complacency, constraints, calculation and collective responsibility). The original version offers a validated English and German scale to assess these determinants with a short 5-item scale (1 item per antecedent) and a long 15-item scale (3 items per antecedent). This sample study protocol provides a step-by-step guidance for the process of adapting the 5C scale to another country, language or cultural context. Data obtained from the 5C scale can support developing, implementing and evaluating an intervention and monitoring of general vaccine acceptance and demand. METHODS AND ANALYSIS: Phase 1 comprises the adaptation of the 5C scale including the translation and back translation of the antecedents, an expert evaluation of the antecedents and the identification of new antecedents as well as a pretest. Phase 2 involves the validation of the translated and potentially expanded scale including the assessment of reliability, construct and concurrent validity of all items of the scale. Code for data analysis is provided. ETHICS AND DISSEMINATION: The University of Erfurt's institutional review board provided ethical clearance (EV-201900416.2). The authors suggest and encourage publicly sharing all data obtained from the translated 5C scale (eg, on publication). The materials and the code for data analysis to support the process described in this protocol are available in https://osf.io/2agxe/. Sharing data on vaccine acceptance and demand is in the public and the scientific interest and will facilitate gaining a global overview of its current state and development over time. The authors of the original 5C scale are currently working on an online platform to facilitate publishing the data and to visualise the psychological antecedents across different countries.

OBJECTIVE: To assess the frequency and phenotype of hexanucleotide repeat expansions in C9ORF72 in a large cohort of patients of Dutch descent with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS). METHODS: Included were 78 patients with fALS, 1,422 with sALS, 246 with PMA, and 110 with PLS, and 768 control subjects. Repeat expansions were determined by a repeat primed PCR. Familial aggregation of dementia and Parkinson disease (PD) was examined among patients with ALS who carried the repeat expansion. RESULTS: The expanded repeat was found in 33 (37%) of all patients with fALS, in 87 (6.1%) patients with sALS, in 4 (1.6%) patients with PMA, and in 1 (0.9%) patient with PLS. None of the controls carried the mutation. Patients with ALS with the repeat expansion had an earlier age at onset (median 59.3 vs 61.9 years, hazard ratio 1.55, p = 5 × 10(-5)) and shorter survival (median 2.5 vs 2.7 years, hazard ratio 1.46, p = 8 × 10(-4)). Dementia, but not PD, occurred nearly twice as often in relatives of patients with the expansion compared to all patients with ALS or controls (p = 9 × 10(-4)). CONCLUSIONS: The hexanucleotide repeat expansion in C9ORF72 is a major cause of fALS and apparently sporadic ALS in the Netherlands. Patients who carry the repeat expansion have an earlier onset, shorter survival, and familial aggregation of dementia. These results challenge the classic definition of fALS and may justify genetic testing in patients with sALS.

Abstract Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34 + -selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb 3 ) and globotriaosylsphingosine (lyso-Gb 3 ) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy.

A new class of poly(ADP-ribose) (pADPr)-binding proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), has been identified by a proteomic approach using matrix-assisted laser-desorption-ionization time-of-flight ('MALDI-TOF') MS. Liquid-phase isoelectric focusing with a Rotofor cell (Bio-Rad) allowed pre-fractionation of proteins extracted from HeLa cells. Rotofor protein fractions were further separated by SDS/PAGE and then transferred to a PVDF membrane. pADPr-binding proteins were analysed by autoradiography of the protein blot after incubation with (32)P-labelled automodified pADPr polymerase-1 (PARP-1). Peptide mass fingerprinting of selected bands identified the most abundant pADPr-binding proteins as hnRNPs, a family of proteins that bind pre-mRNA into functional complexes involved in mRNA maturation and transport to the cytoplasm. Sequence homology database searching against a previously reported pADPr-binding sequence motif revealed that the hnRNPs contain a putative pADPr-binding sequence pattern [Pleschke, Kleczkowska, Strohm and Althaus (2000) J. Biol. Chem. 275, 40974-40980]. pADPr-binding assays performed with synthetic peptides by the dot-blot technique and with nitrocellulose-transferred recombinant hnRNPs confirmed the pADPr-binding protein identification and the specificity of the interaction. These results could establish a link between increased levels of pADPr in DNA damaged cells and the modified protein expression pattern resulting from altered mRNA trafficking.

The objective of this study was to describe the clinical course of acute transverse myelitis in children, to identify prognostic factors, and to compare our findings with published data Twenty-four children, aged 2 to 14 years and admitted with a diagnosis of acute transverse myelitis, were studied. Clinical features and results of investigations were collected at admission and during the course of the disease. Motor, sphincter, and global outcomes were compared with those in the main adult and pediatric series. During the initial phase, the most common presenting symptoms were pain (88%) and fever (58%). Motor loss preceded sphincter dysfunction in two thirds of patients and became bilateral in half of the patients. When maximal deficit was achieved (plateau), the patients presented a combination of sensory, motor, and sphincter dysfunctions without radicular involvement The motor loss consistently involved the lower limbs but was inconsistent and moderate in the upper limbs. The mean duration of the plateau was 1 week. The recovery phase was characterized by a progressive improvement of all deficits. Sphincter dysfunction improved more slowly than did the other deficits. A full recovery was achieved by 31% of the patients; minimal sequelae were present in 25% and mild to severe sequelae in 44%. An unfavorable outcome was associated with complete paraplegia (P = .03) and/or a time to maximal deficit shorter than 24 hours (P = .005). A favorable outcome was associated with a plateau shorter than 8 days (P = .03), the presence of supraspinal symptoms (P = .01), and a time to independent walking shorter than 1 month (P = .01). The course of acute transverse myelitis in children proceeds through three stages, an initial phase, a plateau, and a recovery phase, each characterized by specific clinical features. The global outcome was favorable in 56% of patients. Several prognostic factors were identified.

Secretory breast carcinoma (SBC) is a rare breast carcinoma with distinctive morphologic features and a recurrent specific chromosomal translocation t(12;15)(p13;q25), usually of low histologic grade and favorable prognosis. We describe the morphologic and genetic characteristics of 11 cases of SBC from 10 patients. Histologic and immunohistochemical analyses, fluorescence in situ hybridization using break-apart probes specific to ETV6 on 12p13, reverse transcription polymerase chain reaction with in-house probes specific to the ETV6-NTRK3 gene fusion, and DNA copy number variation by array comparative genomic hybridization analyses were performed on all cases. Seven cases were of low histologic grade, 3 were intermediate, and 1 had high-grade nuclear atypia, necrosis, and numerous mitoses. This patient had a fatal outcome. Five cases displayed low hormonal receptor expression, whereas the rest had basal-type immunoprofiles. All interpretable cases harbored an ETV6-NTRK3 gene fusion by reverse transcription polymerase chain reaction and/or an ETV6 rearrangement by fluorescence in situ hybridization, with duplication of the oncogenic derivative in 2 cases. Array comparative genomic hybridization analysis showed simplex genomic profiles. The 2 cases with ETV6-NTRK3 duplication included a gain of 12p starting from the ETV6 locus to the telomere, associated with a gain of the 15q from the centromere to NTRK3 in 1 case, and in the other a normal profile up to NTRK3 on 15q, and then a loss up to the telomere, suggesting loss of corresponding normal chromosome 15. These findings provide a novel insight into the morphologic and genetic spectrum of SBC, ranging from low-grade to high-grade histology, with occasional low hormonal receptor expression, simplex genomic profiles, and possible unfavorable course.

Susac syndrome is a rare disease of unknown pathogenesis. It is caused by a microangiopathy affecting the arterioles of the brain, retina, and cochlea, giving the classic clinical triad of subacute encephalopathy, visual loss secondary to retinal branch occlusions, and sensorineural hearing loss. The features of four cases of this syndrome are presented. MR imaging, retinal fluorescein angiography, and audiography findings enable diagnosis. Early therapy may reduce sequelae and improve recovery.