Cobalt-56 γ-ray emission lines from the type Ia supernova 2014J.

A type Ia supernova is thought to be a thermonuclear explosion of either a single carbon-oxygen white dwarf or a pair of merging white dwarfs. The explosion fuses a large amount of radioactive (56)Ni (refs 1-3). After the explosion, the decay chain from (56)Ni to (56)Co to (56)Fe generates γ-ray photons, which are reprocessed in the expanding ejecta and give rise to powerful optical emission. Here we report the detection of (56)Co lines at energies of 847 and 1,238 kiloelectronvolts and a γ-ray continuum in the 200-400 kiloelectronvolt band from the type Ia supernova 2014J in the nearby galaxy M82. The line fluxes suggest that about 0.6 ± 0.1 solar masses of radioactive (56)Ni were synthesized during the explosion. The line broadening gives a characteristic mass-weighted ejecta expansion velocity of 10,000 ± 3,000 kilometres per second. The observed γ-ray properties are in broad agreement with the canonical model of an explosion of a white dwarf just massive enough to be unstable to gravitational collapse, but do not exclude merger scenarios that fuse comparable amounts of (56)Ni.

[Acute idiopathic eosinophilic pneumonia in a teenager]. / Le cas clinique du mois. Pneumonie éosinophilique idiopathique aiguë chez une adolescente.

Acute idiopathic eosinophilic pneumonia is a very rare cause of interstitial lung disease in children. Pathophysiological mechanisms and etiology remain poorly understood. It manifests as a febrile dyspnea, progressively worsening. Chest X-ray, performed as first-line, shows bilateral infiltrates. The chest CT confirms a diffuse infiltrative pneumopathy and the bronchoalveolar lavage demonstrates the presence of alveolar hypereosinophilia. The exclusion of other causes of alveolar eosinophilia confirms the diagnosis. A ventilatory support is very often necessary. Systemic corticosteroids provides a spectacular clinical improvement, without recurrence.

La pneumonie éosinophilique idiopathique aiguë est une cause très rare de pneumopathie infiltrante diffuse de l'enfant. Le mécanisme physiopathologique et l'étiologie sont mal connus. Elle se manifeste par une dyspnée fébrile, s'aggravant progressivement. La radiographie thoracique, réalisée en première intention, montre des infiltrats bilatéraux. Le scanner thoracique confirme la pneumopathie infiltrante diffuse et le lavage broncho-alvéolaire démontre la présence d'une hyperéosinophilie alvéolaire. L'exclusion d'autres causes d'éosinophilie alvéolaire permet de confirmer le diagnostic. Un support ventilatoire est très souvent nécessaire. Une corticothérapie systémique permet une amélioration clinique spectaculaire, sans récidive.

Intravenous iron therapy for anemic cancer patients: a review of recently published clinical studies.

Based on available literature and on the present review, IV iron administration to anemic cancer patients can increase significantly the level of Hb, probably independently from the precise mechanism of anemia itself. However, in future studies, the benefit should be evaluated taking into account whether the anemia is due to absolute or functional iron deficiency; therapeutic modalities might be different for these two conditions. Along the same lines, it appears important to further evaluate the respective roles of PO and IV iron therapies and the modalities of their use in clinical practice. Until the results of such studies are available, it appears reasonable to propose IV iron therapy to anemic cancer patients as the resulting rise of Hb level may increase their quality of life and performance status and reduce the need for erythropoietin-stimulating agents and/or blood transfusions.

[Acute disseminated encephalomyelitis: a pediatric case report]. / Encephalomyélite aiguë disséminée: discussion autour d'un cas pédiatrique.

Acute disseminated encephalomyelitis (ADEM) is a disease of the central nervous system (CNS) mainly affecting children. It usually occurs within 2 days to 4 weeks following a triggering factor such a viral infection or an immunization. Clinical presentation is characterized by an acute encephalopathy and by multifocal neurologic abnormalities. In the absence of specific biologic marker, the diagnosis of ADEM is based on clinical, biological and radiological data including cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI). Brain MRI typically shows multifocal lesions predominantly involving the white matter. Treatment is based on high doses of steroids. Intravenous immunoglobulins or plasmapheresis are sometimes required. The prognosis is usually favorable but neurological sequellae can occur.

Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†.

BACKGROUND: The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR(+)), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here. PATIENTS AND METHODS: BOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR(+) advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point. RESULTS: At the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0-34.6 months] compared with 26.6 months (95% CI 22.6-33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73-1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified. CONCLUSIONS: In BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P < 0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting. TRIAL REGISTRATION NUMBER: NCT00863655.

[Anemia in the critically ill child and adult: a narrative review]. / L'anémie aux soins intensifs pédiatriques et adultes: revue narrative.

Anemia is frequent in the pediatric and adult intensive care unit. Anemia decreases oxygen transport which can be harmful in the critically ill patient; it is independently associated with a poor prognosis. The major prophylactic measure against anemia is the limitation of blood draws: several approaches can be used to limit phlebotomy overdraw without harming the patient. Red blood cell transfusion is the quickest way to increase the hemoglobin level, but it is not without risk. It is therefore important to promote the use of evidence-based transfusion strategies. Iron could be useful in case of iron deficiency, but this condition is difficult to diagnose in the critically ill patient. Erythropoietin is no longer relevant in the intensive care unit in the era of restrictive transfusion practice, at least for its hematological effects. Several questions remain to be addressed in order to improve anemia management in the intensive care unit.

Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial.

BACKGROUND: Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. METHODS: Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. RESULTS: The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. CONCLUSIONS: The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.

[High energy proton therapy for extraocular tumors, neurotrophic keratitis and functional consequence: A series of 3 cases]. / Protonthérapie haute énergie des tumeurs extra-oculaires, kératite neurotrophique et conséquence fonctionnelle : une série de 3 cas.

INTRODUCTION: High energy proton therapy (HEP) is a form of radiation therapy using protons for extraocular tumors. Its ballistic properties are theoretically advantageous, but the real impact on the surrounding ocular tissues during cerebral and ENT irradiation is poorly documented. We describe three consecutive patients with corneal damage following such irradiation. MATERIALS/METHODS: Post-proton therapy neurotrophic keratitis (NK) is defined as corneal hypo/anesthesia responsible for an alteration of corneal trophicity and graded according to the Mackie classification, in terms of a prospective ophthalmological follow-up protocol for all patients with extraocular tumors treated with HEP. RESULTS: Among 193 patients treated with HEP between 2018 and 2021 for extraocular tumors, three patients developed severe neurotrophic keratitis, i.e. 1.6% of treated patients. According to the Mackie classification, the three patients showed grade 3 NK less than one year after the conclusion of their HEP. These three patients underwent amniotic membrane grafting. They were placed on autologous serum eye drops. Two of the three patients had to be eviscerated. The dose to the cornea was greater than 50 Gray (Gy)_Relative biological effectiveness (RBE) in the three cases. DISCUSSION: The diagnosis and etiological origin of neurotrophic keratitis are often difficult to establish. In these cases, the imputability of radiation therapy, proton therapy in our cases, in the development of neurotrophic keratitis was plausible based on the dosimetry of the patients, all of whom had anterior tumors with a poor prognosis requiring high tumoricidal doses. CONCLUSION: Further studies to establish the impact of proton therapy on corneal sensitivity are necessary. However, this feedback and the multidisciplinary management of tumors can help to limit the risk of some complications of radiation therapy. Early diagnosis allows for appropriate management and could possibly minimize the anatomical and functional ocular complications of neurotrophic keratitis.

Compact sources as the origin of the soft gamma-ray emission of the Milky Way.

The Milky Way is known to be an abundant source of gamma-ray photons, now determined to be mainly diffuse in nature and resulting from interstellar processes. In the soft gamma-ray domain, point sources are expected to dominate, but the lack of sensitive high-resolution observations did not allow for a clear estimate of the contribution from such sources. Even the best imaging experiment revealed only a few point sources, accounting for about 50% of the total Galactic flux. Theoretical studies were unable to explain the remaining intense diffuse emission. Investigating the origin of the soft gamma-rays is therefore necessary to determine the dominant particle acceleration processes and to gain insights into the physical and chemical equilibrium of the interstellar medium. Here we report observations in the soft gamma-ray domain that reveal numerous compact sources. We show that these sources account for the entirety of the Milky Way's emission in soft gamma-rays, leaving at most a minor role for diffuse processes.

Seroprevalence of human parvovirus B19 in a suburban population in São Paulo, Brazil.

OBJECTIVE: To analyze the prevalence of IgG antibodies to human parvovirus B19. METHODS: Cross-sectional study in a suburban community in São Paulo, Southeastern Brazil, between November 1990 and January 1991. Randomly selected (N=435) representative samples of sera were collected from healthy children older than 15 days old and adults up to 40 years old. IgG antibodies were detected using ELISA. RESULTS: High prevalence of IgG antibodies to B19 parvovirus was found in 87% of newborns. The prevalence of maternally derived IgG antibodies exponentially plunged up to the 19th month of age. Low prevalence of antibodies was found in the first 4 years of life, increasing up to 72% in those aged 31-40 years. It was estimated that the average age of first infection in this population is 21 +/- 7 years old and the optimal age for vaccination with a hypothetical vaccine would be 1 year of age. CONCLUSIONS: Parvovirus B19 IgG antibody prevalence was high in newborns and those aged 31-40 years. The analysis by age groups showed a pattern similar to that found in previous studies, i.e., low prevalence of infection in children that increases with age.

Bax and Bid, two proapoptotic Bcl-2 family members, inhibit homologous recombination, independently of apoptosis regulation.

In order to analyse the relationships between regulation of apoptosis and homologous recombination (HR), we overexpressed proapoptotic Bax or only-BH3 Bid proteins or antiapoptotic Bcl-2 or Bcl-XL, in hamster CHO cells or in SV40-transformed human fibroblasts. We measured HR induced by gamma-rays, UVC or a specific double-strand cleavage targeted in the recombination substrate by the meganuclease I-SceI. We show here that the induction of both recombinant cells and recombinant colonies was impaired when expressing Bcl-2 family members, in hamster as well as in human cells. Moreover, the pro- as well as antiapoptotic Bcl-2 family members inhibited HR, independently of degradation of the RAD51 recombination protein and of their impact on apoptosis. These data reveal a mechanism of HR downregulation by potentially proapoptotic proteins, distinct from and parallel to degradation of recombination proteins, a situation that should also optimize the efficiency of programmed cell death.

Appendicitis in pregnancy: a case report and a review of the current literature.

Acute appendicitis is the most common surgical problem in pregnancy. Antibiotic treatment does not always improve the outcome and emergency intervention is required. We present a case of appendicitis complicated by a plastron formation occurring during pregnancy and the outcome.

[Arterial duplex and aortic valve stenosis: sensitivity and specificity of findings]. / Echo-Doppler artériel et sténose valvulaire aortique: étude de la sensibilité et de la spécificité des signes.

UNLABELLED: Purposes. In this prospective study, we sought to determine the sensitivity and the specificity of arterial Doppler findings of valvular aortic stenosis (VAS). PATIENTS AND METHODS: 20 control subjects and 20 patients with various degrees of VAS underwent Doppler ultrasound of the carotids, abdominal aorta, renal arteries and limb arteries. We analyzed and compared the shape of the spectral profiles, peak systolic velocity (PSV), systolic upstroke time (SUT) and systolic upstroke index (SUI) of every tracing. The protodiastolic notch (PDN) of the common femoral arteries were recorded too. RESULTS: VAS hardly modifies the overall shape of the Doppler spectrums of the aorta or limb arteries but it implies a biphasic deformation or a doubling of the systolic peak of the neck vessels. We also encountered biphasic profiles in renal arteries of patients with tight VAS. The PSV, SUI and depth of the PDN tend to diminish in cases of VAS but the variations are inconstant and rarely proportional to the severity of the narrowing. The increase of the SUT, on the contrary, is linearly correlated to the severity of the stenosis in every arterial system: SUTs in the common carotid artery, internal carotid artery or brachial artery that are shorter than or equal to 70 milliseconds (msec) are the obvious marks of the absence of VAS. It was not possible to differentiate between the intermediate stenoses (aortic valve area between 0.8 and 2 square centimeters) whereas critical aortic stenoses, whose area is less than or equal to 0.7 square centimeter, can be detected by the presence of at least two of the four following criteria of SUT: equal to or above 180 msec for the common carotid, 200 msec for the internal carotid, 130 msec for the aorta and 110 msec for the common femoral artery. CONCLUSION: During routine arterial Doppler ultrasound, a precise analysis of the spectrums and some SUT measurements allow the assessment of the aortic valve.

Quantitation of functional mitral regurgitation during bicycle exercise in patients with heart failure.

OBJECTIVES: We sought to examine the feasibility and reliability of quantifying mitral regurgitation (MR) during exercise by Doppler echocardiography in patients with heart failure and to assess the relationship between dynamic MR and systolic pulmonary artery pressure changes. BACKGROUND: The severity of MR can be quantified by using several echocardiographic methods. Quantitation of MR during dynamic exercise has not yet been performed. METHODS: Symptom-limited, semi-supine two-dimensional and Doppler echocardiograms during bicycle exercise were obtained in 27 consecutive patients with heart failure and functional MR. Regurgitant volume was measured at rest and during exercise by the proximal isovelocity surface area (PISA) method and by quantitative Doppler echocardiography. Exercise-induced changes in regurgitant volume were compared with changes in the regurgitant jet area to left atrial area ratio, vena contracta width and trans-tricuspid pressure gradient. RESULTS: The regurgitant volume measured by the PISA method increased from 21 +/- 12 ml (range 5 to 55) at rest to 39 +/- 23 ml (range 8 to 85) during exercise (p < 0.0001). The difference between two observers was low for both rest (2.0 +/- 2.7 ml) and exercise measurements (3.5 +/- 6.2 ml). The regurgitant volume measured by quantitative Doppler echocardiography increased from 29 +/- 13 to 49 +/- 24 ml (p = 0.0001). Excellent correlation between the two methods was obtained with exercise (r = 0.92). Exercise-induced changes in regurgitant volume, as measured by the PISA method, correlated well with regurgitant volume changes measured by quantitative Doppler echocardiography (r = 0.88), changes in vena contracta width (r = 0.82) and changes in trans-tricuspid pressure gradient (r = 0.73), but not with changes in regurgitant jet area to left atrial area ratio (r = 0.29). Seventeen patients stopped exercise because of fatigue and 10 because of dyspnea. These 10 patients exhibited greater increases in regurgitant volume (34 +/- 6 vs. 11 +/- 8 ml), corresponding to a significant elevation of the trans-tricuspid gradient (48 +/- 14 vs. 20 +/- 14 mm Hg). CONCLUSIONS: Quantitation of functional MR during exercise is feasible in patients with heart failure. There is a good correlation between regurgitant volume measured during exercise by the PISA method and that obtained by quantitative Doppler echocardiography, suggesting that the technique is reliable. An increase in mitral regurgitant volume during dynamic exercise correlates well with elevation of systolic pulmonary artery pressure.

Adjuvant chemotherapy in 2005: standards and beyond.

The 2003 St. Gallen consensus panel divided the many available adjuvant chemotherapy (CT) regimens into those with "standard efficacy" (ACx4, CMFx6) and those with "superior efficacy" (FA(E)Cx6, CA(E)Fx6, A(E)-->CMF, TACx6, ACx4--> paclitaxel (P)x4 or docetaxel (D)x4) but also greater complexity, toxicity and cost. This paper will summarize the latest information on long-term side effects of the "superior" regimens and 5-year benefits reported in taxane trials, including those of a "new" sequential regimen, FECx3--> docetaxelx3. Rapidly expanding evidence of marked heterogeneity in the magnitude of CT benefits according to the tumour oestrogen receptor (ER) status, a claim made for many years by IBCSG investigators, will be reviewed; it will lead to the conclusion that a revolution needs to take place in the way oncologists think about the CT added value and design adjuvant clinical trials. The conclusions proposed to the 2005 St. Gallen consensus panel are that: adequately dosed anthracycline-based CT regimens remain an acceptable standard for many women; a lower threshold for using taxanes in sequence or combination with anthracyclines (A) is justified in the presence of an ER-negative or low-ER tumour status, other aggressive biologic features (such as HER-2 overexpression), fear about A-induced cardiotoxicity; no recommendation can yet be made as far as the optimal taxane-A regimen, the best taxane or the best taxane schedule.

[Amaurosis fugax of cardiac origin]. / Amaurose fugace d'origine cardiaque.

We present the case of a 49 year old woman who was admitted to the emergency department for dyspnoea, transient amaurosis and limbs oedema. During hospitalisation a full workup revealed multisystemic thrombosis and dilated cardiomyopathy in relation with viral myocarditis due to Coxackie B infection. Diagnosis and treatment will be discussed in light of the litterature.