[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.

[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.

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.

[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.

Autoimmune haemolytic anaemia in a patient treated with capecitabine.

A 61-year-old female, followed-up for a metastatic breast cancer, was admitted in our institution with conjunctival icterus, asthenia and abdominal crampoid pain. The patient was included in a clinical trial comparing the efficiency of capecitabine monotherapy versus capecitabine conjugated with a new biological agent in a randomised and double blind trial. The patient was in the capecitabine alone arm. Biological tests performed upon admission suggested the diagnosis of haemolytic anaemia. Moreover, the direct Coombs test result was twice positive indicating autoimmune haemolytic anaemia. Capecitabine has been reported to cause haemolysis either alone or combined with lapatinib, each time with a mechanism other than immunological. In this clinical case, capecitabine is the most likely factor causing an autoimmune haemolytic anaemia.

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

OBJETIVO: Analisar a prevalência de anticorpos IgG ao parvovírus humano B19. MÉTODOS: Estudo transversal em uma comunidade de subúrbio de São Paulo, Brasil, de novembro 1990 a janeiro de 1991. Amostras aleatórias (N=435) e representativas de soro foram coletadas de crianças sadias a partir de 15 dias de idade e de adultos com até 40 anos. Os anticorpos IgG ao parvovírus humano B19 foram detectados pelo teste ELISA. RESULTADOS: A prevalência de anticorpos IgG ao parvovírus B19 foi de 87 por cento dos recém-nascidos. A prevalência de anticorpos IgG de origem materna decaiu exponencialmente até o 19o mês de idade. Baixa prevalência de anticorpos foi observada nos primeiros quatro anos de vida, aumentando até 72 por cento no grupo etário de 31-40 anos. A idade média de aquisição da primeira infecção nesta comunidade é de 21 ± 7 anos. A idade ótima para se vacinar as crianças desta comunidade com uma vacina hipotética é de um ano de idade. CONCLUSÕES: A prevalência de anticorpos IgG ao parvovírus B19 foi alta entre recém-nascidos e no grupo etário 31-40 anos. A análise por estrutura etária mostrou padrão similar aos estudos prévios relacionados à baixa prevalência de infecção em crianças que aumenta com a idade.

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.

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.

National survey of molecular epidemiology of Staphylococcus aureus colonization in Belgian cystic fibrosis patients.

OBJECTIVES: Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is poorly defined in cystic fibrosis (CF) patients, and S. aureus detection may be hampered by the presence of small colony variants (SCVs). We conducted a multicentre survey to determine the prevalence of S. aureus and MRSA colonization in Belgian CF patients and characterize the phenotype and clonal distribution of their staphylococcal strains. METHODS: S. aureus isolated from CF patients attending nine CF centres were collected. Oxacillin resistance was detected by oxacillin agar screen and mecA PCR. Antibiotic susceptibility was tested by microdilution. MRSA strains were genotyped by PFGE and SCCmec typing and compared with hospital-associated MRSA strains. RESULTS: Laboratories used a diversity of sputum culture procedures, many of which appeared substandard. S. aureus was isolated from 275/627 (44%) CF patients (20% to 72% by centre). The prevalence of SCV colonization was 4%, but SCVs were almost exclusively recovered from patients in two centres performing an SCV search. Phenotypically, 14% of S. aureus isolates were oxacillin-resistant: 79% carried mecA and 19% were SCVs lacking mecA. The mean prevalence of 'true' MRSA colonization was 5% (0% to 17% by centre). By PFGE typing, 67% of CF-associated MRSA were related to five epidemic clones widespread in Belgian hospitals. CONCLUSIONS: This first survey of S. aureus colonization in the Belgian CF population indicated a diversity in local prevalence rates and in proportion of oxacillin-resistant and SCV phenotypes, probably related to variation in bacteriological methods. These findings underscore the need for standard S. aureus detection methods and MRSA control policies in Belgian CF centres.

[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.

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.

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.