Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients.

BACKGROUND: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity. PATIENTS AND METHODS: This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI Cmin) and 3-month PSA response. RESULTS: From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI Cmin was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI Cmin was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Cmin was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cmin above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months otherwise, P = 0.044). CONCLUSIONS: We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.

Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients.

BACKGROUND: Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib. METHODS: Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation. RESULTS: Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25 kg m(-2). Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25 kg m(-2) experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3-13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009). CONCLUSION: Patients with sarcopenia and a BMI<25 kg m(-2) experienced significantly more DLTs during the first cycle of treatment.

Low national breast and cervical cancer-screening rates in American Indian and Alaska Native women with diabetes.

BACKGROUND: The cervical cancer mortality rate for American Indian and Alaska Native women is twice that of all races in the United States. To date the only published national breast and cervical cancer-screening rates for American Indian and Alaska Native women are based on self-reported data. When the Indian Health Service (IHS) conducts an annual audit on patients with diabetes, it includes cancer screening. This observational study presents national breast and cervical cancer-screening rates for American Indian and Alaska Native women with diabetes. METHODS: Cancer-screening rates were extracted from the 1995 diabetic audit for the 12 IHS areas. These rates were compared with rates for women without diabetes of the same age, 50 to 69 years, by chart review, at four IHS hospitals in the Aberdeen IHS area. RESULTS: Screening rates for women with diabetes in the 12 areas varied: mammogram (ever) 35% to 78%; clinical breast examination (last year) 28% to 70%, and Papanicolaou smear (last year) 26% to 69%. The Aberdeen IHS area women with diabetes had 51% more clinic visits per year than women without diabetes, but the groups had similar screening rates. CONCLUSION: Cancer-screening rates for American Indian and Alaska Native women vary by region. In the Aberdeen IHS area, women with diabetes had more visits (missed opportunities) but similar screening rates as women without diabetes. The diabetic audit could be used to monitor national IHS cancer-screening trends for women with diabetes and in the Aberdeen IHS area for all women aged 50 to 69 years.

Fetal distress increases interleukin-6 and interleukin-8 and decreases tumour necrosis factor-alpha cord blood levels in noninfected full-term neonates.

OBJECTIVE: To assess the influence of fetal distress on interleukin-1beta, interleukin-6, interleukin-8 and on tumour necrosis factor-alpha blood levels in noninfected full-term neonates. STUDY DESIGN: In a multicentre prospective study, cord blood samples were obtained at time of delivery from 234 noninfected full-term neonates for the purposes of measuring serum levels of interleukin-1beta, interleukin-6, interleukin-8 and tumour necrosis factor-alpha using immunoassays. Women were classified into four groups according to the mode of delivery (vaginal delivery or caesarean section) and the presence or absence of fetal distress. The role of labour was also investigated. RESULTS: No significant relationship was found between cytokine cord blood levels and the mode of delivery. Fetal distress was associated with an increase in interleukin-6 (P = 0.01) and interleukin-8 (P < 0.001) levels, and a decrease in tumour necrosis factor-alpha (P < 0.001). Labour was also associated with a significant increase in interleukin-6 and interleukin-8 cord blood levels (P = 0.01 and P < 0.001, respectively). CONCLUSION: Fetal distress and labour were each associated with elevated interleukin-6 and interleukin-8 cord blood levels in noninfected full term neonates while only fetal distress was associated with decreased tumour necrosis factor-alpha levels.

Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes.

Erythrokeratodermias are a clinically heterogeneous group of rare autosomal dominant disorders of cornification with overlapping features including hyperkeratosis and erythema. We ascertained five extended pedigrees with different phenotypes for a linkage study. Three families presented with localized erythrokeratodermia variabilis, and one with erythrokeratodermia and ataxia. Another family had Greither disease associated with variable hyperkeratotic plaques. Despite their phenotypic differences, both erythrokeratodermia variabilis and erythrokeratodermia with ataxia map to a common region in 1p34-p35. Multipoint linkage and haplotype analyses place erythrokeratodermia variabilis between the marker D1S496 and D1S186 with a maximum LOD score of 12.88. Our linkage results provide compelling evidence for genetic homogeneity among families of mixed European and French-Canadian origin. In contrast, results excluded Greither's disease from the established erythrokeratodermia variabilis gene region indicating genetic heterogeneity of erythrokeratodermias. Based on recombinations, two genes assigned to 1p34-p35 were excluded: cartilage matrix protein and avian myelocytosis viral oncogene. Connexin-37 (GJA4), a member of the connexin gene family, maps within the erythrokeratodermia variabilis region and is an attractive candidate gene. Direct sequencing of the coding region of GJA4 in four patients revealed several variations, including a novel polymorphism within the 5' cytoplasmic domain, but no pathogenic mutations were found, thus excluding Connexin-37 as a candidate. There is evidence, however, that other epidermally expressed connexins cluster in this region, and one may yet be determined to play a role in the pathogenesis of erythrokeratodermia variabilis.

[Severe head injuries in neonates and infants: physiopathological and therapeutic aspects]. / Traumatismes crâniens graves du nouveau-né et du nourrisson: particularités physiopathologiques et thérapeutiques.

Severe head injuries in infants have specific circumstances such as obstetrical injury, battered infant, shaken infant. Pediatric scales must be used for neurological evaluation, the Bicêtre scale being a sensitive index of clinical course. Transfontanellar ultrasound can be useful as first line tool of evaluation of brain injury, but computerized tomography scan is necessary to correctly assess the brain lesions and the presence of hematoma. Hemorragic lesions can rapidly lead to hypovolemic state which must be prevented, or treated without delay. Treatment requires hemodynamics and hydroelectrolytic support, measures to control intracranial hypertension, sedation, and neurosurgical intervention according to the hemorragic lesions.

Neonatal nosocomial respiratory infection with coronavirus: a prospective study in a neonatal intensive care unit.

The aim of this prospective study was to evaluate the incidence of viral respiratory infection in hospitalized premature newborn infants and to assess the role of coronaviruses. All hospitalized premature infants with a gestational age less than or equal to 32 weeks were included. Tracheal or nasopharyngal specimens were studied by immunofluorescence for coronaviruses, respiratory syncytial virus, adenoviruses, influenza and parainfluenza viruses. Forty premature infants were included; 13 samples were positive in 10 newborns (coronaviruses n = 10; influenza 1 n = 2; adenovirus n = 1). None was positive at admission. All premature infants infected with coronaviruses had symptoms of bradycardia, apnea, hypoxemia, fever or abdominal distension. Chest X-ray revealed diffuse infiltrates in two cases. However, no significant difference was observed between infected and non-infected premature infants for gestational age, birth weight, duration of ventilation, age at discharge, incidence of apnea or bradycardia. Nosocomial respiratory tract infection with coronaviruses appears to be frequent. The clinical consequences should be evaluated in a larger population.

[Prenatal diagnosis of congenital cystic adenomatoid malformation of lung: perinatal management. Apropos of 4 cases]. / Malformation kystique adénomatoïde pulmonaire congénitale de diagnostic anténatal: prise en charge périnatale. A propos de quatre observations.

BACKGROUND: Cystic adenomatoid malformation of the lung can be seen by ultrasonography during pregnancy. Surgical excision of the affected lobe is indicated during the first days of life. CASES REPORT: Four neonates were admitted to an intensive care unit from March 1988 to February 1992, due to cystic adenomatoid malformation of the lung, that had been diagnosed by ultrasonography at 19, 22, 34 and 37 weeks of gestational age, respectively. These malformations were not associated with other abnormalities and were type I (three cases) and II (one case) according to Stocker's classification. Only one patient became symptomatic, requiring intubation by 72 hours of age. Surgical excision of the affected lobe was performed in three patients at 4 hours, 2 and 7 days of life, respectively, with a normal long-term survival. A segmental resection was performed at 5 days of life in the remaining symptomatic patient but persistence of cystic lesions required lobectomy at 10 months. CONCLUSIONS: Early perinatal management of cystic adenomatoid malformations of the lung is necessary as surgical excision is indicated as soon as possible, even in asymptomatic patients.

[Pathogen role of coronavirus in pediatric intensive care: retrospective analysis of 19 positive samples with indirect immunofluorescence]. / Rôle pathogène des coronavirus en réanimation pédiatrique: analyse rétrospective de 19 prélèvements positifs en immunofluorescence indirecte.

BACKGROUND: Coronaviruses (CV) are ARN-containing agents that are responsible for mild upper respiratory tract infections in adults and children. Their pathogenicity in neonates is not wellknown. POPULATION AND METHODS: Eighty five samples of tracheal or nasopharyngeal secretions were obtained from January to October 1991 from 53 children (29 less than 1 month of age; 19 from 1 month to 1 year; five older than 1 year). They were examined for respiratory syncytial virus, adenovirus, myxovirus influenza and parainfluenza and coronavirus by immunofluorescence (IF). RESULTS: Nineteen samples from nine newborns and three infants were positive for coronavirus. The mean birth weight of the nine neonates was 2100 +/- 840 g; their mean gestational age was 34 +/- 5 weeks and their mean age at diagnosis was 21 +/- 9 days. Apnea and bradycardia were the main symptoms in this group. Blood C-reactive protein was not elevated and blood cultures were sterile. One infant was admitted for near-miss; the two others were admitted at birth because they suffered from chronic lung disease (pulmonary hypoplasia and bronchopulmonary dysplasia). An acute episode of pulmonary deterioration occurred at the time of coronavirus infection. Both died one at 4 months and the other at 10 months. CONCLUSION: Coronaviruses seem to be responsible for respiratory tract infections in hospitalized neonates and chronically ventilated infants.

[Fibrofolliculoma. Treatment with copper vapor laser]. / Le fibrofolliculome. Traitement par laser à vapeur de cuivre.

There are many clinical presentations to fibrofolliculoma, described by Birt, Hogg and Dubé: the solitary and multiple forms, with or without other skin tumors, could also be markers of intestinal polyposis. Little is known of its pathogenesis. A case of multiple fibrofolliculoma of the face and neck is described. A new therapeutic approach by copper vapour laser is proposed.

[Severe hypernatremic dehydration disclosing Netherton syndrome in the neonatal period]. / Déshydratation hypernatrémique sévère révélant un syndrome de Netherton en période néonatale.

BACKGROUND: Netherton's syndrome is characterized by ichthyosis, trichorrhexis invaginata and other air shaft anomalies, and atopic diathesis. The ichthyosis is present at birth and can be complicated by hypernatremic dehydration. CASE REPORT: Adrien was the first child of non-consanguineous parents. His birth weight was 3,110 g. Ichthyosis was present at birth and the diagnosis of Netherton's syndrome was subsequently confirmed by skin biopsy. He was admitted to intensive care at the age of 4 days for a 20% loss of weight and dehydration. His blood chemistry was: Na+ = 192 mmol/l; K+ = 6.9 mmol/l; Cl- = 136 mmol/l; urea = 21 mmol/l; glucose = 12.1 mmol/l; creatinine = 209 mumol/l; hematocrit = 51%. Urinary analysis gave: Na+ = 113 mmol/l; K+ = 97 mmol/l; urea = 105 mmol/l. Progressive rehydration resulted in normal diuresis 24 hours later and a slow normalization of natremia to 138 mmol/l on day 10. Despite preventive i.v. phenobarbital, he developed convulsions on day 5 when his natremia was 177 mmol/l i.e. after a drop of 0.6 mmol/hour. The convulsions disappeared when he was given phenytoin and placed on respiratory support, but status epilepticus appeared on day 18 with normal natremia. This status epilepticus was not influenced by several antiepileptic drugs and was only cured when the patient was given tetracosactide followed by hydrocortisone plus sodium valproate. Adrien is now 3 years old and is neurologically and mentally normal. CONCLUSION: Hypernatremic dehydration can be a complication of neonatal ichthyosis; it may be severe with very high blood sodium concentration. Corticosteroids can be useful for treating persistent convulsions.

Acrokeratosis paraneoplastica (Bazex' syndrome).

A 55-year-old white man born in Canada presented with all the clinical features of acrokeratosis paraneoplastica of Bazex. He showed the characteristic violaceous erythema and scaling of the nose and face, the aural helices, and the palmoplantar regions with severe nail dystrophy. Extensive examinations failed to reveal any associated malignancy up to 5 months after the onset of the skin eruption. While the skin was improving, and although the patient was still asymptomatic except for a weight loss of 5 kg, evidence of metastatic squamous cell carcinoma of the cervical region was obtained. Only palliative treatment could be undertaken. The bizarre clinical aspects of the syndrome are reviewed.

[Peristomal pyoderma gangrenosum in a patient with ulcero-hemorrhagic rectocolitis]. / Pyoderma gangrenosum péri-stomale chez un patient atteint de recto-colite ulcéro-hémorragique.

Cutaneous manifestations of chronic ulcerative colitis are numerous and present in 20 p. 100 of the patients. The case of a 49-year old man with peristomal pyoderma gangrenosum (PG) is presented. In November, 1983, one year after the onset of chronic ulcerative colitis, the patient underwent total colectomy. The formation of an ileal reservoir resulted in a pelvic abscess which necessitated right lower ileostomy. Because of severe ulcerations around the stoma, the ileostomy was transferred to the left lower abdomen. Similar inflammatory ulcerations developed, and the diagnosis of pyoderma gangrenosum was made. The patient responded very well to dapsone combined with prednisone for only 6 months. The possibility of PG being an autoimmune condition is discussed, as well as the differential diagnosis. The several therapeutic approaches are summarized. The peristomal localization of PG in this patient suffering from chronic ulcerative colitis seems to be rather unique. No other case has been reported so far, to our knowledge.

Increased Frequency of Apo E-ND phenotype and hyperapobeta-lipoproteinemia in normolipidemic subjects with xanthelasmas of the eyelids.

Apolipoprotein E isomorphs in very low density lipoproteins and apolipoprotein B of low density lipoproteins were measured in the plasma of normolipidemic subjects with xanthelasmas of the eyelids and in appropriate control groups. All patients tested in the experimental group had an apolipoprotein EII to apolipoprotein EIII ratio typical of the heterozygous state for familial dysbetalipoproteinemia, a hyperapobetalipoproteinemia, or both. Some patients had concomitant atherosclerosis. This is the first report of an increased frequency of the apolipoprotein E-ND phenotype in normolipidemic xanthelasma. This condition should not be dismissed as benign; tissue lipid deposition in the absence of hyperlipidemia might be related to the presence of lipoproteins of abnormal composition with an enhanced atherogenic potential.

[Supratentorial hemorrhage of hypertensive origin during operation: an unusual complication of surgery on the posterior fossa in the sitting position (author's transl)]. / Hémorragie supra-tentorielle peropératoire d'origine hypertensive: complication inhabituelle d'une chirurgie de la fosse postérieure en postition assise.

The authors report a case of a massive hemorrhage in the basal ganglia after an uncomplicated posterior fossa intervention for removal of an isolated metastasis of a breast carcinoma. The etiology of this large hematoma was most likely secondary to a sudden rise of the arterial blood pressure during the removal of the tumor, probably due to an irritation of the vaso-motor centers of the medulla. This complication is exceptional since only two similar cases have been reported in the literature, but this possibility should be kept in mind in any patient developing a progressive hemiparesis and deterioration of the level of consciousness immediately after a sub-occipital craniectomy.