Consistency of safety profile of new oral anticoagulants in patients with renal failure.

BACKGROUND: The use of new oral anticoagulants (NOACs) in patients with impaired renal function has raised major concerns, in particular the possibility of an increased risk of bleeding due to accumulation. The aims of this work were to assess the safety of NOACs in patients with renal failure and describe the relationship between clinical events and drug renal excretion magnitude. METHODS: All phase III trials comparing NOACs with vitamin K antagonists (VKAs) in patients with estimated glomerular filtration (eGFR) rate < 50 mL min(-1) were eligible. The main safety and efficacy outcomes were major bleeding and thrombosis. A meta-regression was performed to estimate the correlation between the treatment effect estimate and the percentage of renal excretion. RESULTS: Nine studies (12 272 patients) were included. A significantly greater relative reduction in major bleeding was seen for NOACs with renal excretion <50% (RR, 0.61; CI, 0.51-0.74) than for those with high renal excretion (RR, 0.96; CI, 0.85-1.07) (interaction test, P < 0.0001). A linear relationship between the relative risk of major bleeding and the magnitude of renal excretion was found by meta-regression (R(2)  = 0.66, P = 0.03). For thrombosis, a greater treatment effect of NOA vs. INR-adjusted VKA was observed in patients with eGFR < 50 mL min(-1) (RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal excretion was found. CONCLUSIONS: New oral anticoagulants were at least as effective as VKAs, with reduced risks of major bleeding and thrombosis in patients with eGFR < 50 mL min(-1) . The renal excretion of these new drugs seemed to modify the safety profile, contrary to the efficacy.

[Very preterm infant (< 32 weeks) vs very low birth weight newborns (1500 grammes): comparison of two cohorts]. / Grands prématurés infant (< 32 semaines) vs nouveau-nés de très faible poids de naissance (< 1500 grammes): comparison de deux cohortes.

UNLABELLED: Studies concerning very preterm newborns are either defined by birth weight (<1500 g) or gestational age (<32 weeks). The aim of our study was to underline limits of cohort definitions by birth weight. METHODS: Data come from the Nord Pas de Calais EPIPAGE cohort. Every birth occurring in 1997 before 32 weeks or with a birth weight less than 1500 g and transferred in a neonatal unit was included. Two cohorts were defined, one by gestational age (<32 weeks), the other by birth weight (<1500 g). Two subgroups could be defined from these to cohorts: group A (<32 weeks and > or =1500 g), from cohort (<32 weeks), group B (> or =32 weeks and <1500 g) from cohort (<1500 g). RESULTS: Five hundred nine newborns were included. Perinatal characteristics of both cohorts seemed comparable. The analysis by subgroups A and B revealed an excess of pulmonary and neurological morbidity in very preterm infant compared to very low birth weight newborn. This was linked to an excess of growth restricted newborns in this cohort with more advanced gestational ages. CONCLUSION: Cohorts of very preterm newborns should rather be defined by gestational age. If not possible, results in very low birth weight cohorts should also be given by gestational age and rate of growth restriction should be described.

[Steinert's disease and pregnancy. A case report and recent literature]. / Maladie de Steinert et grossesse. A propos d'un cas et des données récentes de la littérature.

Steinert's disease or myotonic dystrophy is a heredo-degenerative neuroendocrinal dystrophy. It is an autosomal dominant disorder. The arising of a congenital myotonic dystrophy of one of the new-born children of the maternity hospital enabled to diagnose the Steinert's disease of his mother. A review of the international literature enabled us to recall its interactions with pregnancy. There is an aggravation of myotonia and multiple obstetric complications such as miscarriage, premature onset of labor, polyhydramnios, stillbirth, difficulties during the evacuation, atonic postpartum hemorrhage, anesthetic-accidents. The congenital variant of myotonic dystrophy (6 to 30% of the cases) is a severe disease with a high mortality. It is only seen in the offspring of mothers who themselves have myotonic dystrophy. The myotonic dystrophy gene has been isolated and the mutation-causing myotonic dystrophy was found to result from a series of trinucleotide (CTG) repeats located in the 3' untranslated region of the gene. The direct diagnosis is henceforth possible both on the fetus and parents. Steinert's disease and its association with pregnancy are rare, especially when the affected parent has hypogonadism. The diagnosis of the congenital form is difficult because of the mother is unaware of the disorder. Family and personal history may give hints: hydramnios, appearance delay and reduced fetal movements, and the association at birth of generalized hypotonia with neonatal respiratory distress.

Pharmacokinetic study of piperacillin in newborns relating to gestational and postnatal age.

The pharmacokinetics of piperacillin after a single 75-mg/kg intravenous injection as analyzed in 28 neonates with gestational ages of 29 to 40 weeks (A = 29 to 31 weeks, B = 33 to 35 weeks, C = 38 to 42 weeks) and birth weights of 860 to 3900 g during 35 courses. Serum concentrations of piperacillin were determined by high pressure liquid chromatography. A one compartment open model characterized the disposition of piperacillin. Twenty courses were given between Day 3 and Day 5 of life. The elimination half-life and total body clearance were related to gestational age. Differences were significant between Groups A and B and Group C for half-life (4.3 +/- 1.9 and 3.35 +/- 0.75 vs. 2.47 +/- 0.72 hours) and for clearance (1.68 +/- 0.6 and 1.8 +/- 0.4 vs. 2.46 +/- 0.36 ml/min/kg). Volumes of distribution were similar in the 3 groups, from 516 +/- 108 to 633 +/- 226 ml/kg. Fourteen courses were given from Day 9 to Day 11 of life. The same differences were observed between Groups A and B and Group C. Elimination half-life was significantly reduced with simultaneous increase of the total body clearance. In clinical practice, 75-mg/kg intravenous injections every 12 hours during the first week of life and every 8 hours in the second week provide appropriate concentrations in infants of less than 36 weeks gestational age. In full term newborns the 75-mg dosage is appropriate but the number of injections must be increased to 3/24 h for the first week and 4 times daily thereafter.

Respiratory mechanics in mechanically ventilated newborns: a comparison between passive inflation and occlusion methods.

A passive inflation method was described for measuring total respiratory elastance and resistance during mechanical ventilation in adult patients (Rossi et al., J Appl Physiol 58:1849, 1985). We applied this method to preterm and full-term mechanically ventilated newborn infants and we compared the results with those obtained by the occlusion method. We performed 37 tests in 16 newborn infants (B.W. 880-4,500 g; G.A. 28-42 weeks), between 1 and 45 days of postnatal age, ventilated with a Servo Ventilator 900C, set in controlled-volume mode. Flow was measured through a pneumotachograph inserted between the endotracheal tube (ETT) and the breathing circuit, tidal volume by integration of flow and airway pressure directly at the airway opening. Flow, volume, and pressure were recorded on an X/Y plotter to obtain pressure-volume (P/V), flow-volume (V/V) loops, and pressure-time curves. Occlusion was performed by using the end-inspiratory and the end-expiratory pause buttons of the ventilator. Analysis of P/V and V/V loops provided respiratory system compliance (Crs, infl.), resistance (Rrs, infl.), and "intrinsic positive end-expiratory pressure" (PEEPi, infl.). These values were compared with Crs, occl., Rrs, occl., and PEEPi, occl. measured by the occlusion method. The measurements were well correlated (Crs, infl./Crs, occl.: r = 0.90; Rrs, infl./Rrs, occl.: r = 0.91; PEEPi, infl./PEEPi, occl.: r = 0.91). Rrs, infl./Rrs, occl. and PEEPi, infl./PEEPi, occl. did not differ significantly. However, Crs, occl. was 15% higher than Crs, infl. (P less than 0.01). The passive inflation method is simple to use and well tolerated in preterm and full-term ventilated newborn infants, it provides accurate results, and can be a good alternative to occlusion methods. It requires, however, a constant inflation flow and adaptation to the ventilator.

[Acute bacterial and fungal neonatal meningitis]. / Méningites néonatales aiguës bactériennes et fongiques.

Neonatal meningitis has two closely related features: the mechanism of infection and the nature of the pathogen. When transmitted from mother to foetus, the infection is mainly caused by one of three microorganisms: Streptococcus group B, Escherichia coli or Listeria monocytogenes. It may occur before birth, in which case meningitis is of early onset and has a rather poor prognosis. When it occurs later, the infection is a pathological consequence of physiological bacterial colonization, and its symptoms and prognosis are those of post-natal meningitis. Post-natal infections are facilitated by a pre-existing pathology or by prematurity. The responsible organisms (Gram-positive or Gram-negative bacteria, or yeasts) are often multiresistant. Advances in biology provide increasingly clearer explanation of the cerebral complications that determine the medium- and long-term prognosis. The variety of organisms and their frequent resistance to antibacterials make it necessary to use antibiotics that possess an exceptionally broad spectrum.

Neonatal hypertension and thrombosis of the ductus arteriosus.

In a case of neonatal hypertension, radiographic findings showed multiple thromboembolism from the ductus arteriosis diverticulum. Hypertension was well controlled by captopril during the neonatal period. The long-term follow-up of 8 years with normal cardiovascular and renal function indicates a good prognosis for acquired renovascular neonatal hypertension.

[Cerebral magnetic resonance imaging in the neonatal period. Initial results]. / Imagerie cérébrale par résonance magnétique en période néonatale. Résultats initiaux.

The place of neonatal cerebral MRI and its specific contribution compared with conventional imaging techniques were evaluated in 36 patients. The difficulties specific to the patient population studied met during this preliminary period are described, with their local solutions. A preliminary evaluation of the diagnostic and prognostic value of MRI according to the disease state and gestational age is presented. The specific contribution of MRI compared with transfontanellar ultrasonography and CT scan is discussed.

Risk factors for fatal pulmonary interstitial emphysema in neonates.

Among 315 infants treated for respiratory distress syndrome (RDS) over a 2 year period, 32 prematures were studied retrospectively with the diagnosis of pulmonary interstitial emphysema (PIE). Eighteen died. In this group, birth weight below 1600 g, need for oxygen above 0.6 on the 1st day and appearance of bilateral pulmonary interstitial emphysema within the first 48 h of life were significant risk factors, with a mortality rate of 94%. In order to recognize one or more early criteria predictive of fatal PIE, we compared ventilation parameters on day 1 between neonates with fatal PIE and those with the same birth weight and initial severity of RDS but without PIE treated during the same period. High positive inspiratory pressure on day 1 was found to be the most significant parameter associated with further appearance of fatal pulmonary interstitial emphysema. A cut-off level of 26 cm H2O was found to be discriminant. These criteria may be useful in selecting those neonates who might best benefit from a new therapy such as high frequency ventilation, before irreversible lesions appear.

[Efficacy of percutaneous caffeine in the treatment of apnea in the premature infant]. / Efficacité de la caféine transcutanée dans le traitement des apnées du prématuré.

In 18 prematures (gestational age less than 32 weeks), an aqueous monohydrated caffeine colloidal gel was administered topically. High plasma levels were rapidly obtained with a loading dose divided in 4 applications by massaging, 1 ml of gel per kg body weight, at 12 hour intervals (18 mg caffeine base/kg). Maintenance was then instituted with a dose of 0.5 ml/kg/day. Treatment was initiated before 8 days of life, in children under assisted ventilation but without severe pulmonary involvement, during the period of weaning from the respirator. A good local and general tolerance was invariably observed and remarkable therapeutic efficacy was obtained.

Evolution of the prematurity before the 32nd week from 1980 to 1985 in a tertiary perinatal center in Lille, France.

127 infants were born alive before the 32nd week of gestation in the H. Salengro obstetrical unit from the University Hospital of Lille from January 1980 to December 1985. During this period the annual number of deliveries was constant, 2700. Two periods were considered, 1980-1982 and 1983-1985. The number of such premature infants increased slightly: from 56 to 71. The most striking feature was the dramatic increase in infants born after induction of delivery for fetal reasons. Another finding is the statistically significant lowering of gestational age and birthweight of the spontaneously born infants. These trends counterweight the efficacy of the policy of prevention. When considering the morbidity and the mortality, hyaline membrane disease still plays a preeminent role in this population.

Proximal phocomelia and radial ray aplasia in fetal valproic syndrome.

We describe a child with multiple congenital anomalies born to a women treated with valproic acid (1000 mg/day) for post traumatic epilepsy. Defects included the typical dysmorphism of the "fetal valproic syndrome", bilateral radial ray aplasia, unilateral proximal phocomelia of the upper limb, kidney hypoplasia and brain atrophy. A direct teratogenic effect of valproic acid is suspected on an experimental basis, and validated by two previous reports of radial defects after valproic acid exposure.

The internal cavoatrial derivation for temporary vascular exclusion of the liver in the dog.

Vascular exclusion of the liver by clamping the hepatic pedicle and inserting an internal cavoatrial shunt allows bloodless hepatic surgery to be performed. The internal cavoatrial shunt performed on 30 dogs was studied to define its optimal hemodynamic characteristics. The internal diameter should measure half the caliber of the inferior vena cava and the total surface of the holes allowing blood flow to the shunt must be three times the internal caliber of the shunt. The aortic clamping associated with the clamping of the hepatic pedicle and the insertion of the internal cavoatrial shunt considerably diminishes the arterial blood pressure variations resulting from the splanchnic stasis. Administration of methylprednisolone (30 mg/kg) at the beginning of the experiment also plays a role in preventing alterations in the small intestine.

[Porcelain gallbladder and cancer (author's transl)]. / Vésicules porcelaines et cancers.

The porcelain gallbladder is a rare entity. It reaches especially the old woman. Most of the porcelain gallbladders have a great clinical latence. A cancer of the gallbladder exists in eleven per cent of the cases: this justifies a systematic cholecystectomy of the calcified gallbladders, even if they are asymptomatic. Another digestive cancer exists in nine per cent of the cases. Three personal observations of porcelain gallbladder which are associated with a cancer are described: they confirm the facts of the literature.

[Granular cell myoblastoma or Abrikosov's tumor of the esophagus]. / Tumeur à cellules granuleuses, dite tumeur d'Abrikossoff, de l'oesophage.

Granular cell myoblastoma or Abrikossoff's tumor of the esophagus are exceptional: fiveteen cases have been described in the literature. In this work we present the following case: discovery of a sub mucosal tumor during a systematic fibroscopic examination of an anemix patient. Only histological examination was able to make the diagnosis.

[Effect of commonly practiced manoeuvres in vascular microsurgery. Study under the scanning electron microscope (author's transl)]. / Retentissement des manoeuvres couramment pratiquées en microchirurgie vasculaire. Etude au microscope électronique à balayage.

The authors studied in 100 Wistar rats the manoeuvres that may commonly be carried out during vascular microanastomosis of diameter less than 3 mm (aorta and posterior vena cava): clamping for 30 to 45 minutes, bipolar electrocoagulation of the collateral arteries, more or less marked pinching of the vascular wall. The risk of thrombosis seems all the greater when: --the surgeon is inexperienced: viz. trauma with the forceps, parietal tears at the level of the stitches, two many threads passed for hemostasis (all these factors accentuate the fibrinoid and platelet deposits); --bipolar electrocoagulation of a collateral artery applied too close to the vessel to be anastomosed (less than 1 mm.)The formation of a smooth and regular fibrinous pseudo-intima appears within 48 to 72 hours which may explain the elective onset of thromboses before this delay.