[Complication rates after amniocentesis in twin pregnancies: a case control study and review of the literature]. / Evaluation de la fréquence des complications après amniocentèse dans les grossesses gémellaires: étude cas témoins et revue de la literature.

BACKGROUND: Twin pregnancies nave a nigner risk of fetal malformation than singleton pregnancies. The literature suggests a higher risk of fetal loss associated to amniocentesis in twin pregnancies compared to singleton ones. However, published studies are very heterogeneous, rarely controlled or are not taking into account many confounding factors. OBSERVATIONS: To assess all complications that can be associated with amniocentesis in twin pregnancies. MATERIALS AND METHODS: We collected retrospectively medical data concerning twin pregnancies that underwent an amniocentesis in Erasme and Edith Cavell (IMEC) hospitals in Brussels since February 2002. We compared all the complications to those of twin pregnancies that haven't undertaken amniocentesis and singleton pregnancies that underwent amniocentesis. The cases and control groups were matched for age, parity and gestational age at the time of amniocentesis. RESULTS: 94 cases of twin pregnancies that underwent amniocentesis (group I) were included and compared to 94 twin pregnancies that haven't undertaken amniocentesis and 94 singleton pregnancies that underwent amniocentesis. The rate of intra-uterine growth restriction and pregnancies obtained by assisted reproductive medicine was significantly higher in the group I for the latter, the rate of late miscarriage was 2.1%, the rate of overall foetal loss is 2.68%, the rate of overall preterm birth ≤ 37 SA was 59.3% (6.4% ≤ 28 SA and 29.8% ≤ 34 SA). These complications were not significantly higher than those of the control groups after multivariable logistic regression analysis. CONCLUSION: Our data showed no increased risk of foetal loss or preterm birth among twins that underwent amniocentesis compared to controls.

[Medical abortion and fetuses born lifeless registration]. / L'interruption médicale de grossesse et la déclaration des foetus " nés sans vie ".

The late miscarriages, the in utero deaths, the medical abortion are so many situations which lead to the tragic delivery of a lifeless born fetus. Since the 2nd half of the 20th century, the contraception, the ultrasound, the medically assisted procreation, the notions of desired pregnancies or invaluable pregnancies modified our glance to the fetus. The prenatal diagnosis allowed anticipating dramatic situations which previously arose at birth or afterwards. The professionals of the perinatal medicine wonder about the care of this particular mourning. Every stage of this difficult process for the parents since the announcement of an anomaly to the fetus, the prognosis evaluation, the decision-making then its realization is decoded. This necessarily multidisciplinary practice brought closer the professionals of the birth. It is a question of respecting the parents who wish recognition of the dead fetus to ritualize this loss as much as those for whom the symbolism is not the same and for whom in case of obligation of recognition the emotional consequences could be disastrous. The answer to be given to these requests requires remaining vigilant in order not to modify the legal status of the embryo or the fetus and not to call into question the legitimacy of the termination of pregnancy.

Les fausses couches tardives, les morts in utero, les interruptions médicales de grossesses sont autant de situations qui conduisent à l'accouchement d'un foetus né sans vie. Depuis la 2e moitié du XXe siècle, la limitation du nombre d'enfants comme la notion d'enfant désiré voire surinvesti, la contraception, la procréation médicalement assistée, l'échographie, ont modifié notre regard sur le foetus. Le diagnostic anténatal a permis d'anticiper des situations dramatiques qui auparavant survenaient à la naissance ou après. Les professionnels de la médecine périnatale s'interrogent sur la prise en charge de ce deuil particulier. Chaque étape de ce cheminement difficile pour les parents depuis l'annonce d'une anomalie chez le foetus, l'évaluation pronostique, la prise de décision puis sa réalisation est décodée. Cette pratique obligatoirement multidisciplinaire a rapproché les professionnels de la naissance. Il s'agit de respecter les parents qui souhaitent que soit faite une place symbolique au foetus mort pour ritualiser cette perte autant que ceux pour qui la symbolique n'est pas la même et pour lesquels l'obligation de reconnaissance pourrait accentuer la souffrance psychologique de manière désastreuse. La réponse à donner à ces demandes nécessite par ailleurs de rester vigilant afin de ne pas modifier le statut juridique de l'embryon ou du foetus, ce qui affaiblirait automatiquement la légitimité de l'interruption volontaire de grossesse.

[Prenatal screening: the example of Down's syndrome screening]. / Le dépistage prénatal : 1'exemple de la trisomie 21.

Prenatal screening for Down's syndrome initially targeted high-risk pregnant women (> 35 years old). However, the vast majority of babies with Down's syndrome are born to younger women (as the majority of babies are born in this age category). It was first discovered that some serum analytes were altered in pregnancies affected with Down's syndrome (triple test). In the nineties, the association between an increased nuchal translucency measurement and trisomy 21 was noted. The use of this measurement in combination with serum markers has enabled an increased detection rate but still at the cost of a false positive rate of around five percent (combined test). Recently, major advances in sequencing technologies have allowed reasearchers to make use of the cell free fetal DNA in maternal blood. This new test (named non invasive prenatal test) made it into clinical use as early as 2011 in some countries. Its sensitivity is above 99 % for trisomy 21 and the false positive rate is very low. It is risk-free and much more accurate than previous approaches. It is largely favored over an invasive test by high risk women (advanced maternal age or high-risk combined test). Its use is still restricted by a high cost which is for the moment still entirely beared by the patient. The availability of NIPT in our routine practice and the increased complexity of screening options have highlighted the need for a more dedicated counselling consultation before Down's syndrome screening is performed.

Study of correlation between forced vital capacity and demand for healthcare services in severe asthmatics.

BACKGROUND: Involvement of the small airways may be related to increased severity and increased demand for health care services and incurring in high costs, private or for the healthcare system. The hyperinflation consequent to this involvement reduces lung volumes, such as FVC, FEV1 and SVC. The aim of this study was to evaluate the correlation between the predicted values of FVC, FEV1 and SVC with the demand for healthcare services by severe asthmatics. METHODS: We retrospectively evaluated in order of arrival, the medical records of 98 patients with severe asthma, in step 4 treatment in the intercritical period of the disease, correlating the number of times each patient sought health care services represented by admissions to the ER, ICU and hospital wards due to asthma, in the year before the last spirometry and the predicted values of FVC, FEV1 and SVC. RESULTS: Our sample showed a clear and significant negative correlation between the predicted values of FVC, FEV1 and SVC and demand for healthcare services. CONCLUSION: For this sample we conclude, that reduced forced vital capacity correlated with asthma severity, defined by greater demand for care in the ER, ICU and hospital ward and was more evident in women.

The clinical and integrated management of COPD.

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60%predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2<88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe or "very severe COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneusly published in Multidisciplinary Respiratory Medicine 2014; 9:25.

γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia.

Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV reactivation after allo-SCT and reduced leukemic relapse. Given the potential of Vδ2-negative γδT cells to recognize CMV-infected cells and tumor cells, the molecular biology of distinct γδT-cell subsets expanding during CMV reactivation after allo-SCT was investigated. Vδ2(neg) γδT-cell expansions after CMV reactivation were observed not only with conventional but also cordblood donors. Expanded γδT cells were capable of recognizing both CMV-infected cells and primary leukemic blasts. CMV and leukemia reactivity were restricted to the same clonal population, whereas other Vδ2(neg) T cells interact with dendritic cells (DCs). Cloned Vδ1 T-cell receptors (TCRs) mediated leukemia reactivity and DC interactions, but surprisingly not CMV reactivity. Interestingly, CD8αα expression appeared to be a signature of γδT cells after CMV exposure. However, functionally, CD8αα was primarily important in combination with selected leukemia-reactive Vδ1 TCRs, demonstrating for the first time a co-stimulatory role of CD8αα for distinct γδTCRs. Based on these observations, we advocate the exploration of adoptive transfer of unmodified Vδ2(neg) γδT cells after allo-SCT to tackle CMV reactivation and residual leukemic blasts, as well as application of leukemia-reactive Vδ1 TCR-engineered T cells as alternative therapeutic tools.

An unusual case of congenital cardiac cyst of the interventricular septum.

We present a very rare case of a neonatal multiple haemangiomatosis with a cystic interventricular cardiac haemangioma. An anechoic cyst of 10 mm of diameter, located in the superior third of the interventricular septum was found by foetal echocardiography at 30 weeks of pregnancy. The baby was born at 39 weeks of pregnancy and the skin was covered with multiple purple cutaneous haemangiomas. As neonatal haemangiomatosis may be associated with visceral haemangiomas, the diagnosis of cardiac haemangioma was considered and transthoracic echocardiography revealed a translucent cyst consistent with this diagnosis. At 6 months of age, the cardiac mass was barely visible and most cutaneous lesions had regressed without treatment. Cardiac haemangiomas must be considered in the diagnosis of cystic masses, and the present case emphasizes the tendency towards spontaneous regression of these lesions.

Candidate genes for COPD in two large data sets.

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Antenatal embolization of a large chorioangioma by percutaneous Glubran 2 injection.

We describe a case of a large chorioangioma diagnosed at 18 weeks' gestation. Because of advanced fetal heart failure at 23 weeks' gestation, embolization of the chorioangioma's vessels was performed by percutaneous injection of Glubran 2 surgical glue. There was no immediate secondary effect of treatment. Devascularization was complete and durable. Signs of fetal cardiac failure normalized after 1 month and a healthy infant was delivered at 38 weeks. To our knowledge this is the first reported case of perinatal survival after successful embolization of a chorioangioma using tissue glue.

Antenatal diagnosis of a sacrococcygeal teratoma.

Although rare, sacrococcygeal teratoma is the most common congenital tumor. We report a case of a precociously diagnosed and rapidly growing cystic lesion. These tumors may be associated with hemodynamic and hemorrhagic complications. Therefore, affected fetuses should be carefully followed during the entire pregnancy by ultrasound and MR imaging in order to evaluate the evolution of the mass, its consequences on the fetal organs and to appreciate the wellbeing of the fetus. Delivery and post natal work up can therefore be optimized.

Standards of care and clinical predictors in patients hospitalised for a COPD exacerbation--the Italian SOS (Stratification Observational Study).

BACKGROUND AND AIMS: Hospitalisations for chronic obstructive pulmonary disease (COPD) exacerbations are major events in the natural history of the disease in terms of survival, quality of life and risk of further episodes of exacerbation. The aims of study were to evaluate: 1. adherence to recommended standards of care; and 2. clinical factors influencing major outcomes during hospitalisation for an episode of COPD exacerbation and within a 6-month follow-up. METHODS: An observational, prospective study was conducted in 68 centres. Assessment of standards of care included diagnostic procedures (such as pulmonary function tests and microbiology) and management options (such as drug therapies, vaccinations and rehabilitation). Outcome measures relevant to the hospitalisation were: survival, need for mechanical ventilation, and length of stay (LOS). Outcomes at 6-months were: survival, exacerbations and hospitalisations for an exacerbation. Multivariate logistic regression was applied to evaluate the relation between clinical factors and outcomes. RESULTS: 931 patients were enrolled. Only 556 patients (59.7%) were diagnosed COPD and stratified for severity with the support of spirometry (FEV1/VC < or = 0.7) and were considered for outcome analysis. Among treatments, pulmonary rehabilitation and anti-smoking counselling were applied infrequently (14.5 and 8.1% of patients, respectively). Within six months 63 COPD patients (17.7%) had at least one episode of exacerbation prompting a further hospitalisation and 19 died (5.3%). Predictor of mortality was the co-morbidity Charlson index (odds ratio, OR 10.3, p=0.03 CI: 1.25-84.96). A further hospitalisation was predicted by hospitalisation for an exacerbation in the previous 12 months (OR 3.59, p=0.003 CI: 1.54-8.39). CONCLUSIONS: Standards of care were far lower than recommended, in particular 40% of patients were labelled as COPD without spirometry. COPD patients with a second hospitalisation in 12 months for an exacerbation had about 3 times the risk of suffering a new episode and hospitalisation in the following six months.

GOLD severity stratification and risk of hospitalisation for COPD exacerbations.

BACKGROUND AND AIM: The Italian Costs for Exacerbations in COPD ("ICE") study, following a pharmacoeconomic assessment of costs due to COPD exacerbations (primary endpoint), aimed also at evaluating (secondary endpoint) which clinical factors, among those considered for cost-analysis, may, at follow up, present a risk of new exacerbations and re-admission to hospital. MATERIALS AND METHODS: A prospective, multicentre study was carried out on COPD patients admitted to 25 Hospital Centres as a result of an exacerbation from October-December 2002. Following discharge, a 6-month follow-up was performed in each patient via three bi-monthly telephone interviews with a questionnaire administered by an investigator clinician. RESULTS: 570 patients were eligible for data processing, mean age 70.6 years (+/- 9.5 standard deviation, SD), males 69.2%. According to GOLD, severity stratification was as follows: moderate 36.4%; severe 31.3%; very severe 32.3%. 282 patients experienced at least one exacerbation at follow up, 42% of exacerbations requiring hospitalisation. No significant association was seen between exacerbations and GOLD stage or co-morbidities or treatments except LTOT. Conversely, COPD functional severity influenced hospitalisations very significantly, with relative risks 2.6 (95% Confidence Interval, CI 1.8-3.8) and 2.0 (CI 1.3-2.8) (GOLD very severe versus moderate and severe, respectively), and 1.3 (CI 0.85-2.1) (GOLD severe versus moderate). Hospitalisations were also significantly associated with treatments denoting more severe conditions (oral corticosteroids, oral theophylline, and LTOT). CONCLUSIONS: Severity stratification of COPD patients according to respiratory function classes as outlined in GOLD guidelines and need for LTOT are confirmed as important predictors of hospitalisation for an exacerbation.

Costs of chronic obstructive pulmonary disease (COPD) in Italy: the SIRIO study (social impact of respiratory integrated outcomes).

Chronic respiratory diseases affect a large number of subjects in Italy and are characterized by high socio-health costs. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and costs generated in 1 year by a population of patients with chronic obstructive pulmonary disease (COPD) in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data from COPD patients who reported spontaneously to pneumological centers participating in the study, the corresponding economic outcomes being assessed at baseline and after a 1-year survey. A total of 748 COPD patients were enrolled, of whom 561 [408 m, mean age 70.3 years (SD 9.2)] were defined as eligible by the Steering Committee. At the baseline visit, the severity of COPD (graded according to GOLD 2001 guidelines) was 24.2% mild COPD, 53.7% moderate and 16.8% severe. In the 12 months prior to enrollment, 63.8% visited a general practitioner (GP); 76.8% also consulted a national health service (NHS) specialist; 22.3% utilized Emergency Care and 33% were admitted to hospital, with a total of 5703 work days lost. At the end of the 1-year survey, the severity of COPD changed as follows: 27.5% mild COPD, 47.4% moderate and 19.4% severe. Requirement of health services dropped significantly: 57.4% visited the GP; 58.3% consulted an NHS specialist; 12.5% used Emergency Care and 18.4% were hospitalized. Compared to baseline, the mean total cost per patient decreased by 21.7% (p<0.002). In conclusion, a significant reduction in the use of health resources and thus of COPD-related costs (both direct and indirect costs) was observed during the study, likely due to a more appropriate care and management of COPD patients.

In utero urinary bladder rupture: a case report.

We report a case of foetal urinary bladder rupture due to posterior urethral valves. A megacystis was diagnosed in a male foetus during routine second trimester ultrasound examination. The diagnosis of bladder rupture was made as, one week later, the bladder became undetectable with the appearance of ascites. During the follow-up, no oligohydramnios developed and intercurrent ascites resolved spontaneously. There are three described mechanisms releasing bladder hyperpressure: bladder diverticles, unilateral vesicoureteral reflux and bladder rupture. In this case, another mechanism might be involved: a patent urachus. The urethral valves were resected and no other surgical treatment was needed. The renal function remained normal. No long-term vesical follow-up of this pathology is available in the literature.

Costs of asthma in Italy: results of the SIRIO (Social Impact of Respiratory Integrated Outcomes) study.

Bronchial asthma is a costly disease and the correlated social impact is ever increasing. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and the costs generated in 1 year by asthmatic patients investigated in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data of 577 patients with bronchial asthma who reported spontaneously to the pneumology centers involved in the study. Of these, 485 patients (300 f, mean age 49.2 years+/-16.3 S.D.) were eligible for analysis. At the baseline visit, the asthma severity was as follows: 26.2% intermittent, 37.1% mild persistent, 29.5% moderate, and 6.6% severe. In the 12 months prior to enrollment, 243 patients (50.1%) had visited the general practitioner (GP); 349 (72%) consulted a National Health Service (NHS) specialist; 68 (14%) utilized Emergency Care; and 50 (10.3%) had been admitted to hospital on account of asthma, with a total of 2059 work days lost. At the end of the 1-year survey, asthma severity changed as follows: 32.8% intermittent, 38.1% mild persistent, 23.7% moderate, and 4.3% severe, with a substantial drop in corresponding outcomes: 39.6% visited their GP, 51.5% visited an NHS specialist, 5.2% used Emergency Care, and 4.3% were admitted to hospital. Compared to baseline, the total average cost per patient decreased globally by 17.9% (p<0.001) after the 1-year survey. In conclusion, during the study period we observed a significant decline in health resources consumption and thus in asthma cost of illness, even though specific costs for the pharmaceutical treatment of asthma increased substantially. These results are likely due to a more strict control of patients and to their more appropriate clinical management.

Efficacy of pulmonary rehabilitation in chronic respiratory failure (CRF) due to chronic obstructive pulmonary disease (COPD): The Maugeri Study.

UNLABELLED: While the effectiveness of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) is well established, its effectiveness in the most severe category of COPD, i.e. patients with chronic respiratory failure (CRF), is less well known. OBJECTIVE: To verify the effects of PR in patients with CRF, and compare the level of improvement with PR in these patients to that of COPDs not affected by CRF. METHODS: A multi-centre study was carried out on COPD patients with versus without CRF. The PR program included educational support, exercise training, and nutritional and psychological counselling. Lung function, arterial gases, walk test (6MWT), dyspnoea (MRC; BDI/TDI), and quality of life (MRF(28); SGRQ) were evaluated. RESULTS: Thousand forty seven consecutive COPD inpatients (327 with CRF) were evaluated. In patients with CRF all parameters improved after PR (0.001). Mean changes: FEV(1), 112 ml; PaO(2), 3.0 mmHg; PaCO(2), 3.3 mmHg; 6MWT, 48 m; MRC, 0.85 units; MRF(28) total score, 11.5 units. These changes were similar to those observed in patients without CRF. CONCLUSIONS: This study, featuring the largest cohort so far reported in the literature, shows that PR is equally effective in the more severe COPD patients, i.e. those with CRF, and supports the prescription of PR also in these patients.

Perineal lipoma in a newborn boy--a case report.

We report the case of a newborn presenting with a pediculated mass arising from the anal margin. Antenatal sonogram and magnetic resonance imaging were unable to diagnose the precise nature of the lesion. Sacrococcygeal teratoma, an enterogenous cyst, a polyp, a prolapse or other perineal tumors were all proposed as possible entities. At birth, no other anatomic anomaly than this homogenous 2 cm para-anal lesion was seen. Excision of the mass was performed under general anesthesia. The postoperative histological exam showed mature fat cells. Reviewing the literature, there have been few previously reported cases of congenital perineal lipoma. It is a rare, benign and easy-to-treat condition that can be evocated by morphological sonography or magnetic resonance imaging (MRI).

Evolution of fetal ultrasonography.

The authors wish to highlight the evolution that has occurred in fetal ultrasound in recent years. A first significant evolution lies in the increasing contribution of first trimester ultrasound for the detection of fetal anomalies. Malformations of several organs and systems have been diagnosed during the first trimester. Furthermore the systematic measurement of the fetal neck translucency has led to increasing rate of detection of aneuploidies and heart malformations. For several years now, three-dimensional (3D) and 4D ultrasound (US) have been used as a complementary tool to 2D US for the evaluation of fetal morphology. This brings an improved morphologic assessment of the fetus. Applications of the techniques are increasing, especially for the fetal face, heart and extremities. The third field where fetal US is continuously providing important information is the knowledge of the natural history of diseases. This has brought significant improvement in the postnatal management of several diseases, especially urinary tract dilatation and broncho-pulmonary malformation.