Pharmacological enhancement of mGlu5 receptors rescues behavioral deficits in SHANK3 knock-out mice.

SHANK3 (also called PROSAP2) genetic haploinsufficiency is thought to be the major cause of neuropsychiatric symptoms in Phelan-McDermid syndrome (PMS). PMS is a rare genetic disorder that causes a severe form of intellectual disability (ID), expressive language delays and other autistic features. Furthermore, a significant number of SHANK3 mutations have been identified in patients with autism spectrum disorders (ASD), and SHANK3 truncating mutations are associated with moderate to profound ID. The Shank3 protein is a scaffold protein that is located in the postsynaptic density (PSD) of excitatory synapses and is crucial for synapse development and plasticity. In this study, we investigated the molecular mechanisms associated with the ASD-like behaviors observed in Shank3Δ11-/- mice, in which exon 11 has been deleted. Our results indicate that Shank3 is essential to mediating metabotropic glutamate receptor 5 (mGlu5)-receptor signaling by recruiting Homer1b/c to the PSD, specifically in the striatum and cortex. Moreover, augmenting mGlu5-receptor activity by administering 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide ameliorated the functional and behavioral defects that were observed in Shank3Δ11-/- mice, suggesting that pharmaceutical treatments that increase mGlu5 activity may represent a new approach for treating patients that are affected by PMS and SHANK3 mutations.

Radical hypo-fractionated radiotherapy with volumetric modulated arc therapy in lung cancer : A retrospective study of elderly patients with stage III disease.

BACKGROUND: This study aimed to analyse the feasibility and acute toxicity of radical hypo-fractionated radiotherapy (RT) for elderly patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We conducted a retrospective evaluation of treatment with volumetric modulated arc therapy (VMAT) of elderly patients affected by stage III inoperable NSCLC. The dose prescription was 56 Gy in 20 fractions, 55 Gy in 22 fractions, or 50 Gy in 20 fractions. Target volume included only the primary lesion and the infiltrated lymph nodes. The primary end point was acute and late toxicity, while secondary end points were progression-free survival (PFS), and overall survival (OS). RESULTS: In all, 41 patients were included in this analysis. The mean age of the patients was 78.6 years, and 22 patients had staged IIIA while 19 patients had stage IIIB disease. All but one patient had pathological nodal involvement; 15 patients received chemotherapy before RT. Acute grade 1-2 toxicity was recorded in 25 (61%) patients. Late toxicity was recorded in 13 (32%) patients. No cases of G3 or G4 toxicity were recorded. Complete response was obtained in two (5%) patients, 26 (63%) showed a partial response, and two (5%) experience disease progression. At a mean follow-up of 9.9 months (range, 1.1-25.4), 17 patients had died from disease progression, one died from other causes, and 23 were alive. Median OS was 13.7 ± 1.5 months (95% CI: 10.7-16.7), OS at 12 and 18 months was 51.3 ± 9.5% and 35.1 ± 10.1%, respectively. Median PFS was 13.7 ± 2.3 months (95% CI: 9.1-18.2), and PFS at 12 and 18 months was 50.1 ± 9.9% and 38.9 ± 10.4%, respectively. CONCLUSION: Radical hypo-fractionated VMAT is a promising treatment for locally advanced NSCLC in the elderly. The use of hypo-fractionated radiotherapy for lung cancer in older patients can be considered a valuable approach, particularly for patients with poor performance status or refusing other treatment approaches.

Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections.

BACKGROUND: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. METHODS: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17­109 days, 64. 1% boys), hospitalized in the Pediatric Departments at "Sapienza" University Rome and Bambino Gesù Children's Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. RESULTS: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. CONCLUSIONS: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found. TRIAL REGISTRATION: Policlinico Umberto I: protocol 213/14, 3085/13.02.2014, retrospectively registered. Bambino Gesù Children's Hospital: protocol n. RF-2010-2317709.

Global seroprevalence of rubella among pregnant and childbearing age women: a meta-analysis.

Background: We conducted a meta-analysis of articles published between January 2000 and July 2016 with the aim of defining the proportion of rubella seronegative women of childbearing age (WCBA), providing the best information available on the seroprevalence of rubella in this population. We selected articles published in the time period between 2000 and 2016. The pooled prevalence of rubella seronegative women was calculated by a fixed effect model and a random effect model, according to the heterogeneity among studies. Studies were sub-grouped by population type (pregnant women and WCBA with no mention of ongoing pregnancy) and by geographic area [World Health Organization (WHO) region]. Sensitivity analysis was performed to assess the stability of results. We found important differences in rubella seronegativity prevalence estimates by WHO Region. About 88% of the studies conducted on pregnant women reported a seronegativity rate >5%. The pooled rubella seronegativity prevalence was 9.3%. When considering population groups, we obtained a seronegativity pooled estimate of 9.4% for pregnant women and of 9.5% for WCBA with no mention of ongoing pregnancy. This meta-analysis shows that the proportion of WCBA who are susceptible to rubella is still high. The figures are worrisome, taking into account that the WHO set at 5% the rubella susceptibility threshold for WCBA.

[Detection and early treatment of subjects at high risk of clinical psychosis: Definitions and recommendations]. / Détection et traitement précoce des sujets à haut risque clinique de psychose : définitions et recommandations.

In children and adolescents, psychotic disorders already represent one of the leading causes of disability-adjusted life years. During the past two decades, early detection of risk for psychosis has been intensively investigated, and in particular, predictive power for early signs of risk has been initiated and translated into clinical practice. In particular, the attenuated and transient positive symptoms of the ultra-high risk criteria, and the basic symptom criterion "cognitive disturbances", open promising routes to an indicated prevention and have recently been considered by the European Psychiatric Association (EPA) as diagnostic criteria of a psychosis-risk syndrome. The EPA recently provided evidence-based recommendations on the early detection of clinical high risk (CHR) for psychosis in patients with mental distress. In 2015, experts in the field of early detection conducted a meta-analysis reporting on studies examining conversion rates to psychosis in non-overlapping samples meeting at least one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria, examining the effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates. In the 42 identified samples, comprising more than 4000 CHR patients who had been mainly identified by means of UHR criteria and/or the basic symptom criterion 'cognitive disturbances' (COGDIS), conversion rates showed considerable heterogeneity. While UHR and COGDIS criteria were related to comparable conversion rates until a 2-year follow-up, rates for COGDIS were significantly higher for follow-up periods beyond 2 years. Differences in onset and frequency requirements of symptomatic UHR criteria, or in their different consideration of functional decline, substance use and co-morbidity, did not seem to have an impact on conversion rates. The 'genetic risk and functional decline' UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for the early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states. The EPA guidance on early intervention aimed to provide evidence-based recommendations on early intervention in CHR states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were also made by experts in the field of early intervention in psychoses and derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. In addition to analyses of treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status. Overall, age-related specificities and developmental transitions in the early detection and intervention in psychoses should be better accounted for in future research.

Incidence of surgical site infections in children: active surveillance in an Italian academic children's hospital.

BACKGROUND: Surgical Site Infections (SSIs) account for 16-34% of all health-care associated infections. This study aimed to assess the incidence rate of SSIs in children who underwent surgical procedures in an academic children's hospital in Italy. STUDY DESIGN: Prospective cohort study. METHODS: We actively followed-up 0-17 year old children at 30 days of surgical procedures without implants conducted during one index week per quarter, from the second quarter of 2014, to the first quarter of 2016 (8 index weeks in total). Follow up data were collected by telephone interview, or derived by clinical records if patients were still hospitalized. SSIs were defined according to case definitions of Centers for Diseases Control, Atlanta, USA. We calculated cumulative incidence of SSIs per 100 surgical procedures, by patient characteristics, procedure characteristics, and quarter. To investigate variables associated with SSIs, we compared characteristics of procedures with SSIs with those of procedures without SSIs. RESULTS: Over the study period, SSI incidence was 1.0% (19 cases/1,830 surgical procedures). SSI incidence was significantly lower after ear, nose and throat procedures compared to all other procedures, and significantly decreased over time. Duration of surgery was a risk factor for SSIs; patients with SSIs had a significantly longer total length of stay (LOS), due to a prolonged post-operative LOS. CONCLUSION: As reported in adults, this study confirms that SSIs are associated with longer hospitalizations in children. Active surveillance of SSIs is an important component of the overall strategy to reduce the incidence of these infections in children.

Roux-en-Y hepatico-jejunostomy for a left segmental graft: Do not twist the loop, stick it!

Biliary complications remain a major challenge for long-term success after LT, as it is, as a rule, the most common technical - early and late - complication that occurs, and because these complications contribute to a significant number of late graft losses and retransplantations. In the pediatric age group, both biliary atresia, as the patient's condition, and the use of a left liver graft, obtained by a liver division technique, make it necessary for the use of a Roux-en-Y jejunal loop for the biliary reconstruction in the majority of cases. A slight modification of the technique is presented, consisting of a straight positioning along the cut surface (rather than the conventional position that results in a harpoon shape). A favorable outcome in terms of a technical complication and graft survival was observed. This way of doing this is an interesting variation and adds to the surgical armamentarium.

Splitting livers: Trans-hilar or trans-umbilical division? Technical aspects and comparative outcomes.

UNLABELLED: Controversy remains about the best line of division for liver splitting, through Segment IV or through the umbilical fissure. Both techniques are currently used, with the choice varying between surgical teams in the absence of an evidence-based choice. We conducted a single-center retrospective analysis of 47 left split liver grafts that were procured with two different division techniques: "classical" (N = 28, Group A) or through the umbilical fissure and plate (N = 19, Group B). The allocation of recipients to each group was at random; a single transplant team performed all transplantations. Demographics, characteristics, technical aspects, and outcomes were similar in both groups. The grafts in Group A, prepared with the classical technique, were procured more often with a single BD orifice compared with the grafts in Group B; however, this was not associated with a higher incidence of biliary problems in this series of transplants (96% actual graft survival rate [median ± s.d. FOLLOW-UP: 26 ± 20 months]). Both techniques provide good quality split grafts and an excellent outcome; surgical expertise with a given technique is more relevant than the technique itself. The classical technique, however, seems to be more flexible in various ways, and surgeons may find it to be preferable.

Whooping cough, twenty years from acellular vaccines introduction.

Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

Epidemiology of pertussis in Italy: disease trends over the last century.

We reviewed the epidemiology of pertussis in Italy over the last 125 years to identify disease trends and factors that could have influenced these trends. We described mortality rates (1888-2012), case fatality rates (1925-2012), cumulative incidence rates (1925-2013) and age-specific incidence rates (1974-2013). We compared data from routine surveillance with data from a paediatric sentinel surveillance system to estimate under-notification. Pertussis mortality decreased from 42.5 per 100,000 population in 1890 to no reported pertussis-related death after 2002. Incidence decreased from 86.3 per 100,000 in 1927 to 1 per 100,000 after 2008. Vaccine coverage increased from 32.8% in 1993 to about 96% after 2006. As for under-notification, mean sentinel/routine surveillance incidence ratio increased with age (from 1.8 in <1 year-olds to 12.9 in 10-14 year-olds). Pertussis mortality decreased before the introduction of immunisation. Incidence has decreased only after the introduction of pertussis vaccine and in particular after the achievement of a high immunisation coverage with acellular vaccines. Routine surveillance does not show an increase in cumulative incidence nor in ≥ 15 year-olds as reported by other countries. Underrecognition because of atypical presentation and the infrequent use of laboratory tests may be responsible for under-notification, and therefore affect incidence reports and management of immunisation programmes.

Coinfection in acute gastroenteritis predicts a more severe clinical course in children.

The objectives of this study were to determine the incidence of enteric pathogens causing acute gastroenteritis (AGE) among hospitalized children in a large Italian hospital, to measure the incidence of coinfections, and to compare the clinical characteristics of those infected with one versus multiple agents. A prospective study was conducted from March 2010 to April 2011 at the Bambino Gesù Pediatric Hospital in Rome, Italy. All patients between 1 month and 16 years of age admitted to the Pediatric Department with a diagnosis of AGE were eligible for enrollment. Two stool samples for each patient were tested for gastrointestinal pathogens. We summarized the clinical severity of episodes, describing the duration of diarrhea, duration and frequency of vomiting, fever, and severity of dehydration. All the patients underwent medical evaluation with estimation of dehydration. One or more etiological agents were detected in 151 out of 232 patients (65.1%), while we did not detect any etiological agent in 81 (34.9%). Rotavirus was detected in 96 (63.6%), adenovirus in 17 (11.2%), norovirus in 7 (4.6%), toxin-producing Clostridium difficile in 23 (15.2%), Salmonella spp. in 15 (9.9%, B group in 12/15 and D group in 3/15), C. perfringens in 12 (7.9%), Campylobacter spp. in 6 (4%), and verotoxigenic Escherichia coli (VTEC) in 2 (1.3%). In 27 children out of 151 (17.9%), we found evidence of coinfection. Coinfection with rotavirus and toxin-producing C. difficile was the most common (63%). Children with coinfection had a more severe clinical presentation and had a higher probability to be severely dehydrated, independently of age and living community type.

DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia.

This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.

Moderate hypofractionation and simultaneous integrated boost with volumetric modulated arc therapy (RapidArc) for prostate cancer. Report of feasibility and acute toxicity.

PURPOSE: In the present study, the acute toxicity profiles for prostate patients treated with simultaneous integrated boost (SIB) with volumetric modulated arcs in a hypofractionated regime are reported. PATIENTS AND METHODS: A total of 70 patients treated with RapidArc between May 2010 and September 2011 were retrospectively evaluated. Patients were stratified into low (36%), intermediate (49%), and high-risk (16%) groups. Target volumes (expanded to define the planning volumes (PTV)) were clinical target volume (CTV) 1: prostate; CTV2: CTV1 + seminal vesicles; CTV3: CTV2 + pelvic nodes. Low-risk patients received 71.4 Gy to PTV1; intermediate-risk 74.2 Gy to PTV1 and 61.6 or 65.5 Gy to PTV2; high-risk 74.2 Gy to PTV1, 61.6 or 65.5 Gy to PTV2, and 51.8 Gy to PTV3. All treatments were in 28 fractions. The median follow-up was 11 months (range 3.5-23 months). The acute rectal, gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to EORTC/RTOG scales. RESULTS: Acute toxicities were recorded for the GU [G0 = 31/70 (44%), G1 = 22/70 (31%); G2 = 16/70 (23%); G3 = 1/70 (1%)], the rectum [G0 = 46/70 (66%); G1 = 12/70 (17%); G2 = 12/70 (17%); no G3], and the GI [G0 = 54/69 (77%); G1 = 11/69 (16%); G2 = 4/69 (6%); no G3]. Median time to rectal, GU, and GI toxicities were 27, 30, and 33 days, respectively. Only the GI toxicity correlated with stage and pelvic irradiation. Univariate analysis presented significant correlations between GI toxicity and intestinal irradiation (V(50 Gy) and V(60 Gy)). In the multivariate analysis, the only significant dosimetric variable was V(50 Gy) for the intestinal cavity. CONCLUSION: Moderate hypofractionation with SIB and RapidArc was shown to be safe, with acceptable acute toxicity. Longer follow-up is needed to assess late toxicity and clinical outcome.

Nasopharyngeal microbiota in hospitalized children with Bordetella pertussis and Rhinovirus infection.

Despite great advances in describing Bordetella pertussis infection, the role of the host microbiota in pertussis pathogenesis remains unexplored. Indeed, the microbiota plays important role in defending against bacterial and viral respiratory infections. We investigated the nasopharyngeal microbiota in infants infected by B. pertussis (Bp), Rhinovirus (Rv) and simultaneously by both infectious agents (Bp + Rv). We demonstrated a specific nasopharyngeal microbiome profiles for Bp group, compared to Rv and Bp + Rv groups, and a reduction of microbial richness during coinfection compared to the single infections. The comparison amongst the three groups showed the increase of Alcaligenaceae and Achromobacter in Bp and Moraxellaceae and Moraxella in Rv group. Furthermore, correlation analysis between patients' features and nasopharyngeal microbiota profile highlighted a link between delivery and feeding modality, antibiotic administration and B. pertussis infection. A model classification demonstrated a microbiota fingerprinting specific of Bp and Rv infections. In conclusion, external factors since the first moments of life contribute to the alteration of nasopharyngeal microbiota, indeed increasing the susceptibility of the host to the pathogens' infections. When the infection is triggered, the presence of infectious agents modifies the microbiota favoring the overgrowth of commensal bacteria that turn in pathobionts, hence contributing to the disease severity.

Performance of a component-based allergen-microarray in the diagnosis of cow's milk and hen's egg allergy.

BACKGROUND: The food challenge test (FCT) is the gold standard for the diagnosis of food allergy. This procedure is time consuming, costly and can induce potentially severe symptoms. An ideal in vitro test should allow to avoid the FCT. Objective To assess the clinical performance of microarray for specific IgE (sIgE) detection in children with challenge-proven/excluded cow's milk (CM) or hen's egg (HE) allergy. METHODS: One-hundred and four children with suspected IgE-mediated hypersensitivity to CM or HE were studied. In all patients, skin prick test, ImmunoCAP, microarray and FCT were performed. RESULTS: The microarray components Bos d 8 for CM (27/58 patients) and Gal d 1 (20/46 patients) and Gal d 2 (24/46) for HE were the most frequently recognized allergens. Using the FCT results as the reference parameter, sIgE to Bos d 8 and Gal d 1 had the highest area under the curves. These were not significantly different from those obtained using the ImmunoCAP. Use of 95% clinical decision points (CDP) for sIgE to Bos d 8 and Gal d 1 resulted in higher negative predictive values (78% and 79%, respectively) than those obtained with the ImmunoCAP (57% and 59%). CONCLUSIONS: Our results show that in children with suspected CM or HE allergy, the microarray has a good ability to predict the FCT results. In a clinical application perspective, the microarray could be used as a second-level assay, if the ImmunoCAP sIgE is <95% CDP. This approach would lead to a decrease in the number of the FCT to be performed, as well as of positive FCTs with a subsequent decrease in severe reaction risk.

Correlation between abnormal brain excitability and emotional symptomatology in paediatric migraine.

We investigated a possible correlation between brain excitability in children with migraine and tension-type headache (TTH) and their behavioural symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The mismatch negativity (MMN) and P300 response were recorded in three successive blocks to test the amplitude reduction of each response from the first to the third block (habituation). MMN and P300 habituation was significantly lower in migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05). In migraineurs, but not in TTH patients, significant positive correlations between the P300 habituation deficit and the CBCL scores were found (P < 0.05), meaning that the migraineurs with the most reduced habituation showed also the worst behavioural symptomatology. To the best of our knowledge, this is the first study showing a correlation between neurophysiological abnormality and emotional symptomatology in migraine, suggesting a role of the latter in producing the migrainous phenotype.

Prevention of congenital rubella and congenital varicella in Europe.

Despite the availability of safe and efficacious vaccines, cases of congenital rubella and varicella syndrome still occur in Europe. As of 2004, several countries had high proportions of women of childbearing age that were susceptible to rubella and varicella virus infection.

Role of tricuspid regurgitation in fetal echocardiographic diagnosis of pulmonary atresia with intact ventricular septum.

OBJECTIVE: Pulmonary atresia with intact ventricular septum (PAIVS) is a rare cardiac malformation with a broad spectrum of anatomical manifestations, varying from types suitable for biventricular repair to those with diminutive right ventricle and primitive ventriculocoronary connections (VCC), more suitable for single-ventricle palliation or heart transplantation. We sought to test whether tricuspid regurgitation is an easily detectable prenatal criterion with which to identify PAIVS patients at lower risk of needing postnatal single-ventricle palliation. METHOD: We identified retrospectively patients with both fetal diagnosis and postnatal confirmation of PAIVS who were seen at Bambino Gesù Hospital between January 2000 and December 2006. Tricuspid valve/mitral valve (TV/MV) ratio, presence and severity of tricuspid regurgitation and direct visualization of VCC were evaluated by echocardiography both pre- and postnatally. RESULTS: We identified 22 patients with a prenatal diagnosis of PAIVS. Four pregnancies were terminated and one fetus was lost to follow-up, leaving 17 patients for the analysis. Based on postnatal cardiac catheterization and/or echocardiography we divided our population in two groups: Group 1 included 10 patients with VCC; Group 2 included seven patients without VCC. At fetal echocardiography, tricuspid regurgitation was absent in all ten Group 1 patients and present in all seven Group 2 patients. VCC were seen directly in 6/10 Group 1 patients and in no Group 2 patients. A cut-off value of 0.56 for the TV/MV ratio was highly predictive of VCC during fetal life, with a sensitivity of 100% and a specificity of 90%. CONCLUSIONS: The absence of tricuspid regurgitation in fetuses affected by PAIVS is a strong prenatal echocardiographic predictor of VCC, as is a TV/MV ratio < 0.56. Fetuses presenting with tricuspid regurgitation and relatively large right ventricle are at lower risk of needing single-ventricle palliation postnatally. This inforation could be helpful for appropriate prenatal counseling and postnatal decision-making.