Balloon Aortic Valvuloplasty as Bridge-to-Decision in High Risk Patients with Severe Aortic Valve Stenosis

Background. A sizable group of patients with symptomatic aortic stenosis (AS) can undergo neither surgical aortic valve replacement (AVR) nor transcatheter aortic valve implantation (TAVI) because of clinical contraindications. The aim of this study was to assess the potential role of balloon aortic valvuloplasty (BAV) as a “bridge-to-decision” in selected patients with severe AS and potentially reversible contraindications to definitive treatment. Methods. We retrospectively enrolled 645 patients who underwent first BAV at our Institution between July 2007 and December 2012. Of these, the 202 patients (31.2%) who underwent BAV as bridge-to-decision (BTD) requiring clinical re-evaluation represented our study population. BTD patients were further subdivided in 5 groups: low left ventricular ejection fraction; mitral regurgitation grade ≥3; frailty; hemodynamic instability; comorbidity. The main objective of the study was to evaluate how BAV influenced the final treatment strategy in the whole BTD group and in its single specific subgroups. Results. Mean logistic EuroSCORE was 23.5±15.3%, mean age was 81±7 years. Mean transaortic gradient decreased from 47±17 mmHg to 33±14 mmHg. Of the 193 patients with BTD-BAV who received a second heart team evaluation, 72.5% were finally deemed eligible for definitive treatment (25.4%for AVR; 47.2% for TAVI): respectively, 96.7% of patients with left ventricular ejection fraction recovery; 70.5% of patients with mitral regurgitation reduction; 75.7% of patients who underwent BAV in clinical hemodynamic instability; 69.2% of frail patients and 68% of patients who presented relevant comorbidities. 27.5% of the study population was deemed ineligible for definitive treatment and treated with standard therapy/repeated BAV. In-hospital mortality was 4.5%, cerebrovascular accident occurred in 1% and overall vascular complications were 4% (0.5% major; 3.5% minor). Conclusions. Balloon aortic valvuloplasty should be considered as bridge-to-decision in high-risk patients with severe aortic stenosis who cannot be immediate candidates for definitive percutaneous or surgical treatment.

Severe Accident Simulation of Small Modular Reactors

Since the Three Mile Island Unit 2 (TMI-2), accident in 1979 which led to the meltdown of about one half of the reactor core and to limited releases of radioactive materials to the environment, an important international effort has been made on severe accident research. The present work aims to investigate the behaviour of a Small Modular Reactor during severe accident conditions. In order to perform these analyses, a SMR has been studied for the European reference severe accident analysis code ASTEC, developed by IRSN and GRS. In the thesis will be described in detail the IRIS Small Modular Reactor; the reference reactor chosen to develop the ASTEC input deck. The IRIS model was developed in the framework of a research collaboration with the IRSN development team. In the thesis will be described systematically the creation of the ASTEC IRIS input deck: the nodalization scheme adopted, the solution used to simulate the passive safety systems and the strong interaction between the reactor vessel and the containment. The ASTEC SMR model will be tested against the RELAP-GOTHIC coupled code model, with respect to a Design Basis Accident, to evaluate the capability of the ASTEC code on reproducing correctly the behaviour of the nuclear system. Once the model has been validated, a severe accident scenario will be simulated and the obtained results along with the nuclear system response will be analysed.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

OBJECTIVES: Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. METHODS: A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2-4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). RESULTS: There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). CONCLUSIONS: If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.

Long-term outcome of symptomatic severe ostial vertebral artery stenosis (OVAS)

The optimal management of patients with symptomatic severe ostial vertebral artery stenosis (OVAS) is currently unclear. We analyzed the long-term outcome of consecutive patients with OVAS who received either medical treatment (MT) or vertebral artery stenting (VAS).

Improved detection of blood stream pathogens by real-time PCR in severe sepsis

Evaluation of the technical and diagnostic feasibility of commercial multiplex real-time polymerase chain reaction (PCR) for detection of blood stream infections in a cohort of intensive care unit (ICU) patients with severe sepsis, performed in addition to conventional blood cultures.

Impact of chorioamnionitis and preeclampsia on neurodevelopmental outcome in preterm infants below 32 weeks gestational age

ABSTRACT Aim: Intrauterine conditions may interfere with fetal brain development. We compared the neurodevelopmental outcome between infants <32 weeks gestational age after maternal preeclampsia or chorioamnionitis and controls. Methods: Case-control study on infants with maternal preeclampsia, chorioamnionitis and controls (each n = 33) matched for gestational age. Neurodevelopment at two years was assessed with the Bayley Scales of Infant Development II. Results: Ninety-nine infants were included with a median gestational age of 29 weeks (range 25-32). Median mental developmental index (MDI) was 96 in the control, 90 in the chorioamnionitis and 86 in the preeclampsia group. Preeclampsia infants had a lower MDI compared with the control group (univariate p = 0.021, multivariate p = 0.183) and with the chorioamnionitis group (univariate p = 0.242; multivariate p = 0.027). Median psychomotor index was 80.5 in the control, 80 in the preeclampsia and 85 in the chorioamnionitis group, and was not different between these three groups (p > 0.05). Chorioamnionitis or preeclampsia exposure was not associated with major neurodevelopmental impairments (cerebral palsy, MDI<70, PDI<70). Conclusion: The results of this preliminary study suggest that preeclampsia and chorioamnionitis play a relatively minor role among risk factors for adverse neurodevelopment outcome. Postnatal factors such as ventilation and bronchopulmonary dysplasia may have a greater impact on neurodevelopmental outcome.

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult-onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early-onset myopathy was rapidly progressive. At 8 years, the patient is wheel-chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A > G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non-affected adults. The phenotypic spectrum of tRNA(Leu(UUR)) m.3302A > G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.

Intensity-modulated radiotherapy for a rendu-osler-weber disease patient with recurrent severe epistaxis: a case report

We present a case of a Rendu-Osler-Weber disease patient with recurrent life threatening epistaxis demanding multiple blood transfusions despite of repetitive endoscopic laser and electrocoagulations, endovascular embolisation, septodermoplasty, and long-term intranasal dressings. As alternative treatment modalities repeatedly failed and the patient became almost permanently dependent on nasal dressing, we performed a highly conformal intensity-modulated radiotherapy of the nasal cavity; a total dose of 50 Gy in 2 Gy single fractions was applied. The therapy was very well tolerated, no acute toxicities occurred. Two weeks after the last radiation dose had been applied, the nasal dressing could be removed without problems. Endoscopical control revealed an almost avascular white mucosa without any trace of bleeding spots; previously existing hemangiomas and crusts had disappeared. After a 1-year-follow up, the patient had no significant recurrent epistaxis.

Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass

Glucagon-like peptide-1 (GLP-1) receptors are highly overexpressed in benign insulinomas, permitting in vivo tumour visualisation with GLP-1 receptor scanning. The present study sought to evaluate the GLP-1 receptor status in vitro in other pancreatic disorders leading to hyperinsulinaemic hypoglycaemia, specifically after gastric bypass surgery.

Increasing hematocrit above 28% during early resuscitative phase is not associated with decreased mortality following severe traumatic brain injury

To prevent iatrogenic damage, transfusions of red blood cells should be avoided. For this, specific and reliable transfusion triggers must be defined. To date, the optimal hematocrit during the initial operating room (OR) phase is still unclear in patients with severe traumatic brain injury (TBI). We hypothesized that hematocrit values exceeding 28%, the local hematocrit target reached by the end of the initial OR phase, resulted in more complications, increased mortality, and impaired recovery compared to patients in whom hematocrit levels did not exceed 28%.

Ultrastructural changes in diaphragm neuromuscular junctions in a severe mouse model for Spinal Muscular Atrophy and their prevention by bifunctional U7 snRNA correcting SMN2 splicing

In Spinal Muscular Atrophy (SMA), the SMN1 gene is deleted or inactivated. Because of a splicing problem, the second copy gene, SMN2, generates insufficient amounts of functional SMN protein, leading to the death of spinal cord motoneurons. For a "severe" mouse SMA model (Smn -/-, hSMN2 +/+; with affected pups dying at 5-7 days), which most closely mimicks the genetic set-up in human SMA patients, we characterise SMA-related ultrastructural changes in neuromuscular junctions (NMJs) of two striated muscles with discrete functions. In the diaphragm, but not the soleus muscle of 4-days old SMA mice, mitochondria on both sides of the NMJs degenerate, and perisynaptic Schwann cells as well as endoneurial fibroblasts show striking changes in morphology. Importantly, NMJs of SMA mice in which a modified U7 snRNA corrects SMN2 splicing and delays or prevents SMA symptoms are normal. This ultrastructural study reveals novel features of NMJ alterations - in particular the involvement of perisynaptic Schwann cells - that may be relevant for human SMA pathogenesis.

Influenza A(H1N1) infection and severe cardiac dysfunction in adults: A case series

BACKGROUND: While viral myocarditis and heart failure are recognized and feared complications of seasonal influenza A infection, only limited information is available for 2009 influenza A(H1N1)-induced heart failure. METHODS AND MAIN FINDINGS: This case series summarizes the disease course of four patients with 2009 influenza A(H1N1) infection who were treated at our institution from November 2009 until September 2010. All patients presented with severe cardiac dysfunction (acute heart failure, cardiogenic shock or cardiac arrest due to ventricular fibrillation) as the leading symptom of influenza A(H1N1) infection. Two patients most likely had pre-existent cardiac pathologies, and three required catecholamine therapy to maintain hemodynamic function. Except for one patient who died before influenza A(H1N1) infection had been diagnosed, all patients received antiviral therapy with oseltamivir and supportive critical care. Acute respiratory distress syndrome due to influenza A(H1N1) infection developed in one patient. Heart function normalized in two of the three surviving patients but remained impaired in the other one at hospital discharge. CONCLUSIONS: Influenza A(H1N1) infection may be associated with severe cardiac dysfunction which can even be the leading clinical symptom at presentation. During an influenza pandemic, a thorough history may reveal flu-like symptoms and should indicate testing for H1N1 infection also in critically ill patients with acute heart failure.

Management of hemorrhage in severe pelvic injuries

Major pelvic trauma results in high mortality. No standard technique to control pelvic hemorrhage has been identified.

Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia

Adverse events in utero may predispose to cardiovascular disease in adulthood. The underlying mechanisms are unknown. During preeclampsia, vasculotoxic factors are released into the maternal circulation by the diseased placenta. We speculated that these factors pass the placental barrier and leave a defect in the circulation of the offspring that predisposes to a pathological response later in life. The hypoxia associated with high-altitude exposure is expected to facilitate the detection of this problem.

Long-term clinical outcomes in patients diagnosed with severe digital ischemia

To investigate the aetiology and long-term clinical outcomes of patients diagnosed with digital ischemia.