Predictive value of Cardiac Magnetic Resonance: new and old parameters in the natural history of repaired Tetralogy of Fallot.

BACKGROUND: Patients with repaired Tetralogy of Fallot (rTOF) often develop pulmonary regurgitation (PR) and right ventricle (RV) dysfunction, experiencing increased mortality and morbidity rates in adulthood. Pulmonary valve replacement (PVR) timing to address PR is controversial. Cardiac Magnetic Resonance (CMR) is the gold standard for morpho-functional evaluation of complex cardiopathies. This study aims to identify CMR parameters predictive of adverse outcomes to help defining the best therapeutic management of rTOF patients. METHODS: 130 rTOF patients who underwent CMR (2006-2019) were enrolled in this retrospective single-center study. CMR, clinical, ECG and exercise data were analyzed. Univariate and multivariate analyses identified clinical and CMR parameters predictive of adverse outcomes both individually (e.g., death, arrhythmias, heart failure (HF), pharmacological therapy, QRS ≥ 160ms) and as composite outcome. RESULTS: Univariate analysis confirmed RV volumes and RV ejection fraction corrected for PR as adverse outcome predictors and identified interesting correlations: pulmonary artery bifurcation geometry and abnormal interventricular septum (IVS) motion with arrhythmias (p < .001; p = .037), HF (p = .049; p = .005), composite outcome (p = .039; p = .009); right atrium (RA) dimensions with the composite outcome and the outcomes individually (p < .001). The best predictive models by multivariate analysis included sex (male), RV and RA dilation for QRS ≥ 160ms, time form repair to CMR, age at TOF repair and IVS fibrosis for pharmacological therapy. CONCLUSIONS: Besides RV volumes, new adverse prognostic factors could guide rTOF therapeutic management: pulmonary arteries morphology, abnormal IVS motion, RV dysfunction, RA dilation. Perspective multicentric evaluation is needed to specify their effective role.

Methane in aquifers and alluvium overlying a coal seam gas region: Gas concentrations and isotopic differentiation.

The detection and attribution of methane in aquifers overlying oil and gas reservoirs has recently gained increasing attention internationally. The Surat Basin, in the Great Artesian Basin (GAB), Australia, hosts a coal seam gas (CSG) reservoir, with feedlots, town water supply, mines and agriculture that extract groundwater from aquifers that underly and overly the gas reservoir. This study aimed to use a multi-isotopic approach to differentiate biogenic methane generated in situ in GAB aquifers and the Condamine Alluvium, from the biogenic CSG produced from the underlying Walloon Coal Measures reservoir, to understand if gas had migrated or not. Dissolved methane (0.001 to 160 mg/l) and total methane concentrations (up to 91,818 ppmv) were measured using closed sampling methods and were higher than from open direct fill sampling (<0.001 to 25.4 mg/l), especially in gassy bores that contain dissolved methane above 10 to 13 mg/l. The CSG production waters and a gassy overlying aquifer bore had the most depleted water isotopes, and also the most enriched δ13C-DIC indicating strong methanogenesis. The majority of aquifers have isotopic signatures (δ13C-DIC, CH4 and CO2) indicating in situ methane production by primary CO2 reduction or fermentation, distinct from secondary microbial CO2 reduction in the CSG reservoir. Fractionation factors support methane production mainly via CO2 reduction, with fermentation in a subset of aquifer samples. The gas wetness parameters (636 to 20,000) are consistent with mainly microbial gases, with low dissolved ethane (max 0.04 mg/l). The majority of aquifer and alluvium samples in this study are consistent with in situ methane production, not migration, however in several gassy bores the methane source could not be clearly identified. This study is broadly applicable to understanding methane sources in aquifers overlying CSG reservoirs.

Cardiovascular mortality in patients with acute and chronic coronary syndrome: insights from the clinical evidence on ticagrelor.

OBJECTIVE: The purpose of this review is to discuss cardiovascular mortality as clinical outcome in the setting of both acute and chronic coronary syndromes (ACS and CCS) with a focus on the clinical evidence supporting the mortality benefit of ticagrelor across multiple subpopulations. MATERIALS AND METHODS: Papers considered for this review were retrieved from a PubMed search, using different combinations of keywords (e.g., mortality AND coronary syndrome AND dual antiplatelet therapy AND ticagrelor), without limitations in terms of publication date and language. RESULTS: Prevention of ischemic events and death is of outmost relevance in patients with ACS and CCS, given the high rate of recurrence of such events and fatalities. Owing to the evolving nature of patients with CCS, characterized by a broad spectrum of clinical presentations and previous medical history, as well as the advances in the therapeutic and invasive management of ACS, greater attention to the rate of hard clinical outcomes, improvement in the long-term prognosis, and reduction in the residual risk of recurrent events are increasingly reported among cardiologists. Dual antiplatelet therapy (DAPT) is the cornerstone of antithrombotic therapy aimed at lowering the rate of ischemic events and death in patients treated both conservatively and invasively after ACS, as well as improving prognosis in patients with CCS. Significant differences are emerging among oral P2Y12 inhibitors with regards to mortality benefit. CONCLUSIONS: Ticagrelor is an effective and well-tolerated option to attain a meaningful and clinically relevant reduction in cardiovascular mortality in both acute and chronic settings across a broad range of high-risk patient subpopulations with an acceptable payoff in terms of bleeding risk.

Real-world effectiveness of long acting aripiprazole: Treatment persistence and its correlates in the Italian clinical practice.

OBJECTIVES: To identify the variables that are associated with persistence to Aripiprazole-Long Acting (A-LAI), in adult patients with schizophrenia. METHODS: Observational, retrospective, non-interventional study involving 261 patients with schizophrenia. RESULTS: Eighty-six percent of study subjects were persistent for at least 6 months. All subjects with baseline CGI-S of 1 or 2, 95% of subjects with CGI-S of 3, 86% with CGI-S of 4, 82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7 were persistent. A-LAI treatment continuation rate was higher in patients with: 1) baseline CGI score ≤ 4; 2) schizophrenia dimension (LDPS) mania score ≤ 5; 3) psychotic spectrum schizoid score ≤ 11. CONCLUSIONS: A relatively high number of patients (n = 225, 86%) were persistent to A-LAI for at least 6 months. Not surprisingly, very severe patients were more unlikely to be persistent. However, it is noteworthy that a large number of subjects with high CGI score at the time when A-LAI was started (82% of subjects with CGI-S of 5, 73% of subjects with CGI of 6 and 90% of subjects with CGI of 7) were persistent. Larger, controlled, prospective and longer studies are warranted.

Clinical comparison between simple laminectomy and laminectomy plus posterior instrumentation in surgical treatment of cervical myelopathy.

BACKGROUND: Posterior stabilization in patients treated with laminectomy for spondylotic cervical myelopathy is still a debate. Despite both being reported in literature by several authors, some controversies still exist. The aim of this study is to compare clinical and radiological outcomes in patients treated with laminectomy or laminectomy with posterior stabilization. MATERIAL AND METHODS: We retrospectively evaluated 42 patients affected by cervical myelopathy (mean age 70.43 ± 5.03 years), 19 treated with laminectomy (group A) and 23 with laminectomy and posterior instrumentation (group B). Neurological status was assessed with Nurick scale, pain with VAS and radiological parameters with C2-C7 SVA, T1 slope and C2-C7 lordosis, clinical function with modified Japanese Orthopaedic Association score (JOA). Also, surgery time and blood loss were recorded. Student's t test was used for continuous variables, while Kruskal-Wallis test was used for categorical values. RESULTS: No differences were found in postoperative Nurick scale (p = 0.587), VAS (p = 0.62), mJOA (p = 0.197) and T1 slope (p = 0.559), while laminectomy with fusion showed better postoperative cervical lordosis (p = 0.007) and C2-C7 SVA (p < 0.00001), but higher blood loss (p < 0.00001) and surgical time (p < 0.00001). Both groups showed better Nurick scale (p = 0.00017 for group A and p = 0.00081 for group B), VAS (p = 0.02 for group A and p = 0.046 for group B) and mJOA (p < 0.00001 for both groups) than preoperative values. CONCLUSIONS: Both treatments are a valuable choice, offering some benefits and disadvantages against each other. Each procedure must be carefully evaluated on the basis of patients' general status, preoperative pain, signs of instability and potential benefits from cervical alignment correction.

'Real-life' report on the management of chronic GvHD in the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current 'real life' situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.

Surgical treatment of osteoporotic thoraco-lumbar compressive fractures: the use of pedicle screw with augmentation PMMA.

INTRODUCTION: The osteoporosis prevalence in population is age related. The aim of this single-center observational study was evaluate the middle- to long-term performance of cement (PMMA) augmented fenestrated pedicle screws in elderly patients with thoraco-lumbar compressive fractures by osteoporosis. MATERIALS AND METHODS: From 2011 to 2015 we treated 52 patients (20 males and 32 females) suffering from somatic osteoporotic fractures (T10-L2). The average age was 73.4 years, with an age range between 65 and 82 years. The treatment consisted of stabilization with pedicle screw augmentation with PMMA cement. Patients were clinically evaluated with Visual Analyzing System scale (VAS scale) and with low back disability questionnaire Oswestry, in pre and post surgery and during the follow up at 12 and 24 months. RESULTS: A total of 410 fenestrated pedicle screws with PMMA augmentation were implanted. No cases of loosening or pulling out of screws were recorded. There have been n 3 cases of thrombophlebitis, treated with oral anticoagulant drugs and 1 case of post-operative death due to ventricular fibrillation. No neurological complications occurred during the study. The mean VAS score decreased from 8.5 to 4.8 and the result remained stable during follow up. Oswestry questionnaire showed a mean decrease of low back pain of 24% in post-op period. CONCLUSION: Fenestrated screws with PMMA augmentation offers a possibility to treat patients with reduced bone quality due to severe osteoporosis.

Treatment of coronary bifurcation lesions with bioresorbable vascular scaffolds.

AIM: Aim of the study was to report on the feasibility and early safety and efficacy of Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) for coronary artery bifurcations (CABs) treatment at a single high-volume center. METHODS: All patients treated with Absorb implantation at our institution from March 2013 to March 2014 were enrolled in the prospective, single-center, ongoing, all-comers registry, which has the main purpose of evaluating the safety and efficacy of Absorb implantation in unselected patients treated in daily practice. In-hospital and at follow-up clinical outcomes of 46 patients undergoing treatment with Absorb in 46 CAB lesions were reported in the present study. RESULTS: Treated CAB lesions involved the left main in 13.0% of cases, the left anterior descending artery in 65.0%, the left circumflex in 19.6%, and the right coronary artery in 2.2%. Bifurcations were classified as true (47.8%) and non-true (52.2%) according to the Medina classification. The provisional and the two-BVS techniques were used in 78.3% and 21.7%, respectively. Two-BVS techniques included: mini-crush 13.0%; reverse culotte 2.2%; T-stenting 2.2%; and V-stenting 4.3%. No in-hospital adverse events occurred. At 6 months no adverse events occurred. Only one case of target lesion revascularization was observed at day 227. No stent thrombosis occurred during follow-up. CONCLUSION: Our preliminary experience suggested that CABs treatment with Absorb is feasible and associated with promising immediate and short-term clinical outcomes. However, larger studies with long-term follow-up are needed to adequately address the safety and efficacy of BVS use in CABs.

Haemorrhagic cystitis in haematopoietic stem cell transplantation (HSCT): a prospective observational study of incidence and management in HSCT centres within the GITMO network (Gruppo Italiano Trapianto Midollo Osseo).

UNLABELLED: Haemorrhagic cystitis (HC) is a recognised complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). This study evaluates the incidence and severity of HC in patients undergoing allogeneic HSCT during hospitalisation and within the first 100 days following transplant, looking at the use of prophylaxis, management of HC, outcomes at 100 days post transplant, and to identify any correlations between development of HC and the different conditioning regimens for transplant or HC prevention methods used. RESULTS: Four hundred and fifty patients (412 adult and 38 paediatric) were enrolled in this prospective, multicentre, and observational study. HC was observed in 55 patients (12.2%) of which 8/38 were paediatric (21% of total paediatric sample) and 47/412 adults (11.4% of total adult sample). HC was observed primarily in the non-related HSCT group (45/55; 81.8%, p= 0.001) compared to sibling and myeloablative transplant protocols (48/55; 87.3%; p= 0.008) and with respect to reduced intensity conditioning regimens (7/55;12.7%). In 33 patients with HC (60%), BK virus was isolated in urine samples, a potential co-factor in the pathogenesis of HC. The median day of HC presentation was 23 days post HSCT infusion, with a mean duration of 20 days. The most frequent therapeutic treatments were placement of a bladder catheter (31/55; 56%) and continuous bladder irrigation (40/55; 73%). The range of variables in terms of conditioning regimens and so on, makes analysis difficult. CONCLUSIONS: This multi-centre national study reported similar incidence rates of HC to those in the literature. Evidence-based guidelines for prophylaxis and management are required in transplant centres. Further research is required to look at both prophylactic and therapeutic interventions, which also consider toxicity of newer conditioning regimens.

A PHACES syndrome unmasked by propranolol interruption in a tetralogy of Fallot patient: case report and extensive review on new indications of beta blockers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and usually they don't require specific therapy. In 10-20% of cases IHs are able to generate complication and medical/surgical intervention is needed. For many decades standard treatment consisted in oral or intralesional corticosteroids until Leaute-Labreze and colleagues published the first report on the efficacy of propranolol for cutaneous infantile hemangiomas in 2008. IHs can be sometimes part of complex syndrome. Here we report the case of a patient with tetralogy of Fallot operated at 5 month of age who stopped propranolol treatment for hypoxic spells and unusually developed facial and subglottic IHs configuring the diagnosis of PHACES syndrome (posterior fossa brain malformations, hemangioma, arterial anomalies, cardiac defects and/or aortic coarctation, ocular anomalies and sternal defects). To our knowledge this is the first report in the international literature of a delayed appearance of an infantile hemangioma involving the skin and the airways (PHACES syndrome). The pathophysiological explanation relies on the mechanism of action of propranolol which seems to act initially with vasoconstriction, down-regulating proangiogenetic factors and inducing endothelial cell apoptosis. Many decades since their introduction ß-blockers are useful in a growing group of diseases. The pleiotropic effect of ß-adrenoceptors antagonists is not yet deeply understood, residing in neurohormonal regulation systems and angiogenesis and proving to be an effective treatment from cardiovascular to oncological illnesses.

Towards true unipolar ECG recording without the Wilson central terminal (preliminary results).

We present an innovative bio-potential front-end capable of recording true unipolar ECG leads for the first time without making use of the Wilson central terminal. In addition to the convenience in applications such as continuous monitoring and rapid diagnosis, the information in unipolar recordings may yield unique diagnostic information as it avoids the need to essentially subtract data or make use of the averaging effect imposed from the Wilson central terminal. The system also allows direct, real-time software calculation of signals corresponding to standard ECG leads which achieve correlations in excess of 92% with a gold standard ECG during a parallel in vivo recording. In addition, the implemented circuit is wideband (0.05-1000 Hz), compatible with standard (Ag/AgCl) bio-potential electrodes, and dry (paste-less) textile electrodes. The circuit is also low power, requiring less than 50 mW (when powered at 12 V) per standard ECG lead (two channels required). It is therefore well suited for wearable, long-term applications.

Moderate alcohol consumption predicts long-term mortality in elderly subjects with chronic heart failure.

OBJECTIVE: Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. SETTINGS: community-dwelling from 5 regions of Italy. PARTICIPANTS: A cohort of 1332 subjects aged 65 and older. MEASUREMENT: Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). RESULTS: In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; p<0.01) but it is predictive of mortality in the presence of CHF (HR=1.29; CI 95% 1.05-1.97; p<0.05). CONCLUSIONS: Our data demonstrates that moderate alcohol consumption is associated with an increased long-term mortality risk in the elderly in the presence of CHF.

Noncoronary aortic cusp rupture in an adult patient with ventricular septal defect: echocardiographic diagnosis.

Aortic regurgitation is a common complication of ventricular septal defects. The most common mechanism is right or noncoronary cusp prolapse. Other mechanisms are right or noncoronary cusp fibrosis resulting in thickening and restricted motion of the leaflets or infective endocarditis leading to cusp perforation. We describe a case of subacute and severe aortic regurgitation due to noncoronary cusp prolapse resulting in the development of a large aneurysm and rupture of the noncoronary sinus of Valsalva into the right atrium.

Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures.

UNLABELLED: This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures. INTRODUCTION: Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis. METHODS: We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophage colony stimulating factor (M-CSF), transforming growth factor ß (TGFß), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohistochemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines. RESULTS: We found an increase of RANKL/OPG ratio, M-CSF, SOST and DKK-1 in fractured patients, whereas TGFß was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFß compared to bone, whereas the production of DKK-1 and SOST was higher in bone. CONCLUSIONS: We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

Combined left pulmonary artery sling transposition and tracheal lobe resection through a median sternotomy: a case report.

INTRODUCTION: The aim of this paper was to report the management of a very rare malformative association of Left Pulmonary Artery (LPA) sling and Tracheal Lobe which is not still reported in scientific literature. MATERIALS AND METHODS: The Authors describe the clinical case of a 6 years old girl that was admitted for chronic respiratory symptoms associated with recurrent upper respiratory infections. The CT-scan with virtual bronchoscopy showed an ectopic bronchus arising from the right side of the upper third of the trachea and ending in an accessory pulmonary lobe, covered by normal pleura, located in the upper mediastinum. The tracheo-broncoscopy showed a stenotic tracheal lumen with complete cartilaginous ring with an evident vascular pulsation in the middle of stenotic tract. An angio-CT confirmed the vascular anomalies with the LPA which passes between the lower trachea and the accessory tracheal bronchus and the coexistence of a persistent left superior vena cava. The surgical approach, after the thoracoscopic exploration, was a double procedure through a median sternotomy with cardiopulmonary bypass has permitted to excise completely the tracheal lobe and to reimplant the left pulmonary artery into the main pulmonary artery. RESULTS: No more upper respiratory symptoms or pulmonary infections have been observed during the clinical and instrumental follow up. CONCLUSIONS: Current controversy in the management of Pulmonary Artery sling include surgical approach (median sternotomy versus left thoracotomy), use or non-use of cardiopulmonary bypass, and reimplantation versus translocation with distal tracheal resection. In our experience LPA reimplantation and tracheal lobe resection have been made easily and safely by the same sternotomy utilized for the cardio-pulmonary by-pass.

Remifentanil-TCI and propofol-TCI for conscious sedation during fibreoptic intubation in the acromegalic patient.

BACKGROUND AND OBJECTIVE: To evaluate the use of remifentanil-propofol administered as target-controlled infusion during awake fibreoptic intubation for anticipated difficult tracheal intubation in acromegalic patients. METHOD: In all, 20 consecutive acromegalic patients underwent elective endonasal endoscopic transsphenoidal pituitary surgery. After premedication with midazolam 0.03 mg kg(-1), initially a target-controlled infusion of remifentanil 1.0 ng mL(-1) and propofol 1.5 microg mL(-1) was started. The fibreoptic intubation was performed by the same physician experienced with the fibreoptic technique. During the fibreoptic procedure the target concentrations of remifentanil and propofol ranged between 1.0 and 5.0 ng mL(-1), and between 1.5 and 3.5 microg mL(-1), respectively. Changes in heart rate and mean arterial pressure were recorded during airway manipulation, during tracheal intubation, and at 1 and 3 min after. On the first postoperative day, patient recall and level of discomfort during fibreoptic intubation were evaluated. RESULTS: Endotracheal intubation was efficaciously and quickly secured in all patients. A significant increase in mean arterial pressure and heart rate was recorded only during tracheal intubation (P < 0.05). Oxygenation was sufficient and no bradypnea or apnoea was recorded. All patients later described their anaesthetic experience as satisfactory. During fibreoptic intubation, remifentanil (ng mL(-1)) and propofol (microg mL(-1)) mean effect-site concentrations were 3.2 +/- 0.3 and 2.0 +/- 1.0, respectively. CONCLUSION: Remifentanil and propofol target-controlled infusion provided satisfactory conscious sedation allowing for successful oral fibreoptic intubation in acromegalic patients with no recall.

Role and effectiveness of cardiovascular magnetic resonance in the diagnosis, preoperative evaluation and follow-up of patients with congenital heart diseases.

The substantial advances in the medical and surgical treatment of congenital heart diseases have dramatically improved patients' life expectancy, as well as increased the number of those needing lifelong monitoring to identify complications and residual defects. Magnetic resonance imaging (MRI) is an ideal imaging modality for the follow-up of these young patients owing to its noninvasiveness, high reproducibility and morphological and functional accuracy. This paper describes the most appropriate MRI techniques and sequences for the study of cardiovascular heart diseases on the basis of an analysis of MRI studies carried out between January 2003 and June 2006 on 274 patients affected by all of the main congenital cardiovascular malformations, as well as a review of the literature. The advantages of MRI with respect to other imaging techniques, the problems encountered and the main clinical applications and indications of MRI, with special reference to the most common disease entities, are then discussed to define the role, the utility and the future perspectives of this imaging technique in the study of congenital heart diseases.